OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a child with neurodevelopmental disorder caused by homozygous frameshift variant of the TRAPPC6B gene, and to provide reference for the diagnosis of the disease. METHODS: A child with neurodevelopmental disorder caused by homozygous variant of TRAPPC6B gene who was admitted to the Children's Hospital Affiliated to Zhengzhou University in March 2023 due to "inability to stand and walk independently at 1 year and 3 months old" was selected as the study object. The clinical data were collected by retrospective analysis method. Target region high-throughput sequencing was carried out on the child and parental peripheral blood samples, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The pathogenicity of variant was rated according to the Standards and Guidelines for the Interpretation of Sequence Variants released by American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as ACMG guidelines). The study has been approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethic No.2022-K-L025). RESULTS: The child was a 1-year-and-3-months-old boy whose parents were sib mating. The child presented with global developmental delay, microcephaly and short stature. MRI showed poor white matter myelination, abnormal signals of bilateral periventricular white matter and bilateral external sac, thin corpus callosum, and widening of the third ventricle. Genetic testing revealed that the TRAPPC6B gene of the child had a homozygous variant of c.240_241delAA (p.Q80Hfs*34), which was inherited from his parents. According to the ACMG guidelines, this variant was judged to be potentially pathogenic (PVS1_Strong+PM2_Supporting+PM3_Supporting), resulting in premature occurrence of terminator codons and a change in the three-dimensional structure of protein. The variant was located in the functional domain, which may directly affect the functional domain of the protein, resulting in functional domain defects. CONCLUSION The frameshift variation of TRAPPC6B gene c.240_241delAA (p.Q80Hfs*34) has not been reported, which may be the genetic cause of neurodevelopmental disorders in child in this study. These findings expand the variation spectrum of TRAPPC6B gene and provide basis for genetic counseling and prenatal diagnosis of this family.
Humans ; Infant ; Male ; Frameshift Mutation ; Homozygote ; Neurodevelopmental Disorders/genetics* ; Phenotype

Objective:To observe the effectiveness of extracorporeal counterpulsation therapy in patients with heart failure in ischaemic cardiomyopathy.Methods:A total of 112 patients with ischemic cardiomyopathy and heart failure admitted to the Second Affiliated Hospital of Xingtai Medical College from August 2020 to June 2023 were prospectively selected and divided into two groups by random number table method. The control group was treated with conventional drugs and conventional cardiac rehabilitation program, and the observation group was combined with external counterbeating therapy on the basis of the control group. The levels of N-terminal B-type brain natriuretic peptide (NTproBNP), soluble growth stimulation-expression gene-2 protein (sST2), neutrophil gelatinase-associated lipid carrier protein (NGAL), galactin-3 (Gal-3), cardiopulmonary exercise test (CPET) parameters and cardiac ultrasound indexes were compared between the two groups before and after treatment. The curative effect and the rate of re-hospitalization within 6 months were compared between the two groups.Results:After treatment, the levels of NTproBNP, sST2, NGAL and Gal-3 in the observation group were lower than those in the control group: (1941.36 ± 312.59) ng/L vs. (2674.22 ± 404.64) ng/L, (44.78 ± 3.97) ng/L vs. (52.45 ± 4.13) ng/L, (22.63 ± 3.65) μg/L vs. (26.41 ± 3.77) μg/L, (4.63 ± 1.29) ng/L vs. (6.11 ± 1.78) ng/L, there were statistical differences ( P<0.05); the maximum kilogram oxygen uptake (VO 2max/kg), maximum kilogram oxygen uptake as a percentage of predicted value (VO 2max/kg%pred), maximum minute ventilation as a percentage of predicted value (VEmax%pred) in the observation group were higher than those in the control group: (22.41 ± 2.23) ml/(min·kg) vs. (21.35 ± 2.09) ml/(min·kg), (83.79 ± 11.04)% vs. (78.74 ± 10.14)%, (88.95 ± 12.74)% vs. (75.45 ± 11.14)%, there were statistical differences ( P<0.05 or <0.01); the left ventricular ejection fraction (LVEF) in the observation group was higher than that in the control group and the left ventricular posterior wall thickness (LVPWT) and left ventricular posterior wall end-systolic thickness (PWS) were lower than those in the control group: (50.12 ± 3.87)% vs. (48.63 ± 3.74)%, (8.77 ± 1.58) mm vs. (9.63 ± 1.97) mm, (9.34 ± 1.54) mm vs. (10.14 ± 1.79) mm, there were statistical differences ( P<0.05). There was no statistical difference in the total effective rate between the two groups ( P>0.05). The patient readmission rate within 6 months of follow-up in the observation group was lower than that in the control group: 5.45%(3/55) vs. 20.00%(11/55), there was statistical difference( χ2 = 5.24, P<0.05). Conclusions:Extracorporeal counterpulsation therapy for the treatment of heart failure in ischaemic cardiomyopathy can improve the cardiorespiratory function, reduce the expression of NTproBNP, sST2, NGAL and Gal-3, and decrease the patient readmission rate.

