Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

[摘 要] 目的：探讨内吞作用相关基因FCHO2在各亚型乳腺癌中的表达及其与乳腺癌患者的预后和免疫细胞浸润的相关性。方法：应用免疫组化法和bc-GenExMiner v5.0数据库数据分析FCHO2在各亚型乳腺癌组织中的表达，通过GEO和TIMER数据库数据分析FCHO2与各亚型乳腺癌患者预后和免疫细胞浸润的关系，利用STRING和GEPIA数据库数据分析与FCHO2的互作蛋白网络和其与互作蛋白的相关性，通过UALCAN和DAVID数据库数据对乳腺癌组织中FCHO2表达相关基因进行KEGG和GO分析。结果：免疫组化法结果显示，FCHO2在管腔型和HER2+乳腺癌组织中均呈高表达（均P<0.05），且与HER2和Ki67表达有关联（P=0.03和P=0.007）。FCHO2高表达的管腔型乳腺癌患者总生存期（OS）和无复发生存期（RFS）均明显缩短（均P<0.05）。FCHO2蛋白与EPS15等多种蛋白表达相关且构成蛋白-蛋白互作网络。KEGG和GO分析显示，乳腺癌组织中FCHO2相关表达基因主要与昼夜节律、自噬等生物学过程有关，涉及叉头框蛋白O（FoxO）和TGF-β等信号通路。FCHO2表达与各亚型乳腺癌组织中的免疫细胞浸润相关（均P<0.05）。结论：FCHO2在管腔型、HER2+乳腺癌组织中呈高表达，且与管腔型乳腺癌患者预后及免疫细胞浸润相关，其可能成为乳腺癌治疗的潜在靶点。

[摘 要] 目的：探讨内吞作用相关基因FCHO2在各亚型乳腺癌中的表达及其与乳腺癌患者的预后和免疫细胞浸润的相关性。方法：应用免疫组化法和bc-GenExMiner v5.0数据库数据分析FCHO2在各亚型乳腺癌组织中的表达，通过GEO和TIMER数据库数据分析FCHO2与各亚型乳腺癌患者预后和免疫细胞浸润的关系，利用STRING和GEPIA数据库数据分析与FCHO2的互作蛋白网络和其与互作蛋白的相关性，通过UALCAN和DAVID数据库数据对乳腺癌组织中FCHO2表达相关基因进行KEGG和GO分析。结果：免疫组化法结果显示，FCHO2在管腔型和HER2+乳腺癌组织中均呈高表达（均P<0.05），且与HER2和Ki67表达有关联（P=0.03和P=0.007）。FCHO2高表达的管腔型乳腺癌患者总生存期（OS）和无复发生存期（RFS）均明显缩短（均P<0.05）。FCHO2蛋白与EPS15等多种蛋白表达相关且构成蛋白-蛋白互作网络。KEGG和GO分析显示，乳腺癌组织中FCHO2相关表达基因主要与昼夜节律、自噬等生物学过程有关，涉及叉头框蛋白O（FoxO）和TGF-β等信号通路。FCHO2表达与各亚型乳腺癌组织中的免疫细胞浸润相关（均P<0.05）。结论：FCHO2在管腔型、HER2+乳腺癌组织中呈高表达，且与管腔型乳腺癌患者预后及免疫细胞浸润相关，其可能成为乳腺癌治疗的潜在靶点。

The innovation of integrating medical treatment and prevention mechanisms is a key task deployed by the government, aiming to promote the construction of a Healthy China and address the prevalent "treatment over prevention" mindset in healthcare services and society. Vaccination is an effective strategy for preventing and controlling infectious diseases; however, adult vaccination rates in China remain low due to insufficient awareness and enthusiasm among the public and healthcare professionals. In recent years, various regions have begun to explore the model of physicians in medical institutions prescribing vaccines to improve vaccination rates. This article analyzes the positioning, current implementation status, and challenges of vaccine prescriptions, and proposes recommendations advocating policy formulation, improving service models and supporting measures, improving funding mechanisms, and strengthening publicity and education to promote the widespread implementation and effectiveness of vaccine prescriptions.

