High blood glucose variability may predict poor outcomes in patients with spontaneous cerebellar hemorrhage undergoing surgical operation: a retrospective study.

BACKGROUND: Elevated blood glucose (BG) variability has been reported as an independent risk factor for poor prognosis in a variety of diseases. This study aimed to investigate the association between BG variability and clinical outcomes in patients with spontaneous cerebellar hemorrhage (SCH) undergoing surgical operation. METHODS: This retrospective cohort study of the consecutive patients admitted to the department of Neurosurgery, the Affiliated Hospital of Qingdao University between January 2014 and June 2022 with the diagnosis of SCH underwent surgical intervention. BG analysis was continuously and routinely performed. BG variability was represented by the standard deviation (SD) of the serial measurements within the first 7 days. The general characteristics, imageological information, blood glucose level, and surgical information were reviewed and compared through medical records. RESULTS: A total of 115 patients (65 male and 50 female) were enrolled. Out of all 115 patients, the overall clinical outcomes according to the modified Rankin Scale (mRS) were poor (mRS 3-6) in 31 patients (26.96%) and good (mRS 0-2) in 84 patients (73.04%). Twelve of the 115 patients died during hospitalization, and the mortality rate was 10.43%. Multivariate logistic regression analysis showed that SD of BG (odds ratio (OR), 4.717; 95% confidence interval (CI), 1.054-21.115; P = 0.043), GCS (OR, 0.563; 95% CI, 0.330-0.958; P = 0.034), and hematoma volume (OR, 1.395; 95% CI, 1.118-1.748; P = 0.003) were significant predictors. The area under the ROC curve of SD of BG was 0.911 (95% CI, 0.850-0.973; P < 0.001) with a sensitivity and specificity of 90.3% and 83.3%, respectively, and the cut-off value was 1.736. CONCLUSIONS: High BG Variability is independently correlated with the 6-month poor outcomes in patients with SCH undergoing surgical operation.

Lack of sphingomyelin synthase 2 reduces cerebral ischemia/reperfusion injury by inhibiting microglial inflammation in mice.

Recanalization of blood flow after ischemia can lead to ischemia/reperfusion injury, and inflammation plays an important role in the mechanisms behind cerebral ischemia/reperfusion injury. Sphingomyelin synthase 2 (SMS2) deficiency reduces inflammation; however, the effect and mechanism of action of SMS2 on the inflammatory response after cerebral ischemia/reperfusion injury are still unclear. Wild-type (WT) and SMS2 knockout C57BL/6 mice were used to establish a model of cerebral ischemia/reperfusion. The neurological deficit score was evaluated with Longa's method, and infarct volume was evaluated by magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining. Neurological deficit and infarct volume were used to evaluate the degree of cerebral ischemia/reperfusion injury in mice. Western blotting, reverse transcription-quantitative PCR and immunofluorescence were used to detect the expression profiles. The neurological deficit score of SMS2-/- mice was significantly lower than that of WT mice at 72 h after cerebral ischemia/reperfusion injury (P=0.027), but not significantly different at 24 h (P=0.064). Compared with WT mice at 24 and 72 h after cerebral ischemia/reperfusion, the infarct volume of SMS2-/- mice was decreased, the expression of pro-inflammatory cytokines galectin 3 and interleukin-1ß were decreased, the activation of microglia was decreased, and the nuclear translocation of NF-κB p65 was decreased, but the expression of the anti-inflammatory factor arginase 1 was increased. Lack of SMS2 in mice can help to reduce the inflammatory reaction by inhibiting the activation of NF-κB signaling pathway, further attenuating cerebral ischemia/reperfusion injury in mice.

Protective effects of histone deacetylase inhibition by Scriptaid on brain injury in neonatal rat models of cerebral ischemia and hypoxia.

