Analysis of multiple factors influencing the survival of patients with advanced gastric cancer.

OBJECTIVE: The aim of this study was to investigate the main factors influencing the survival of patients with advanced gastric cancer. METHODS: The clinicopathological data of 120 patients with advanced gastric cancer were analyzed retrospectively, and clinical and pathological data were collected. Tumor tissue staging and grading were re-evaluated, and 5-year overall survival was followed up. The classified data were described by percentages, and the continuous data were described by standard deviations or medians. Univariate analysis was performed using the χ2 test or rank-sum test, followed by Kaplan-Meier survival analysis to calculate the median survival time and 5-year cumulative survival. A multivariate Cox regression model was used to evaluate the independent risk factors affecting survival. The test level was α = 0.05. RESULTS: Patients were followed up for 0 to 60 months, the 5-year overall survival rate was 36.2%, and the median survival time was 53.0 ± 1.461 months. K-M and log-rank test results revealed that tumor location, degree of differentiation, depth of invasion, regional lymph node involvement, and postoperative tumor stage were correlated with a decreased 5-year survival rate (P < 0.05). A multivariate Cox risk regression model was used to analyze the degree of histological differentiation (HR = 1.441; 95% CI = 1.049-1.979; P = 0.024), regional lymph node (HR = 1.626; 95% CI = 1.160-2.279; P = 0.005), and pTNM stage (HR = 2.266; 95% CI = 1.335-3.847; P = 0.002), which are independent risk factors for poor survival. Tumor location (P = 0.191), invasion depth (P = 0.579) and tumor size (P = 0.324) were not found to be independent risk factors. CONCLUSION: The degree of tumor differentiation, regional lymph node metastasis and postoperative pathological stage were found to be independent risk factors for 5-year overall survival in patients with advanced gastric cancer. Standardized and reasonable lymph node dissection and accurate postoperative pathological staging were very important.

[Advance of research on the role of BCL11A in the occurrence and treatment of ß-Thalassemia].

ß-Thalassemia is a single-gene disease caused by mutations in ß-globin and has a distinct geographical characteristics. Current treatment for patients with moderate to severe thalassemia has mainly relied on long-term blood transfusion and/or hematopoietic stem cell transplantation. B cell lymphoma/leukemia 11A (BCL11A) as a transcriptional repressor plays a vital role in monitoring γ/ß hemoglobin switching, maintaining the normal function of hematopoietic stem cells, and regulating erythrocyte differentiation and lymphocyte development. With the rapid progress in gene editing technology, the BCL11A as a therapeutic target for ß-thalassemia has shown promising results. This article has systematically summarized the regulatory mechanism and therapeutic potential of the BCL11A, with an aim to provide new ideas for the treatment of ß-thalassemia.

Etiologic evaluation and pregnancy outcomes of fetal growth restriction (FGR) associated with structural malformations.

This study aimed to evaluate the etiology and pregnancy outcomes of fetuses underwent invasive prenatal diagnosis for fetal growth restriction (FGR) accompanied by structural malformations. Data from 130 pregnancies referred for prenatal diagnosis for FGR accompanied by structural malformations were obtained between July 2011 and July 2023. Traditional karyotyping was conducted for all the subjects. A total of 37 (28.5%) cases of chromosomal abnormalities were detected by karyotyping, including 30 cases of numerical anomalies and seven cases of unbalanced structural anomalies. Trisomy 18 was the most common abnormalities, accounting for 51.4%, significantly higher than any other chromosomal abnormality. The cohort was predominantly comprised of early-onset FGR (88.5%) compared to late-onset FGR (11.5%). The incidences of chromosomal abnormalities in this two groups were 29.6% (34/115) and 20.0% (3/15), respectively (p > 0.05). The majority (74.6%, 97/130) of the cohort were affected by a single system malformation, with chromosomal abnormalities found in 19.6% (19/97) of cases. In pregnancies of structural malformations involving two and multiple systems, the frequencies were 56.5% (13/23), and 50.0% (5/10), respectively. Single nucleotide polymorphism array (SNP array) was performed in parallel for 65 cases, revealing additional 7.7% cases of copy number variants (CNVs) compared to karyotyping. Polymerase chain reaction (PCR) was used for detection of cytomegalovirus (CMV) DNA in 92 cases. All fetuses with FGR associated with two or more system malformations were either terminated or stillborn, irrespective of chromosomal aberrations. Conversely, 71.8% of pregnancies with a single-system malformation and normal genetic testing results resulted in live births. Furthermore, two (2.2%) cases tested positive for CMV DNA, leading to one termination and one case of serious developmental disorder after birth. Our study suggests that structural malformations associated with FGR are more likely to affect a single organ system. When multiple systems are involved, the incidence of chromosomal abnormalities and termination rates are notably high. We advocate for the use of CMA and CMV DNA examinations in FGR cases undergo invasive prenatal diagnosis, as these tests can provide valuable insights for etiological exploration and pregnancy management guidance.

