Diagnosis of Rare Bone Infection Caused by Nocardia by 16S rRNA Gene Sequencing.

Nocardia is an aerobic actinomycete that causes serious opportunistic infections in immunocompromised individuals. Gene sequencing is the gold standard for pathogenic bacteria diagnosis. This study uses 16S rRNA gene sequencing to diagnose three cases of bone infections caused by Nocardia, including one rare case (N. cyriacigeorgica), and the clinial features, etiological characteristics, treatment, and prognosis of the patients.

The value of clinical parameters combined with magnetic resonance imaging (MRI) features for preoperatively distinguishing different subtypes of uterine sarcomas: An observational study (STROBE compliant).

To investigate clinical parameters combined with magnetic resonance imaging (MRI) features including apparent diffusion coefficient (ADC) values in preoperative identification of different subtypes of uterine sarcomas including uterine leiomyosarcoma (LMS), endometrial stromal sarcoma (ESS), and carcinosarcoma (CS).Data from 71 patients with uterine sarcoma confirmed by surgery and pathology were collected. The clinical characteristics, conventional MRI features, mean ADC values, minimum ADC values, and lesion-muscle ADC ratio (rADC) values were compared with different subtypes of uterine sarcomas.Age, clinical manifestation, tumor location, shape, and T1-weighted image (T1WI) signals were significantly different between CS and LMS or ESS (all P < .01). The presence of band sign was significantly higher in ESS than in LMS or CS (both P < .001). The cystic change or necrosis and enhancement could help to differentiate LMS from ESS or CS (both P < .02). Significant differences were observed in T2-weighted image (T2WI) signals of the solid components of LMS compared with CS (P < .001). There was a significant difference between ESS and CS in the rADC values (P = .004).Clinical parameters combined with MRI features could help narrowing preoperative diagnostic possibilities in distinguishing subtypes of uterine sarcomas. These findings may be beneficial in helping guide operative decisions.

Corosolic Acid Inhibits Cancer Progress Through Inactivating YAP in Hepatocellular Carcinoma.

Chemotherapy is critical for the treatment of hepatocellular carcinoma (HCC). Despite the proapoptotic effects of corosolic acid (CA) treatment, its underlying mechanism is not completely clear. The aim of this study was to determine the molecular mechanism of CA in HCC treatment. MTT assay was used to determine the IC50 of CA. Immunoprecipitation and immunofluorescence were used to detect the interaction and subcellular localization of Yes-associated protein (YAP) and mouse double minute 2 (MDM2). In addition, in vivo xenotransplantation was performed to assess the effects of CA, YAP, and MDM2 on tumorigenesis. The IC50 of CA was about 40 M in different HCC cell lines, and CA decreased YAP expression by reducing its stability and increasing its ubiquitination. CA treatment and MDM2 overexpression significantly decreased the crosstalk between YAP and cAMP-responsive element-binding protein (CREB), TEA domain transcription factor (TEAD), and Runt-related transcription factor 2 (Runx2). CA stimulation promoted the translocation of YAP and MDM2 from the nucleus to the cytoplasm and increased their binding. In addition, CA treatment obviously reduced tumorigenesis, whereas this effect was abolished when cells were transfected with sh-MDM2 or Vector-YAP. The present study uncovered that CA induced cancer progress repression through translocating YAP from the nucleus in HCC, which might provide a new therapeutic target for HCC.

STAT3­regulated long non­coding RNAs lnc­7SK and lnc­IGF2­AS promote hepatitis C virus replication.

Long non­coding RNAs (lncRNAs) are a class of RNAs that do not code protein but are important in diverse biological processes. In previous years, with the application of high­throughput sequencing, a large number of lncRNAs associated with virus infections have been identified and intensively investigated, however, there are few studies examining the association between lncRNAs and HCV replication. Previous studies have demonstrated that signal transducer and activator of transcription 3 (STAT3) is activated by the hepatitis C virus (HCV) and in turn increases the replication of HCV. However, the detailed molecular mechanism is only partially understood. In the present study, using human lncRNA polymerase chain reaction (PCR) arrays, it was identified that lnc­IGF2­AS, lnc­7SK, lnc­SChLAP1 and lnc­SRA1 are upregulated by STAT3. In addition, among these four lncRNAs, only lnc­IGF2­AS and lnc­7SK were involved in HCV replication. Transfection of siRNA lnc­7SK and siRNA lnc­IGF2­AS partially inhibited the replication of HCV in Huh7 cells. Data also indicated that when transfected with siRNA lnc­7SK and siRNA lnc­IGF2­AS, the expression of phosphatidylinositol 4­phosphate (PI4P), which was identified to be associated with HCV replication, was reduced. Thus, the present study identified two new types of lncRNAs, lnc­IGF2­AS and lnc­7SK, which can be upregulated by STAT3 and are involved in HCV replication by regulating PI4P.

The STAT3-regulated long non-coding RNA Lethe promote the HCV replication.

BACKGROUND: Long non-coding RNAs (lncRNAs) are a class of RNAs that do not code protein but play important roles in diverse biological processes. In recent years, with the application of high-throughput sequencing, a great deal of lncRNAs associated with virus infections have been discovered and intensively studied, but there are few studies about the relationship between lncRNAs and HCV replication. METHODS: We identify that several lncRNAs can be upregulated and downregulated by phosphorylated STAT3 by using human PCR array method. And among these lncRNAs, lnc-Lethe was involved in the HCV replication. Transfection of siRNA Lethe partially blocked the replication of HCV in Huh7 cells. RESULTS: In the present study, we have established that phosphorylated STAT3 can promote the HCV replication. Data also indicated that when transfected with siRNA Lethe, the expression levels of PKR, OAS and IRF1, which were all ISGs, were all up regulated. CONCLUSIONS: Based on our findings from Lethe knockdown, we have identified that Lethe, which was upregulated by activated STAT3, may promoting the replication of HCV through a negative regulatory mechanism of type I IFN response.