BACKGROUND: Neonatal hypoxia-ischemia brain damage (HBID) can cause a series of neurological sequelae, such as movement and cognitive impairment, and there is currently no clinically effective treatment. Changes in epigenetic processes had been shown to be involved in the development of a series of neurodegenerative diseases, and HDAC inhibition by Scriptaid had been shown to reduce severe traumatic brain injury by suppressing inflammatory responses. This study investigated the protective effect of HDAC inhibition by Scriptaid after HBID. METHODS: We established the neonatal rat HBID model, and used intraperitoneal injection of HDAC inhibitor scriptaid as a treatment. 7 days after HBID, nuclear magnetic resonance imaging (MRI) was used to detect infarct volume. The otarod test, wire hang test and Morris water maze were used to evaluate the HBID model of neurobehavioral dysfunction. Immunoblotting, immunofluorescence, and quantitative real-time PCR (RT-qPCR) were used to detect gene expression. RESULTS: HDAC inhibition by Scriptaid treatment could not only reduce the infarct volume and neuronal degeneration in HBID rats, but also helped to improve their neurobehavioral dysfunction. 7 days after HBID, the expression of HDAC-1, HDAC-2 and HDAC-3 in the infarct volume of HBID + Veh group rats were much more than that in sham group (P<0.05), but Scriptaid could significantly inhibit those expression (P<0.05), and significantly increased the acetylation of H3 and H4 in HBID rats. In vivo and vitro results demonstrated that Scriptaid had no significant effect on oligodendrocyte MBP protein expression after OGD, but Scriptaid -treated microglia cultures had protective effects on OGD-treated OLG, M1 microglia suppressed OLG activity after OGD, and M2 enhanced its activity. In vivo experiments at 7 days after HBIDI injury showed that Scriptaid could promote the polarization of microglia into M2 microglia, reduced the expression of pro-inflammatory factors, and enhance the expression of anti-inflammatory cytokines. CONCLUSION: After HBID, HDAC inhibitor Scriptaid inhibits inflammatory responses and protects the brain by promoting the polarization of microglia in brain tissue to M2 microglia.

Boosting of Hepatitis B Virus-Specific T Cell Responses After Pegylated-Interferon-α-2a Therapy for Hepatitis B e Antigen-Positive Pediatric Patients.

Treatment of chronic hepatitis B with pegylated-interferon-α-2a (PegIFNα) in pediatric patients can lead to a higher rate of hepatitis B virus (HBV) surface antigen (HBsAg) loss than in adults. However, the mechanism of underlying immune response is not clear. The aim of this study was to explore innate and adaptive immunity, especially HBV-specific T cell responses in hepatitis B e antigen (HBeAg)-positive pediatric patients, who have experienced HBsAg loss. Isolated lymphocytes of 20 HBeAg-positive pediatric patients were collected every 12 weeks until treatment was stopped. The phenotype of T/natural killer (NK) cells and function of HBV-specific T cells were analyzed by flow cytometry. The frequency of CD69 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expressed on T cells and TRAIL on CD56hi NK cells in patients with HBsAg loss was remarkably higher compared with nonresponse patients. Furthermore, in vitro peptide stimulation of HBV-specific T cell responses was increased in patients with HBsAg loss when compared with week 0 and 48, and correlated with decline of viral load. The PegIFNα therapy in pediatric patients triggered T/NK cell activation and HBV-specific T cell responses, thereby contributing to successful viral control.

Effect of lncRNA BNC2-AS1 on the Proliferation, Migration and Invasion of Gastric Cancer Cells.

Background: Gastric cancer is one of the most common cancers and is the second leading cause of cancer mortality worldwide. The present study aimed to investigate the potential biological effect of long non-coding RNA (lncRNA) BNC2-AS1 on the proliferation, migration, and invasion of cervical cancer cells. Methods: BNC2-AS1 small interfering RNA (siRNA) was transfected into SGC7901 and BGC823 gastric cancer cell lines, with negative siRNA serving as a control. A reverse transcription-quantitative polymerase chain reaction assay was performed to confirm the knockdown of BNC2-AS1. Cell Counting Kit (CCK)-8 and colony-forming unit (CFU) assays were performed to evaluate the effect of BNC2-AS1-knockdown on SGC7901 and BGC823 cell proliferation. A wound healing assay was performed to evaluate the effect of BNC2-AS1-knockdown on SGC7901 and BGC823 cell proliferation and migration. A tumor invasion assay was used to evaluate the effect of BNC2-AS1-knockdown on SGC7901 and BGC823 cell invasion. The expression level of BNC2-AS1 was efficiently knocked down by siRNA 48 hours post-transfection. Results: The results of CCK8 and CFU assays showed that BNC2-AS1-knockdown significantly decreased gastric cancer cell proliferation. Wound healing assay results indicated that BNC2-AS1-knockdown markedly suppressed gastric cancer cell proliferation and migration. Tumor invasion assay results demonstrated that BNC2-AS1-knockdown significantly suppressed gastric cancer cell invasion. Conclusions: BNC2-AS1 levels in gastric cancer SGC7901 and BGC823 cell lines can be efficiently knocked down using the siRNA strategy, and the BNC2-AS1 knockdown can significantly suppress the tumor characteristics of gastric cancer cells, including the ability of proliferation, migration, and invasion.

Association of characteristics of HBV quasispecies with hepatitis B surface antigen seroconversion after pegylated interferon-α-2a treatment in child patients.

