Rhodium(III) Complex Noncanonically Potentiates Antitumor Immune Responses by Inhibiting Wnt/ß-Catenin Signaling.

Metal-based chemoimmunotherapy has recently garnered significant attention for its capacity to stimulate tumor-specific immunity beyond direct cytotoxic effects. Such effects are usually caused by ICD via the activation of DAMP signals. However, metal complexes that can elicit antitumor immune responses other than ICD have not yet been described. Herein, we report that a rhodium complex (Rh-1) triggers potent antitumor immune responses by downregulating Wnt/ß-catenin signaling with subsequent activation of T lymphocyte infiltration to the tumor site. The results of mechanistic experiments suggest that ROS accumulation following Rh-1 treatment is a critical trigger of a decrease in ß-catenin and enhanced secretion of CCL4, a key mediator of T cell infiltration. Through these properties, Rh-1 exerts a synergistic effect in combination with PD-1 inhibitors against tumor growth in vivo. Taken together, our work describes a promising metal-based antitumor agent with a noncanonical mode of action to sensitize tumor tissues to ICB therapy.

Neonatal tachypnea caused by diaphragmatic paralysis: A case report.

BACKGROUND: Diaphragmatic paralysis is typically associated with phrenic nerve injury. Neonatal diaphragmatic paralysis diagnosis is easily missed because its manifestations are variable and usually nonspecific. CASE SUMMARY: We report a 39-week-old newborn delivered via vaginal forceps who presented with tachypnea but without showing other birth-trauma-related manifestations. The infant was initially diagnosed with pneumonia. However, the newborn still exhibited tachypnea despite effective antibiotic treatment. Chest radiography revealed right diaphragmatic elevation. M-mode ultrasonography revealed decreased movement of the right diaphragm. The infant was subsequently diagnosed with diaphragmatic paralysis. After 4 weeks, tachypnea improved. Upon re-examination using M-mode ultrasonography, the difference in bilateral diaphragmatic muscle movement was smaller than before. CONCLUSION: Appropriate use of M-mode ultrasound to quantify diaphragmatic excursions could facilitate timely diagnosis and provide objective evaluation.

Up-Regulation of S100A8 and S100A9 in Pulmonary Immune Response Induced by a Mycoplasma capricolum subsp. capricolum HN-B Strain.

Mycoplasma capricolum subsp. capricolum (Mcc), a member of the Mycoplasma mycoides cluster, has a negative impact on the goat-breeding industry. However, little is known about the pathogenic mechanism of Mcc. This study infected mice using a previously isolated strain, Mcc HN-B. Hematoxylin and eosin staining, RNA sequencing, bioinformatic analyses, RT-qPCR, and immunohistochemistry were performed on mouse lung tissues. The results showed that 235 differentially expressed genes (DEGs) were identified. GO and KEGG enrichment analyses suggested that the DEGs were mainly associated with immune response, defensive response to bacteria, NF-kappa B signaling pathway, natural killer cell-mediated cytotoxicity, and T cell receptor signaling pathway. RT-qPCR verified the expression of Ccl5, Cd4, Cd28, Il2rb, Lck, Lat, Ptgs2, S100a8, S100a9, and Il-33. The up-regulation of S100A8 and S100A9 at the protein level was confirmed by immunohistochemistry. Moreover, RT-qPCR assays on Mcc HN-B-infected RAW264.7 cells also showed that the expression of S100a8 and S100a9 was elevated. S100A8 and S100A9 not only have diagnostic value in Mcc infection but also hold great significance in clarifying the pathogenic mechanism of Mcc. This study preliminarily elucidates the mechanism of Mcc HN-B-induced lung injury and provides a theoretical basis for further research on Mcc-host interactions.

Current and future trends of acupuncture as an adjuvant therapy in cancer: A bibliometric and visual analysis.

