Diagnostic Value of Combined-Diagnostic Methods of Brain Tuberculoma Tissue Specimens: A Case Series.

Background: The diagnosis of brain tuberculoma (BT) is sometimes challenging. Herein, we presented a case series to evaluate the combined-diagnostic methods, including acid-fast bacilli (AFB) stain, polymerase chain reaction (PCR), Gene Xpert, and histopathology, of tuberculoma tissue specimens (TTSs). Patients and Methods: A total of 16 patients (11 human immunodeficiency virus [HIV]-positive, 5 HIV-negative) with BT confirmed by combined-diagnostic methods of TTS were included in this study. Clinical data, including clinical symptoms, laboratory tests, neuroimaging features, histopathology, treatment, and prognosis, were assessed in all patients. Results: There were 10 male and 6 female patients (range, 18-73 years). Acid-fast bacilli stain and PCR of TTSs were positive in 11 and 10 patients, respectively. The sensitivity of Gene Xpert of TTSs was (80.0%; 8/10). Nine (56.3%; 9/16) patients were diagnosed with BT by histopathology. After receiving antituberculosis treatment, 12 (75.0%; 12/16) patients improved clinically to a considerable extent. Conclusions: The combined-diagnostic methods of TTS may improve the diagnostic efficiency of BT.

Clinical characteristics and prognostic analysis of patients with HIV and glioma: A case series and literature review.

Cerebral glial tumors have become increasingly common in human immunodeficiency virus (HIV)-positive patients. The present study aimed to report a series of such cases, explore their clinical and pathological characteristics and subject all the reported cases to a survival analysis. The characteristics, management and prognosis of 10 HIV-positive patients with brain gliomas enrolled in a single hospital were investigated in detail. Immunohistochemical assessment of CD31, CD68 and CD163 was performed in the 10 HIV-positive patients with glioma and 18 HIV-negative patients with glioma. The relevant literature was also reviewed using relevant search terms. The potential predictive factors were screened by univariate and multivariate logistic regression analyses, and a nomogram was established based on the potential predictive factors. A total of 50 patients, including the 10 primary cases, were included in the survival analysis. The median survival time was 9 months. The gliomas of HIV-negative patients had a lower cell count of CD163+ cells than those of HIV-positive patients. High CD4+ T-cell count and the use of highly active antiretroviral therapy (HAART) tended to increase the median survival duration, although not significantly according to the log-rank analysis. In the univariate analysis, only surgery, radiotherapy (RT) and World Health Organization (WHO) tumor grade had significant associations with overall survival. In the multivariate analysis, only RT and WHO grade were independent predictors. In conclusion, gliomas may occur more frequently in HIV-positive populations than is currently recognized. The survival duration of most HIV-positive patients with glioma is determined by the tumor rather than HIV status. Adjuvant radiotherapy and the WHO grade of the glioma are predicted to be independent prognostic factors. Surgical resection followed by RT plus regular HAART is recommended for patients with glioma who are HIV-positive.

The comparison of the watertight and non-watertight dural closure in supratentorial craniotomy: A single-institute 10-year experience with 698 patients.

Watertight dural closure (WTDC) is considered crucial by many neurosurgeons in cranial base surgery, infratentorial craniotomy, and spinal intradural procedure. Whether WTDC also reduce complications remains controversial in supratentorial craniotomy. The objective of this study is to investigate the relationship between WTDC and CSF-related complications in supratentorial craniotomy for the resection of space-occupying lesions. A retrospective analysis of patients who suffered from intracranial space-occupying lesions at Beijing Ditan Hospital between January 2011 and December 2021 was conducted. A total of 698 cases were reviewed with attention to the operative approach, subgaleal fluid collection, wound healing impairment, postoperative infection, and post-craniotomy headaches. The study included a total of 423 patients with WTDC and 275 patients without WTDC. Patients without WTDC had a significantly higher rate of infection (10.9% vs 4.5% with WTDC, P = .001). The rate of subgaleal fluid collection was 9.7% in the WTDC group and 11.3% in the non-WTDC group, but this difference was not statistically significant (P = .502). They suffered from a greater incidence of post-craniotomy headaches in the WTDC group (13.5% vs 9.5% in the non-WTDC group), but without statistical significance (P = .109). We also found no difference in wound healing impairment (P = .719). There is less postoperative infection associated with WTDC during intracranial space-occupying lesion removal than without WTDC in supratentorial craniotomy.