BACKGROUND: The correlation between hepatitis B surface antigen (HBsAg) seroconversion and the characteristics of HBV quasispecies (QS) before and during pegylated interferon-α-2a (PEG-IFN-α-2a) treatment in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) children has not yet been reported. METHODS: 35 patients, including 18 HBsAg seroconverters (SS) and 17 non-seroconverters (SN), were enrolled. Serum samples were collected before treatment and at weeks 12 and 24 of treatment. Sequences within the basal core promoter/pre-core (BCP/PC) and S/reverse transcriptase (S/RT) region were analysed by next-generation sequencing. RESULTS: There was no significant difference in the baseline diversity of HBV QS (Shannon entropy [Sn]; Hamming distance [HD]) in either region between the two groups. The baseline mutations A1762T/G1764A, C1913A, and T2003A/G or C2004T were correlated with non-response to therapy (P=0.025, P=0.036, P=0.032, respectively). After 24 weeks of therapy, HBV diversity within the BCP/PC region in the SS group notably declined (Sn: P=0.002; HD: P=0.011), while that of the SN group was nearly unchanged. As for the S/RT region, 24 weeks of treatment made no significant difference on QS diversity in either group. CONCLUSIONS: Our data demonstrated that the baseline viral mutations and dynamic changes in HBV QS diversity within the BCP/PC region were closely related to HBsAg seroconversion in HBeAg-positive CHB children treated with PEG-IFN-α-2a.

RETRACTED: Down-regulation of lncRNA ADAMTS9-AS2 contributes to gastric cancer development via activation of PI3K/Akt pathway.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Panels from Figure 2C appear similar to panels from Figure 2D of the article that Zhang M., Gao C., Yang Y., Li G., Dong J., Ai Y., Ma Q. and Li W. have published in Cellular Physiology and Biochemistry 42 (2017) 211-221 https://doi.org/10.1159/000477314. Regions of panels 'Control' and 'si-ADAMTS9-AS2' from Figure 3B appear similar to regions of panels 'Control' and 'si-ADAMTS9-AS2' from Figure 6C. Regions of panel 'si-ADAMTS9-AS2' from Figure 3D appear similar to regions of panel 'pc-CSTB+si-CSTB' from Figure 3B of the article that Jian Zhang, ZhenFeng Shi, JinXing Huang and XiaoGuang Zou have published in Oncology Research 24 (2016) 487­494 http://dx.doi.org/10.3727/096504016X14685034103752. Panel 'Control' from Figure 4B appears similar to panel 'pc-CSTB+si-CSTB' from Figure 4B of the article published by Oncology Research 24 (2016) 487. Regions of panels from Figure 6B appear similar to each other, as well as to regions of panels from Figure 2 of the article that Xiantao Sun, Yang Bai, Chao Yang, Shengyun Hu, Zhili Hou and Guixian Wang have published in Artificial Cells, Nanomedicine, and Biotechnology 47 (2019) 2536-2544 https://doi.org/10.1080/21691401.2019.1621328. Regions of panels from Figure 6D appear similar to each other, as well as to regions of 'Hypoxia' panel from Figure 1B of the article that Fei Kong, Juan Jin, Xiaolin Lv, Yubo Han, Xue Liang, Yanyu Gao and Xinglin Duan have published in Biomedicine & Pharmacotherapy 109 (2019) 716-725 https://doi.org/10.1016/j.biopha.2018.10.079. Although this article was published earlier than some of the other articles, the Editor decided to retract this article given concerns about the reliability of the data. Also, the corresponding author has not responded to the journal request to comment on the complaints and to provide the raw data of the results presented by the article.

CircRNAs as Potential Biomarkers in Gastrointestinal Tract Tumors: Opportunities and Challenges.

Most digestive system tumors have poor prognoses due to the lack of specific biomarkers. Circular RNAs (circRNAs) regulate the expression of genes and play essential roles in digestive system tumorigenesis. Here we review circRNA functions in gastrointestinal tract tumors. CircRNAs are promising biomarkers for clinical applications for gastrointestinal tract tumors.

Increased Expression of Long Noncoding RNA RP11-62F24.2 in Gastric Cancer and Its Clinical Significance.

BACKGROUND: Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides and have no proteincoding capacity. In recent years, they have been believed to be major players in biological processes. However, there is limited understanding of the many lncRNAs' expressions and their clinical significances in gastric cancer. METHODS: Quantitative RT-PCR was performed to investigate the lncRNA expression in gastric cancer. Then, we further explored the potential association between RP11-62F24.2 level and the clinicopathological features in gastric cancer tissue samples. RESULTS: The results showed that RP11-62F24.2 was significantly upregulated in gastric cancer tissues compared with matched normal tissues (p < 0.05). Its expression level was significantly correlated with invasion and tumor size. CONCLUSIONS: These results indicated that lncRNA RP11-62F24.2 may be a potential biomarker in the diagnosis of gastric cancer.