AIM:Study on the bioequivalence of rivaroxaban tablets from two different manufactur-ers in healthy subjects under fasting and postpran-dial conditions.METHODS:Adopting a single cen-ter,randomized,open,fasting and postprandial,four cycle,fully repeated crossover trial design.28 healthy male and female subjects were given oral administration of either the test or reference for-mulation(10 mg)on an empty stomach or in a post-prandial state,with a cleaning period of 7 days be-tween cycles.The concentration of rivaroxaban in the plasma(heparin sodium)of the subjects was measured using liquid chromatography tandem mass spectrometry(LC-MS/MS),and pharmacoki-netic(PK)parameters were calculated using Phoe-nix WinNonlin 7.0 software to evaluate the bio-equivalence of the test and reference formulations.RESULTS:Fasting group:After oral administration of the investigational drug,the Cmax of the test formula-tion and reference formulation were(200.96±68.99)ng/mL and(196.96±50.97)ng/mL,respec-tively,and the AUC0-t were(1 439.93±493.94)h·ng·mL-1 and(1 395.90±411.49)h·ng·mL-1,respectively,the AUC0-∞ were(1 506.56±511.47)h·ng·mL-1 and(1 451.94±417.89)h·ng·mL-1,respectively,the 90％confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ were 91.87％-103.37％,95.00％-105.07％,95.33％-105.57％,respectively,the 90％CI of the intra-individual standard devia-tion ratio(SWT/SWR)for Cmax,AUC0-t,AUC0-∞were 0.88-1.73,0.74-1.45 and 0.72-1.41,respectively.Post-prandial group:After oral administration of the ex-perimental drug,the Cmax of the test and reference formulations were(241.23±54.44)ng/mL and(226.54±48.04)ng/mL,respectively,and the AUC0-t were(1 383.26±437.05)h·ng·mL-1 and(1 333.54±372.53)h·ng·mL-1,respectively,the AUC0-∞ were(1 404.01±439.89)h·ng·mL-1 and(1 352.31±374.45)h·ng·mL-1,respectively,the 90％confi-dence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ were 100.92％-110.50％,98.30％-108.31％,and 98.46％-108.39％,respective-ly,the 90％CI of the intra-individual standard devia-tion ratio(SWT/SWR)for Cmax,AUC0-t and AUC0-∞ were 0.63-1.29,0.78-1.61 and 0.79-1.61,respectively.CONCLUSION:Bioequivalence of the two prepara-tions in fasting and postprandial state in healthy subjects.

This study aims to establish BHK-21 stable cell lines expressing APN from four species(human,pig,dog,and cat),the APN fragments were amplified from pEGFP-C1-APN plasmids of the four species stored in the laboratory to generate the recombinant plasmids pcDNA4.0-APN.Af-ter the recombinant plasmids were transfected into BHK-21 cells,the stable BHK-21 cell lines ex-pressing the APNs were selected by two rounds of limited dilution.The constructed BHK-21 cell lines were identified by indirect immunofluorescence assay(IFA),and their susceptibility to PD-CoV and TGEV was tested for these four cell lines.Virus infection experiments revealed that PD-CoV infected cells expressing human,pig,and dog APNs,while it did not infect cells expressing cat APN.Simultaneously,TGEV infected cells expressing pig,dog,and cat APNs,but did not infect cells expressing human APN.The results suggest that the risk of cross-species infection for different coronaviruses and the established cell line can be used effectively to evaluate the virus in-fection.The findings also revealed that PDCoV has the potential risk of cross-species infection of human and dog,and TGEV has the potential risk of cross-species infection of dog and cat.These results provide a basis for the prevention and control strategy of coronaviruses.