Clinical factors predictive of new-onset seizure in patients with AIDS-related brain parenchymal lesion.

PURPOSE: This study aimed to determine the clinical characteristics and risk factors of new-onset seizure in patients with AIDS-related brain parenchymal lesion. METHODS: A retrospective case-control study from January 2015 to December 2021 was conducted to determine the clinical characteristics and etiology of seizures in patients with AIDS-related brain parenchymal lesion. Univariate and multivariate logistic regression analyses were used to identify risk factors associated with seizures. Receiver operating characteristic (ROC) curve was used to analyze seizure prediction efficiency. RESULTS: Among a total of 343 patients with AIDS-related brain lesions, 222 had brain parenchymal lesions. Of the 222 patients in the series (range: 16-81 y), 69 reported an episode of at least one seizure. A logistic regression analysis showed that tuberculoma, cortex involvement, and lesions in parietal lobe were found to have a strong association with higher incidence of seizures, whereas lesions in the periventricular area was less prone to seizure. The area under the ROC curve of these factors was 0.733, indicating these factors could predict seizure effectively. Amongst the 69 patients with seizures in multivariate analysis using logistic regression, multiple lesions significantly associated with focal to bilateral tonic-clonic seizures, and lesions in temporal lobe independently associated with focal impaired awareness seizure. CONCLUSIONS: Our study identified the underlying predictors between seizures and the clinical characteristics in a large population of patients with AIDS-related brain parenchymal lesions. These findings would provide further insights into developing effective prevention and treatment strategies aimed at improving the quality of life in the HIV population.

Clinical pathology of primary central nervous system lymphoma in HIV-positive patients-a 41 Chinese patients retrospective study.

OBJECTIVES: The purpose of this study was to investigate the clinicopathological characteristics of primary central nervous system lymphoma (PCNSL). METHODS: We collected 41 PCNSL formalin-fixed, paraffin-embedded (FFPE) samples from human immunodeficiency virus (HIV)-positive patients and performed HE (haematoxylin-eosin) staining, immunohistochemistry (IHC) staining, in situ hybridization, fluorescence in situ hybridization (FISH). Real-time quantitative polymerase chain reaction (RT-qPCR) was performed in 9 cases of FFPE samples. Meanwhile, we analysed the clinical pathological significance of the results. RESULTS: Seven patients had diffuse large B-cell lymphoma (DLBCL) with germinal centre B-cell (GCB)-like DLBCL, 32 had activated B-cell (ABC)-like DLBCL, and 2 had Burkitt lymphoma (BL). GCB-like DLBCL patients were older at onset (P = 0.040).A lower CD4+ T-cell count and a decrease in cerebrospinal fluid (CSF) glucose content were more frequent in ABC-like DLBCL (P = 0.012, P = 0.006). Overexpression of P53 was more in ABC-like DLBCL (P = 0.041). 73.2 % cases were Epstein-Barr encoding region (EBER) positive, which was more likely in ABC-like DLBCL patients (P = 0.037). EBV DNA were detected in 5/7 EBER-negative DLBCL cases and none (0/2) of the BL cases. All the cases were negative for HHV8 staining. None of the 7 Double expressor lymphoma (DEL) cases had BCL2, BCL6, or c-MYC genetic rearrangements. CONCLUSIONS: HIV-related PCNSL showed unique clinical pathological significance. None of EBV detected in HIV-related BL and without HHV8 infectious are new sights in our single-center study of Chinese HIV-related PCNSL patients.