Quasispecies characteristics in mother-to-child transmission of hepatitis B virus by next-generation sequencing.

OBJECTIVES: To identify within-host quasispecies characteristics of hepatitis B virus (HBV) in mothers and children infected via mother-to-child transmission (MTCT). METHODS: Using next-generation sequencing (NGS), we analyzed sequences within the non-overlapping pre-core/core (pre-C/C) gene in 37 mother-child pairs. RESULTS: Phylogenetic and Highlighter analyses suggested that both a single strain and multiple distinct strains may be transmitted in MTCT of HBV. However, analysis of reassembled viral sequences revealed a relatively narrow distribution of variants in children, which was confirmed by a lower viral diversity in children than that in mothers. New closely related variants with combinations of two to five high-frequency mutations were observed in seven children with elevated ALT levels; the new variants out-competed the transmitted maternal variants to become the dominant strains in five of them. Furthermore, 30 mutations with a frequency >1% of all viruses within-host were present in those children; the mutations caused 19 amino-acid substitutions. Interestingly, almost all were located within the well-known T-cell or B-cell epitopes. CONCLUSIONS: There are restrictive changes that occur in the early stages of chronic HBV infection through MTCT with different clinical consequences. These data might have important implications for future investigations of interrelated immunopathogenesis and therapeutic strategies.

[Hepatitis B virus replication and viral gene expressions do not affect CDC37 level in hepatocytes in vitro].

OBJECTIVE: To study the influence of hepatitis B virus (HBV) replication and expressions of different viral genes on CDC37 level in hepatocytes. METHODS: We amplified and cloned 6 HBV genes (P, preS1, preS2, S, C and X) into pCMV expression vectors, which were transfected in Huh7 and HepG2 hepatoma cell lines, and CDC37 expression level in the cells was detected using Western blotting. Wealso cloned the promoter sequence of CDC37 into pGL3 vector, and co-transfected pGL3 with pCMV recombinant plasmids into Huh7 and HepG2 cells and the fluorescent signals were detected. To study the influence of HBV replication on CDC37 expression, we constructed 1.28-copy overlength genomes of HBV genotypes B, C, D and CD recombinant. The overlength HBV genomes were transformed into Adeasier-1 cells for recombination and into 293 cells for packaging. Huh7 and HepG2 cell lines infected with the packaged HBV recombinant adenoviruses were examined for CDC37 expression with Western blotting. RESULTS: Western blotting showed that the expression of different HBV genes did not obviously affect the protein level of CDC37 in the hepatocytes. The protein expression of HBV genes had no effect on the activity of CDC37 promoter. Huh7 and HepG2 cells infected with 1.28-copy HBV replicon showed no significant changes in the expression level of CDC37. CONCLUSION: HBV replication and its gene expression have no effect on the level of CDC37 in hepatocytes in vitro.

Hepatitis B virus genotype B and mutations in basal core promoter and pre-core/core genes associated with acute-on-chronic liver failure: a multicenter cross-sectional study in China.

BACKGROUND AND AIM: In China, acute-on-chronic liver failure (ACLF) is mostly caused by hepatitis B virus (HBV). However, the mechanism remains unclear. This study aims to investigate the association between both HBV genotype and mutations in basal core promoter (BCP) and pre-core/core (pre-C/C) regions with the development of HB-ACLF. METHODS: A multicenter cross-sectional study was performed in China. Serum samples from 522 patients were analyzed, including 231 patients with mild-chronic hepatitis B (CHB-M), 84 with severe-chronic hepatitis B (CHB-S) and 207 with HB-ACLF. HBV genotype and related mutations in the BCP and pre-C/C regions were determined by direct sequencing. RESULTS: A significantly higher ratio of HBV genotype B to C was detected in HB-ACLF patients than in CHB-M or CHB-S patients. The A1762T/G1764A, A1846T and G1896A mutations were significantly more common in HB-ACLF patients infected with either genotype B or C as compared with CHB-M, whereas the C1913A/G and A2159G mutations were more associated with HB-ACLF in genotype C patients. Comparing with CHB-S, the A1762T/G1764A mutation in genotype B and the A2159G mutation in genotype C were significantly more common in HB-ACLF patients. A multivariate analysis showed that factors such as HBV genotype B, age ≥40 years and A1762T/G1764A, A1846T and G1896A mutations were independently associated with the development of HB-ACLF. CONCLUSION: Chronic HBV infection with genotype B, A1762T/G1764A, A1846T and G1896A mutations has a higher possibility to develop HB-ACLF. These virological factors could serve as possible molecular markers for prediction of the clinical outcomes of chronic HBV infection.

