The EFNA4 gene is a potential prognostic biomarker in pancreatic cancer: a bioinformatics analysis.

Background: Pancreatic cancer is a highly aggressive malignancy with poor prognosis, and there is an urgent need to understand its molecular mechanisms for early diagnosis and treatment. Despite surgical resection being the only effective treatment, most patients are diagnosed at an advanced stage, missing the optimal window for therapy. Identifying novel biomarkers is crucial for prognostic assessment, treatment planning, and early intervention. Ephrin A4 (EFNA4), a member of the receptor tyrosine kinase family, is involved in vascular and epithelial development via regulation of cell migration and rejection. However, the role of EFNA4 in pancreatic cancer has not been reported. Therefore, our study aimed to clarify the role of EFNA4 in pancreatic cancer through bioinformatics analysis and vitro experiments. Methods: The expression of EFNA4 and its potential value as a diagnostic and prognostic biomarker in pancreatic cancer was analyzed using data from The Cancer Genome Atlas (TCGA) and the Gene Expression Profiling Interactive Analysis (GEPIA) database. According to the expression level of EFNA4, patients were divided into high expression group and low expression group, and the correlation between overall survival (OS) and disease-free survival (DFS) with different expression levels of EFNA4 and clinical parameters were analyzed. Subsequently, reverse-transcription quantitative polymerase chain reaction (RT-qPCR) was performed to detect EFNA4 expression. The proliferation, invasion, and cloning ability of the cells were detected via Cell Counting Kit 8 (CCK8), Transwell, and plate cloning assays, respectively. Results: EFNA4 is highly expressed in pancreatic cancer, and upregulation of EFNA4 is associated with poor prognosis. In this study, EFNA4 expression was correlated with T stage and TNM (tumor-node-metastasis) stage of pancreatic cancer, and the median survival time and progression-free survival (PFS) were worse in those with high EFNA4 expression (394 days) than in those with low expression (525 days) [hazard ratio (HR): 1.47, 95% confidence interval (CI): 1.00-2.16, P=0.047]. In addition, EFNA4 was also found to be involved in the regulation of signal pathways such as cell adhesion, cyclic AMP, insulin secretion, pancreatic secretion, and protein digestion and absorption. In vitro experiments demonstrated that EFNA4 knockdown significantly inhibited the proliferation, cloning ability, and invasiveness of the PANC-1 and SW1990 pancreatic cancer cell lines. Conclusions: The abnormal expression of EFNA4 in pancreatic cancer is associated with poor prognosis. Knockout of EFNA4 gene could significantly inhibit the proliferation and invasion of pancreatic cancer cells. Therefore, EFNA4 may be one of the molecular targets for poor prognosis of patients with pancreatic cancer.

Geniposide effectively safeguards HT22 cells against Aß-induced damage by activating mitophagy via the PINK1/Parkin signaling pathway.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the significant involvement of amyloid-beta (Aß) peptide in its pathogenesis. Geniposide, derived from the versatile medicinal of Gardenia jasminoides, is one of the active compounds studied extensively. The objective was to explore the impact of geniposide on Aß25-35-induced damage in HT22 cells, specifically focusing on its modulation of PINK1/Parkin-mediated mitophagy. In our investigation, geniposide exhibited remarkable restorative effects by enhancing cell viability and preserving the mitochondrial membrane potential. Moreover, it effectively reduced and mitigated the oxidative stress and apoptosis rates induced by Aß25-35. Notably, geniposide exhibited the capacity to enhance autophagic flux, upregulate LC3II and Beclin-1 expression, and downregulate the expression of p62. Furthermore, geniposide positively influenced the expression of PINK1 and Parkin proteins, with molecular docking substantiating a strong interaction between geniposide and PINK1/Parkin proteins. Intriguingly, the beneficial outcomes of geniposide on alleviating the pronounced apoptosis rates, the overproduction of reactive oxygen species, and diminished the PINK1 and Parkin expression induced by Aß25-35 were compromised by the mitophagy inhibitor cyclosporine A (CsA). Collectively, these findings suggested that geniposide potentially shields HT22 cells against neurodegenerative damage triggered by Aß25-35 through the activation of mitophagy. The insights contribute valuable references to the defensive consequences against neurological damage of geniposide, thereby highlighting its potential as a therapeutic intervention in AD.

