Objective To investigate the expression levels of LINC02009 and LOC107984895 in peripheral lymphocytes of patients with atrial fibrillation and their clinical significance.Methods A total of 75 hospitalized patients with atrial fibrillation(50 with persistent atrial fibrillation and 25 with paroxysmal atrial fibrillation)from Kunming First People's Hospital between January 2023 and December 2023 were selected as study subjects,along with 50 normal control patients.Real-time quantitative PCR was used to detect the expression levels of LINC02009 and LOC107984895 in peripheral blood leukocytes of patients with atrial fibrillation.Logistic regression analysis was employed to assess the relationship between expression levels and risk factors for atrial fibrillation,and ROC curves were used to predict the diagnostic cut-off values for LINC02009 and LOC107984895 in diagnosing atrial fibrillation.Results There were statistically significant differences in baseline diseases such as hypertension and coronary heart disease,biochemical indicators such as Cr and BNP,and myocardial remodeling indicators such as LAd and LVEF between the AF(paroxysmal atrial fibrillation and persistent atrial fibrillation)group and the Normal group(P＜0.05).The expression levels of LINC02009 and LOC 107984895 in the plasma of the atrial fibrillation group were significantly higher than those in the control group(P＜0.05)and were negatively correlated with LVEF(P＜0.05).The areas under the curve(AUC)of LINC02009 and LOC 107984895 in predicting atrial fibrillation were 0.967(95％CI:0.938～0.995)and 0.900(95％CI:0.838～0.963),respectively.The optimal cut-off values were 1.985 and 0.915,with sensitivities of 88％and 76％,respectively,and specificities of 94％and 90％,respectively.Conclusion LINC02009 and LOC 107984895 are independent risk factors for atrial fibrillation and have certain predictive value for the occurrence of atrial fibrillation.

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 and genetic characteristics of a child with intellectual development disorder and seizures due to a variant of AP2M1 gene. METHODS: Clinical data of a child with intellectual development disorder and epilepsy who was admitted to the Department of Pediatric Neurology of the Third Affiliated Hospital of Zhengzhou University in January 2021 were retrospectively analyzed. Peripheral blood samples of the child and his parents were collected for whole exome sequencing. Candidate variant was verified by Sanger sequencing and pathogenicity analysis. The three-dimensional structure of the AP2M1 protein was visualized using Chimera v1.10.1 software. Pathogenicity of candidate variant was classified according to the Standards and Guidelines for the Interpretation of Sequence Variants from the American College of Medical Genetics and Genomics American College of Medical Genetics (ACMG). With "AP2M1 gene" "epilepsy" "intellectual disability" as the keywords, relevant cases were searched from CNKI, Wanfang Data knowledge service platform and PubMed databases with the search time spanning from the establishment of the database to September 2024. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2020-57). RESULTS: The child was a 8-years-and-6-months-old boy, who could raise his head at 3 months and sit alone at 8 months old. He could not walk alone at 1 year old and underwent 2 months' rehabilitation treatment, and could walk alone and call his parents at 1-and-a-half-years-old. At 4-years-and-10-months-old, he started to have frequent seizures, manifesting as low level of consciousness, body shaking, accompanied by blinking, lasting about a few seconds several times a day and could be relieved. With the treatment of sodium valproate combined with lamotrigine, the convulsions were controlled, but his movement and cognition were lagged behind. DNA sequencing revealed that he has harbored a novel variant of the AP2M1 gene (NM_004068.3) c.508C>T (p.Arg170Trp). Sanger sequencing confirmed that both of his parents were of the wild-type. According to the guidelines from the American College for Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PS2+PS4+PM1+PM2+PP2+PP3). The difference between the wild-type and mutant AP2M1 proteins can be clearly viewed through its three-dimensional structure. Two previous reports have included 5 cases due to the same variant. Common manifestations have included seizures (100%, 5/5), motor retardation (100%, 5/5), intellectual impairment (100%, 5/5), autism spectrum disorder (60%, 3/5), ataxia (100%, 5/5), and special facial features (20%, 1/5). CONCLUSION The c.508C>T (p.Arg170Trp) variant of the AP2M1 gene may underlie the intellectual retardation and seizure in this child.
Humans ; Male ; Child ; Intellectual Disability/genetics* ; Seizures/genetics* ; Exome Sequencing ; Mutation