Diversity and distribution analysis of eukaryotic communities in the Xiangshan Bay, East China sea by metabarcoding approach.

Eukaryotic communities play an important role in the coastal ecosystem of Xiangshan Bay, a narrow semi-closed bay famous for fisheries and marine farming. However, information on the diversity and composition of eukaryotic communities in Xiangshan Bay remains unclear. In this study, the metabarcoding approach was utilized to comprehensively investigate the eukaryotic plankton community structure and dominant taxa, particularly eukaryotic microalgae, in the Xiangshan Bay over a period of four months in 2018. The results showed that the three major phyla were Arthropoda, Chlorophyta, and Bacillariophyta. The richness indices revealed that species richness peaked in February and was at its lowest in May. Diversity indices showed that the samples collected in May had the lowest diversity. Centropages was detected in the samples of all months, however, its highest dominance was observed in the samples collected in February. In addition, compared to other months, a greater proportion of eukaryotic microalgae was witnessed in March. The three eukaryotic algae with highest abundances in March were Cyclotella, Prorocentrum, and Thalassiosira. Moreover, high diversity of pico-sized (0.2-2.0 µm) phytoplankton (which are often easily missed by microscopy) was discovered in this study by using metabarcoding approach. This study highlights the strength and significance of the metabarcoding approach to uncover a large number of eukaryotic species which remains undetectable during application of conventional approaches. The findings of this study reveals that the eukaryotic community structure varies noticeably in both time and space throughout sampling period, with temperature being the most important environmental factor influencing these changes. This study lays a solid foundation to understand eukaryotic plankton composition, temporal and spatial dynamics and the distribution mechanism of eukaryotic plankton community in Xiangshan Bay, providing theoretical reference for further studies related to marine ecology.

Post-translational modifications in diabetic cardiomyopathy.

The increasing attention towards diabetic cardiomyopathy as a distinctive complication of diabetes mellitus has highlighted the need for standardized diagnostic criteria and targeted treatment approaches in clinical practice. Ongoing research is gradually unravelling the pathogenesis of diabetic cardiomyopathy, with a particular emphasis on investigating various post-translational modifications. These modifications dynamically regulate protein function in response to changes in the internal and external environment, and their disturbance of homeostasis holds significant relevance for the development of chronic ailments. This review provides a comprehensive overview of the common post-translational modifications involved in the initiation and progression of diabetic cardiomyopathy, including O-GlcNAcylation, phosphorylation, methylation, acetylation and ubiquitination. Additionally, the review discusses drug development strategies for targeting key post-translational modification targets, such as agonists, inhibitors and PROTAC (proteolysis targeting chimaera) technology that targets E3 ubiquitin ligases.

Regulation of N6 -methyladenosine modification in erythropoiesis and thalassemia.