BACKGROUND: Acupuncture, as one of the representatives of complementary therapies, is often used as an adjunctive therapy in the treatment of cancer and related complications with beneficial results. METHODS: We selected the Web of Science Core Collection (WOSCC) database as the data source and searched to obtain relevant literatures on the application of acupuncture in cancer treatment. The relevant literature was analyzed using CiteSpace (version 6.1.R6) and VOSviewer (version 1.6.20). RESULTS: A total of 592 publications were included, with an overall upward trend in the number of publications. There were 135 countries or institutions involved, with China as the most published country. There were 1888 related institutions, and Memorial Sloan Kettering Cancer Center was the institution with the most publications. A total of 3067 authors were involved, and there were obvious collaborations between authors. There were 190 related journals, and J Clin Oncol was the most cited journal. The most frequently occurring keywords were breast cancer and management, but also other related topics such as quality of life, chemotherapy, and complementary. CONCLUSION: Acupuncture is gaining increasing attention as an adjunctive therapy in cancer treatment programs. Currently, relevant research focuses on acupuncture to alleviate cancer-induced comorbid symptoms, such as pain and insomnia. Future research is gradually shifting toward spiritual care, Colorectal Cancer Surgery, and systematic review.

Cu(II) complex that synergistically potentiates cytotoxicity and an antitumor immune response by targeting cellular redox homeostasis.

Developing anticancer drugs with low side effects is an ongoing challenge. Immunogenic cell death (ICD) has received extensive attention as a potential synergistic modality for cancer immunotherapy. However, only a limited set of drugs or treatment modalities can trigger an ICD response and none of them have cytotoxic selectivity. This provides an incentive to explore strategies that might provide more effective ICD inducers free of adverse side effects. Here, we report a metal-based complex (Cu-1) that disrupts cellular redox homeostasis and effectively stimulates an antitumor immune response with high cytotoxic specificity. Upon entering tumor cells, this Cu(II) complex enhances the production of intracellular radical oxidative species while concurrently depleting glutathione (GSH). As the result of heightening cellular oxidative stress, Cu-1 gives rise to a relatively high cytotoxicity to cancer cells, whereas normal cells with low levels of GSH are relatively unaffected. The present Cu(II) complex initiates a potent ferroptosis-dependent ICD response and effectively inhibits in vivo tumor growth in an animal model (c57BL/6 mice challenged with colorectal cancer). This study presents a strategy to develop metal-based drugs that could synergistically potentiate cytotoxic selectivity and promote apoptosis-independent ICD responses through perturbations in redox homeostasis.

Development and verification of a 10K liquid chip for Hainan black goat based on genotyping by pinpoint sequencing of liquid captured targets.

BACKGROUND: China has thousands years of goat breeding and abundant goat genetic resources. Additionally, the Hainan black goat is one of the high-quality local goat breeds in China. In order to conserve the germplasm resources of the Hainan black goat, facilitate its genetic improvement and further protect the genetic diversity of goats, it is urgent to develop a single nucleotide polymorphism (SNP) chip for Hainan black goat. RESULTS: In this study, we aimed to design a 10K liquid chip for Hainan black goat based on genotyping by pinpoint sequencing of liquid captured targets (cGPS). A total of 45,588 candidate SNP sites were obtained, 10,677 of which representative SNP sites were selected to design probes, which finally covered 9,993 intervals and formed a 10K cGPS liquid chip for Hainan black goat. To verify the 10K cGPS liquid chip, some southern Chinese goat breeds and a sheep breed with similar phenotype to the Hainan black goat were selected. A total of 104 samples were used to verify the clustering ability of the 10K cGPS liquid chip for Hainan black goat. The results showed that the detection rate of sites was 97.34% -99.93%. 84.5% of SNP sites were polymorphic. The heterozygosity rate was 3.08%-36.80%. The depth of more than 99.4% sites was above 10X. The repetition rate was 99.66%-99.82%. The average consistency between cGPS liquid chip results and resequencing results was 85.58%. In addition, the phylogenetic tree clustering analysis verified that the SNP sites on the chip had better clustering ability. CONCLUSION: These results indicate that we have successfully realized the development and verification of the 10K cGPS liquid chip for Hainan black goat, which provides a useful tool for the genome analysis of Hainan black goat. Moreover, the 10K cGPS liquid chip is conducive to the research and protection of Hainan black goat germplasm resources and lays a solid foundation for its subsequent breeding work.

