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Background: [18 F]-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has the ability to detect local and/or regional recurrence as well as distant metastasis. We aimed to evaluate the prognosis value of PET/CT in locoregional recurrent nasopharyngeal (lrNPC). Methods: A total of 451 eligible patients diagnosed with recurrent I-IVA (rI-IVA) NPC between April 2009 and December 2015 were retrospectively included in this study. The differences in overall survival (OS) of lrNPC patients with and without PET/CT were compared in the I-II, III-IVA, r0-II, and rIII-IVA cohorts, which were grouped by initial staging and recurrent staging (according to MRI). Results: In the III-IVA and rIII-IVA NPC patients, with PET/CT exhibited significantly higher OS rates in the univariate analysis (P = 0.045; P = 0.009; respectively). Multivariate analysis revealed that with PET/CT was an independent predictor of OS in the rIII-IVA cohort (hazard ratio [HR] = 0.476; 95% confidence interval [CI]: 0.267 to 0.847; P = 0.012). In the rIII-IVA NPC, patients receiving PET/CT sacns before salvage surgery had a better prognosis compared with MRI alone (P = 0.036). The recurrent stage (based on PET/CT) was an independent predictor of OS. (r0-II versus [vs]. rIII-IVA; HR = 0.376; 95% CI: 0.150 to 0.938; P = 0.036). Conclusion: The present study showed that with PET/CT could improve overall survival for rIII-IVA NPC patients. PET/CT appears to be an effective method for assessing rTNM staging. [ABSTRACT FROM AUTHOR]

Background: The conversion of phytosterols to steroid synthons by engineered Mycolicibacteria comprises one of the core steps in the commercial production of steroid hormones. This is a complex oxidative catabolic process, and taking the production of androstenones as example, it requires about 10 equivalent flavin adenine dinucleotide (FAD). As the high demand for FAD, the insufficient supply of FAD may be a common issue limiting the conversion process. Results: We substantiated, using the production of 9α-hydroxy-4-androstene-3,17-dione (9-OHAD) as a model, that increasing intracellular FAD supply could effectively increase the conversion of phytosterols into 9-OHAD. Overexpressing ribB and ribC, two key genes involving in FAD synthesis, could significantly enhance the amount of intracellular FAD by 167.4% and the production of 9-OHAD by 25.6%. Subsequently, styrene monooxygenase NfStyA2B from Nocardia farcinica was employed to promote the cyclic regeneration of FAD by coupling the oxidation of nicotinamide adenine dinucleotide (NADH) to NAD+, and the production of 9-OHAD was further enhanced by 9.4%. However, the viable cell numbers decreased by 20.1%, which was attributed to sharply increased levels of H2O2 because of the regeneration of FAD from FADH2. Thus, we tried to resolve the conflict between FAD regeneration and cell growth by the overexpression of catalase and promotor replacement. Finally, a robust strain NF-P2 was obtained, which could produce 9.02 g/L 9-OHAD after adding 15 g/L phytosterols with productivity of 0.075 g/(L h), which was 66.7% higher than that produced by the original strain. Conclusions: This study highlighted that the cofactor engineering, including the supply and recycling of FAD and NAD+ in Mycolicibacterium, should be adopted as a parallel strategy with pathway engineering to improve the productivity of the industrial strains in the conversion of phytosterols into steroid synthons. [ABSTRACT FROM AUTHOR]

Background: Increased frequency of circulating double negative T (DNT, CD4-CD8-CD3+) cells with protective immune function has been observed in human immunodeficiency virus (HIV) infection and tuberculosis (TB). Here the role of circulating TCRαβ+ DNT cells was further investigated in HIV/TB co-infection.Methods: A cross-sectional study was conducted to investigate the frequency and functional profiles of peripheral TCRαβ+ DNT cells including apoptosis, chemokine and cytokine expression among healthy individuals and patients with TB, HIV infection and HIV/TB co-infection by cell surface staining and intracellular cytokine staining combined with flow cytometry.Results: Significantly increased frequency of TCRαβ+ DNT cells was observed in HIV/TB co-infection than that in TB (p < 0.001), HIV infection (p = 0.039) and healthy controls (p < 0.001). Compared with TB, HIV/TB co-infection had higher frequency of Fas expression (p = 0.007) and lower frequency of Annexin V expression on TCRαβ+ DNT cells (p = 0.049), and the frequency of Annexin V expression on Fas+TCRαβ+ DNT cells had no significant difference. TCRαβ+ DNT cells expressed less CCR5 in HIV/TB co-infection than that in TB (p = 0.014), and more CXCR4 in HIV/TB co-infection than that in HIV infection (p = 0.043). Compared with healthy controls, TB and HIV/TB co-infection had higher frequency of TCRαβ+ DNT cells secreting Granzyme A (p = 0.046; p = 0.005). In TB and HIV/TB co-infection, TCRαβ+ DNT cells secreted more granzyme A (p = 0.002; p = 0.002) and perforin (p < 0.001; p = 0.017) than CD4+ T cells but similar to CD8+ T cells.Conclusions: Reduced apoptosis may take part in the mechanism of increased frequency of peripheral TCRαβ+ DNT cells in HIV/TB co-infection. TCRαβ+ DNT cells may play a cytotoxic T cells-like function in HIV/TB co-infection. [ABSTRACT FROM AUTHOR]