In eukaryotic RNA, N6 -methyladenosine (m6 A) is a prevalent form of methylation modification. The m6 A modification process is reversible and dynamic, written by m6 A methyltransferase complex, erased by m6 A demethylase, and recognized by m6 A binding proteins. Through mediating RNA stability, decay, alternative splicing, and translation processes, m6 A modification regulates gene expression at the post-transcriptional level. Erythropoiesis is the process of hematopoietic stem cells undergoing proliferation, a series of differentiation and maturation to form red blood cells (RBCs). Thalassemia is a common monogenic disease characterized by excessive production of ineffective RBCs in the peripheral circulation, resulting in hemolytic anemia. Increasing evidence suggests that m6 A modification plays a crucial role in erythropoiesis. In this review, we comprehensively summarize the function of m6 A modification in erythropoiesis and further generalize the mechanism of m6 A modification regulating ineffective erythropoiesis and fetal hemoglobin expression. The purpose is to improve the understanding of the pathogenesis of erythroid dysplasia and offer new perspectives for the diagnosis and treatment of thalassemia.

The interactions between ineffective erythropoiesis and ferroptosis in ß-thalassemia.

In Guangxi, Hainan, and Fujian Province in southern China, ß-thalassemia is a frequent monogenic hereditary disorder that is primarily defined by hemolytic anemia brought on by inefficient erythropoiesis. It has been found that ineffective erythropoiesis in ß-thalassemia is closely associated with a high accumulation of Reactive oxygen species, a product of oxidative stress, in erythroid cells. During recent years, ferroptosis is an iron-dependent lipid peroxidation that involves abnormalities in lipid and iron metabolism as well as reactive oxygen species homeostasis. It is a recently identified kind of programmed cell death. ß-thalassemia patients experience increased iron release from reticuloendothelial cells and intestinal absorption of iron, ultimately resulting in iron overload. Additionally, the secretion of Hepcidin is inhibited in these patients. What counts is both ineffective erythropoiesis and ferroptosis in ß-thalassemia are intricately linked to the iron metabolism and Reactive oxygen species homeostasis. Consequently, to shed further light on the pathophysiology of ß-thalassemia and propose fresh ideas for its therapy, this paper reviews ferroptosis, ineffective erythropoiesis, and the way they interact.

Integrated profiling identifies ferredoxin 1 as an immune-related biomarker of malignant phenotype in glioma.

Background: Glioma, a highly resistant and recurrent type of central nervous system tumor, poses a significant challenge in terms of effective drug treatments and its associated mortality rates. Despite the discovery of Ferredoxin 1 (FDX1) as a crucial participant in cuproptosis, an innovative mechanism of cellular demise, its precise implications for glioma prognosis and tumor immune infiltration remain inadequately elucidated. Methods: To analyze pan-cancer data, we employed multiple public databases. Gene expression evaluation was performed using tissue microarray (TMA) and single-cell sequencing data. Furthermore, four different approaches were employed to assess the prognostic importance of FDX1 in glioma. We conducted the analysis of differential expression genes (DEGs) and Gene Set Enrichment Analysis (GSEA) to identify immune-related predictive signaling pathways. Somatic mutations were assessed using Tumor Mutation Burden (TMB) and waterfall plots. Immune cell infiltration was evaluated with five different algorithms. Furthermore, we performed in vitro investigations to evaluate the biological roles of FDX1 in glioma. Results: Glioma samples exhibited upregulation of FDX1, which in turn predicted poor prognosis and was positively associated with unfavorable clinicopathological characteristics. Notably, the top four enriched signaling pathways were immune-related, and the discovery revealed a connection between the expression of FDX1 and the frequency of mutations or the TMB. The FDX1_high group exhibited heightened infiltration of immune cells, and there existed a direct association between the expression of FDX1 and the regulation of immune checkpoint. In vitro experiments demonstrated that FDX1 knockdown reduced proliferation, migration, invasion and transition from G2 to M phase in glioma cells. Conclusion: In glioma, FDX1 demonstrated a positive association with the advancement of malignancy and changes in the infiltration of immune cells.