The innovation of integrating medical treatment and prevention mechanisms is a key task deployed by the government, aiming to promote the construction of a Healthy China and address the prevalent "treatment over prevention" mindset in healthcare services and society. Vaccination is an effective strategy for preventing and controlling infectious diseases; however, adult vaccination rates in China remain low due to insufficient awareness and enthusiasm among the public and healthcare professionals. In recent years, various regions have begun to explore the model of physicians in medical institutions prescribing vaccines to improve vaccination rates. This article analyzes the positioning, current implementation status, and challenges of vaccine prescriptions, and proposes recommendations advocating policy formulation, improving service models and supporting measures, improving funding mechanisms, and strengthening publicity and education to promote the widespread implementation and effectiveness of vaccine prescriptions.

Purpose To evaluate the added value of time of flight(TOF)and point spread dispersion(PSF)reconstruction in mediastinal lymph node metastasis of lung cancer in 18F-FDG PET/CT imaging.Materials and Methods Sixty-eight lung cancer patients with mediastinal lymph node metastasis who underwent PET/CT examination in the First People's Hospital of Foshan from March 9,2020 to July 23,2021 were analyzed retrospectively.The different methods,including ordered subsets estimation maximization(OSEM),OSEM+TOF,OSEM+PSF,OSEM+TOF+PSF,were used to reconstruct the images.The resolution of different reconstruction algorithms for mediastinal lymph node metastasis of lung cancer,as well as the differences of signal-to-noise ratio(SNR)and standard uptake value(SUV)were compared,respectively.Results The highest values of SUVmean,SUVmax and SNR were obtained via OSEM+TOF+PSF method,which increased by 21.99%,22.86%and 60.14%,compared with conventional OSEM method(t=28.321,19.11,11.059,all P<0.01).The difference percentage in smaller lesions that diameter≤22 mm was significantly higher than that in larger lesions that diameter>22 mm(24.1%vs.21.1%,25.3%vs.19.3%,70.6%vs.63.3%;Z=-3.658,-4.313,-2.154,all P<0.05),and the difference percentage in low contrast lesions that SNR≤15.31 was significantly higher than that in high contrast lesions that SNR>15.31(23.6%vs.21.4%,25.3%vs.21.1%,85.7%vs.46.0%;Z=-3.519,-2.336,-5.106,all P<0.05).Among the evaluation results of lesion detectability of different reconstruction algorithms,OSEM+TOF+PSF image showed the mediastinal lymph node metastasis most clearly(87.4%of the lesions were clearly existing),which was significantly higher than that of OSEM image(73.1%of lesions were clearly existing)(χ2=11.704,P=0.001),however,the proportion of lesions clearly existing in OSEM+PSF image did not significantly increase compared with OSEM image(73.1%vs.75.8%;χ2=0.361,P=0.548).Conclusion The combination of TOF and PSF can significantly improve the detection ability,SNR and SUV of mediastinal lymph node metastasis of lung cancer,especially in small and low contrast lesions.

Humans ; Cross-Sectional Studies ; SARS-CoV-2 ; COVID-19 Vaccines/therapeutic use* ; Pandemics ; COVID-19/prevention & control* ; China/epidemiology* ; Attitude ; Vaccination

