OBJECTIVE: To analyze RELT gene mutation found in a pedigree with clinical features and inheritable pattern consistent with amelogenesis imperfecta (AI) in China, and to study the relationship between its genotype and phenotype. METHODS: Clinical and radiological features were recorded for the affected individuals. Peripheral venous blood samples of the patient and family members were collected for further study, and the genomic DNA was extracted to identify the pathogenic gene. Whole exome sequencing (WES) was performed to analyze the possible pathogenic genes, and Sanger sequencing was performed for validation. SIFT and PolyPhen-2 were used to predict and analyze the mutation effect. Comparison of RELT amino acids across different species were performed by using Uniprot website. In addition, the three-dimen-sional structures of the wild type and mutant proteins were predicted by Alphafold 2. RESULTS: The proband exhibited typical hypocalcified AI, with heavy wear, soft enamel, rough and discolored surface, and partial enamel loss, while his parents didn ' t have similar manifestations. WES and Sanger sequencing results indicated that the proband carries a homozygous frameshift mutation in RELT gene, NM_032871.3: c.1169_1170del, and both of his parents were carriers. This mutation was predicted to be pathogenic by SIFT and PolyPhen-2. Up to now, there were 11 mutation sites in RELT gene were reported to be associated with AI, and all of the patients exhibited with hypocalcified AI. Compared with the wild-type RELT protein, the mutant protein p. Pro390fs35 conformation terminated prematurely, affecting the normal function of the protein. CONCLUSION Through phenotype analysis, gene sequencing, and functional prediction of a Chinese family with typical amelogenesis imperfecta, this study found that RELT gene frameshift mutation can lead to protein dysfunction in AI patients. Further research will focus on the role and mechanism of RELT in enamel development at the molecular and animal levels, providing molecular biology evidence for the genetic counseling, prenatal diagnosis, and early prevention and treatment of AI.
Humans ; Amelogenesis Imperfecta/genetics* ; Frameshift Mutation ; Male ; Pedigree ; Female ; China ; Exome Sequencing ; Phenotype ; Adult

Follicular lymphoma (FL) is highly heterogeneous with different histopathologic grades. Its biological characteristics and clinical management are different. This study retrospectively analyzed 18F-FDG PET-CT metabolic parameters, clinical features, and their relationship with prognosis in 161 FL patients with different histopathological grades (grade 1-2, grade 3A, grade 3B) at the Shanxi Cancer Hospital. There were 93 cases in the grade 1-2 group, 40 cases in the grade 3A group, and 28 cases in the grade 3B group. The expression of LDH, CD10, EZH2, c-Myc, and CD37 proteins was correlated with histological grade (grade 1-2, grade 3A, and grade 3B) (all P values<0.05) . The SUVmax, TLG, TBR, and TLR for the three groups were different (all P values<0.05) . The optimal thresholds of SUVmax, MTV, TLG, TBR, and TLR for predicting FL disease progression were 8.32, 201.31, 2 342.55, 6.56, and 3.52, respectively, and the rate of disease progression increased in patients with higher thresholds (all P value<0.05) . β 2-MG (>2.3 μg/L) , Follicular lymphoma international prognostic index-1 (FLIPI-1) score (3-5 points) , negative CD37 expression, positive c-Myc expression, and TLG (>2 342.55 g) were all independent risk factors for PFS in the FL patients ( HR=3.609, 2.509, 0.255, 3.506, 13.531, all P value<0.05) . 18F-FDG PET-CT is a powerful complement to FL histopathological grading and the combination of the two may better predict the prognosis of FL patients.

Autoimmune glial fibrillary acidic protein astrocytopathy(GFAP-A) is a novel autoimmune disease of the central nervous system.The disease can affect any region of the cerebrum, cerebellum, optic nerve, and spinal cord, with encephalitis, meningoencephalitis and encephalomyelitis being the most common.Patients usually present with headache, fever, disturbance of consciousness, autonomic dysfunction, and visual impairment, and the diagnosis is mainly based on positive anti-glial fibrillary acidic protein antibodies in cerebrospinal fluid and serum.The disease is sensitive to glucocorticoids, with 70% of patients responding well to high-dose glucocorticoid pulse therapy and having a good prognosis.About one in five patients have residual nervous system sequelae, requiring long-term immunosuppressive therapy.This paper reviews the etiology, pathogenesis, clinical features, diagnosis and differential diagnosis, treatment and prognosis of GFAP-A by analyzing relevant studies at home and abroad, in order to deepen the understanding of this disease and provide references for its clinical diagnosis and treatment.

