Yazhuo Zhang

Investigation of the clinical value of total saliva flow rates

The symptom of dry mouth was correlated with unstimulated (UWSFR) and stimulated (SWSFR) whole-saliva flow rate on chewing medical paraffin in 62 patients with dry-mouth complaints (30 with Sjögrens syndrome, 32 with sialosis) and 23 controls. The symptom of dry mouth was classified into grades 0,1,2,3,4 according to a Treatment Emergent Symptom Scale (TESS). UWSFR and SWSFR were determined after fasting in the morning. UWSFR was 0.070 +/- 0.089 ml/min in Sjögrens syndrome, 0.175 +/- 0.115 ml/min in sialosis, 0.330 +/- 0.188 ml/min in controls. SWSFR was 0.709 +/- 0.720 ml/min in Sjögrens syndrome, 1.561 +/- 0.867 ml/min in sialosis, 1.894 +/- 0.661 ml/min in controls. A highly significant correlation was found between TESS score and UWSFR and between TESS score and SWSFR. Only UWSFR was decreased in the patients with a TESS score of 1 or 2, while both UWSFR and SWSFR were significantly decreased in the patients with TESS scores of 3, 4. It is concluded that UWSFR is more sensitive in relation to dry-mouth complaints than SWSFR, and that a mild dry mouth is mainly related to decreased UWSFR.

Endoscopic transsphenoidal treatment of pituitary adenomas.

Abstract Objective: To explore the techniques and methods of endoscopic transnasal transsphenoid surgery for pituitary adenoma. Method: We treated 678 cases with pituitary adenoma by endoscopic transsphenoidal surgery between May 2000 and May 2006. All cases were operated through a transnasal transsphenoid approach between the nasal septum and middle nasal concha, first to enlarged sphenoid ostium and opened sellar floor with a high-speed drill and then removed the tumor step by step. Sixty-two percent of cases (420 cases) got 6–24 months of follow-up. Results: Among the 678 pituitary adenomas, tumor removal was total in 543 (80.1%), subtotal in 118 (17.4%) and partial in 17 (2.5%). Ninety-eight percent (643 of 655 cases) obtained an improvement in clinical symptoms at some extent after the operation. Post-operative complication (including subarachnoid hemorrhage, nasal cavity bleed, nostril infection, nasal wing deformation and cerebrospinal fluid nasal leakage) occurred in 21 patients (3%). Among the 420 follow-up patients, tumor in four cases recurred 2 years after the first operation. Conclusion: Endoscopic transsphenoidal surgery of pituitary adenomas is a valuable microinvasive neurosurgery technique of minimal invasiveness, being effective and safe, yet requiring simple manipulation. With technological and scientific advancements, endoscopic transsphenoidal surgery will improve and develop step by step.

Assessment of endoscopic treatment for middle cranial fossa arachnoid cysts

BackgroundEndoscopic cystocisternotomy is one of three surgical methods used to treat middle cranial fossa arachnoid cysts. There is debate about which method is the best.ObjectiveThe aim of this study is to evaluate the effectiveness and safety of endoscopic cystocisternotomy for treatment of arachnoid cysts of the middle cranial fossa.MethodsThirty-two patients with arachnoid cysts of the middle cranial fossa who had undergone endoscopic cystocisternal fenestration between 2004 and 2009 were studied retrospectively. Data were obtained on clinical and neuroradiological presentation, indications to treat, surgical technique, complications, and the results of clinical and neuroradiological follow-up.ResultsAmong the 27 patients with symptoms before surgery, 8 had disappearance of symptoms and 17 had improvement of symptoms. The cyst was reduced in size or it completely disappeared in 24 (75%) patients. The incidence rate of complications was 18.8%.ConclusionsEndoscopic cystocisternal fenestration is an effective treatment for symptomatic arachnoid cysts of the middle cranial fossa and should be the initial surgical procedure.