Icariin promotes osteogenic differentiation through the mmu_circ_0000349/mmu-miR-138-5p/Jumonji domain-containing protein-3 axis.

Circular RNAs (circRNAs) regulate Jumonji domain-containing protein-3 (JMJD3) by sponging with microRNAs (miRNAs). This study aimed to investigate the role of icariin on specific circRNA/miRNA/JMJD3 axis in osteogenic differentiation of MC3T3-E1 cells. CircRNA sequencing was performed on the MC3T3-E1 cells induced by osteogenic differentiation medium for 1 d (negative control (NC) group) and 14 d (osteogenesis group). And mmu_circ_0000349 was verified using Sanger sequencing, ribonuclease R degradation, and actinomycin D assay. The function of mmu_circ_0000349 was validated by detecting the expressions of osteogenic differentiation markers, alkaline phosphatase (ALP), and runt-related transcription (RUNX2), via real-time quantitative PCR (qPCR) and Western blotting or ALP and alizarin red staining assay. Dual luciferase reporter gene assay confirmed the relationship between mmu_circ_0000349 and mmu-miR-138-5p (or mmu-miR-138-5p and JMJD3). Meanwhile, the JMJD3 binding to mmu_circ_0000349 was screened using an RNA pull-down assay. qPCR and Western blotting confirmed the effect of icariin on the mmu_circ_0000349/mmu-miR-138-5p/JMJD3 axis and osteogenic differentiation. As MC3T3-E1 osteogenic differentiation progressed, the JMJD3 expression level increased. A total of 361 circRNAs exhibited differences between the NC and osteogenesis groups. After validation, mmu_circ_0000349 was further analyzed as it exhibited the largest expression. And mmu_circ_0000349 was identified as a stable circular structure. Overexpression of mmu_circ_0000349 increased the expression levels of ALP and RUNX2, enhanced ALP activity, and increased the number of mineralized nodules; contrarily, inhibition of mmu_circ_0000349 exerted opposite effects. The data also confirmed that mmu_circ_0000349 regulated JMJD3 by sponging with mmu-miR-138-5p. With the increase in icariin concentration and time for treatment, the expression levels of mmu_circ_0000349, JMJD3, ALP, and RUNX2 also increased, whereas that of mmu-miR-138-5p decreased. In conclusion, Icariin promoted osteogenic differentiation by regulating the mmu_circ_0000349/mmu-miR-138-5p/JMJD3 pathway. Therefore, this provides a theoretical basis for the treatment of diseases related to osteogenic differentiation.

Unraveling the activation process and core driver genes of HSCs during cirrhosis by single-cell transcriptome.

Worldwide, cirrhosis is a common cause of death, manifesting itself as fibrosis of the liver tissue. When the liver is damaged, the liver produces fibrotic, proliferative myofibroblasts, which are formed by the differentiation of activated hepatic stellate cells. There are no effective antifibrotic treatment options. To deeply explore the activation process of hepatic stellate cells (HSCs) and to discover better therapeutic target genes, single-cell RNA sequencing data on 13 non-cirrhotic liver tissue samples and 10 cirrhotic liver tissue samples were analyzed. We identified activated HSCs from the mesenchymal cell population with high expression of ACTA2. By pseudo-time analysis, we found that the key genes for the differentiation of HSCs into myofibroblasts were C3, CCDC80, COL1A1, COL3A1, DCN, FBLN1, IGFBP3, MXRA5, SERPINE1, and MYH11. Then, we found that the main regulators of HSCs from inactive to activated state were NTF3, NTRK3, NTRK2, JAG1, NOTCH3, ESAM, and CD46 by cell-cell communication analysis. In addition, we found that the top2 hub genes of activated HSCs were CRIP1 and ACTA2. The experimental results show that the top2 hub genes were significantly overexpressed in cirrhotic samples. Our work dissected key intercellular regulators and core driver genes during hepatic stellate cell activation during cirrhosis through single-cell transcriptome data analysis, providing a research strategy to discover rational therapeutic targets for cirrhosis and some important information for gene targeting therapy.