Diagnostic value of EBV-DNA in CSF for PCNSL in AIDS patients with focal brain lesions: A meta-analysis of diagnostic test.

BACKGROUND: Epstein-Barr virus (EBV) infection plays a crucial role in the progression of acquired immunodeficiency syndrome related primary central nervous system lymphoma (AR-PCNSL). This study aimed at evaluating the diagnostic value of cerebrospinal spinal fluid (CSF) EBV-deoxyribonucleic acid (DNA) for PCNSL in patients with infection of human immunodeficiency (HIV) virus through a meta-analysis of diagnostic test. METHODS: A systematic search in PubMed, Embase, Web of Science, Wanfang, Chinese Biomedical Database and Chinese National Knowledge Infrastructure was conducted before May 10, 2022. Heterogeneity among the studies was assessed using Q test and I2 statistics. Publication bias was assessed using the Deek's funnel plot asymmetry test. Statistical analyses were performed using Stata 16.0 software. The pooled sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratios (DOR) and 95% confidence intervals (CI) were caculated to evaluate the diagnostic value. A symmetric receiver operating characteristic (SROC) curve and the area under the SROC curve (AUC) were constructed to evaluate the test-performance. RESULTS: Twelve studies were included in the final analyses, with a total of 141 patients with AR-PCNSL and 590 controls. The pooled diagnostic values were sensitivity of 0.83 (95% CI: 0.73-0.90), specificity of 0.95 (95%CI: 0.89-0.98), PLR of 17.8 (95%CI: 6.8-46.1), NLR of 0.17 (95%CI: 0.10-0.30), DOR of 102 (95%CI: 28-379), and AUC of 0.94 (95%CI: 0.91-0.96). CONCLUSION: In summary the overall diagnostic value of CSF EBV-DNA is very high and it can be a reliable diagnostic biomarker for AR-PCNSL.

Paclitaxel-Containing Extract Exerts Anti-Cancer Activity through Oral Administration in A549-Xenografted BALB/C Nude Mice: Synergistic Effect between Paclitaxel and Flavonoids or Lignoids.

Taxus yunnanensis is a paclitaxel-containing herb with traditional usage in cancer treatment, and its extract possesses great oral bioavailability of paclitaxel. However, it is elusive whether paclitaxel-containing extract (HDS-1) can exert anti-tumor effect through oral administration and how other components contribute to its efficacy. Therefore, we investigate the oral-route anti-tumor effect of HDS-1 in A549-bearing mice. HDS-1-derived flavonoids (HDS-2) and lignoids (HDS-3) are hypothesized to contribute to HDS-1's efficacy, and their effects of enhancing enterocytic absorption and cytotoxicity of paclitaxel are validated in 2 permeability experiments and apoptosis-related assay, respectively. In vivo, A549 growth is significantly inhibited by 86.1 ± 12.94% (P < 0.01) at 600 mg/kg of HDS-1 and 65.7 ± 38.71% (P < 0.01) at 200 mg/kg. HDS-2 and HDS-3 significantly reduce the efflux ratio of paclitaxel to 2.33 and 3.70, respectively, in Caco-2 permeability experiment and reduce paclitaxel reflux in MDCK-MDR1 experiment. Furthermore, HDS-2 and HDS-3 potentiated paclitaxel-induced cytotoxicity by 19.1-22.45% (P < 0.05) and 10.52-18.03% (P < 0.05), respectively, inhibited the expression of cyclinB1, Bcl-2, and pMCL-1, and increased the percentage of necrosis cell in the condition of paclitaxel exposure. Conclusively, paclitaxel-containing extracts exert anti-cancer effects through oral administration, and flavonoid and lignoids contribute to its anti-cancer effect through simultaneously improving enterocytic absorption of paclitaxel and the cytotoxic effect of paclitaxel.