Hepatitis B virus genotype B with G1896A and A1762T/G1764A mutations is associated with hepatitis B related acute-on-chronic liver failure.

The existence of statistical associations between hepatitis B-related acute-on-chronic liver failure and both hepatitis B virus (HBV) genotype and mutations in the basal core promoter (BCP) and precore (PC) regions needs to be confirmed. A total of 322 patients with a chronic HBV infection, including 77 with hepatitis B-related acute-on-chronic liver failure, 109 with hepatocellular carcinoma (HCC) and 136 with chronic hepatitis B (CHB) were enrolled. The HBV genotype and the presence of mutations in the BCP/PC regions were determined by direct sequencing, and the frequencies were compared in the three patient groups. Overall, 198/322 (61.5%) were infected with genotype B and 124/322 (38.5%) with genotype C. Genotype B was significantly more frequent in patients with acute-on-chronic liver failure than CHB (92.2% vs. 60.3%, P < 0.001). As a contrast, genotype C was more common in patients with HCC than CHB (58.7% vs. 39.7%, P = 0.003). In genotype B patients, the A1762T/G1764A, A1846T, and G1896A mutations were significantly more prevalent in patients with acute-on-chronic liver failure than CHB (50.7% vs. 28.0%, P = 0.004; 59.2% vs. 34.1%, P = 0.002; 69.0% vs. 41.5%, P = 0.001, respectively). In multivariate analysis, the risk factors for acute-on-chronic liver failure were genotype B, A1762T/G1764A, and G1896A. In conclusion, CHB patients with genotype B, G1896A, and A1762T/G1764A had a higher tendency to develop liver failure than patients with genotype C. Therefore, HBV genotyping and detecting G1896A and A1762T/G1764A mutations might have important clinical implications as predictive risk factors for hepatitis B-related acute-on-chronic liver failure.

Cytoplasm affects grain weight and filled-grain ratio in indica rice.

BACKGROUND: Cytoplasmic effects on agronomic traits--involving cytoplasmic and nuclear genomes of either different species or different cultivars--are well documented in wheat but have seldom been demonstrated in rice (Oryza sativa L.). To detect cytoplasmic effects, we introgressed the nuclear genomes of three indica cultivars--Guichao 2, Jiangchengkugu, and Dianrui 449--into the cytoplasms of six indica cultivars - Dijiaowujian, Shenglixian, Zhuzhan, Nantehao, Aizizhan, and Peta. These 18 nuclear substitution lines were evaluated during the winter season of 2005 in Sanya, Hainan, China, and during the summer season of 2006 in Kunming, Yunnan, China. The effects of 6 cytoplasm sources, 3 nucleus sources, 2 locations and their interactions were estimated for plant height, panicle length, panicle number per plant, spikelet number per panicle, grain weight, filled-grain ratio, and yield per plot. RESULTS: For five of the seven traits, analysis of variance showed that there were no significant cytoplasmic effects or interactions involving cytoplasmic effects. The effect of cytoplasm on 1000-grain weight was highly significant. Mean 1000-grain weight over the two locations in four of the six cytoplasms clustered close to the overall mean, whereas plants with Nantehao cytoplasm had a high, and those with Peta cytoplasm a low mean grain weight. There was a highly significant three-way interaction affecting filled-grain ratio. At Sanya, cytoplasms varied in very narrow ranges within nuclear backgrounds. Strong cytoplasmic effects were observed only at Kunming and in only two of the three nuclear backgrounds; in the Jianchenkugu nuclear background, there was no evidence of strong cytoplasmic effects at either location. In the Dianrui 449 and Guichao 2 nuclear background evaluated at Kunming, filled-grain ratios of the six cytoplasms showed striking rank shifts CONCLUSIONS: We detected cytoplasmic variation for two agronomically important traits in indica rice. The cytoplasm source had a significant effect on grain weight across the two experimental locations. There was also a significant cytoplasmic effect on filled-grain ratio, but only in two of three nuclear background and at one of the two locations. The results extend our previous findings with japonica rice, suggesting that the selection of appropriate cytoplasmic germplasm is broadly important in rice breeding, and that cytoplasmic effects on some traits, such as filled-grain ratio, cannot be generalized; effects should be evaluated in the nuclear backgrounds of interest and at multiple locations.