The retrospective data analysis on the pedigree of nervous system diseases in children.

Nowadays, the development of diagnosis and treatment technology is constantly changing the pedigree and classification of nervous system diseases. Analyzing changes in earlier disease pedigrees can help us understand the changes involved in disease diagnosis from a macro perspective, as well as predict changes in later disease pedigrees and the direction of diagnosis and treatment. The inpatients of the neurology department from January 2012 to December 2020 in Hunan Children's Hospital were retrospectively analyzed. There were 36,777 patients enrolled in this study. The next analysis was based on factors like age, gender, length of stay (LoS), number of patients per month and per year (MNoP and ANoP, respectively), and average daily hospital cost (ADHE). To evaluate the characteristics of neurological diseases, we applied a series of statistical tools such as numerical characteristics, boxplots, density charts, one-way ANOVA, Kruskal-Wallis tests, time-series plots, and seasonally adjusted indices. The statistical analysis of neurological diseases led to the following conclusions: First, children having neurological illnesses are most likely to develop them between the ages of 4 and 8 years. Benign intracranial hypertension was the youngest mean age of onset among the various neurologic diseases, and most patients with bacterial intracranial infection were young children. Some diseases have a similar mean age of onset, such as seizures (gastroenteritis/diarrhea) and febrile convulsions. Second, women made up most patients with autoimmune diseases of the central nervous system. Treatment options for inherited metabolic encephalopathy and epilepsy are similar, but they differ significantly for viral intracranial infection. Some neurologic diseases were found to have seasonal variations; for example, infectious diseases of the central nervous system were shown to occur more commonly in the warm season, whereas, autoimmune diseases primarily appeared in the autumn and winter months. Additionally, the number of patients admitted to hospitals with intracranial infections and encephalopathy has dramatically dropped recently, but the number of patients with autoimmune diseases of the central nervous system and hereditary metabolic encephalopathy has been rising year over year. Finally, we discovered apparent polycentric distributions in various illnesses' density distributions. The study offered an epidemiological basis for common nervous system diseases, including evidence from age of onset, number of cases, and so on. The pedigree of nervous system diseases has significantly changed. The proportion of patients with neuroimmune diseases and genetic metabolic diseases is rising while the number of patients with infection-related diseases and uncertain diagnoses is decreasing. The existence of a disease multimodal model suggests that there is still a lack of understanding of many diseases' diagnosis and treatment, which needs to be improved further because accurate diagnosis aids in the formulation of individualized treatment plans and the allocation of medical resources; additionally, there is still a lack of effective treatment for most genetic diseases. The seasonal characteristics of nervous system diseases suggest the need for the improvement of sanitation, living conditions, and awareness of daily health care.

Multisystem Mitochondrial Disease Associated With a Mare m.10000G>A Mitochondrial tRNA Gly (MT-TG) Variant.

Background: Mitochondrial diseases are clinically heterogeneous, can occur at any age, and can manifest with a wide range of clinical symptoms. They can involve any organ or tissue, characteristically involve multiple systems, typically affecting organs that are highly dependent on aerobic metabolism, and making a definitive molecular diagnosis of a mitochondrial disorder is challenging. Methods: Clinical data of the proband and his family members were gathered in a retrospective study. Whole-exome sequencing and full-length sequencing of the mitochondrial genome that were performed on peripheral blood, urine, and oral mucosa cells were applied for genetic analysis. Results: In this study, we reported a childhood-onset mitochondrial phenotype in a 13-year-old patient. Analysis of the next-generation sequencing data of the nuclear genome and the full-length sequencing of the mitochondrial genome revealed the rare m.10000G>A variant in MT-TG that was present at variable heteroplasmy levels across tissue types: 32.7% in the blood, 56.15% in urinary epithelial cells, and 27.3% in oral mucosa cells. No variant was found in the peripheral blood of his mother and sister. No pathogenic mutation of nDNA was found. Conclusion: Our results added evidence that the de novo m.10000G>A variation in the highly conserved sequence of MT-TG appears to suggest a childhood-onset mitochondrial phenotype in the 13-year-old patient, thus broadening the genotypic interpretation of mitochondrial DNA-related diseases.