Cordyceps militaris extract induces apoptosis and pyroptosis via caspase-3/PARP/GSDME pathways in A549 cell line.

Cordyceps militaris (CM) is traditionally used as dietary therapy for lung cancer patients in China. CM extract (CME) is hydrosoluble fraction of CM and extensively investigated. Caspase-3-involved cell death is considered as its major anticancer mechanism but inconclusive. Therefore, we explore its caspase-3-dependent programmed cell death nature (apoptosis and pyroptosis) and validate its caspase-3-dependent property in loss-of-function experiment. Component profile of CME is detected by High Performance Liquid Chromatography- quadrupole time-of-flight mass spectrometry (HPLC-qTOF). Results show that CME causes pyroptosis-featured cell bubbling and cell lysis and inhibits cell proliferation in A549 cell. CME induces chromatin condensing and makes PI+/annexin V+ staining in bubbling cells, indicating genotoxicity, apoptosis, and pyroptosis cell death are caused by CME. High concentration of CME (200 µg/ml) exerts G2/M and G0 cell cycles arresting and suppresses P53-downstream proliferative proteins, including P53, P21, CDC25B, CyclinB1, Bcl-2, and BCL2 associated agonist of cell death (BAD), but 1-100 µg/ml of CME show less effect on proteins above. Correspondingly, caspase-3 activity and caspase-3 downstream proteins including pyroptotic effector gasdermin-E (GSDME) and apoptotic marker cleaved-poly-ADP-ribose polymerase (PARP) are significantly promoted by CME. Moreover, regarding membrane pore formation in pyroptotic cell, expression of membrane GSDME (GSDME antibody conjugated with PE-Cy7 for detection in flow cytometry) is remarkably increased by CME treatment. By contrast, other pyroptosis-related proteins such as P2X7, NLRP3, GSDMD, and Caspase-1 are not affected after CME treatment. Additionally, TET2 is unexpectedly raised by CME. In present of caspase-3 inhibitor Ac-DEVD-CHO (Ac-DC), CME-induced cytotoxicity, cell bubbling, and genotoxicity are reduced, and CME-induced upregulation of apoptosis (cleaved-PARP-1) and pyroptosis (GSDME-NT) proteins are reversed. Lastly, 22 components are identified in HPLC-qTOF experiment, and they are classified into trophism, neoadjuvant component, cytotoxic component, and cancer deterioration promoter according to previous references. Conclusively, CME causes caspase-3-dependent apoptosis and pyroptosis in A549 through caspase-3/PARP and caspase-3/GSDME pathways, and it provides basic insight into clinic application of CME for cancer patients.

Prognostic significance of long non coding maternally expressed gene 3 in pediatric acute myeloid leukemia.

ABSTRACT: The purpose of this study was to evaluate the correlation of long non-coding RNA maternally expressed gene 3 (Lnc-MEG3) with disease features, treatment response, and survival in pediatric acute myeloid leukemia (AML) patients.Among 92 de novo pediatric AML patients (before treatment and after 1 course of induction) and 40 controls, bone marrow mononuclear cells were obtained. Then, Lnc-MEG3 expression was determined by reverse transcription quantitative polymerase chain reaction. After 1 course of standard induction therapy of pediatric AML patients, complete remission (CR) was assessed. Furthermore, event-free survival (EFS) and overall survival (OS) were determined according to follow-up data.Lnc-MEG3 was reduced in pediatric AML patients compared with controls. In pediatric AML patients, Lnc-MEG3 was correlated with French-American-Britain subtypes and lower Chinese Medical Association risk stratification, while it was not associated with cytogenetic features, FLT3-ITD mutation, CEBPA mutation, NPM1 mutation, WT1 mutation, or National Comprehensive Cancer Network risk stratification. After 1 course of treatment, Lnc-MEG3 exhibited an up-regulation trend. Furthermore, Lnc-MEG3 was of no difference before treatment between patients with and without CR, while elevated Lnc-MEG3 and change of Lnc-MEG3 after 1 course of treatment were associated with increased CR rate. Additionally, increased Lnc-MEG3 expression before treatment was associated with longer EFS but not OS, while enhanced Lnc-MEG3 expression after 1 course of treatment was correlated with both prolonged EFS and OS.Lnc-MEG3 may have clinical significance as a biomarker for assisting with disease management, treatment optimization, and prognosis improvement in pediatric AML patients.