Hepatitis C virus represses the cellular antiviral response by upregulating the expression of signal transducer and activator of transcription 3 through sponging microRNA­122.

MicroRNAs (miRNAs) are small, non­coding RNAs that inhibit the expression of target protein coding genes at the post­transcriptional level. miR­122 is a liver specific miRNA. Notably, miR­122 is used by the hepatitis C virus (HCV) for triggering viral replication by interacting with the 5' untranslated region of the HCV RNA. The present study demonstrated that miR­122 inhibited the expression of signal transducer and activator of transcription 3 (STAT3), an antivirus response repressor. The HCV RNA acted as an 'miRNA sponge', which upregulated the expression of STAT3 by sealing miR­122. Subsequently, it was confirmed that this miR­122 sponge function of HCV RNA repressed the expression of polyinosinic­polycytidylic acid­stimulated type I interferons. The present study provided a deeper understanding of the complex role of miR­122 in the progression of HCV infection and supported the miR­122 inhibition strategy in anti­HCV infection treatment.

Efficacy of 2years of entecavir plus adefovir therapy in patients with chronic hepatitis B who had failed on prior nucleos(t)ide analog treatment.

Entecavir (ETV) plus adefovir (ADV) combination therapy may be a promising option for chronic hepatitis B (CHB) patients who have failed on prior nucleos(t)ide analog (NA) treatment. However, the long-term efficacy and safety of this combination are not well-defined. In a single-center, retrospective study, 104 patients (mean age 31.7 years; 88.5% male) with HBV DNA >10(3)IU/mL who had received one or multiple prior NAs for ⩾ 6 months (median 44.5 months) were treated for ⩾ 24 months with ETV (0.5mg/day) plus ADV (10mg/day). Among patients with available samples, 44/90 (48.9%) had drug-resistant mutations. At 2 years, HBV DNA levels were undetectable (<12 IU/mL) in 52/104 (50.0%) patients. The mean HBV DNA level was 2.0 ± 1.2 log 10 IU/mL, and it was decreased by 3.2 ± 2.0 log 10 IU/mL from the pre-combination treatment (V0) value. The 2-year HBeAg loss rate was 14.4% (13/90), HBeAg seroconversion rate was 10.0% (9/90), and ALT normalization rate was 75%. In multivariate analyses, the prior NA treatment duration, the V0 HBV DNA level, and the HBV DNA reduction at 1 year after ETV+ADV therapy were associated with the virological response after 2 years. No patients developed renal impairment, clinical decompensation or new HCC, and no relapses of HCC or deaths occurred. Thus, 2-year rescue therapy with ETV+ADV was effective and well-tolerated in CHB patients who had previously failed on multiple NA treatments. The HBV DNA level just before ETV+ADV combination therapy and the decrease of HBV DNA at 1 year could predict the efficacy of 2 years of ETV+ADV treatment.

[Long-term assessment of relapse and associated risk factors in chronic hepatitis C patients treated with interferon and ribavirin].

OBJECTIVE: To investigate viral relapse and the associated risk factors during a long-term follow-up study of chronic hepatitis C (CHC) patients who achieved end-of-treatment response (ETR) after interferon and ribavirin therapy. METHODS: This retrospective study was conducted on 146 CHC patients treated with a combination of ribavirin and pegylated (PEG) interferon-alpha (IFNa) (n=126) or conventional IFNa (n=20) for 24 (hepatitis C virus (HCV) non-genotype 1b) or 48 (HCV genotype 1b) weeks. The main outcome measure was serum HCV RNA load. The risk factors analyzed included age, sex, HCV genotype, baseline HCV RNA load, and IFN type. RESULTS: The mean follow-up time for all patients was 33.45+/-16.41 months (range: 12-85 months). The cumulative relapse rate during follow-up was 14.80%. The relapse rate within six months (8.90%) was significantly higher than other periods during two years of follow-up, and no relapse occurred after 30 months. Of all relapsers (n=20), 65% occurred within six months, followed by 35% within 7-24 months after antiviral therapy. The relapse rates in patients with HCV genotype 1b and non-1b were not significantly different (20.37% vs. 12.12%, X2 =1.517, P=0.315). The mean baseline HCV RNA load was significantly higher in the relapsers than that in the non-relapsers (t=0.915, P=0.362). Relapse rates were similar in patients treated with PEG-IFNa-2b, PEG-IFNa-2a and IFNa (12.12% vs. 13.97% vs. 15.00%, respectively; X2=0.104, p=0.949). The mean age of relapsers was significantly higher than that of non-relapsers (P less than 0.005). CONCLUSION: The maximum probability of relapse for CHC patients exists within six months from when ETR is achieved by interferon and ribavirin therapy. A lower risk for relapse persists past this period. Thus, ETR CHC patients, especially older patients, should be carefully monitored during the two years after cessation of antiviral therapy. Standard antiviral therapy based on HCV genotype eliminates the influence of viral factors on treatment-response.