Proposing Two Local Modeling Approaches for Discriminating PGI Sunite Lamb from Other Origins Using Stable Isotopes and Machine Learning.

For the protection of Protected Geographical Indication (PGI) Sunite lamb, PGI Sunite lamb samples and lamb samples from two other banners in the Inner Mongolia autonomous region were distinguished by stable isotopes (δ13C, δ15N, δ2H, and δ18O) and two local modeling approaches. In terms of the main characteristics and predictive performance, local modeling was better than global modeling. The accuracies of five local models (LDA, RF, SVM, BPNN, and KNN) obtained by the Adaptive Kennard-Stone algorithm were 91.30%, 95.65%, 91.30%, 100%, and 91.30%, respectively. The accuracies of the five local models obtained by an approach of PCA-Full distance based on DD-SIMCA were 91.30%, 91.30%, 91.30%, 100%, and 95.65%, respectively. The accuracies of the five global models were 91.30%, 91.30%, 91.30%, 100%, and 91.30%, respectively. Stable isotope ratio analysis combined with local modeling can be used as an effective indicator for protecting PGI Sunite lamb.

Key genes in the liver fibrosis process are mined based on single-cell transcriptomics.

At present, there is no effective treatment for liver fibrosis, and treatment options are limited. Liver fibrosis remains a cancer with a high mortality rate. During liver injury, hepatic stellate cells transdifferentiate into myofibroblasts capable of proliferation, migration, and invasion. The transcriptomes of more than 60,000 human single cells were analyzed in 9 cirrhotic tissue samples and 11 normal liver tissue samples in order to identify key regulatory factors and core driver genes for myofibroblast transformation. Through cell communication analysis, we obtained the key cytokines of hepatic stellate cells regulating myofibroblasts, such as PDGFA, PDGFAR, PGF, NTF3, etc. At the same time, we also obtained key driver genes related to myofibroblast characteristics, such as LUM,GGT5, RBP1, ASPN,DCN, etc., through single-nucleus consensus weighted gene co-expression network analysis (scWGCNA). In addition, since APOE also plays a very important role in myofibroblasts, we also explored the driver genes associated with APOE, such as THY1,MMP2,COL3A1, etc. We analyzed the core driver gene of hepatic stellate cell transformation into myofibroblasts at the single-cell level in the process of liver fibrosis, providing valuable information for the future targeted gene diagnosis and treatment of liver fibrosis.

Clinical features of obstructive sleep apnea in children with obesity. / è‚¥èƒ–å„¿ç«¥é˜»å¡žæ€§ç¡çœ å‘¼å¸æš‚åœçš„ä¸´åºŠç‰¹å¾.