Functional Group Modification and Bonding Characteristics of Ti3 C2 MXene-Organic Composites from First-Principles Calculations.

The unique physical structure and abundant surface functional groups of MXene make the grafted organic molecules exhibit specific electrical and optical properties. This work reports the results of first-principles calculations to investigate the composite systems formed by different organic molecular monomers, namely acrylic acid (AA), acrylamide (AM), 1-aziridineethanol (1-AD) and glucose, and Ti3 C2 MXene saturated with different functional groups, namely -OH, -O and -F. The results show that the interaction between organic molecules and the MXene surface depends on the type of functional groups of the organic molecules, while the strength of the interaction is determined by the type of surface functional groups and the number of hydrogen bonds. The bare Ti3 C2 and Ti3 C2 (OH)2 can readily form strong chemical and hydrogen bonds with AA and AM molecules, leading to strong adsorption energy and a large amount of charge transfer, while the interaction between organic molecules and MXene saturated by -F or -O groups mainly exhibits physical interactions, accompanied by low adsorption energy and a small amount of charge transfer. This research provides theoretical guidance for the synthesis of high-performance MXene organic composite systems.

IncRNA MVIH correlates with disease features, predicts treatment response and survival in pediatric acute myeloid leukemia.

OBJECTIVE: Long non-coding RNA microvascular invasion in hepatocellular carcinoma (lnc-MVIH) is correlated with unfavorable prognosis in several malignancies, while limitedly studied in pediatric acute myeloid leukemia (AML). This study aimed to investigate the correlation of lnc-MVIH with disease features, response to induction therapy, and survival in pediatric AML patients. METHODS: A total of 129 de novo pediatric AML patients who were retrospectively analyzed and 60 children with non-malignant hematological diseases who underwent bone marrow examination were reviewed as controls. Bone marrow mononuclear cells (BMMCs) were isolated from all participants to detect lnc-MVIH expression by reverse transcription-quantitative polymerase chain reaction. The complete remission status after 1 course of induction therapy, event-free survival, and overall survival of pediatric AML patients were recorded. RESULTS: Lnc-MVIH was upregulated in pediatric AML patients compared with controls (p < 0.001). In pediatric AML patients, lnc-MVIH was correlated with increased bone marrow blasts, less inv(16) or t(16;16) abnormity, and higher Chinese Medical Association (CMA) risk stratification (all p < 0.05), whereas its correlation with National Comprehensive Cancer Network (NCCN) risk stratification was not statistically significant (p = 0.098). As for prognosis, lnc-MVIH high expression patients presented with lower complete response rate to 1 course of induction therapy (61.5% vs. 79.7%, p = 0.024), shorter event-free survival (median 12.0 months vs. 22.0 months, p = 0.006), and overall survival (median 28.0 months vs. 42.0 months, p = 0.043) compared with lnc-MVIH low expression patients. CONCLUSION: Lnc-MVIH correlates with poor treatment response and unfavorable survival in pediatric AML.

Should we prescribe anticonvulsants for acute herpes zoster neuralgia and to prevent postherpetic neuralgia?: A protocol for meta-analysis and benefit-risk assessment.