Recovery of 1887 metagenome-assembled genomes from the South China Sea.

The South China Sea (SCS) is a marginal sea characterized by strong land-sea biogeochemical interactions. SCS has a distinctive landscape with a multitude of seamounts in its basin. Seamounts create "seamount effects" that influence the diversity and distribution of planktonic microorganisms in the surrounding oligotrophic waters. Although the vertical distribution and community structure of marine microorganisms have been explored in certain regions of the global ocean, there is a lack of comprehensive microbial genomic surveys for uncultured microorganisms in SCS, particularly in the seamount regions. Here, we employed a metagenomic approach to study the uncultured microbial communities sampled from the Xianbei seamount region to the North Coast waters of SCS. A total of 1887 non-redundant prokaryotic metagenome-assembled genomes (MAGs) were reconstructed, of which, 153 MAGs were classified as high-quality MAGs based on the MIMAG standards. The community structure and genomic information provided by this dataset could be used to analyze microbial distribution and metabolism in the SCS.

Causal associations between leisure sedentary behaviors and sleep status with frailty: insight from Mendelian randomization study.

BACKGROUND: Observational studies have suggested that sedentary behaviors and sleep status are associated with frailty. However, it remains unclear whether these associations are causal. METHODS: Using summary statistics from genome-wide association studies, we evaluated the causal effect of modifiable risk factors, including leisure sedentary behaviors and sleep status on the frailty index (FI) using two-sample univariable and multivariable Mendelian randomization (MR) analyses. Genetic correlations were tested between the correlated traits. RESULTS: We identified potential causal associations between the time spent watching television (ß = 0.26, 95% confidence interval [CI]: 0.21-0.31, P = 3.98e-25), sleep duration (ß = -0.18, 95%CI: -0.26, -0.10; P = 6.04e-06), and daytime napping (ß = 0.29, 95%CI: 0.18-0.41, P = 2.68e-07) and the FI based on the inverse-variance-weighted method. The estimates were consistent across robust and multivariate MR analyses. Linkage disequilibrium score regression detected a genetic correlation between the time spent watching television (Rg = 0.43, P = 6.46e-48), sleep duration (Rg = -0.20, P = 5.29e-10), and daytime napping (Rg = 0.25, P = 3.34e-21) and the FI. CONCLUSIONS: Genetic predispositions to time spent watching television and daytime napping were positively associated with the FI, while sleep duration was negatively associated with the FI. Our findings offer key insights into factors influencing biological aging and suggest areas for interventions to promote healthy aging and slow down the aging process.

Peripheral blood circular RNA circ-0008102 may serve as a novel clinical biomarker in beta-thalassemia patients.

Circular RNA circ-0008102 has previously been found dysregulated in ß-thalassemia (ß-thal) in circRNAs microarray (GSE196682 and GSE241141). Our study is aimed at identifying whether circ-0008102 could be a novel biomarker in ß-thal. The peripheral blood of pediatric ß-thal patients with (n = 39) or without (n = 20) blood transfusion and healthy controls (n = 30) was selected. qRT-PCR, ROC curve analysis, Spearman correlation analysis, and FISH were used to analyze clinical value of circ-0008102. qRT-PCR confirmed that circ-0008102 expression in pediatric ß-thal patients without blood transfusion was significantly higher. ROC curves analysis showed that the AUC of circ-0008102 for differentiating patients without blood transfusion from patients with blood transfusion and healthy controls with an AUC of 0.733 and 0.711. Furthermore, circ-0008102 expression was positively correlated with the levels of RBC, HbF, ß-globin, and γ-globin mRNA, but was negatively corrected with the levels of HbA and Cr. circ-0008102 was mainly located in the cytoplasm. circ-0008102 could induce the activation of γ-globin and negatively regulate the expression of the five highest-ranking candidate miRNAs (miR-372-3p, miR-329-5p, miR-198, miR-152-5p, and miR-627-3p) in K562 cells. CONCLUSION: We demonstrate that peripheral blood upregulated circ-0008102 may serve as a novel clinical biomarker for pediatric ß-thal without blood transfusion. WHAT IS KNOWN: • CircRNAs are known to be involved in various human diseases, and several circRNAs are regarded as a class of promising blood-based biomarkers for detection of ß-thal. • CircRNAs exert biological functions by epigenetic modification and gene expression regulation, and dysregulated circRNAs in ß-thal might be involved in the induction of HbF in ß-thal. WHAT IS NEW: • Peripheral blood circ-0008102 maybe serve as a novel clinical biomarker for detection of pediatric ß-thal without blood transfusion. • Circ-0008102 participates in the pathogenesis of ß-thal through regulating γ-globin expression, and negatively regulates the expression of miR-372-3p, miR-329-5p, miR-198, miR-152-5p and miR-627-3p.

