OBJECTIVE: To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. METHODS: The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). RESULTS: Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a "cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. CONCLUSION The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.
Humans ; Male ; Female ; Child, Preschool ; Infant ; Child ; Olivopontocerebellar Atrophies/genetics* ; Arginine-tRNA Ligase/genetics* ; Mutation ; Cerebellar Diseases

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a child with Progressive familial intrahepatic cholestasis type 8 (PFIC8). METHODS A child with PFIC diagnosed at Beijing Children's Hospital Affiliated to Capital Medical University in September 2025 was selected as the study subject. Peripheral venous blood samples were collected from the child and her parents. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out. Candidate variants were validated by Sanger sequencing. The pathogenicity of the candidate variants was classified based on the guidelines from American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Beijing Children's Hospital Affiliated to Capital Medical University (Ethics No.: 2023-E-126-Y). RESULTS: The proband, a 2-month-old female infant, had manifested jaundice of the skin and sclera, and slightly distended abdomen. She had no visible abdominal wall varicose veins, soft abdomen, and no palpable masses. Biliary atresia was ruled out by intraoperative cholangiography. WES revealed that she has harbored compound heterozygous variants of KIF12 gene, namely c.809C>T (p.Ala270Val) and c.1313G>A (p.Arg438Lys), which were verified by Sanger sequencing to have derived from her mother and father, respectively. According to the ACMG guidelines, both variants were classified as variants of uncertain significance (VUS). Based on the pre-defined search strategy, 10 articles were retrieved, which involved 25 PFIC cases, including 5 from China. Together with the proband of this study, the 26 PFIC patients have primarily presented with high GGT cholestasis, with the genetic cause in all cases attributed to variants of the KIF12 gene. CONCLUSION The c.809C>T and c.1313G>A compound heterozygous variants of the KIF12 gene probably underlay the pathogenesis of cholestatic liver disease in this child. Above findings have enriched the mutational and phenotypic spectra of PFIC8.
Humans ; Kinesins/genetics* ; Female ; Cholestasis, Intrahepatic/genetics* ; Infant ; Heterozygote ; Mutation ; Exome Sequencing ; Male

Objective:Assessing the therapeutic efficacy of methotrexate(MTX)-modified magnetic nanoparticles in thermo-chemotherapy for rat breast cancer and its impact on immune function.Methods:Female Wistar rats were subcutaneously inoculated with breast cancer Walker-256 cells to establish a transplantation tumor model,and injected with polyethyleneimine(PEI)-modified Fe3O4 magnetic nanoparticles(47T group,42T group and multiple 42T group)or MTX-modified Fe3O4 magnetic nanoparticles(47TC group,42TC group and multiple 42TC group)for thermotherapy under the magnetic field at different temperatures(47℃and 42℃).The rats injected with MTX-modified magnetic fluid only(MFC group)and the tumor-bearing rats without any treatment(blank control group),with irradiation treatment in an alternating magnetic field only for 30 minutes(M group),with injection of PEI-modified magnetic fluid only(MF group),with treatment of MTX-mono drug(MTX group)and not inoculated with tumor cells(normal group)were used as control groups.X-ray radiography was used to display the distribution of magnetic fluid in the tumor tissue 24 hours,2 weeks and 2 months after intra-tumor injection.After 24 hours of treatment,three rats were selected from each of the 47T and 47TC groups,and the effect of magnetic fluid on tumor cells was observed under an electron microscope after execution.After 14 days of treatment,the tumor volume of rats was measured and statistically analyzed.At the same time,4 rats were selected from each of the 47TC,47T,42TC,42T,MFC,MTX,blank control and normal groups,and the levels of IL-2,IFN-γ and IL-4 in peripheral blood were detected by ELISA method.The remaining rats were observed for long-term survival.Results:The magnetic nanoparticles were evenly distributed in the center of the tumor but unevenly distributed at the tumor's edge;they primarily localize amomg tumor cells and can penertrate into tumor cells.Tumor growth was inhibited in rats in the 47TC,47T,multiple 42TC and multiple 42T groups(all P<0.05),and the survival rates of the rats were high.As compared with the blank control group,the levels of IL-2 and IFN-γ were increased while the IL-4 level was decreased in the 47TC and 47T groups(all P<0.05).Conclusion:Thermo-chemotherapy at 47℃for 30 minutes and multiple sessions at 42℃for 60 minutes can partially inhibit tumor growth and prolong rat survival.This effect maybe related to the thermo-chemotherapy at 47℃for 30 minutes which can activate the body's immune function.

Objective:To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. Methods:The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). Results:Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a " cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. Conclusion:The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.