OBJECTIVES: To study the clinical features of obstructive sleep apnea (OSA) in children with obesity. METHODS: A retrospective analysis was performed on the medical data of 33 obese children aged 7-15 years, who were diagnosed with OSA and received polysomnography (PSG) in the Department of Respiratory Medicine in Shenzhen Children's Hospital. Fifty OSA children with normal body weight, matched for sex and age, were enrolled as the control group. RESULTS: Among the 33 obese children with OSA, the three most common daytime symptoms were inattention in 30 children (91%), somnolence in 22 children (67%), and morning fatigue in 21 children (64%), and the three most common nocturnal symptoms were snoring in 27 children (82%), mouth breathing in 20 children (61%), and sweating in 16 children (49%). Compared with the reference values of normal children, both the OSA + obesity group and the control group had prolonged light sleep, shortened deep sleep, and a significantly shortened rapid eye movement (REM) period, while there was no significant difference in these indices between the two groups (P>0.05). The apnea-hypopnea index, obstructive apnea/hypopnea index, and oxygen desaturation index in both REM and non-REM periods in the OSA +obesity group were significantly higher than those in the control group (P<0.05), while the lowest blood oxygen saturation during sleep was significantly lower in the OSA + obesity group (P<0.05). CONCLUSIONS: The children with obesity and OSA have the main daytime symptoms of inattention, somnolence, and morning fatigue and the main nocturnal symptoms of snoring, mouth breathing, and sweating. There is no significant difference in sleep structure between OSA children with obesity and those with normal body weight; however, respiratory events and blood oxygen saturation decline are more severe in OSA children with obesity. Citation.

MicroRNA-506-3p inhibits colorectal cancer cell proliferation through targeting enhancer of zeste homologue 2.

A large number of studies have shown that microRNA (miRNA) has an important relationship with the occurrence and development of colorectal cancer (CRC), but its specific molecular mechanism has not been fully elucidated. This study is to explore the influence of miR-506-3p on the malignant behavior of CRC and its underlying molecular mechanism. Our results show that miR-506-3p was lowly expressed and enhancer of zeste homologue 2 (EZH2) was highly expressed in CRC. Overexpressing miR-506-3p or silencing EZH2 inhibited CRC cell proliferation, migration and invasion and promoted apoptosis. Inhibiting miR-506-3p promoted CRC cell proliferation, migration and invasion but inhibited apoptosis. These impacts were reversed after co-transfecting si-EZH2. Further mechanism studies have shown that miR-506-3p can reduce EZH2 expression in CRC cells by binding to the 3'UTR end of EZH2. In summary, the results of this study show that miR-506-3p inhibited CRC progression through targeting EZH2 expression. This provides a new molecular target for the clinical treatment of CRC in the future.

[Clinical features of sleep-disordered breathing in children with neuromuscular disease].

OBJECTIVE: To study the clinical features of sleep-disordered breathing (SDB) in children with neuromuscular disease (NMD). METHODS: A retrospective analysis was performed on the medical data of 18 children who were diagnosed with NMD and underwent polysomnography (PSG) (NMD group). Eleven children without NMD who had abnormal sleeping habit and normal sleep structure on PSG were enrolled as the control group. The two groups were compared in terms of the daily and nocturnal symptoms of SDB, incidence rate of obstructive sleep apnea (OSA), pulmonary function, end-tidal partial pressure of carbon dioxide (PetCO2), features of sleep structure, and sleep respiratory events. RESULTS: In the NMD group, 16 children (89%) had related daily and nocturnal symptoms of SDB, and the youngest age was 1 year at the onset of such symptoms. Compared with the control group, the NMD group had significant reductions in total sleep time and sleep efficiency (P < 0.05), a significant reduction in the proportion of rapid eye movement (REM) sleep (P < 0.05), significant increases in obstructive apnea and hypopnea events (P < 0.05) and oxygen reduction events during REM sleep (P < 0.05), and a significant reduction in blood oxygen saturation during REM sleep (P < 0.05). In the NMD group, 17 children (94%) were diagnosed with OSA, and all children had normal lung function and PetCO2. CONCLUSIONS: There is a high proportion of children with SDB among the children with NMD, and SDB can be observed in the early stage of NMD, which results in the damage of sleep structure and the reduction in sleep efficiency. Respiratory events are mainly obstructive events, and oxygen reduction events are mainly observed during REM sleep.

Predictors of postoperative biochemical remission in acromegaly.