Cycloplatinated (II) Complex Based on Isoquinoline Alkaloid Elicits Ferritinophagy-Dependent Ferroptosis in Triple-Negative Breast Cancer Cells.

The development and optimization of metal-based anticancer drugs with novel cytotoxic mechanisms have emerged as key strategies to overcome chemotherapeutic resistance and side effects. Agents that simultaneously induce ferroptosis and autophagic death have received extensive attention as potential modalities for cancer therapy. However, only a limited set of drugs or treatment modalities can synergistically induce ferroptosis and autophagic tumor cell death. In this work, we designed and synthesized four new cycloplatinated (II) complexes harboring an isoquinoline alkaloid C∧N ligand. On screening the in vitro activity of these agents, we found that Pt-3 exhibited greater selectivity of cytotoxicity, decreased resistance factors, and improved anticancer activity compared to cisplatin. Furthermore, Pt-3, which we demonstrate can initiate potent ferritinophagy-dependent ferroptosis, exhibits less toxic and better therapeutic activity than cisplatin in vivo. Our results identify Pt-3 as a promising candidate or paradigm for further drug development in cancer treatment.

[Application of whole exome sequencing for the inferential analysis of recessive genetic disease carrier status for couples with a child died of Primary immunodeficiency].

OBJECTIVE: To explore the value of whole exome sequencing for the inferential analysis of recessive genetic disease carrier status for couples with a child died of Primary immunodeficiency (PID). METHODS: Clinical data was collected from four couples with a childbearing history of PID who had sought genetic counseling and undergone genetic testing at Henan Provincial People's Hospital from February 2017 to December 2021. Whole exome sequencing (WES) was performed on both partners of each couple, and candidate variants were validated by Sanger sequencing and fluorescent quantitative PCR. Prenatal diagnosis was conducted on fetuses of these couples after confirming the variants. RESULTS: A total of six variants were detected in four genes including IL2RG, BTK, CYBB, and DUOX2. Among these, the c.1265G>A and c.3329G>A variants of the DUOX2 gene and the c.676C>T variant of the IL2RG gene were previously known as pathogenic variants. On the other hand, the Exon5_8del variant of the IL2RG gene, the c.184_185delAC variant of the BTK gene, and the c.472A>T variant of the CYBB gene were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics, the IL2RG: Exon5_8del, BTK: c.184_185delAC and CYBB: c.472A>T variants were classified as likely pathogenic (PVS1+PM2_Supporting+PP4).Prenatal diagnosis was conducted for three couples during their subsequent pregnancies, and the results revealed that the fetuses had the wild-type genotypes at the c.184_185 position of the BTK gene, the c.472 position of the CYBB gene, and the c.676 position of the IL2RG gene. Follow-up examinations one year after birth has found no abnormality in the infants. CONCLUSION: WES is an important tool to infer and analyze the carrier status for couples who had given births to children died of PID and improve the positive detection rate.

Immune Cells in the Spleen of Mice Mediate the Inflammatory Response Induced by Mannheimia haemolytica A2 Serotype.

(1) Background: Mannheimia haemolytica (M. haemolytica) is an opportunistic pathogen and is mainly associated with respiratory diseases in cattle, sheep, and goats. (2) Methods: In this study, a mouse infection model was established using a M. haemolytica strain isolated from goats. Histopathological observations were conducted on various organs of the mice, and bacterial load determination and RNA-seq analysis were specifically performed on the spleens of the mice. (3) Results: The findings of this study suggest that chemokines, potentially present in the spleen of mice following a M. haemolytica challenge, may induce the migration of leukocytes to the spleen and suppress the release of pro-inflammatory factors through a negative feedback regulation mechanism. Additionally, an interesting observation was made regarding the potential of hematopoietic stem/progenitor cells congregating in the spleen to differentiate into immune cells, which could potentially collaborate with leukocytes in their efforts to counteract M. haemolytica invasion. (4) Conclusions: This study revealed the immune regulation mechanism induced by M. haemolytica in the mouse spleen, providing valuable insights into host-pathogen interactions and offering a theoretical basis for the prevention, control, and treatment of mannheimiosis.

Integrated Analysis of Transcriptome and Metabolome Profiles in the Longissimus Dorsi Muscle of Buffalo and Cattle.