First Report of Filipino ß0-Thalassemia/ß-Thalassemia in a Chinese Family.

A pregnant woman living in Fujian Province, southeastern China, presented due to a risk of having a baby with ß-thalassemia major, during her second pregnancy, since she and her husband were suspected as ß-thalassemia carriers and their affected daughter was a transfusion-dependent patient. Using the common α-thalassemia and ß-thalassemia genotypes test, the pregnant woman was diagnosed as a ß-thalassemia carrier with ßIVS-2 - 654 (C→T)/ßN genotype and her daughter had a homozygosity for IVS - 2 - 654 (C→T) mutation, however, no abnormalities were detected in her husband. SMRT identified a Filipino ß0-deletion in her husband, and MLPA also revealed an unknown deletion in the HBB gene. Electrophoresis showed approximately 350 bp of the PCR product, and the ß-Filipino genotype presented novel fracture fragments ranging from 5,112,884 to 5,231,358 bp, and lacked a 118,475 bp fragment relative to the wild-type sequence. The daughter was therefore diagnosed with the ßIVS-2 - 654 (C→T)/ßFilipino genotype. Prenatal diagnosis with umbilical cord blood at 27th week of gestation showed heteroztgosity for IVS - 2 - 654 (C→T) mutation in the fetus and continued pregnancy was recommended. In conclusion, we identified the Filipino ß0-deletion in a Chinese family, from Fujian area, for the first time, during prenatal screening.

Experience of copy number variation sequencing applied in spontaneous abortion.

PURPOSE: We evaluated the value of copy number variation sequencing (CNV-seq) and quantitative fluorescence (QF)-PCR for analyzing chromosomal abnormalities (CA) in spontaneous abortion specimens. METHODS: A total of 650 products of conception (POCs) were collected from spontaneous abortion between April 2018 and May 2020. CNV-seq and QF-PCR were performed to determine the characteristics and frequencies of copy number variants (CNVs) with clinical significance. The clinical features of the patients were recorded. RESULTS: Clinically significant chromosomal abnormalities were identified in 355 (54.6%) POCs, of which 217 (33.4%) were autosomal trisomies, 42(6.5%) were chromosomal monosomies and 40 (6.2%) were pathogenic CNVs (pCNVs). Chromosomal trisomy occurs mainly on chromosomes 15, 16, 18, 21and 22. Monosomy X was not associated with the maternal or gestational age. The frequency of chromosomal abnormalities in miscarriages from women with a normal live birth history was 55.3%; it was 54.4% from women without a normal live birth history (P > 0.05). There were no significant differences among women without, with 1, and with ≥ 2 previous miscarriages regarding the rate of chromosomal abnormalities (P > 0.05); CNVs were less frequently detected in women with advanced maternal age than in women aged ≤ 29 and 30-34 years (P < 0.05). CONCLUSION: Chromosomal abnormalities are the most common cause of pregnancy loss, and maternal and gestational ages are strongly associated with fetal autosomal trisomy aberrations. Embryo chromosomal examination is recommended regardless of the gestational age, modes of conception or previous abortion status.