Attention deficit hyperactivity disorder is a common neurodevelopmental disorder characterized by persistent attention deficit, hyperactivity, and impulsive behaviors that are not consistent with developmental age.Academic and vocational difficulties, social exclusion, and delinquent behaviors are manifested in daily life.It is also commonly accompanied by psychiatric problems.At the same time, mental problems are common, and the overall quality of life is greatly affected, placing a heavy burden on society as well as the family.International attention deficit hyperactivity disorder experts have developed a common and comprehensive International Classification of Functioning, Disability and Health core set of classifications for assessing individual functioning in attention deficit hyperactivity disorder.

Objective To investigate the role of PSMA4 in the prognosis,diagnosis and immune infiltration of lung adenocarcinoma(LUAD),and explore its underlying mechanism.Methods The expression profiles and clinical data of LUAD patients were sourced from the Cancer Genome Atlas(TCGA)database.The expression level of PSMA4 in LUAD tissues(n=539)and normal tissues(n=59)were compared using the Wilcoxon rank-sum test.The expression levels of PSMA4 in LUAD tissues and normal tissues were validated by analyzing the GSE40791 and GSE10072 LUAD datasets obtained from the Gene Expression Omnibus(GEO)database.In addition,tumor and adjacent non-cancerous tissues were collected from 10 LU AD undergoing lung biopsy by fiberoptic bronchoscopy in Second Affiliated Hospital of Army Medical University from January to December 2023.The PSMA4 expression in above samples was further verified using RT-qPCR.RT-qPCR was performed to detect the expression of PSMA4 in lung cancer cells and normal lung epithelial cells.Functional enrichment analysis and immune cell infiltration analysis were conducted on the cells with high and low expression of PSMA4.Cox regression analysis and Kaplan-Meier(KM)survival analysis were used to determine the diagnostic and prognostic value of PSMA4 for LUAD,and a nomogram was constructed to predict the overall survival rate at different time points.Results The analysis of TCGA datasets,GSE40791,and GSE10072 LUAD data revealed that PSMA4 expression was significantly higher in LUAD tissues than in normal tissues(P＜0.01).RT-qPCR further confirmed that the expression of PSMA4 was obviously elevated in LUAD tissues and lung cancer cells than adjacent non-cancerous tissues and normal lung epithelial cells(P＜0.01).High PSMA4 expression could be regarded as a marker for LUAD diagnosis and poor prognosis,and was associated with reduced proportions of Tem cells,TFH cells,B cells,NK cells,Tcm cells,and mast cells in the tumor microenvironment.Conclusion PSMA4 presents significant diagnostic performance for LUAD,and is closely associated with the prognosis and immune infiltration of this malignancy.

Objective:Induced pluripotent stem cells (iPSCs) cell lines were established using peripheral blood mononuclear cells (PBMCs) from a patient suffering from neonatal respiratory distress syndrome (NRDS) who carried Adenosine triphosphate-binding cassette transporter A3 ( ABCA3) compound heterozygous mutations. Methods:Cell experimental research.Peripheral venous blood was collected and PBMCs were isolated and cultured in vitro. PBMCs were transfected with non-integrated Sendai vector carrying reprogramming factors.The chromosome karyotypes of the established iPSCs were analyzed.Immunofluorescence and flow cytometry were used to detect pluripotency markers of stem cells and verify their differentiation potential.Sanger sequencing was performed to analyze gene mutations.In addition, short tandem repeat (STR) analysis was performed, polymerase chain reaction(PCR) and agarose gel electrophoresis were used to detect virus residual. Results:Karyotype analysis of established iPSCs cell lines showed normal diploid 46, XY karyotype.Immunofluorescence showed positive staining of stem cell pluripotency markers OCT4, SSEA4, Nanog and Sox2.Flow cytometry was used to detected stem cell pluripotency markers and showed expression of TRA-1-60, SSEA-4 and OCT4.After differentiation into all three germ layers, immunofluorescence was performed to detect ectoderm (Pax-6), mesoderm (Brachyury) and endoderm alpha-fetoprotein markers, and the results showed positive staining, which confirmed that the iPSCs had the potential to differentiate.Sanger sequencing showed c. 3997_3998del and c. 3137C>T compound heterozygous mutations.STR analysis showed they originate from PBMCs, and no Sendai virus residual was detected by PCR and agarose gel electrophoresis.Conclusions:In this study, PBMCs from patient carrying ABCA3 compound heterozygous mutations was used to establish iPSCs cell lines.The research lays a foundation for the study of pathogenesis, therapeutic drug screening and cell therapy of NRDS caused by ABCA3 gene mutations.