Objective:To explore the alterations in gray matter morphology and contributing factors in patients with post-infectious olfactory dysfunction (PIOD) using voxel-based morphometry (VBM) and surface-based morphometry (SBM), thereby providing scientific insights into the neuropathological mechanisms underlying PIOD.Methods:A total of 46 PIOD patients (PIOD group) and 46 normosmic volunteers (control group) were recruited from the Smell and Taste Disorders Clinic of Beijing Anzhen Hospital, Capital Medical University, between January 2020 and December 2024. All participants underwent olfactory psychophysical tests (Sniffin′ Sticks) and olfactory event-related potential (oERP) examination. High-resolution T1-weighted 3D MRI structural images were obtained for both groups. VBM was employed to analyze inter-group differences in gray matter volume, while SBM was used to assess cortical thickness and folding index. Correlations between gray matter volume in significant difference brain regions and disease duration, Sniffin′ Sticks scores, oERP parameters were analyzed. A two-tailed P<0.05 was considered statistically significant. Results:No significant differences were observed in age, sex, education level, or Mini-Mental State Examination (MMSE) scores ( t=1.80, χ2=0.41, t=0.17, t=1.77, all P>0.05). Compared with controls, the PIOD group showed significantly lower Sniffin′ Sticks scores ( t=28.70, P<0.001), prolonged oERP latencies and reduced amplitudes (all P<0.001). VBM revealed significantly reduced gray matter volume in the right orbitofrontal cortex (OFC) in the PIOD group ( t=5.38, P<0.001). SBM demonstrated decreased cortical thickness in the right OFC ( t=5.27, P<0.001), with no significant differences in folding index. The gray matter volume in the right OFC was negatively correlated with disease duration ( r=-0.61, P<0.001), but no significant correlations were found with Sniffin′ Sticks scores or oERP parameters. Conclusion:Patients with PIOD show atrophy in the right OFC, which correlates with disease duration, suggesting that persistent olfactory dysfunction may be associated with neurodegenerative changes.

Objective:To evaluate the therapeutic efficacy of the Wenyang Huazhuo Formula on spontaneous pregnancy outcomes in advanced-age infertile patients with spleen-kidney yang deficiency syndrome.Methods:A retrospective cohort study design was employed to gather clinical data from 303 advanced-age infertile patients with spleen-kidney yang deficiency syndrome who sought treatment at the Department of Reproductive Medicine in the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine between June 2019 and June 2023. Patients were categorized into two groups based on their treatment regiments: a basic treatment group (non-exposed group, n=151) and a group receiving basic treatment in conjunction with the Wenyang Huazhuo Formula (exposed group, n=152). The study compared and analyzed pregnancy outcomes, including time to pregnancy (TTP) within one year, ongoing pregnancy rate, and clinical pregnancy rate, between the two groups over a one-year follow-up period. Additionally, stratified analyses were performed based on age and anti-Müllerian hormone (AMH) levels to evaluate the impact of Wenyang Huazhuo Formula on pregnancy outcomes across different patient subgroups. Results:The TTP in the exposed group was significantly reduced compared with the non-exposed group ( HR=1.70, 95% CI: 1.12-2.57, P=0.013), suggesting a significant shortening of their TTP, and the ongoing pregnancy rate [28.29% (43/152)] and the clinical pregnancy rate [33.55% (51/152)] were significantly higher than those in the non-exposed group [13.91% (21/151), P=0.020; 21.85% (33/151), P=0.023], and the early abortion rate [15.69% (8/51)] was significantly reduced compared with the non-exposed group [36.36% (12/33), P=0.031]. Stratified analyses by age revealed that for patients aged 35-37 years, the exposed group exhibited a significantly shorter TTP ( HR=1.67, 95% CI: 1.03-2.70, P=0.038), while no significant difference in TTP was observed in the 38-44-year old patients ( HR=1.78, 95% CI: 0.77-4.10, P=0.174). Regarding the ongoing pregnancy rate, the exposed group showed a significant higher rate [31.31% (31/99)] than the non-exposed group [13.91% (15/112), P=0.022] among patients aged 35-37 years, whereas no significant difference was observed in the 38-44 years old group ( P=0.386). Stratified analysis based on AMH levels showed that both low AMH levels (<1.68 μg/L) and high AMH levels (≥1.68 μg/L) patients in the exposed group experienced a significant reduction in TTP compared with the non-exposed group ( HR=8.07, 95% CI: 1.04-62.52, P=0.046; HR=1.57, 95% CI: 1.01-2.43, P=0.044, respectively), along with a notable improvement in the ongoing pregnancy rate [13.64% (6/44) vs. 0% (0/29), P=0.038; 34.26% (37/108) vs.17.21% (21/122), P=0.028, respectively]. Further stratified analysis indicated that, compared with patients with low AMH levels, both the exposed group and the non-exposed group of patients with high AMH levels exhibited a significantly shorter TTP ( HR=1.91, 95% CI: 1.02-3.69, P=0.043; HR=9.48, 95% CI: 1.30-69.22, P=0.002, respectively), along with a significantly higher ongoing pregnancy rate ( P=0.014; P=0.008). Conclusion:The Wenyang Huazhuo Formula significantly shortens TTP, enhances both the clinical pregnancy rate and the ongoing pregnancy rate and reduces the early abortion rate in advanced-age infertile women diagnosed with spleen-kidney yang deficiency syndrome.