Intrauterine ultrasound phenotyping, molecular characteristics, and postnatal follow-up of fetuses with the 15q11.2 BP1-BP2 microdeletion syndrome: a single-center, retrospective clinical study.

OBJECTIVES: The 15q11.2 BP1-BP2 microdeletion is associated with neurodevelopmental diseases. However, most studies on this microdeletion have focused on adults and children. Thus, in this study, we summarized the molecular characteristics of fetuses with the 15q11.2 BP1-BP2 microdeletion and their postnatal follow-up to guide prenatal diagnosis. METHODS: Ten thousand fetuses were retrospectively subjected to karyotype analysis and chromosome microarray analysis. RESULTS: Chromosome microarray analysis revealed that 37 (0.4%) of the 10,000 fetuses had 15q11.2 BP1-BP2 microdeletions. The fragment size of the 15q11.2 BP1-BP2 region was approximately 312-855 kb and encompassed TUBGCP5, CYFIP1, NIPA2, and NIPA1 genes. Twenty-five of the 37 fetuses with this microdeletion showed phenotypic abnormalities. The most common ultrasonic structural abnormality was congenital heart disease, followed by renal dysplasia and Dandy-Walker malformation. The 15q11.2 BP1-BP2 microdeletion was inherited from the father and mother in 6 and 10 cases, respectively, and de novo inherited in 4 cases. In the postnatal follow-up, 16.1% of the children had postnatal abnormalities. CONCLUSION: Fetuses with the 15q11.2 BP1-BP2 microdeletion showed high proportions of phenotypic abnormalities, but the specificity of penetrance was low. Thus, fetuses with this syndrome are potentially at a higher risk of postnatal growth/behavioral problems and require continuous monitoring of growth and development.

Genetic testing for fetal loss of heterozygosity using single nucleotide polymorphism array and whole-exome sequencing.

The study explored the clinical significance of fetal loss of heterozygosity (LOH) identified by single-nucleotide polymorphism array (SNP array). We retrospectively reviewed data from pregnant women who underwent invasive diagnostic procedures at prenatal diagnosis centers in southeastern China from December 2016 to December 2021. SNP array was performed by the Affymetrix CytoScan 750 K array platform. Fetuses with LOH were further identified by parental verification, MS-MLPA, and/or trio whole-exome sequencing (trio-WES). The genetic results, fetal clinical manifestations, and perinatal outcome were analyzed. Of 11,062 fetuses, 106 (0.96%) had LOH exhibiting a neutral copy number, 88 (83.0%) had LOH in a single chromosome, whereas 18 (17.0%) had multiple LOHs on different chromosomes. Sixty-six fetuses had ultrasound anomalies (UAs), most frequently fetal growth restriction (18/66 (27.3%)). Parental SNP array verification was performed in 21 cases and trio-WES in 21 cases. Twelve cases had clinically relevant uniparental disomy, five had pathogenic variants, four had likely pathogenic variants, six had variants of unknown significance, and eight had identity by descent. The rate of adverse pregnancy outcomes in fetuses with LOH and UAs (24/66 (36.4%)) was higher than in those without UAs (6/40 (15.0%)) (p < 0.05). LOH is not uncommon. Molecular genetic testing techniques, including parental SNP array verification, trio-WES, methylation-specific multiplex ligation-dependent probe amplification, regular and systematic ultrasonic monitoring, and placental study, can accurately assess the prognosis and guide the management of the affected pregnancy.

Recombinase Polymerase Amplification Combined with Lateral Flow Dipstick Assay for the Rapid and Sensitive Detection of Pseudo-nitzschia multiseries.