Objective To investigate the kinesiophobia level in patients after spinal fracture surgery and their correlations with rehabilitation self-efficacy and adherence. Methods A total of 150 patients who underwent spinal fracture surgery were enrolled in this study. General information was collected from all patients. The Tampa Scale for Kinesiophobia, Self-Efficacy for Rehabilitation Outcomes Scale, department-developed Rehabilitation Adherence Scale and postoperative activity pain [assessed using the Visual Analogue Scale (VAS)] were analyzed. Pearson correlation analysis was used to examine the relationships of kinesiophobia level with rehabilitation self-efficacy and adherence. Multiple linear regression analysis was conducted to identify factors influencing kinesiophobia level. Results The total score of postoperative kinesiophobia level in patients with spinal fracture was (57.14±3.12), which was at a high level. The total score of rehabilitation self-efficacy was (35.19±3.45), which was at a low level. The total score of rehabilitation compliance was (16.46±2.32), which was at a low level. Pearson correlation analysis showed that the total score of kinesiophobia level was negatively correlated with the total score of rehabilitation self-efficacy and rehabilitation compliance (P < 0.05). Univariate analysis revealed statistically significant differences in scores of kinesiophobia level among patients with different educational levels, postoperative activity pain and the presence or absence of postoperative complications (P < 0.05). Multiple linear regression analysis identified self-efficacy (B=-0.271, 95%CI, -0.439 to -0.103), adherence (B=-0.168, 95%CI, -0.331 to -0.004), educational level (B=0.190, 95%CI, 0.020 to 0.361), postoperative complications (B=0.403, 95%CI, 0.233 to 0.573) and postoperative activity pain (B=0.162, 95%CI, 0.003 to 0.320) were the influencing factors of postoperative kinesiophobia level in patients with spinal fracture. Conclusion The patients with spinal fracture have a higher level of kinesiophobia. The influencing factors of level of kinesiophobia are rehabilitation self-efficacy, rehabilitation compliance, education level, postoperative complications and postoperative activity pain.

To investigate the effect of long-term indwelling gastric tube on the prevention and treatment of esophageal stenosis after endoscopic submucosal dissection (ESD) for esophageal circumferential superficial cancer, data of patients with esophageal circumferential superficial cancer who underwent ESD in the First Affiliated Hospital of Nanjing Medical University from January 2018 to December 2021 were retrospectively analyzed. There were 15 patients with gastric tube placement (GTP) after ESD (the GTP group ), and 23 patients without GTP (the non-GTP group). The general information, lesion location, pathological stage, postoperative complications, degree of esophageal stenosis (water intake), pain conditions, number of hospitalizations and medical expenses were compared between the two groups. The results showed that there was no significant difference in age, gender, lesion location or postoperative pathological stage between the two groups ( P>0.05). Compared with the non-GTP group, the rate of water intake in the GTP group was significantly higher (11/15 VS 6/23, P<0.05), the frequency of pain was less in the GTP group (7.3±3.1 times VS 10.7±3.6 times, t=3.00, P<0.05), and the number of hospitalizations and the medical expenses after ESD to before and after stent placement were significantly lower in the GTP group than those in the non-GTP group ( P<0.05). There were no significant differences in the incidence of delayed bleeding and perforation, or time of the first stenosis after ESD between the two groups ( P>0.05). The results of the study initially showed that long-term indwelling gastric tube after ESD can reduce the degree of esophageal stenosis with good safety for esophageal circumferential superficial lesions.