Background: Prenatal cardiac screening is of great importance as it contributes to appropriate neonatal management and helps parents to make a decision regarding their pregnancy. The aim of our study was to evaluate the efficiency of a newly proposed screening protocol in the detection of fetal congenital heart disease (CHD).Methods: This was a prospective study. A total of 52 cases of confirmed CHD fetuses and 248 cases of randomly selected normal fetuses were included in the study. Two sonographers with similar experience performed the cardiac screenings under two different protocols independently. The conventional protocol (Protocol A) paid greater attention to the four-chamber view and the outflow tract views. A 6-month training program was provided to sonographers performing scans under the new protocol (Protocol B), which emphasized systematically evaluating fetal cardiac anatomy and hemodynamics. Color Doppler was mandatory and some ultrasonic signs for special cardiac anomalies were also introduced into this protocol.Results: Protocol B detected more cardiac anomalies than did Protocol A (96.2 % vs. 61.5 %, P < 0.01). Specifically, Protocol B was superior to Protocol A in detecting cardiac malpositions, abnormal systemic and pulmonary venous connection, right aortic arch, transposition of the great arteries, and congenital corrected transposition of the great arteries. By visualizing flow disturbance and retrograde flow with color Doppler, Protocol B was better than Protocol A in screening valvular associated malformations, such as pulmonary atresia, pulmonary stenosis, tricuspid dysplasia, etc. For the normal fetuses, Protocol B was better than Protocol A in reducing the false-positive detection of septal defects.Conclusions: The current study introduces an enhanced protocol for fetal cardiac screening, under which the obstetric screening sonographers systematically identify fetal cardiac anatomy and hemodynamics. A short-term training program makes it possible for the screening sonographers to become familiar with the new protocol, and its value has been confirmed due to improvements made in screening efficiency. [ABSTRACT FROM AUTHOR]

Background: Bone cancer pain (BCP) severely compromises the quality of life, while current treatments are still unsatisfactory. Here, we tested the antinociceptive effects of triptolide (T10), a substance with considerable anti-tumor efficacies on BCP, and investigated the underlying mechanisms targeting the spinal dorsal horn (SDH).Methods: Intratibial inoculation of Walker 256 mammary gland carcinoma cells was used to establish a BCP model in rats. T10 was intrathecally injected, and mechanical allodynia was tested by measuring the paw withdrawal thresholds (PWTs). In mechanism study, the activation of microglia, astrocytes, and the mitogen-activated protein kinase (MAPK) pathways in the SDH were evaluated by immunofluorescence staining or Western blot analysis of Iba-1, GFAP, p-ERK, p-p38, and p-JNK. The expression and cellular localization of histone deacetylases (HDACs) 1 and 2 were also detected to investigate molecular mechanism.Results: Intrathecal injection of T10 inhibited the bone cancer-induced mechanical allodynia with an ED50 of 5.874 μg/kg. This effect was still observed 6 days after drug withdrawal. Bone cancer caused significantly increased expression of HDAC1 in spinal microglia and neurons, with HDAC2 markedly increased in spinal astrocytes, which were accompanied by the upregulation of MAPK pathways and the activation of microglia and astrocytes in the SDH. T10 reversed the increase of HDACs, especially those in glial cells, and inhibited the glial activation.Conclusions: Our results suggest that the upregulation of HDACs contributes to the pathological activation of spinal glial cells and the chronic pain caused by bone cancer, while T10 help to relieve BCP possibly via inhibiting the upregulation of HDACs in the glial cells in the SDH and then blocking the neuroinflammation induced by glial activation. [ABSTRACT FROM AUTHOR]