PURPOSE: Acromegaly is a rare neuroendocrine condition that can lead to significant morbidity. Despite China's vast population size, studies on acromegaly remain sparse. This study aimed to investigate the clinical characteristics and predictors of biochemical remission after surgery for acromegaly using the China Acromegaly Patient Association (CAPA) database. METHODS: A retrospective nationwide study was conducted using patient-reported data from CAPA database between 1998 and 2018. The principal component analysis (PCA) and logistic regression analysis were employed to determine independent predictors of biochemical remission at 3 months in patients after surgery. RESULTS: Of the 546 surgical cases (mean age: 36.8 years; 59.5% females), macroadenomas and invasive tumors (Knosp score 3-4) were 83.9% and 64.1%, respectively. Ninety-five percent of patients were treated with endonasal surgery and 36.8% exhibited biochemical remission at 3-months postoperatively. The following independent predictors of biochemical remission were identified: preoperative growth hormone (GH) levels between 12 and 28 µg/L [odds ratio (OR) = 0.58; 95% confidence interval (CI), 0.37-0.92; p = 0.021], preoperative GH levels > 28 µg/L (OR = 0.55; 95% CI, 0.34-0.88; p = 0.013), macroadenoma (OR = 0.56; 95% CI, 0.32-0.96; p = 0.034), giant adenomas (OR = 0.14; 95% CI, 0.05-0.38; p < 0.001), Knosp score 3-4 (OR = 0.37; 95% CI, 0.24-0.57; p < 0.001), and preoperative medication usage (OR = 2.32; 95% CI, 1.46-3.70; p < 0.001). CONCLUSIONS: In this nationwide study spanning over two decades, we highlight that higher preoperative GH levels, large tumor size, and greater extent of tumor invasiveness are associated with a lower likelihood of biochemical remission at 3-months after surgery, while preoperative medical therapy increases the chance of remission.

Clinical features of sleep-disordered breathing in children with neuromuscular disease / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of sleep-disordered breathing (SDB) in children with neuromuscular disease (NMD).@*METHODS@#A retrospective analysis was performed on the medical data of 18 children who were diagnosed with NMD and underwent polysomnography (PSG) (NMD group). Eleven children without NMD who had abnormal sleeping habit and normal sleep structure on PSG were enrolled as the control group. The two groups were compared in terms of the daily and nocturnal symptoms of SDB, incidence rate of obstructive sleep apnea (OSA), pulmonary function, end-tidal partial pressure of carbon dioxide (PetCO@*RESULTS@#In the NMD group, 16 children (89%) had related daily and nocturnal symptoms of SDB, and the youngest age was 1 year at the onset of such symptoms. Compared with the control group, the NMD group had significant reductions in total sleep time and sleep efficiency (@*CONCLUSIONS@#There is a high proportion of children with SDB among the children with NMD, and SDB can be observed in the early stage of NMD, which results in the damage of sleep structure and the reduction in sleep efficiency. Respiratory events are mainly obstructive events, and oxygen reduction events are mainly observed during REM sleep.

Bioinformatics analysis of differentially expressed genes on alopecia.

The molecular mechanism of alopecia areata (AA) is still elusive and here we utilized bioinformatics methods to analyze AA-related differentially expressed genes. In this study, GSE45512 and GSE45513 were downloaded from the NCBI sub-database Gene Expression Omnibus (GEO). The gene expressions of AA and normal samples were analyzed using the R package limma, which showed significant differences between AA and normal samples in two species. These genes were subject to functional annotation and protein interaction networks. At the same time, gene set enrichment analysis was conducted for all differentially expressed genes. The study revealed that a total of 225 differentially expressed genes were screened from human AA samples, and a total of 337 differentially expressed genes were screened from spontaneous AA skin samples in C3H/HeJ mice. There are 23 differentially expressed genes in the two species. GO and protein interaction network analysis shown gene enrichment in immune-related functions, and these proteins interact with each other. Gene set enrichment analysis showed that differential genes from both species were significantly enriched to chemokine signaling pathways, cytokine-cytokine receptor interactions, staphylococcus aureus infection, and antigen processing and presentation. Moreover, the human down-regulated differential gene not only maps to the alopecia in human phenotype ontology, but also maps to the pathologically relevant phenotype of the skin appendage. In brief, 23 significant differentially expressed genes were screened out coexisting in AA human and mouse by bioinformatics methods. In addition, the result demonstrated that AA is closely related to the immune process and skin appendage lesions. These results provide new ideas for the diagnosis and treatment of AA.