Objective:To compare the efficacy and prognostic evaluation of response evaluation criteria in lymphoma (RECIL) and Lugano classification in patients with 18F-FDG-avid Hodgkin′s lymphoma (HL) and non-HL (NHL) during mid-chemotherapy. Methods:From January 2015 to August 2021, 240 patients (149 males and 91 females, age 50.0(32.0, 62.0) years) with pathologically confirmed lymphoma in Shanxi Cancer Hospital were retrospectively analyzed. Pre-treatment and mid-treatment 18F-FDG PET/CT examinations were performed, and the differences of PET/CT imaging results among patients with different types of lymphoma were analyzed ( χ2 test or Kruskal-Wallis rank sum test). Efficacy evaluation was conducted during mid-chemotherapy, and the results were divided into complete remission (CR), partial remission (PR), stable disease (SD), progressive disease (PD) according to Lugano classification, which were divided into CR, PR, mild remission (MiR), SD, PD according to RECIL. For the better comparison with Lugano classification, MiR was included in PR group (recorded as RECIL-1) and SD group (recorded as RECIL-2) in this study. All patients were followed up, and the progression free survival (PFS) was analyzed. Kappa test, χ2 test or Fisher exact probability method were used to analyze the data, and ROC curve was used to compare the prediction efficiency of different standards. Results:Among 240 patients with different types of lymphoma (96 HL, 30 follicular lymphoma (FL), 114 diffuse large B-cell lymphoma (DLBCL)), there were statistically significant differences in baseline SUV max ( H=54.96, P<0.001) and the sum of longest diameters ( H=15.85, P<0.001). Patients were followed up for 12-89 months, and 26 patients (10.8%) were evaluated as MiR according to the RECIL. The consistency ( Kappa) was 0.84 between results of RECIL-1 and Lugano classification, which was 0.74 between RECIL-2 and Lugano classification (both P<0.001). According to Lugano classification, the PFS rates of patients evaluated as CR, PR, SD and PD were 91.4%(148/162), 57.1%(36/63), 1/3 and 3/12 respectively, which were 91.3%(136/149), 62.8%(49/78), 1/2 and 2/11 for RECIL-1, and 91.3%(136/149), 57.7%(30/52), 71.4%(20/28) and 2/11 for RECIL-2 respectively ( χ2 values: 46.64-52.44, all P<0.001). The AUC of Lugano classification for predicting PFS had a trend to be higher than AUCs of RECIL-1 and RECIL-2 (0.774, 0.758 and 0.746; z values: 1.28, 1.61, P values: 0.200, 0.107). Conclusion:RECIL and Lugano classification have similar efficacy and prognostic evaluation effect on patients with 18F-FDG-avid HL and NHL during mid-chemotherapy.

Objective:To explore the prognostic value of the maximum standardized uptake value reduction proportion (ΔSUVmax%) on 18F-fluorodeoxyglucose (FDG) positron emission tomography combined with computed tomography (PET/CT) imaging, Deauville scores and C-myc gene rearrangement for the prediction of diffuse large B-cell lymphoma (DLBCL) in early chemotherapy. Methods:A total of 83 primary patients with pathologically confirmed DLBCL admitted in Shanxi Provincial Cancer Hospital from September 2010 to December 2016 underwent 18F-FDG PET/CT 1 week before and after early chemotherapy. The patients underwent post-chemotherapy examinations between 17 to 21 days after one cycle ( n=34) or two cycles ( n=49). The region of interest (ROI) was drawn and the ΔSUVmax% was calculated. Deauville 5-point scale was used to score the PET/CT imaging in early chemotherapy. Fluorescence in situ hybridization (FISH) was used to detect C-myc gene rearrangement. The follow-up time was from 36 to 111 months. The primary end-point of the study was progression-free survival (PFS). Receiver operating characteristic (ROC) analysis, χ2 test, Spearman correlation analysis, Log rank test, and Cox regression analysis were used to analyze the data. Results:Of 83 DLBCL patients, 19 progressed during the follow-up period. The optimal cut-off value of ΔSUVmax% for predicting tumor progression in early chemotherapy was 62.59%, and the Deauville score was taken as 5. The differences in sensitivity, specificity, and accuracy between the two methods were not statistically significant ( P>0.05). The ΔSUVmax% were negatively correlated with C-myc gene rearrangement and the Deauville scores ( rs= -0.889, -0.862, P<0.001). However, the Deauville scores was positively correlated with the C-myc gene rearrangement ( rs=0.781, P<0.001). The median PFS were 59 months and 16 months in ΔSUVmax%≥62.59% ( n=57) and ΔSUVmax%<62.59% ( n=26), respectively, with significant difference ( P<0.001). The median PFS for the Deauville score <5 subgroup (61 cases) and =5 subgroup (22 cases) was 59.0 and 15.0 months, respectively, with statistically significant differences ( P<0.001). The median PFS for patients with C-myc rearrangement subgroup (62 cases) and without rearrangement subgroup (21 cases) was 59.0 and 15.0 months, respectively, with statistically significant differences ( P<0.001). The median PFS for ΔSUVmax%<62.59% and Deauville score=5 subgroup, ΔSUVmax%<62.59% and C-myc rearrangement subgroup, Deauville score=5 and C-myc rearrangement subgroup were 15.5 months, 15 months and 13.5 months, respectively, with statistically significant differences ( P<0.001). Conclusion:ΔSUVmax%, Deauville score and C-myc gene rearrangement in early chemotherapy are all associated with PFS in DLBCL patients, and the combination of the two has a good predictive value for the prognosis of DLBCL