OBJECTIVE: To investigate the clinical and prognostic characteristics of primary acute myeloid leukemia (AML) with 11q23/KMT2A rearrangements. METHODS: Clinical data of 90 patients with primary AML and 11q23/KMT2A rearrangements were analyzed retrospectively. RESULTS: By karyotyping analysis, 80 of the 90 patients had translocations involving 11q23/KMT2A, with t(9;11)(p22;q23), t(6;11)(q27;q23), t(10;11)(p12;q23) and t(11;19)(q23;p13) being the most common ones, while 10 cases were found to have non-translocation abnormalities. The overall complete remission (CR) rate was 75.6%, and patients with t(6;11) had lower CR rate compared with non-t(6;11) patients (47.1% vs. 82.2%, P = 0.005). After a median follow-up of 24.5 months, the patients receiving allo-hematopoietic stem cell transplantation (allo-HSCT) had significantly higher 3-year overall survival (OS) (80.3% vs. 16.6%, P < 0.001) and 3-year event-free survival (EFS) (73.5% vs. 16.3%, P < 0.001) compared with non-transplant patients. Patients with t(6;11) had the lowest 3-year OS (11.8% vs. 56.0%, P < 0.001) and 3-year EFS (5.9% vs. 53.8%, P < 0.001) compared with other type of abnormalities. No significant difference was noted in the survival between patients with t(9;11) and non-t(9;11) regardless whether they had received HSCT. CONCLUSION The clinical characteristics of primary AML with 11q23/KMT2A rearrangements are heterogeneous. Patients did not receive HSCT had poorer survival, particularly with the presence of t(6;11). Allo-HSCT could significantly improve the survival of such patients.
Humans ; Retrospective Studies ; Leukemia, Myeloid, Acute/therapy* ; Translocation, Genetic ; Gene Rearrangement ; Prognosis

Objective:To investigate the prognostic value of 18F-FDG PET/CT in patients with locally recurrent nasopharyngeal carcinoma (NPC) receiving chemoradiotherapy, and relationships between different metabolic parameters and peripheral blood inflammation markers. Methods:From January 2013 to June 2016, the data of 56 patients (40 males, 16 females, age 27-81 years) with locally recurrent NPC receiving chemoradiotherapy in the First People′s Hospital of Foshan were retrospectively analyzed. The SUV max, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were determined by 18F-FDG PET/CT and peripheral blood inflammation markers within 1 week before treatment were measured. Spearman rank correlation analysis was used to estimate the correlations between metabolic parameters and inflammation markers. According to the ROC curve, the best cut-off values of the SUV max, MTV and TLG were obtained and used to group patients. The Kaplan-Meier method and Cox regression were used to conduct univariate analysis and multivariate analysis of 3-year locoregional failure-free survival (LRFFS) and 3-year overall survival (OS) in patients with locally recurrent NPC. The prognostic value of metabolic parameters in patients with early and advanced recurrent T(rT) stages were compared. Results:MTV was positively correlated with neutrophils, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and high-sensitivity C-reactive protein (hs-CRP) before treatment in patients with locally recurrent NPC ( rs values: 0.30, 0.30, 0.28, 0.27, all P<0.05); TLG was positively correlated with neutrophils, monocytes, NLR and PLR ( rs values: 0.30, 0.28, 0.32, 0.30, all P<0.05). But there were no correlations between SUV max and peripheral blood inflammation markers ( rs values: from -0.18 to 0.24, all P>0.05). SUV max was an factor affecting 3-year LRFFS of patients undergoing radiotherapy and chemotherapy (hazard ratio ( HR)=3.815(95% CI: 1.278-11.388), P=0.016), while rT stage and MTV were prognostic factors for 3-year OS ( HR values: 4.492(95% CI: 1.474-13.688), 7.238(95% CI: 1.653-31.688), P values: 0.008, 0.009). For patients with advanced rT (rT3-4), the 3-year OS of the MTV≥6.84 cm 3 group was significantly lower than that of MTV<6.84 cm 3 group ( χ2=6.99, P=0.008). Conclusions:SUV max of tumor and MTV before treatment have important prognostic values in patients with locally recurrent NPC receiving chemoradiotherapy, but their predictive effects on prognosis are not the same. The varying effects of local inflammation on metabolic parameters may be one of the important reasons lead to that difference.