The incidence rate of metabolic associated fatty liver disease(MAFLD)is gradually increasing,and it has become a common chronic liver disease globally.MAFLD is closely associated with metabolic dysfunction,with dietary and exercise interventions as the primary treatment method,among which dietary control is of particular importance.This article summarizes related articles on the prevention and treatment of MAFLD through different fasting patterns in recent years,and the analysis showed that by restricting food intake and controlling calorie consumption,fasting therapy can help to reduce body weight and improve metabolic disorders.Further studies and clinical practice are needed to explore and validate the value of different fasting patterns in the prevention and treatment of MAFLD.

Objective:To explore the clinical phenotype and genetic characteristics of a child with neurodevelopmental disorder caused by homozygous frameshift variant of the TRAPPC6B gene, and to provide reference for the diagnosis of the disease. Methods:A child with neurodevelopmental disorder caused by homozygous variant of TRAPPC6B gene who was admitted to the Children′s Hospital Affiliated to Zhengzhou University in March 2023 due to " inability to stand and walk independently at 1 year and 3 months old" was selected as the study object. The clinical data were collected by retrospective analysis method. Target region high-throughput sequencing was carried out on the child and parental peripheral blood samples, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The pathogenicity of variant was rated according to the Standards and Guidelines for the Interpretation of Sequence Variants released by American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as ACMG guidelines). The study has been approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No.2022-K-L025). Results:The child was a 1-year-and-3-months-old boy whose parents were sib mating. The child presented with global developmental delay, microcephaly and short stature. MRI showed poor white matter myelination, abnormal signals of bilateral periventricular white matter and bilateral external sac, thin corpus callosum, and widening of the third ventricle. Genetic testing revealed that the TRAPPC6B gene of the child had a homozygous variant of c. 240_241delAA (p.Q80Hfs*34), which was inherited from his parents. According to the ACMG guidelines, this variant was judged to be potentially pathogenic (PVS1_Strong+ PM2_Supporting+ PM3_Supporting), resulting in premature occurrence of terminator codons and a change in the three-dimensional structure of protein. The variant was located in the functional domain, which may directly affect the functional domain of the protein, resulting in functional domain defects. Conclusion:The frameshift variation of TRAPPC6B gene c. 240_241delAA (p.Q80Hfs*34) has not been reported, which may be the genetic cause of neurodevelopmental disorders in child in this study. These findings expand the variation spectrum of TRAPPC6B gene and provid basis for genetic counseling and prenatal diagnosis of this family.

Objective:To explore the effect of carboxylated polyamidoamine (PAMAM-COOH) in combination with magnesium ions on the remineralization ability of amorphous calcium phosphate (ACP) in inducing remineralization of dentin collagen fibers in a 50% ethanol solution.Methods:Forty-five intact third molars extracted for impaction reasons were obtained from the College & Hospital of Stomatology, Guangxi Medical University. Two types of demineralized dentin specimens were prepared: ①Fully demineralized dentin ( n=30), specimens were immersed in 17% ethylenediaminetetraacetic acid (EDTA) (pH=7.4) at room temperature for 14 days with daily solution refreshment; ②Partially demineralized dentin ( n=15), specimens were treated with 37% phosphoric acid gel (Ultra-Etch, Ultradent) for 15 seconds followed by thorough rinsing with deionized water. Three remineralization groups were established for demineralized dentin treatment: ①Control group, 50% ethanol solution; ②ACMP group, 50% ethanol solution containing amorphous magnesium calcium phosphate (ACMP); ③PAMAM-COOH/ACMP group, 50% ethanol solution incorporating carboxylated polyamidoamine dendrimer-modified ACMP (PAMAM-COOH/ACMP). The chemical composition of remineralization solutions was analyzed by Fourier-transform infrared spectrum (FTIR). The morphology and particle size distribution of nanoparticles were characterized using transmission electron microscope (TEM). The fully demineralized dentin specimens were treated with three different remineralization solutions (37 ℃ for 7 days) respectively. The mineralization of the dentin collagen fibers surface was observed using scanning electron microscope (SEM) and the distribution of minerals inside and outside the collagen fibers was examined by using TEM. The partially demineralized dentin specimens were treated with fluorescence-labeled remineralization solutions (37 ℃ for 7 days) respectively, followed by analysis using confocal laser scanning microscopy (CLSM) to quantitatively evaluate the penetration depth of the mineralization agents. Results:FTIR analysis confirmed the presence of characteristic absorption peaks corresponding to phosphate (PO 43-) groups, carbon-nitrogen bonds, and amide linkages in the PAMAM-COOH/ACMP nanocomposite. TEM observed that the PAMAM-COOH/ACMP nanoparticles exhibited an average particle size of (36.85±8.02) nm in an amorphous state. SEM observation indicates continuous mineral deposition on dentin collagen fibers in the PAMAM-COOH/ACMP group, while no mineral deposition in the control group and only minimal deposition in the ACMP group. TEM showed no mineral deposition inside or outside the collagen fibers in the control group, only external mineral deposition in the ACMP group, and high-density mineral deposition both inside and outside the fibers in the PAMAM-COOH/ACMP group. CLSM analysis revealed a statistically significant difference ( P<0.05) in the depth of mineralized substances entering dentin tubules between ACMP group and PAMAM-COOH/ACMP group. Conclusions:The remineralization system of 50% ethanol solution incorporating PAMAM-COOH/ACMP successfully achieved the internal and external mineralization of demineralized dentin collagen fibers.