Buffalo meat is gaining popularity for its nutritional properties, such as its low fat and cholesterol content. However, it is often unsatisfactory to consumers due to its dark color and low tenderness. There is currently limited research on the regulatory mechanisms of buffalo meat quality. Xinglong buffalo are raised in the tropical Hainan region and are undergoing genetic improvement from draught to meat production. For the first time, we evaluated the meat quality traits of Xinglong buffalo using the longissimus dorsi muscle and compared them to Hainan cattle. Furthermore, we utilized a multi-omics approach combining transcriptomics and metabolomics to explore the underlying molecular mechanism regulating meat quality traits. We found that the Xinglong buffalo had significantly higher meat color redness but lower amino acid content and higher shear force compared to Hainan cattle. Differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were identified, with them being significantly enriched in nicotinic acid and nicotinamide metabolic and glycine, serine, and threonine metabolic pathways. The correlation analysis revealed that those genes and metabolites (such as: GAMT, GCSH, PNP, L-aspartic acid, NADP+, and glutathione) are significantly associated with meat color, tenderness, and amino acid content, indicating their potential as candidate genes and biological indicators associated with meat quality. This study contributes to the breed genetic improvement and enhancement of buffalo meat quality.

Association between COVID-19 and sensorineural hearing loss: Evidence from a Mendelian randomization study in European and East Asian population.

BACKGROUND: Long coronavirus disease (COVID), characterized by persistent and sometimes debilitating symptoms following a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has garnered increasing attention as a potential public health crisis. Emerging evidence indicates a higher incidence of hearing loss in individuals who have had COVID 2019 (COVID-19) compared to the general population. However, the conclusions were inconsistent, and the causal relationship between COVID-19 and sensorineural hearing loss remains unknown. METHODS: To addresses this outstanding issue, we performed Mendelian randomization analysis to detect the causal association between COVID-19 and hearing loss using the largest genome-wide association study data to date in the European population and confirmed the results in the East Asian population. Comprehensively sensitive analyses were followed, including Cochran's Q test, Mendelian randomization (MR)-Egger intercept test, MR-pleiotropy residual sum and outlier, and leave-one-out analysis, to validate the robustness of our results. RESULTS: Our results suggested that there is no causal association between COVID-19 and the risk of hearing loss in the European population. Neither the susceptibility, hospitalization, and severity of COVID-19 on hearing loss (inverse variance weighted method: odds ratio (OR) = 1.046, 95% confidence interval (CI) = 0.907-1.205, p = .537; OR = 0.995, 95% CI = 0.956-1.036, p = .823; OR = 0.995, 95% CI = 0.967-1.025, p = .76). Replicated analyses in the East Asian population yielded consistent results. No pleiotropy and heterogeneity were found in our results. CONCLUSION: In conclusion, our MR results do not support a genetically predicted causal relationship between COVID-19 and sensorineural hearing loss. Thus, the associations observed in prior observational studies may have been influenced by confounding factors rather than a direct cause-and-effect relationship. More clinical and mechanism research are needed to further understand this association in the future.

Overexpression of Pasteurella multocida OmpA induces transcriptional changes and its possible implications for the macrophage polarization.

Pasteurella multocida (P. multocida) is a highly infectious, zoonotic pathogen. Outer membrane protein A (OmpA) is an important virulence component of the outer membrane of P. multocida. OmpA mediates bacterial biofilm formation, eukaryotic cell infection, and immunomodulation. It is unclear how OmpA affects the host immune response. We estimated the role of OmpA in the pathogenesis of P. multocida by investigating the effect of OmpA on the immune cell transcriptome. Changes in the transcriptome of rat alveolar macrophages (NR8383) upon overexpression of P. multocida OmpA were demonstrated. A model cell line for stable transcription of OmpA was constructed by infecting NR8383 cells with OmpA-expressing lentivirus. RNA was extracted from cells and sequenced on an Illumina HiSeq platform. Key gene analysis of genes in the RNA-seq dataset were performed using various bioinformatics methods, such as gene ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, Gene Set Enrichment Analysis, and Protein-Protein Interaction Analysis. Our findings revealed 1340 differentially expressed genes. Immune-related pathways that were significantly altered in rat alveolar macrophages under the effect of OmpA included focal adhesion, extracellular matrix and vascular endothelial growth factor signaling pathways, antigen processing and presentation, nucleotide oligomerization domain-like receptor and Toll-like receptor signaling pathways, and cytokine-cytokine receptor interaction. The key genes screened were Vegfa, Igf2r, Fabp5, P2rx1, C5ar1, Nedd4l, Gas6, Cxcl1, Pf4, Pdgfb, Thbs1, Col7a1, Vwf, Ccl9, and Arg1. Data of associated pathways and altered gene expression indicated that OmpA might cause the conversion of rat alveolar macrophages to M2-like. The related pathways and key genes can serve as a reference for OmpA of P. multitocida and host interaction mechanism studies.