BACKGROUND: Herpes zoster-associated pain [i.e., acute herpes zoster neuralgia (AHN) and postherpetic neuralgia (PHN)] has the potential to cause significant patients' burden and heath resource expenditure. PHN is refractory to the existing treatments, and the consensus is preventing the transition of AHN to PHN is better than treating PHN. Anticonvulsants (e.g., gabapentin, pregabalin) have been recommended as one of the first-line therapies for PHN. In practice, anticonvulsants have also decreased the severity and duration of AHN and reduced the incidence of PHN. Nevertheless, its clinical application to AHN is hampered by inadequate evidence for its efficacy and safety. We performed this protocol for a systematic review to explore the efficacy and safety of anticonvulsants for AHN. Besides, a benefit-risk assessment of anticonvulsants for AHN would be performed to estimate the extent to which these drugs could relieve symptoms and whether the benefits outweigh harms. METHODS: The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) was used to prepare our protocol and the results will be reported according to the PRISMA. We will search the China National Knowledge Infrastructure (CNKI), Chinese VIP Information (VIP), Cochrane Library, Embase, and PubMed databases, from inception to August 2019. Furthermore, Clinicaltrials (http://www.clinicaltrials.com) and Chinese Clinical Trial Registry (http://www.chictr.org.cn/abouten.aspx) will also be searched for relevant studies. Selection of eligible articles and data extraction will be independently performed by reviewers. We will record the characteristic information, pain outcomes, incidence of PHN and adverse effects. Data synthesis and other statistical analyses will be conducted using Review Manager Software 5.3 and STATA13.0. Furthermore, risk of bias assessment, meta-regression and subgroup analyses, publication bias assessment, grading of evidence will be performed for included studies. ETHICS AND DISSEMINATION: As this systematic review will be performed based on published data, no ethical approval is needed. The findings will be submitted in peer-reviewed journals for publication. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019133449.

Downregulation of miR-155-5p facilitates enterovirus 71 replication through suppression of type I IFN response by targeting FOXO3/IRF7 pathway.

Enterovirus 71 (EV71), the major cause of hand-foot-and-mouth disease (HFMD), has evolved diverse strategies to counter the type I interferon (IFN-I) response during infection. Recently, microRNAs have regulatory roles in host innate immune responses to viral infections; however, whether EV71 escapes the IFN-I antiviral response through regulation of miRNAs remains unclear. Using a microarray assay, microRNA-155-5p (miR-155-5p) was found to be significantly up-regulated in serum from patients with EV71 infection and the increased expression of miR-155-5p was further confirmed in vivo and in vitro in response to EV71 infection. miR-155-5p overexpression suppressed EV71 titers and VP1 protein level, while miR-155-5p inhibition had an opposite result. Moreover, we found that miR-155-5p overexpression enhanced EV71 triggered IFN I production and the expressions of IFN-stimulated genes (ISGs), while inhibition of miR-155-5p suppressed these processes. Furthermore, bioinformatics analysis and luciferase reporter assay demonstrated that miR-155-5p directly targeted forkhead box protein O3 (FOXO3) and negatively regulated FOXO3/IRF7 axis, an important regulatory pathway for type I IFN production during EV71 infection. Inhibition of FOXO3 reversed the effects of miR-155-5p inhibitor on EV71 replication and the type I IFN production. Importantly, in EV71 infection mice, agomir-155-5p injection resulted in a significant reduction of viral VP1 protein expressions in brain and lung tissues, increased IFN-α/ß production and increased mice survival rate. In contrast, antagomir-155-5p enhanced EV71 induced these effects. Collectively, our study indicates that weaken miR-155-5p facilitates EV71 replication through suppression of type I IFN response by FOXO3/IRF7 pathway, thereby suggesting a novel strategy for developing effective antiviral therapy.

Synthesis of Heterocyclic Core-Expanded Bis-Naphthalene Tetracarboxylic Diimides.