DNA methylation is an important epigenetic modification in mammals, playing a crucial role in various physiological processes, including cell differentiation and the gene expression regulation. The ten-eleven translocation (TET) protein family of DNA demethylases is integral to the regulation of DNA methylation, as it catalyzes the oxidation of 5-methylcytosine to form 5-hydroxymethylcytosine. During early embryonic development, the genome undergoes extensive DNA demethylation, and any aberration in this reprogramming process can result in abnormal embryonic development and physiological defects in offspring. The TET proteins, due to their unique dynamics and multifaceted roles, facilitate DNA demethylation and are involved in development and maturation of germ cells, the establishment of pluripotency, cell lineage differentiation, and transcriptional processes throughout mammalian embryogenesis. Furthermore, these proteins are closely associated with the maintenance of pregnancy and susceptibility of progeny to disease. Factors such as genetic mutations, maternal health conditions, and exposure to adverse environmental influences can impact TET protein activity, resulting in abnormal patterns of DNA demethylation. A comprehensive investigation of the related mechanisms of TET proteins is essential for enhancing our understanding of epigenetic regulation during early life, diagnosing and treating related diseases such as early fetal development retardation, and informing strategies for the prevention and management of pregnancy.This article reviews the regulatory role of DNA demethylation mediated by TET protein in mammalian embryonic development and pregnancy outcomes.

Indwelling urinary catheterization is one of the most widely used invasive procedures in clinical practice, playing a critical role in disease diagnosis, treatment, and monitoring. In 2024, the European Association of Urology Nurses (EAUN) released the Best Practice Guidelines for Indwelling Urinary Catheterization in Adults-Transurethral and Suprapubic Catheterization (hereinafter referred to as the Guideline), aiming to provide evidence-based clinical guidance and health education information for healthcare professionals. This article interprets the section on "Nursing Principles" within the Guideline, which spans the entire process of catheter management. Key aspects covered include pre-insertion preparation, catheter insertion procedure, catheter maintenance and securement, observation of urine color, prevention of constipation, and catheter removal. The aim is to help urology nurses and related healthcare personnel gain an in-depth understanding of the recommendations in the Guideline, promote its standardized application in clinical practice, improve the quality of indwelling catheter care, and ensure patient safety.

Background and purpose:Human papilloma virus(HPV)infection status is crucial for diagnosing cervical precancerous lesions and classifying cervical cancer.High-risk(HR)HPV is often linked to P16 protein overexpression,so P16 detection via immunohistochemistry(IHC)is commonly used to assess HPV infection.However,the differences between HPV status and P16 expression remains unclear.An in-depth study of the correlation between HPV and P16 is essential for clinical guidance.Methods:We retrospectively collected clinical and pathological data of cervical lesions from 618 patients diagnosed at the Department of Pathology,Fudan University Shanghai Cancer Center from January 2020 to December 2023(Ethical number:050432-4-2307E).Polymerase chain reaction(PCR)reverse dot hybridization was used to detect HPV including HR and low-risk(LR)subtypes,and immunohistochemistry was used to detect P16 for comparative analysis.Based on different clinical and pathological diagnoses,the sensitivity and specificity of P16 expression in evaluating HPV infection were evaluated.Among the 618 cases of cervical lesions,there were 92 cases of cervical squamous cell carcinoma,257 cases of cervical adenocarcinoma,79 cases of high-grade squamous intraepithelial lesions(HSIL),105 cases of low-grade squamous intraepithelial lesions(LSIL),and 85 cases of chronic cervical inflammation.Results:According to clinical diagnosis,the HR-HPV positive rate in cervical squamous cell carcinoma was 88.0%(81/92),the P16 positive rate was 91.3%(84/92),and the overall consistency rate between P16 and HPV detection was 90.2%(88/92);for HR-HPV infection,the sensitivity and specificity of P16 were 96.3%and 45.5%.The positive rate of HR-HPV in adenocarcinoma was 54.5%(140/257),the positive rate of P16 was 58.8%(151/257),and the overall consistency rate between P16 and HPV detection was 82.5%(212/257);for HR-HPV infection,the sensitivity and specificity of P16 were 87.9%and 76.1%.In HSIL,the HR-HPV positive rate was 75.9%(60/79),the positive rate of P16 was 70.9%(56/79),and the overall consistency rate between P16 and HR-HPV detection was 82.2%(65/79);for HR-HPV infection,the sensitivity and specificity of P16 were 85.0%and 73.7%.In LSIL,the HR-HPV positive rate was 73.3%(77/105),the positive rate of P16 was 8.5%(9/105),and the overall consistency rate between P16 and HR-HPV detection was 33.3%(35/105);for HR-HPV infection,the sensitivity and specificity of P16 were 10.4%and 96.4%.In chronic cervical inflammation,the HR-HPV positive rate was 20%(17/85),the positive rate of P16 was 0.0%(0/85);for HR-HPV infection,the sensitivity and specificity of P16 were 0.0%and 100.0%.There was a significant positive correlation between P16 positivity and HPV16/18 in cervical squamous cell carcinoma,adenocarcinoma,and HSIL(P=0.000),while there was no significant correlation in LSIL and chronic cervical inflammation(P＞0.05).Conclusion:In cervical squamous cell carcinoma and adenocarcinoma,the consistency of P16 expression and HPV DNA positivity are high,especially in HPV16/18 subtype.There is a good concordance between HR-HPV positivity and P16 protein overexpression.The positive expression of P16 in HSIL may initially reflect HPV infection status.However,in LSIL and chronic cervicitis,P16 expression may not accurately correlate with HPV infection.The inconsistency between P16 and HPV DNA testing could be influenced by multiple factors,including HPV subtypes,histopathological categories,specimen quality,and technical limitations.In clinical practice,it is recommended to conduct comprehensive analysis or employ multiple diagnostic methods to confirm HPV infection status for precise evaluation.