Background: Transurethral resection of bladder tumor (TURBT) is the standard approach to bladder tumors but suffers from several disadvantages. The aim of this study was to evaluate the safety and efficacy of a novel procedure of retrograde en bloc resection of bladder tumor (RERBT) with conventional monopolar resection electrode for the treatment of superficial bladder tumors. Methods: RERBT and conventional TURBT (C-TURBT) were conducted, respectively, in 40 and 50 patients diagnosed with superficial papillary bladder tumors. In the RERBT group, the tumors were en bloc removed retrogradely under direct vision using a conventional monopolar electrode. Patients' clinicopathological, intraoperative, and postoperative data were compared retrospectively between the RERBT and C-TURBT groups. Results: Of the 90 patients, 40 underwent RERBT and 50 underwent C-TURBT. Both groups were comparable in clinicopathological characteristic. RERBT could be performed as safely and effectively as C-TURBT. There were no significant differences in operative time and surgical complications. The cumulative recurrence rates between groups were similar during up to 18 months follow-up. The detrusor muscle could be identified pathologically in 100% of RERBT tumor specimens and the biopsy of tumor bases, but only in 54 and 70%, respectively, of C-TURBT samples (P < 0.01). Conclusions: The RERBT technique is feasible and safe for superficial bladder tumors using conventional monopolar resection setting, with the advantages of adequate tumor resection and the ability to collect good quality tumor specimens for pathological diagnosis and staging compared to conventional TURBT. [ABSTRACT FROM AUTHOR]

Background: The treatment of bilateral complex renal stones is a tough challenge for urologists. This study aimed to evaluate the efficiency and safety of bilateral ultrasonography-guided multi-tract percutaneous nephrolithotomy (PCNL) combined with EMS lithotripsy for the treatment of such cases.Methods: Twenty-seven patients suffering from bilateral complex renal calculi underwent t bilateral multi-tract PCNL. The PCNL began with the establishment of percutaneous nephrostomy access, which was achieved under ultrasound guidance followed by stone fragment and removal by EMS lithotripsy. The same processes were then performed on the ipsilateral and contralateral renal units until the operation terminated. Sheaths left in situ to provide the tracts for the two-stage and the three-stage PCNL procedures. Peri- and postoperative clinical data were collected and analysed.Results: Renal stones of both sides were completely cleared within three PCNL sessions in 24 cases. Among them, four, thirteen, and seven cases underwent single, second-stage and third-stage procedures, respectively. The total stone-free rate was 88.9%. Three patients failed to receive complete stone clearance. Mean operation time was 78.7 (26-124) min, the mean estimated blood loss was 97.3 (30-250) ml, and the mean length of hospital stay was 18 (10-31) days. No patient required blood transfusion and postoperative fever occurred in 6 cases. Within the follow-up period, stone recurrence occurred in 6 patients.Conclusions: Ultrasonography-guided multi-tract PCNL using EMS is an efficient method for the treatment of complex renal calculi. According to our experience, it is safe to make multiple tracts on both sides simultaneously. [ABSTRACT FROM AUTHOR]

Background: STAT3 signaling plays the pivotal role in tumorigenesis through EZH2 epigenetic modification, which enhanced STAT3 activity by increased tyrosine phosphorylation of STAT3. Here, another possible feedback mechanism and clinical significance of EZH2 and STAT3 were investigated in gastric cancer (GC). Methods: STAT3, p-STAT3 (Tyr 705) and EZH2 expression were examined in 63 GC specimens with matched normal tissues by IHC staining. EZH2 and STAT3 were also identified in five GC cell lines using RT-PCR and western blot analyses. p-STAT3 protein was detected by western blotting. In order to investigate whether EZH2 expression was directly regulated by STAT3, EZH2 expression was further detected using siRNA for STAT3 or IL-6 stimulation, with dual luciferase reporter analyses, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays. The clinical significance of STAT3, p-STAT3 and EZH2 expression was evaluated by multi-factor COX regression and Kaplan-Meier analyses. Results: Hyper-activation of STAT3, p-STAT3 and EZH2 expression were observed in GC cells and tissues. STAT3 signaling was correlated with EZH2 expression in GC (R = 0.373, P = 0.003), which was consistent with our data showing that STAT3 as the transcriptional factor enhanced EZH2 transcriptional activity by binding the relative promoter region (-214 ~ -206). STAT3 was an independent signature for poor survival (P = 0.002). Patients with STAT3+/EZH2+ or p-STAT3+/EZH2+ had a worse outcome than others (P < 0.001); Besides, high levels of STAT3 and EZH2 was associated with advanced TNM staging (P = 0.017). Moreover, treatment with a combination of siSTAT3 and EZH2-specific inhibitor, 3-deazaneplanocin A (DZNEP), increased the apoptotic ratio of cells. It is benefit for targeting STAT3-EZH2 interplay in GC treatment. Conclusions: Our results indicate that STAT3 status mediated EZH2 upregulation, associated with advanced TNM stage and poor prognosis, suggesting that combination with knockdown of STAT3 and EZH2 inhibitor might be a novel therapy in GC treatment. Collectively, STAT3, p-STAT3 and EZH2 expression were provided for the precision medicine in GC patients. [ABSTRACT FROM AUTHOR]