A highly reactive bis-naphthalene tetracarboxylic diimide (bis-NDI) intermediate, TBrDNDI, was designed and synthesized for core-expanded NDIs. Based on this intermediate, we achieved 9- and 11-membered core-expanded bis-NDI derivatives. Through expanding the NDI core and introducing electron-donor or electron-acceptor groups, the frontier energy orbitals, optical and electrical properties of these bis-NDIs can be finely tuned to obtain air-stable ambipolar or n-type materials.

[Performance verification of direct chemiluminescence immunoassay to detect the serum 25-hydroxyvitamin D concentration].

OBJECTIVE: To test the performance of direct chemiluminescence immunoassay(CLIA) in the determination of serum 25-hydroxyvitamin D [25(OH)D] concentration. METHODS: The CLIA analyzer of Italy DiaSorin was used to measure the 25(OH)D concentrations in the Standard Reference Material 972 a of National Institute of Standards and Technology, DiaSorin control materials, blind samples of Vitamin D External Quality Assessment Scheme(DEAQS), and outpatient serum samples. The functional sensitivity, precision, accuracy, recovery, and linearity were evaluated, and the samples of mild hemolysis, 5 days' storage at 4 ₿ and >1 year's storage at-80 ₿were tested for 25(OH)D. RESULTS: The functional sensitivity was<4 ng/mL. The coefficient of variations of intra-and inter batch were<8. 1%. The relative deviation was-3. 1%-5. 7%. The recovery rates were 82. 8%-112. 9% and it had good linearity in the range of 7. 6-128. 1 ng/mL. Compared with fresh serum, the serum 25(OH)D concentration was not affected by mild hemolysis or being stored at 4 ₿for 5 days, but averagely decreased at 7. 6% by being stored at-80 ₿for more than 1 year. Compared with others, the deviation was-2. 9%-3. 6%. The differences in precision, accuracy and recovery of this method among the three different hospitals is slightly. CONCLUSION: The performance of direct CLIA for 25(OH)D assay meet the basic technical requirements for laboratory medicine, and is laborsaving and timesaving.

[Expression Levels of HES1, C-MYC and NF-kB in Peripheral Blood of Patients with T Cell Acute Lymphoblastic Leukemia and Their Significance].

OBJECTIVE: To analyze and investigate the expression levels of HES1, C-MYC and NF-kB in peripheral blood of patients with T cell acute lymphoblastic leukemia (T-ALL) and their significance. METHODS: Sixty patients with T-ALL and 60 patients with acute myelogenous leukemia (AML) diagnosed in our hospital from June 2012 to March 2015 were enrolled in T-ALL group and AML group, respectively. Another 30 healthy people were enrolled in the control group. Peripheral blood was collected to detect the expression levels of HES1, C-MYC and NF-kB by RT-PCR. The general data and the expression of HES1, C-MYC and NF-kB in peripheral blood were compared among the patients with different type of leukemia, cytogenetical types and different prognosis. RESULTS: There was no significant difference in baseline data, such as age and sex among the 3 groups (P＞0.05). The Hb level, WBC and Plt count, BM blast cell ratio in T-ALL and AML groups all were significantly higher than those in control group (P＜0.01), but there were no statistical difference in above-mentioned indicators between T-ALL and AML groups (P＞0.05). The expression levels of HES1, C-MYC and NF-kB in peripheral blood among 3 groups were significantly differenct (P＜0.01), the expressions levels of HES1, C-MYC and NF-kB in T-ALL and AML groups were significantly higher than those in control were significantly group (P＜0.01), moreover, the expression levels of above-mentional indicators in T-ALL groups were significantly higher than than those in AML group (P＜0.01). The expression levels of HES1, C-MYC and NF-kB iin T-ALL patients with poor prognosis were significantly higher than those in T-ALL patients with favorable prognosis (P＜0.01); the expression levels of HES1, C-MYC and NF-kB in peripheral blood of patients with different theraptic efficacy were follow: complete remission group＜partial remission group＜no remission group (P＜0.01). CONCLUSION: The HES1, C-MYC and NF-kB are highly expressed in peripheral blood of the patients with T-ALL, moreover, the expression levels maybe different, because of the cytogenetic, and theraptic efficacy.