[Genetic analysis of two children with developmental delay and intellectual disability].

OBJECTIVE: To explore the genetic etiology of two patients with developmental delay and intellectual disability. METHODS: Two children who were respectively admitted to Henan Provincial People's Hospital on August 29, 2021 and August 5, 2019 were selected as the study subjects. Clinical data were collected, and array comparative genomic hybridization (aCGH) was carried out on the children and their parents for the detection of chromosomal microduplication/microdeletions. RESULTS: Patient 1 was a 2-year-and-10-month female and patient 2 was a 3-year-old female. Both children had featured developmental delay, intellectual disability, and abnormal findings on cranial MRI. aCGH revealed that patient 1 has harbored arr[hg19] 6q14.2q15(84621837_90815662)×1, a 6.19 Mb deletion at 6q14.2q15, which encompassed ZNF292, the pathogenic gene for Autosomal dominant intellectual developmental disorder 64. Patient 2 has harbored arr[hg19] 22q13.31q13.33(46294326_51178264)×1, a 4.88 Mb deletion at 22q13.31q13.33 encompassing the SHANK3 gene, haploinsufficiency of which can lead to Phelan-McDermid syndrome. Both deletions were classified as pathogenic CNVs based on the guidelines of American College of Medical Genetics and Genomics (ACMG) and were not found in their parents. CONCLUSION: The 6q14.2q15 deletion and 22q13-31q13.33 deletion probably underlay the developmental delay and intellectual disability in the two children, respectively. Haploinsufficiency of the ZNF292 gene may account for the key clinical features of the 6q14.2q15 deletion.

Analysis of international competitive situation of key core technology in strategic emerging industries: New generation of information technology industry as an example.

In the context of the current technological revolution and unprecedented major changes, countries are facing the situation of accelerating the development of key core technologies, which is caused by the transformation from the dispute over trade to the dispute over ecology and scientific and technological strength. Competitive situation analysis is an important link of key core technology innovation. The construction of a universal model of international competitive situation analysis of key core technology can provide scientific support for decision makers of science and technology innovation to solve technical difficulties. This study takes the new generation of information technology industry as an example, identifies key core technologies of the industry and evaluates the competitive situation of the major world countries. Studies indicate that in the field of new generation information technology, the US and Japan is in the leading position globally. In addition, China has active innovation activities in all fields, but overall there remains a considerable gap with the world-leading level, and its R&D quality needs to be further improved.

Nanovesicles loaded with a TGF-ß receptor 1 inhibitor overcome immune resistance to potentiate cancer immunotherapy.

The immune-excluded tumors (IETs) show limited response to current immunotherapy due to intrinsic and adaptive immune resistance. In this study, it is identified that inhibition of transforming growth factor-ß (TGF-ß) receptor 1 can relieve tumor fibrosis, thus facilitating the recruitment of tumor-infiltrating T lymphocytes. Subsequently, a nanovesicle is constructed for tumor-specific co-delivery of a TGF-ß inhibitor (LY2157299, LY) and the photosensitizer pyropheophorbide a (PPa). The LY-loaded nanovesicles suppress tumor fibrosis to promote intratumoral infiltration of T lymphocytes. Furthermore, PPa chelated with gadolinium ion is capable of fluorescence, photoacoustic and magnetic resonance triple-modal imaging-guided photodynamic therapy, to induce immunogenic death of tumor cells and elicit antitumor immunity in preclinical cancer models in female mice. These nanovesicles are further armored with a lipophilic prodrug of the bromodomain-containing protein 4 inhibitor (i.e., JQ1) to abolish programmed death ligand 1 expression of tumor cells and overcome adaptive immune resistance. This study may pave the way for nanomedicine-based immunotherapy of the IETs.