Objective:To evaluate whether there is a difference between the lesion volumes detected by 18F-FDG PET/CT imaging and 11C-choline PET/CT imaging based on different threshold delineation methods in patients with nasopharyngeal carcinoma, and to recommend a more clinically appropriate threshold method with reference to lesion volume detected by enhanced MRI. Methods:A retrospective study was conducted on 37 patients(27 males, 10 females, age (51.2±11.9) years) with nasopharyngeal carcinoma diagnosed in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, between October 2015 and May 2017. All patients underwent nasopharyngeal enhanced MRI, 18F-FDG PET/CT and 11C-choline PET/CT scans. Advantage Workstation 4.6 software was used to fuse images of the 3 imaging examinations. The lesion contour was sketched manually based on enhanced MRI sequences to obtain VMRI, and the lesion was sketched in PET images to obtain the corresponding metabolic tumor volume (MTV) by absolute threshold method, relative threshold method and background threshold method respectively. The correlation between ROIs sketched by different threshold methods and ROI in MRI was evaluated by using the Dice similarity coefficient (DSC). Friedman test or repeated measures analysis of variance (corrected by Greenhouse-Geisser) was employed to analyze the differences of MTV or DSC obtained by using 3 threshold methods. Wilcoxon signed-rank test or paired t-test was used to compare the data of different imaging methods. Results:In 18F-FDG PET/CT results, MTVs obtained by using the absolute threshold method, relative threshold method, and background threshold method were 13.21(5.47, 23.16), 10.13(5.67, 16.81), and 13.68(5.77, 25.52)mm 3, respectively, with significant differences ( χ2=17.89, P<0.001). The corresponding DSC differences for the 3 methods were also significant (0.43±0.19, 0.38±0.17 and 0.44±0.17; F=16.35, P<0.001). In 11C-choline PET/CT results, MTV differences based on the 3 threshold methods were significantly different (14.96(6.80, 32.27), 16.28(12.23, 32.47) and 18.97(14.38, 37.02)mm 3;χ2=10.45, P=0.005), and the DSC differences were also significant (0.52±0.21, 0.58±0.13 and 0.62±0.13; F=16.37, P<0.001). The differences in MTV and DSC between FDG and choline groups were also significant ( Z=-3.87, t=-5.57, both P<0.001). The differences between MTVs of 18F-FDG imaging/ 11C-choline imaging and VMRI (24.35(14.48, 36.89)mm 3) were all significantly different ( Z values: from -5.03 to -2.59, all P<0.05). Conclusions:Compared with 18F-FDG PET/CT, the preoperative 11C-choline PET/CT imaging in patients with nasopharyngeal carcinoma is closer to enhanced MRI (gold standard) in the lesion delineation. Compared with ROIs of the other 2 threshold delineation methods, the ROI obtained by the background threshold method is closer to that in enhanced MRI.

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.