Inhibition of microRNA-199a-5p reduces the replication of HCV via regulating the pro-survival pathway.

MicroRNAs (miRNAs) are endogenous, small non-coding RNAs that post-transcriptionally regulate the pathological processes of various liver diseases including hepatitis C virus (HCV) infection. In the present study, we demonstrated that HCV infection enhanced the expression of miR-199a-5p in HCV infected human hepatocytes and Huh7.5.1cells, as well as liver biopsy specimens. Inhibition of miR-199a-5p decreased HCV replication not only in terms of HCV RNA, but also the protein levels of NS3 and NS5A. Furthermore, we discovered that miR-199a-5p knockdown in Huh7.5.1 cells infected with genotype 2a (JFH1) or genotype 1b (SN1a) resulted in the remarkable inhibition of pro-survival pathways, as observed by the down-regulation of p-Akt, p-ERK and ß-catenin protein levels. Moreover, pre-treatment with the pro-survival pathway specific activator prominently ablated the inhibition of HCV replication induced by miR-199a-5p knockdown. Collectively, our results highlight the up-regulation of miR-199a-5p expression with HCV infection and the promotion of HCV replication by miR-199a-5p. Moreover, miR-199a-5p may facilitate HCV replication by regulating pro-survival pathways through PI3K/Akt, Ras/ERK and Wnt/ß-catenin. miR-199a-5p might be a potential drug target for developing a novel strategy to combat HCV infection.

Up-regulation of IL-12 expression in patients with chronic hepatitis B is mediated by the PI3K/Akt pathway.

Hepatitis B virus (HBV) replicates noncytopathically in hepatocytes, but HBV or proteins encoded by HBV genome could induce cytokines, chemokines expression by hepatocytes.IL-12 is a typical proinflammatory cytokine that plays a critical role in host defense against pathogens, including the HBV. However, the role of IL-12 in chronic hepatitis B (CHB) remains unclear. The aims of this study were to detect the expression of IL-12 in CHB patients and explore the molecular mechanism of HBV-induced IL-12 expression. The results showed that serum levels and hepatic expression of IL-12 were significantly upregulated in CHB patients. HBx protein increased IL-12 expression in a dose-dependent manner. Furthermore, inhibition of PI3K/Akt significantly decreased the HBx-induced IL-12 expression and Akt activation. Taken together, these results indicate that the molecular mechanism of HBV-induced IL-12 expression involves activation of the PI3K/Akt pathway by HBx, leading to transactivation of the IL-12 p35 and p40 promoters.

Expression of serum exosomal microRNA-21 in human hepatocellular carcinoma.

New strategies for the diagnosis of hepatocellular carcinoma (HCC) are urgently needed. There is an increasing interest in using microRNAs (miRNAs) as biomarkers in diseases. In this study, we examined the expression of miR-21 in serum exosomes from patients with HCC or chronic hepatitis B (CHB) and investigated the potential clinical significance of miR-21. Quantitative RT-PCR indicated that the concentration of miR-21 was significantly higher in exosomes than in exosome-depleted supernatants or the whole serum. Further, the expression level of serum exosomal miR-21 was significantly higher in patients with HCC than those with CHB or healthy volunteers (P < 0.0001, P < 0.0001, resp.). High level of miR-21 expression correlated with cirrhosis (P = 0.024) and advanced tumor stage (P = 0.001). Although serum level of miR-21 was higher in patients with HCC than in patients with CHB and healthy volunteers, the sensitivity of detection is much lower than using exosomal miR-21. These findings indicate that miR-21 is enriched in serum exosomes which provides increased sensitivity of detection than whole serum. Exosomal miR-21 may serve as a potential biomarker for HCC diagnosis.