The harmful algal bloom (HAB) species Pseudo-nitzschia multiseries is widely distributed worldwide and is known to produce the neurotoxin domoic acid, which harms marine wildlife and humans. Early detection and preventative measures are more critical than late management. However, the major challenge related to early detection is the accurate and sensitive detection of microalgae present in low abundance. Therefore, developing a sensitive and specific method that can rapidly detect P. multiseries is critical for expediting the monitoring and prediction of HABs. In this study, a novel assay method, recombinase polymerase amplification combined with lateral flow dipstick (RPA-LFD), is first developed for the detection of P. multiseries. To obtain the best test results, several important factors that affected the amplification effect were optimized. The internal transcribed spacer sequence of the nuclear ribosomal DNA from P. multiseries was selected as the target region. The results showed that the optimal amplification temperature and time for the recombinase polymerase amplification (RPA) of P. multiseries were 37 °C and 15 min. The RPA products could be visualized directly using the lateral flow dipstick after only 3 min. The RPA-LFD assay sensitivity for detection of recombinant plasmid DNA (1.9 × 100 pg/µL) was 100 times more sensitive than that of RPA, and the RPA-LFD assay sensitivity for detection of genomic DNA (2.0 × 102 pg/µL) was 10 times more sensitive than that of RPA. Its feasibility in the detection of environmental samples was also verified. In conclusion, these results indicated that the RPA-LFD detection of P. multiseries that was established in this study has high efficiency, sensitivity, specificity, and practicability. Management measures made based on information gained from early detection methods may be able to prevent certain blooms. The use of a highly sensitive approach for early warning detection of P. multiseries is essential to alleviate the harmful impacts of HABs on the environment, aquaculture, and human health.

Genetic analysis, ultrasound phenotype, and pregnancy outcomes of fetuses with Xp22.33 or Yp11.32 microdeletions.

OBJECTIVES: The phenotypes of Xp22.33 or Yp11.32 microdeletions comprising the short-stature homeobox (SHOX) gene have been extensively described in adults and children. Herein, the prenatal ultrasound phenotype and pregnancy outcomes of fetuses with Xp22.33/Yp11.32 microdeletions were analyzed to improve our understanding, diagnosis, and monitoring of this genetic condition in the fetal stage. METHODS: A total of 9,100 pregnant women referred to tertiary units for prenatal diagnosis were evaluated by chromosomal microarray analysis(CMA). RESULTS: Seven (0.08 %) fetuses had Xp22.33/Yp11.32 microdeletions, ranging from 243 kb to 1.1 Mb, that comprised SHOX. The ultrasonic phenotypes differed among these fetuses, with three fetuses presenting abnormal bone development, one had labial-palatal deformity and strawberry head, two had an abnormal ultrasonic soft marker, and one had no abnormalities. After genetic counseling, only one couple underwent pedigree assessment, which confirmed the paternal origin of the microdeletion. This infant presented delayed speech development, whereas other three infants showed a typical postnatal development. In three cases, the parents chose to terminate the pregnancy. CONCLUSIONS: The ultrasonic phenotype of fetuses with Xp22.33/Yp11.32 microdeletions resulting in SHOX heterozygosity loss is variable. Prenatal CMA can quickly and effectively diagnose Xp22.33/Yp11.32 microdeletions and SHOX loss, which may help prenatal counseling.

Gastric Ganglioneuroblastoma in an Elderly man: A Case Report and Literature Review.

Background. Ganglioneuroblastoma is a borderline tumor of sympathetic origin that is considered a childhood disease, with the majority of patients occurring in children less than five years old and few patients occurring in adults. There are no treatment guidelines for adult ganglioneuroblastoma. Here, we report a rare patient of adult gastric ganglioneuroblastoma that was completely resected by a laparoscopic approach. Case presentation. A 73-year-old man presented with dull pain in the upper abdomen along with abdominal distension for one month. Gastroscopy examination revealed chronic gastritis and submucosal tumors of the gastric antrum. Endoscopic ultrasonography showed a hypoechoic mass in the gastric antrum arising from the muscularis propria. An abdominal computed tomography scan revealed an irregular soft tissue mass in the gastric antrum with heterogeneous enhancement in the arterial phase. The mass was completely resected by laparoscopic surgery. Postoperative histopathology revealed that the mass contained differentiated neuroblasts, mature ganglion cells and ganglioneuroma components. The pathological diagnosis was ganglioneuroblastoma intermixed, and the patient was determined to be in stage I. The patient received no adjuvant chemotherapy or radiotherapy. At his two-year follow-up, the patient was doing well and showed no signs of recurrence. Conclusion. Despite the rarity of gastric ganglioneuroblastoma as a primary site of origin, it should be considered in the differential diagnosis of gastric masses in adults. Radical surgery is sufficient for the treatment of ganglioneuroblastoma intermixed, and long-term follow-up should be performed.