Objective:To investigate the efficacy of radiotherapy in patients with advanced esophageal cancer receiving first-line chemoimmunotherapy.Methods:A retrospective analysis was conducted on the data of 137 patients with Stage Ⅳ esophageal squamous cell carcinoma (ESCC) treated at our hospital from January 2018 to May 2023. These patients were divided into two groups: a group treated with first-line chemoimmunotherapy combined with radiotherapy (chemoimmunotherapy + radiotherapy group, n = 43) and a group treated with only chemoimmunotherapy ( n = 94). Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between the groups. With overall survival (OS) and progression-free survival (PFS) as study endpoints, the survival data were analyzed using the Kaplan-Meier method, the log-rank test, and the Cox regression method. Results:Before calibration, the chemoimmunotherapy + radiotherapy group significantly outperformed the sole chemoimmunotherapy group in median PFS (13.6 months vs. 7.0 months; HR: 0.501, 95% CI: 0.309-0.811, P = 0.005). After calibration using the COX proportional-hazards model for age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, smoking history, T/N/M stage, and tumor location, the chemoimmunotherapy + radiotherapy group still had significant advantages in PFS (14.7 months vs. 7.0 months; HR: 0.441, 95% CI: 0.261-0.745, P = 0.002). IPTW analysis further confirmed this trend (13.9 months vs. 7.0 months; HR: 0.492, 95% CI: 0.304-0.795, P < 0.001). Specifically, the median OS of the chemoimmunotherapy + radiotherapy group demonstrated significant improvement in all analyses: pre-calibration (29.5 months vs. 18.0 months; HR: 0.507, 95% CI: 0.297-0.867, P = 0.013), after calibration using the Cox model (27.5 months vs. 16.7 months; HR: 0.470, 95% CI: 0.266-0.830, P = 0.009), and after calibration using IPTW (29.5 months vs. 16.9 months; HR: 0.448, 95% CI: 0.262-0.764, P < 0.001). Conclusions:The combination of radiotherapy and first-line chemoimmunotherapy can significantly improve survival outcomes of patients with advanced ESCC, suggesting its potential as a standard treatment strategy.