Objective:Assessing the therapeutic efficacy of methotrexate(MTX)-modified magnetic nanoparticles in thermo-chemotherapy for rat breast cancer and its impact on immune function.Methods:Female Wistar rats were subcutaneously inoculated with breast cancer Walker-256 cells to establish a transplantation tumor model,and injected with polyethyleneimine(PEI)-modified Fe3O4 magnetic nanoparticles(47T group,42T group and multiple 42T group)or MTX-modified Fe3O4 magnetic nanoparticles(47TC group,42TC group and multiple 42TC group)for thermotherapy under the magnetic field at different temperatures(47℃and 42℃).The rats injected with MTX-modified magnetic fluid only(MFC group)and the tumor-bearing rats without any treatment(blank control group),with irradiation treatment in an alternating magnetic field only for 30 minutes(M group),with injection of PEI-modified magnetic fluid only(MF group),with treatment of MTX-mono drug(MTX group)and not inoculated with tumor cells(normal group)were used as control groups.X-ray radiography was used to display the distribution of magnetic fluid in the tumor tissue 24 hours,2 weeks and 2 months after intra-tumor injection.After 24 hours of treatment,three rats were selected from each of the 47T and 47TC groups,and the effect of magnetic fluid on tumor cells was observed under an electron microscope after execution.After 14 days of treatment,the tumor volume of rats was measured and statistically analyzed.At the same time,4 rats were selected from each of the 47TC,47T,42TC,42T,MFC,MTX,blank control and normal groups,and the levels of IL-2,IFN-γ and IL-4 in peripheral blood were detected by ELISA method.The remaining rats were observed for long-term survival.Results:The magnetic nanoparticles were evenly distributed in the center of the tumor but unevenly distributed at the tumor's edge;they primarily localize amomg tumor cells and can penertrate into tumor cells.Tumor growth was inhibited in rats in the 47TC,47T,multiple 42TC and multiple 42T groups(all P<0.05),and the survival rates of the rats were high.As compared with the blank control group,the levels of IL-2 and IFN-γ were increased while the IL-4 level was decreased in the 47TC and 47T groups(all P<0.05).Conclusion:Thermo-chemotherapy at 47℃for 30 minutes and multiple sessions at 42℃for 60 minutes can partially inhibit tumor growth and prolong rat survival.This effect maybe related to the thermo-chemotherapy at 47℃for 30 minutes which can activate the body's immune function.

Objective:To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. Methods:The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). Results:Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a " cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. Conclusion:The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.

Objective To observe the value of radiomics combined with CT features for distinguishing mycoplasma pneumonia(MP)and non-MP in children.Methods Data of 153 children with pneumonia were retrospectively analyzed.The children were divided into MP group(n=101)and non-MP group(n=52)according to mycoplasma RNA detection,and also were divided into training set(n=107,including 71 MP and 36 non-MP)and validation set(n=46,including 30 MP and 16 non-MP)at the ratio of 7∶3.CT findings were compared between groups.Six best CT features were selected in training set using F test algorithm,and a CT model was constructed using logistic regression(LR)method.The best radiomics features were extracted and screened in training set,and machine learning(ML)models were constructed using LR,support vector machine(SVM),random forest(RF),linear discriminant analysis(LDA)and stochastic gradient descent(SGD)classifiers,respectively.Based on the best CT features and radiomics features,CT-ML models were constructed using the above classifiers.Receiver operating characteristic curves were drawn,and the areas under the curve(AUC)were calculated,the efficacy of each model for distinguishing MP and non-MP was evaluated.Results Lesions involved the upper,middle and lower lobe of right lung,thickened bronchial wall,tree bud sign and edge retract sign were the best CT features.AUC of CTLR was 0.710,of MLLR,MLSVM,MLRF,MLLDA and MLSGD in validation set was 0.715,0.663,0.623,0.706 and 0.494,respectively,and MLLR was the optimal radiomics model.AUC of CT-MLLR,CT-MLSVM,CT-MLRF,CT-MLLDA and CT-MLSGD in validation set was 0.813,0.823,0.649,0.796 and 0.665,respectively,and CT-MLSVM was the optimal CT-ML model.In training set,AUC of CT-MLSVM(0.840)was higher than that of CTLR and MLLR model(AUC=0.713,0.740,both P＜0.05).In validation set,no significant difference of AUC was found among CTLR,MLLR and CT-MLSVM(AUC=0.710,0.715 and 0.823,all P＞0.05).Conclusion Radiomics combined with CT features could effectively distinguish MP and non-MP in children.

Perinatal depression is a psychological disorder that occurs during pregnancy and within one year of delivery, which can seriously affect the physical and mental health of pregnant and postpartum women, as well as the cognitive and behavioral abilities of offspring, with potential multigenerational effects. Therefore, it is important to identify its potential modifiable risk factors. Phthalic acid esters (PAEs), as common environmental endocrine disruptors, can affect maternal estrogen through multiple mechanisms and are important potential modifiable risk factors for developing maternal perinatal depression. At present, studies on the correlation between PAEs and perinatal depression are still very limited, and the mechanisms by which PAEs affect perinatal depression have not been clarified. Based on existing epidemiological and toxicological studies at home and abroad, the article briefly introduced the characteristics of multiple pathways, high doses, and long-term exposure to maternal PAEs, focused on reviewing the current status of epidemiological studies, pointed out the possible associations between some specific PAEs exposure and elevated risk of perinatal depression. It also summarized the potential roles of hormone-neurotransmitter pathway, inflammation mediation, gene regulation, and other possible mechanisms in the association between exposure to PAEs and perinatal depression. The article concluded with a look at how future research on the association between exposure to PAEs and perinatal depression can be scientifically validated, with a view to providing more high-quality evidence for the scientific prevention of the onset and progression of maternal depressive symptoms.