Association between INHA gene polymorphisms and litter size in Hainan black goats.

Background: The inhibin alpha (INHA) gene is one of the important genes affecting the reproductive traits of animals. Hainan black goats are the main goat breed in Hainan Island (China), whose development is limited by low reproductive performance. However, the relationship between INHA gene and the reproductive performance of Hainan black goats is still unclear. Therefore, the purpose of this work was to explore the effect of INHA gene polymorphisms on the litter size of Hainan black goats. Methods: Single nucleotide polymorphisms (SNPs) of INHA were detected, and the genetic parameters and haplotype frequency of these SNPs were calculated and association analysis was performed for these SNPs with the litter size. Finally, the SNP with significant correlations to litter size was analyzed by Bioinformatics tools. Results: The results showed that the litter size of individuals with the AC genotype at loci g.28317663A>C of INHA gene was significantly higher than those with the AA genotype. This SNP changed the amino acid sequence, which may affect the function of INHA protein by affecting its structure. Our results suggest that g.28317663A>C loci may serve as a potential molecular marker for improving the reproductive traits in Hainan black goats.

Clearance of bacteria from lymph nodes in sheep immunized with Brucella suis S2 vaccine is associated with M1 macrophage activation.

Ovine brucellosis is a global zoonotic disease of sheep caused by Brucella melitensis, which inflicts a significant burden on human and animal health. Brucella suis strain S2 (B. suis S2) is a smooth live attenuated vaccine for the prevention of ovine brucellosis in China. However, no previous studies have assessed the immunogenicity of B. suis S2 vaccine after oral immunization in sheep. Here, we attempted to evaluate the ovine immune response over the course of B. suis S2 immunization and to identify in vivo predictors for vaccine development. Body temperature, serum Brucella antibodies, serum cytokines (IL-12p70 and interferon [IFN]-γ), and bacterial load in the mandibular lymph nodes (LN), superficial cervical LN, superficial inguinal LN, and spleen were investigated to determine the safety and efficacy of the vaccine. The abnormal body temperature of sheep occurred within 8 days post-infection (dpi). Brucella suis S2 persisted for a short time (< 21 dpi) in the mandibular LN. The highest level of IL-12p70 was observed at 9 dpi, whereas serum IFN-γ levels peaked at 12 dpi. Transcriptome analysis and quantitative reverse transcription PCR were performed to determine gene expression profiles in the mandibular LN of sheep. Antigen processing and presentation pathway was the dominant pathway related to the dataset. Our studies suggest that the immune response in ovine LN resembled type 1 immunity with the secretion of IL-12p70 and IFN-γ after B.suis S2 immunization and the vaccine may eliminate Brucella via stimulation of M1 macrophages through the course of Th cells.

[Clinical and genetic analysis of two children with intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia].

OBJECTIVE: To explore the clinical features and genetic etiology of two children with intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia (MICPCH). METHODS: Two children with MICPCH who were presented at the Henan Provincial People's Hospital between April 2019 and December 2021 were selected as the study subjects. Clinical data of the two children were collected, along with peripheral venous blood samples of them and their parents, and amniotic fluid sample of the mother of child 1. Whole exome sequencing (WES), array-comparative genomic hybridization (aCGH) and real-time quantitative PCR (qPCR) were carried out for the children, their parents and the fetus. The pathogenicity of candidate variants were evaluated. RESULTS: Child 1 was a 6-year-old girl featuring motor and language delay, whilst child 2 was a 4.5-year-old girl mainly featuring microcephaly and mental retardation. WES revealed that child 2 has harbored a 158.7 kb duplication in Xp11.4 (chrX: 41446160_41604854), which has encompassed exons 4~14 of the CASK gene. The same duplication was not found in either of her parents. aCGH revealed that child 1 has harbored a 29 kb deletion at Xp11.4 (chrX: 41637892_41666665), which encompassed exon 3 of the CASK gene. The same deletion was not found in either of her parents and the fetus. The above results were confirmed by qPCR assay. Above deletion and duplication were not found in the ExAC, 1000 Genomes and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as likely pathogenic (PS2+PM2_Supporting). CONCLUSION: The deletion of exon 3 and duplication of exons 4~14 of the CASK gene probably underlay the pathogenesis of MICPCH in these two children, respectively.