A novel circular RNA circFN1 enhances cisplatin resistance in gastric cancer via sponging miR-182-5p.

Cisplatin (CDDP) is commonly used for gastric cancer (GC) chemotherapy. However, after several CDDP-based treatment cycles, patients always acquire chemotherapy resistance, which limits the overall clinical efficacy of the treatment. Clarification of the mechanisms responsible for CDDP resistance is required to improve therapeutic outcomes for patients. Circular RNAs (circRNAs) are noncoding RNAs involved in the pathogenesis of cancer, although their role in the mechanism underlying CDDP resistance in GC remains unknown. In the present study, we explored the underlying roles of circRNAs in the modulation of CDDP resistance in CDDP-sensitive and CDDP-resistant human GC cells. Using RNA sequencing and quantitative reverse transcription polymerase chain reaction, expression of circFN1 (originating from exons 10, 11, and 12 of the FN1 gene hsa_circ_0058147) was higher in CDDP-resistant GC cells and tissues. CircFN1 upregulation in GC patients treated by CDDP was significantly correlated with aggressive biological behavior. CircFN1 promoted viability and inhibited apoptosis of GC cells exposed to CDDP in vivo and in vitro. Furthermore, circFN1 suppressed GC cell apoptosis by "sponging" miR-182-5p. These findings demonstrate the involvement of circFN1 in CDDP resistance of GC and implicate circFN1 as a therapeutic target for GC patients treated with CDDP. It provides novel evidence of the function of circRNAs as microRNA sponges and highlight a potential therapeutic target for extinguishing CDDP resistance in patients with GC.

Integrated Proteomics and Metabolomics Analysis Provides Insights into Ganoderic Acid Biosynthesis in Response to Methyl Jasmonate in Ganoderma Lucidum.

Ganoderma lucidum is widely recognized as a medicinal basidiomycete. It was previously reported that the plant hormone methyl jasmonate (MeJA) could induce the biosynthesis of ganoderic acids (GAs), which are the main active ingredients of G. lucidum. However, the regulatory mechanism is still unclear. In this study, integrated proteomics and metabolomics were employed on G. lucidum to globally identify differences in proteins and metabolites under MeJA treatment for 15 min (M15) and 24 h (M24). Our study successfully identified 209 differential abundance proteins (DAPs) in M15 and 202 DAPs in M24. We also identified 154 metabolites by GC-MS and 70 metabolites by LC-MS in M24 that are involved in several metabolic pathways. With an in-depth analysis, we found some DAPs and metabolites that are involved in the oxidoreduction process, secondary metabolism, energy metabolism, transcriptional and translational regulation, and protein synthesis. In particular, our results reveal that MeJA treatment leads to metabolic rearrangement that inhibited the normal glucose metabolism, energy supply, and protein synthesis of cells but promoted secondary metabolites, including GAs. In conclusion, our proteomics and metabolomics data further confirm the promoting effect of MeJA on the biosynthesis of GAs in G. lucidum and will provide a valuable resource for further investigation of the molecular mechanisms of MeJA signal response and GA biosynthesis in G. lucidum and other related species.