Redox-Activatable Magnetic Nanoarchitectonics for Self-Enhanced Tumor Imaging and Synergistic Photothermal-Chemodynamic Therapy.

Oral squamous cell carcinoma (OSCC) is a prevalent malignancy of the head and neck region associated with high recurrence rates and poor prognosis under current diagnostic and treatment methods. The development of nanomaterials that can improve diagnostic accuracy and therapeutic efficacy is of great importance for OSCC. In this study, a redox-activatable nanoarchitectonics is designed via the construction of dual-valence cobalt oxide (DV-CO) nanospheres, which can serve as a contrast agent for magnetic resonance (MR) imaging, and exhibit enhanced transverse and longitudinal relaxivities through the release and redox of Co3+ /Co2+ in an acidic condition with glutathione (GSH), resulting in self-enhanced T1 /T2 -weighted MR contrast. Moreover, DV-CO demonstrates properties of intracellular GSH-depletion and hydroxyl radicals (•OH) generation through a Fenton-like reaction, enabling strengthened chemodynamic (CD) effect. Additionally, DV-CO displays efficient near-infrared laser-induced photothermal (PT) effect, thereby exhibiting synergistic PT-CD therapy for suppressing OSCC tumor cells. It further investigates the tumor-specific self-enhanced MR imaging of DV-CO both in subcutaneous and orthotopic OSCC mouse models, and demonstrate the therapeutic effects of DV-CO in orthotopic OSCC mouse models. Overall, the in vitro and in vivo findings highlight the excellent theranositc potentials of DV-CO for OSCC and offer new prospects for future advancement of nanomaterials.

Mutation analysis of GJB2, SLC26A4, GJB3 and mtDNA12SrRNA genes in 251 non-syndromic hearing loss patients in Fujian, China.

OBJECTIVES: The molecular etiology of non-syndromic hearing loss (NSHL) in Southeastern China (Fujian) has not been precisely identified. our study selected patients with NSHL and analyzed their causative genes, which helped to improve the accuracy of the diagnosis of hereditary hearing loss (HHL) and its treatment. METHODS: 251 unrelated patients who attended the otolaryngology clinic of Fujian Maternal and Child Health Hospital with hearing loss were enrolled to our study. All patients had genetic tests and listening tests, of which 251 were diagnosed with NSHL. In addition, we used whole-exome sequencing (WES) in a patient who has a significant family history of HHL but negative for gene chip testing, as well as in his family members. RESULT: Among of 251 patients, Nucleotide changes were found in 63 cases (25.09%), including 34 located in GJB2(13.5%, including 235delC and 299_300delAT), 13 located in SLC26A4(5.18%, including c.919-2G > A and 2168 A > G), 1 located in GJB3(0.4%,538C > T) and 16 located in mtDNA12SrRNA (6.37%,1555 A > G). In addition, we discuss the process of identifying novel PLS1 mutations from 251 patients. CONCLUSION: Our results demonstrate the conventional deafness gene mutation in 251 NSHL patients in Fujian, China. Compared with the other area of China, we have a lower detection rate, but GJB2 235delC remains the most common mutation in Fujian. In addition, we discuss the process of discovering novel mutation locus for deafness, which provides an understanding for deafness diagnosis and genetic testing.