Objective:To explore the effect of carboxylated polyamidoamine (PAMAM-COOH) in combination with magnesium ions on the remineralization ability of amorphous calcium phosphate (ACP) in inducing remineralization of dentin collagen fibers in a 50% ethanol solution.Methods:Forty-five intact third molars extracted for impaction reasons were obtained from the College & Hospital of Stomatology, Guangxi Medical University. Two types of demineralized dentin specimens were prepared: ①Fully demineralized dentin ( n=30), specimens were immersed in 17% ethylenediaminetetraacetic acid (EDTA) (pH=7.4) at room temperature for 14 days with daily solution refreshment; ②Partially demineralized dentin ( n=15), specimens were treated with 37% phosphoric acid gel (Ultra-Etch, Ultradent) for 15 seconds followed by thorough rinsing with deionized water. Three remineralization groups were established for demineralized dentin treatment: ①Control group, 50% ethanol solution; ②ACMP group, 50% ethanol solution containing amorphous magnesium calcium phosphate (ACMP); ③PAMAM-COOH/ACMP group, 50% ethanol solution incorporating carboxylated polyamidoamine dendrimer-modified ACMP (PAMAM-COOH/ACMP). The chemical composition of remineralization solutions was analyzed by Fourier-transform infrared spectrum (FTIR). The morphology and particle size distribution of nanoparticles were characterized using transmission electron microscope (TEM). The fully demineralized dentin specimens were treated with three different remineralization solutions (37 ℃ for 7 days) respectively. The mineralization of the dentin collagen fibers surface was observed using scanning electron microscope (SEM) and the distribution of minerals inside and outside the collagen fibers was examined by using TEM. The partially demineralized dentin specimens were treated with fluorescence-labeled remineralization solutions (37 ℃ for 7 days) respectively, followed by analysis using confocal laser scanning microscopy (CLSM) to quantitatively evaluate the penetration depth of the mineralization agents. Results:FTIR analysis confirmed the presence of characteristic absorption peaks corresponding to phosphate (PO 43-) groups, carbon-nitrogen bonds, and amide linkages in the PAMAM-COOH/ACMP nanocomposite. TEM observed that the PAMAM-COOH/ACMP nanoparticles exhibited an average particle size of (36.85±8.02) nm in an amorphous state. SEM observation indicates continuous mineral deposition on dentin collagen fibers in the PAMAM-COOH/ACMP group, while no mineral deposition in the control group and only minimal deposition in the ACMP group. TEM showed no mineral deposition inside or outside the collagen fibers in the control group, only external mineral deposition in the ACMP group, and high-density mineral deposition both inside and outside the fibers in the PAMAM-COOH/ACMP group. CLSM analysis revealed a statistically significant difference ( P<0.05) in the depth of mineralized substances entering dentin tubules between ACMP group and PAMAM-COOH/ACMP group. Conclusions:The remineralization system of 50% ethanol solution incorporating PAMAM-COOH/ACMP successfully achieved the internal and external mineralization of demineralized dentin collagen fibers.

Objective:To investigate the correlations and regression models among adenoid-nasopharynx measurement indices (the linear ratio A/N, the two-dimensional area ratio 2D_A/N, and the three-dimensional volume ratio 3D_A/N), to evaluate the feasibility of predicting three-dimensional parameters from two-dimensional measurements.Methods:This cross-sectional study analysed 4 307 CBCT scans and lateral nasopharyngeal radiographs from 4-12-year-old children (July 2023-January 2025). Children with acute infection, major systemic disease, craniofacial anomalies, prior maxillofacial surgery, poor-quality images, or no consent were excluded. 3D_A/N was defined as adenoid volume/(adenoid+airway volume); 2D_A/N as adenoid area/total area; and linear A/N as adenoid thickness/nasopharyngeal thickness. Pearson correlation and multiple linear regression were used to quantify 2D-to-3D agreement, and independent-sample t-tests were employed to compare age, sex and seasonal subgroups. Results:(1) Significant sex-related differences in adenoid hypertrophy were detected at ages 5, 8, 9 and 11 years. In the 5-year-old group, females had significantly higher 3D_A/N and 2D_A/N values than males (3D_A/N: 0.76±0.10 vs. 0.74±0.10, t=-1.99, P=0.047; 2D_A/N: 0.66±0.10 vs. 0.64±0.09, t=-2.71, P=0.007). In the 8-year-old group, males exhibited significantly higher A/N and 3D_A/N values than females (A/N: 0.64±0.06 vs. 0.63±0.06, t=4.49, P<0.001; 3D_A/N: 0.66±0.12 vs. 0.64±0.12, t=2.00, P=0.046). In the 9-year-old group, males showed significantly higher 3D_A/N values than females (0.65±0.11 vs. 0.63±0.12, t=2.46, P=0.014). In the 11-year-old group, males had significantly higher A/N values than females (0.62±0.06 vs. 0.59±0.05, t=4.79, P<0.001). (2) The linear A/N ratio correlated moderately with 3D_A/N ( r=0.82), whereas, 2D_A/N showed an excellent correlation ( r=0.97); multiple regression confirmed 2D_A/N as the principal predictor of 3D_A/N. (3) Seasonal analysis revealed markedly greater adenoid hypertrophy in winter than in summer for children aged 4-9 years, while, no seasonal difference was found in the 10-12 year group; overall, winter hypertrophy was most pronounced in younger children. Conclusion:2D_A/N demonstrates a marked advantage in predicting 3D_A/N. When combined with A/N and age factors, it can effectively model changes in the 3D volume ratio of the adenoid, underscoring the clinical value of lateral cephalometric measurements for evaluating adenoid hypertrophy in children. Moreover, adenoid hypertrophy is influenced by age, sex and seasonal factors.