Brain astrocytoma misdiagnosed as anti-NMDAR encephalitis: a case report.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, which is the most common type of autoimmune encephalitis, is caused by the production of autoantibodies against NMDA receptor. Anti-NMDAR encephalitis patients present with various non-specific symptoms, such as abnormal psychiatric or behaviour, speech dysfunction, cognitive dysfunction, seizures, movement disorders, decreased level of consciousness, and central hypoventilation or autonomic dysfunction. CASE PRESENTATION: A 67-year-old man presented with new-onset focal seizures. The brain magnetic resonance imaging (MRI) plain scan and enhanced scan showed abnormal signal on the proximal midline frontoparietal junction region. Anti-NMDAR antibody was detected in cerebrospinal fluid (CSF) and serum using a commercial kit (Euroimmune, Germany) by indirect immunofluorescence testing (IIFT) according to the manufacturer's instructions for twice. Both of the test results were positive in CSF and serum. The patient was diagnosed as anti-NMDAR encephalitis and then was treated repeatedly with large dose of intravenous corticosteroids and gamma globulin. Accordingly, the refractory nature of seizures in this case may be attributed to NMDAR autoantibodies. When the patient presented at the hospital for the third time, the brain MRI revealed an increase in the size of the frontal parietal lesion and one new lesion in the left basal ganglia. The patient underwent a surgical biopsy and astrocytoma was confirmed by histopathology. CONCLUSIONS: Although the sensitivity and specificity of anti-NMDAR-IgG antibodies in CSF to diagnose anti-NMDAR encephalitis are close to 100%, it is not absolute. Anti-NMDAR antibodies were positive, which might make the diagnosis more complex. The diagnosis of atypical presentation of anti-NMDAR encephalitis requires reasonable exclusion of other disorders.

Prognostic value of ATAD3 gene cluster expression in hepatocellular carcinoma.

ATPase family AAA domain-containing protein 3 (ATAD3) is a mitochondrial membrane-bound ATPase that is involved in a number of cellular processes and is linked with the progression of various types of malignancies. In primates, the ATAD3 gene cluster contains ATAD3A, ATAD3B and ATAD3C. The association between ATAD3 gene cluster expression and hepatocellular carcinoma (HCC) remains unknown. Therefore, the present study examined the prognostic significance of ATAD3 gene cluster expression in patients with HCC. Box plots of expression differences between HCC and normal liver tissues for the ATAD3 family genes were obtained from the online tool Gene Expression Profiling Interactive Analysis. Data from 360 patients with HCC in The Cancer Genome Atlas database were analyzed. Kaplan-Meier analysis and a Cox regression model were used to calculate median survival time (MST) and overall survival (OS). ATAD3A and ATAD3B expression levels were higher in HCC compared with normal liver tissues (P<0.05). However, ATAD3C expression was significantly decreased in HCC tissues compared with normal liver tissues (P<0.05). ATAD3A [P=0.017, hazard ratio (HR)=1.54, 95% confidence interval (CI)=1.08-2.20; adjusted P=0.032; adjusted HR=1.52; 95% CI=1.04-2.22] and ATAD3B (P=0.026, HR=1.49, 95% CI=1.05-2.13; adjusted P=0.031, adjusted HR=1.52, 95% CI=1.04-2.21) expression levels were significantly associated with OS. A joint-effects analysis revealed that patients with high ATAD3A and ATAD3B expression had reduced OS rates compared with patients with low ATAD3A and ATAD3B expression (P=0.007, HR=1.77, 95% CI=1.16-2.69; adjusted P=0.013, adjusted HR=1.76, 95% CI=1.13-2.75). In conclusion, ATAD3A and ATAD3B may serve as potential prognostic biomarkers for patients with HCC.

Detection of goat meat adulteration by real-time PCR based on a reference primer.

Economically motivated adulteration (EMA) has become one of the most concerned food safety issues. However, existing mainstream PCR methods could neither achieve qualitative detection purposes, nor detect all possible meat species involved in adulteration. When meat has been adulterated with unidentified species but the result indicates no adulteration, it is a false negative; when meat has not been adulterated deliberately but has somehow been polluted during its processing or packaging, a false positive emerges. A novel reference primer based real-time PCR approach was developed in this study for quantitative determination of goat meat adulterated with pork. By calculating the ratio of Ct (specificity/reference), a good linear correlation (R2 = 0.9929) could be deduced for the goat meat content. We also successfully amplified simulated samples and the results showed high accuracy with an average recovery of 108.74% for the samples.