Objective:To study the relationship between endoplasmic reticulum stress (ERS) and apoptotic protein and myocardial pathological changes in rats after endostar combined with low-dose X-ray irradiation.Methods:Forty SD rats were evenly divided into four groups: control group (intraperitoneal injection of equal volume physiological saline, once per day, 14 d), endostar group (intraperitoneal injection of endostar 6 mg/kg, once per day, 14 d), irradiation group (15 Gy divided into 3 times X-ray irradiation) and combination group (intraperitoneal injection of endostar after irradiation at the same dose and time as the endostar group). At 1 and 6 months after treatment, myocardial tissues of rats were prepared for HE staining and Masson staining to observe the myocardial histological changes. TUNEL assay was used to detect myocardial cell apoptosis, and ImageJ software was utilized to calculate myocardial collagen volume fraction (CVF). The expression levels of ERS and apoptotic protein glucose-regulated protein 78 (GRP78), protein kinase-like endoplasmic reticulum kinases (PERK), CCAAT/enhancer binding protein homologous protein (CHOP) and cysteine-containing aspartate-specific protease-12 (Caspase-12) were detected by Western blot. One-way ANOVA was conducted using GraphPad Prism 8.0.1 software, and comparison between two groups was conducted using t-test. Results:At 6 months after treatment, the myocardial interstitium in the irradiation and combination groups was widened, showing strip-like or reticular fibrosis changes, and the myocardial interstitium had diffuse collagen fiber deposition. Compared with the control group, CVF was increased significantly (both P<0.01). At 1 and 6 months after treatment, the apoptotic index of myocardial cells in the combination group was significantly higher than that in the control group ( P<0.05, <0.001). At 1 and 6 months after treatment, the expression levels of GRP78 protein in the irradiation and combination groups were increased (all P<0.01), and the expression levels of PERK and CHOP proteins in the combination group were increased compared to those in the control group (both P<0.05). At 6 months after treatment, the expression levels of PERK and CHOP proteins in the irradiation group were increased compared to those in the control group (both P<0.05). Compared with the control group, Caspase-12 expression levels at 1 and 6 months after treatment were increased in the endostar, irradiation and combination groups (all P<0.05). Conclusions:The expression levels of ERS and apoptotic proteins are related to cardiac injury caused by irradiation in rats. After low-dose X-ray combined with endostar treatment, ERS is aggravated and myocardial apoptosis is increased.

Objective:To investigate therapeutic effect of cisplatin sequential recombinant human vascular endostatin thoracic perfusion in treatment of malignant pleural effusion.Methods:A total of 80 patients with malignant pleural effusion in Maoming People's Hospital from January 2018 to February 2021 were enrolled, and all patients were divided into 2 groups according to the random number table methods, each group with 40 cases. The control group was treated with small-bore catheter minimally invasive drainage combined with cisplatin thoracic perfusion, and the study group was treated with small-bore catheter minimally invasive drainage combined with cisplatin sequential recombinant human vascular endostatin thoracic perfusion. And then the clinical efficacy, expressions of vascular endothelial growth factor (VEGF) expression, pain degree and adverse reactions were compared of both groups.Results:The treatment efficacy rate of the study group was higher than that of the control group [90% (36/40) vs. 75% (30/40)], and the difference was statistically significant ( χ2 = 5.04, P < 0.05). After treatment, the level of VEGF in pleural fluid and serum of the study group was lower than that of the control group [(304±106) pg/ml vs. (598±159) pg/ml,(103±43) pg/ml vs. (189±49) pg/ml], and the difference was statistically significant ( t = 6.62, P < 0.001; t = 6.23, P < 0.001). After treatment, the visual analogue scale (VAS) score of the study group was lower than that of the control group [(3.7±0.3) scores vs. (4.4±0.7) scores], and the difference was statistically significant ( t = 2.10, P < 0.05). The incidence of adverse reactions including stethalgia, fever, nausea and vomiting in both groups had no statistically significant differences (all P > 0.05). Conclusions:Cisplatin sequential recombinant human vascular endostatin thoracic perfusion combined with small-bore catheter minimally invasive drainage can effectively ameliorate clinical symptoms, inhibit the expression of VEGF, and alleviate pain degree with no serious adverse reactions in patients with malignant pleural effusion.