[Prenatal genetic analysis of a fetus with Miller-Dieker syndrome].

OBJECTIVE: To explore the genetic basis for fetus with bilateral lateral ventriculomegaly. METHODS: Fetus umbilical cord blood and peripheral blood samples of its parents were collected. The fetus was subjected to chromosomal karyotyping, whilst the fetus and its parents were subjected to array comparative genomic hybridization (aCGH). The candidate copy number variation (CNV) were verified by qPCR, Application goldeneye DNA identification system was used to confirm the parental relationship. RESULTS: The fetus was found to have a normal karyotype. aCGH analysis indicated that it has carried a 1.16 Mb deletion at 17p13.3, which partially overlapped with the critical region of Miller-Dieker syndrome (MDS), in addition with a 1.33 Mb deletion at 17p12 region, which is associated with hereditary stress-susceptible peripheral neuropathy (HNPP). Its mother was also found to harbor the 1.33 Mb deletion at 17p12. qPCR analysis confirmed that the expression levels of genes from the 17p13.3 and 17p12 regions were about the half of that in the normal control, as well as the maternal peripheral blood sample. Parental relationship was confirmed between the fetus and its parents. Following genetic counseling, the parents has chosen to continue with the pregnancy. CONCLUSION: The fetus was diagnosed with Miller-Dieker syndrome due to the de novo deletion at 17p13.3. Ventriculomegaly may be an important indicator for prenatal ultrasonography in fetuses with MDS.

Left atrial reservoir strain measurements derived from intracardiac echocardiography in patients with atrial fibrillation: comparison with transthoracic echocardiography.

BACKGROUND: Intracardiac echocardiography (ICE) provides accurate left atrial (LA) anatomical information in the procedure of atrial fibrillation (AF) ablation but lacks LA functional assessment. LA reservoir strain (LASr) is an excellent marker of LA reservoir function. This study aimed to assess the agreement between LASr derived from ICE and transthoracic echocardiography (TTE) in AF patients and analyze the reproducibility of LASr assessed by ICE combined with speckle tracking imaging. METHODS: This study prospectively enrolled 110 patients with a clinical diagnosis of AF who were ready for AF ablation, including 71 patients with paroxysmal AF and 39 with persistent AF. TTE and ICE examinations were performed on each individual before AF ablation. LASr measurements derived from ICE and TTE images were using dedicated LA-tracking software. Pearson correlation coefficients (r) and Bland-Altman plots were used to evaluate the agreement of LASr between the two modalities. Intraclass correlation coefficients (ICCs) were used to assess intra- and inter-observer reproducibility. RESULTS: The agreement between LASr obtained from ICE and TTE, especially between LASrLPV (LASr derived from LA left pulmonary vein view of ICE) and LASrTTE (LASr derived from TTE) were good in both paroxysmal and persistent AF patients [r = 0.890 (P < 0.001) for overall population; r = 0.815 (P < 0.001) and Bias ± LOA: -0.3 ± 9.9% for paroxysmal AF; r = 0.775 (P < 0.001) and Bias ± LOA: -2.6 ± 3.9% for persistent AF, respectively]. But the values of LASr derived from ICE were slightly lower than those of TTE, especially in patients with persistent AF. The ICCs for LASr derived from ICE were excellent (all ICCs > 0.90). CONCLUSIONS: In patients with AF, LASr derived from ICE demonstrated excellent reproducibility and showed good agreement with LASr obtained from TTE. Obtaining LASr from ICE images may be a supplementary method to evaluate LA reservoir function in AF patients and expands the potential of ICE in the field of cardiac function assessment.