A deep learning model integrating FCNNs and CRFs for brain tumor segmentation

HighlightsA deep learning model integrating FCNNs and CRFs for brain tumor segmentation.The integration of FCNNs and CRF‐RNN improves the segmentation robustness.A segmentation model with Flair, T1c, and T2 scans achieves competitive performance. Abstract Accurate and reliable brain tumor segmentation is a critical component in cancer diagnosis, treatment planning, and treatment outcome evaluation. Build upon successful deep learning techniques, a novel brain tumor segmentation method is developed by integrating fully convolutional neural networks (FCNNs) and Conditional Random Fields (CRFs) in a unified framework to obtain segmentation results with appearance and spatial consistency. We train a deep learning based segmentation model using 2D image patches and image slices in following steps: 1) training FCNNs using image patches; 2) training CRFs as Recurrent Neural Networks (CRF‐RNN) using image slices with parameters of FCNNs fixed; and 3) fine‐tuning the FCNNs and the CRF‐RNN using image slices. Particularly, we train 3 segmentation models using 2D image patches and slices obtained in axial, coronal and sagittal views respectively, and combine them to segment brain tumors using a voting based fusion strategy. Our method could segment brain images slice‐by‐slice, much faster than those based on image patches. We have evaluated our method based on imaging data provided by the Multimodal Brain Tumor Image Segmentation Challenge (BRATS) 2013, BRATS 2015 and BRATS 2016. The experimental results have demonstrated that our method could build a segmentation model with Flair, T1c, and T2 scans and achieve competitive performance as those built with Flair, T1, T1c, and T2 scans. Graphical abstract Figure. No Caption available.

TLR9 expression is associated with prognosis in patients with glioblastoma multiforme

The aim of this study was to determine if there was an association between expression of toll-like receptor 9 (TLR9) in glioblastoma tissue and patient outcome in glioblastoma multiforme. Further, we characterized the direct in vitro effects of the TLR9 agonist, CpG oligodeoxynucleotide (ODN), commonly used as a vaccine adjuvant in cancer immunotherapy, on glioma cells. TLR9 expression was assessed using immunohistochemical techniques, and enzyme-linked immunosorbent assays were used to investigate the expression of other proteins in glioma cells relevant to immunotherapy. There was a highly significant difference in both progression-free survival and overall survival between TLR9+ and TLR9- patients, with poorer outcome in TLR9+ patients. In in vitro glioma cells, there was a positive correlation between the protein levels of TLR9 and both matrix metalloproteinase (MMP)-2 and MMP-9 (p<0.05), but no relationship between TLR9 levels and levels of interleukin-6, transforming growth factor-β2 or signal transducer and activator of transcription (STAT)-3 (p>0.05). Our data indicate that expression of TLR9 correlates with shorter progression-free survival and overall survival in patients with glioblastoma multiforme. Our findings also indicate that caution is warranted when directly injecting the TLR9 agonist CpG ODN into glioma tissues as part of glioma immunotherapy. Because the CpG ODN is a TLR9 agonist, we recommend caution when using CpG ODN in immunotherapy.

Lower PRDM2 expression is associated with dopamine-agonist resistance and tumor recurrence in prolactinomas.

BackgroundDopamine agonists (DAs) are the first-line treatment for prolactinomas, which account for 25–30% of functioning pituitary adenomas, and bromocriptine (BRC) is the only commercially available DAs in China. However, tumors are resistant to therapy in 5–18% of patients.MethodsThe exomes of six responsive prolactinomas and six resistant prolactinomas were analyzed by whole-exome sequencing.ResultsUsing stringent variant calling and filtering parameters, ten somatic variants that were mainly associated with DNA repair or protein metabolic processes were identified. New resistant variants were identified in multiple genes including PRDM2, PRG4, MUC4, DSPP, DPCR1, RP1L1, MX2, POTEF, C1orf170, and KRTAP10-3. The expression of these genes was then quantified by real-time reverse-transcription PCR (RT–qPCR) in 12 prolactinomas and 3 normal pituitary glands. The mRNA levels of PRDM2 were approximately five-fold lower in resistant prolactinomas than in responsive tumors (p < 0.05). PRDM2 protein levels were lower in resistant prolactinomas than in responsive tumors, as determined by Western blotting and immunohistochemical analysis (p < 0.05). Overexpression of PRDM2 upregulated dopamine receptor D2 (D2DR) and inhibited the phosphorylation of ERK1/2 in MMQ cells. PRDM2 showed a synergistic effect with BRC on the inhibition of prolactin (PRL) secretion and MMQ cell viability, and low PRDM2 expression was associated with tumor recurrence.ConclusionsPRDM2 downregulation may play a role in dopamine-agonist resistance and tumor recurrence in prolactinomas.

Expression of estrogen receptor α and growth factors in human prolactinoma and its correlation with clinical features and gender

Background: Many studies demonstrate that growth factors play an important role in the pathogenesis of prolactinoma induced by estrogen. The effects of estrogen are mainly mediated through its nuclear receptor (ERα); however, expression of ERα and growth factors in prolactinoma and healthy pituitary and their relationship remain obscure. Aim: To obtain new insights regarding the expression differences of these factors and their relationship and to investigate the correlation between gender and clinical features in patients with prolactinoma. Subjects and methods: A total of 21 human prolactinomas and 6 healthy human pituitaries were examined for mRNA expression of ERα, basic fibroblast growth factor (bFGF), transforming growth factor α (TGFα), TGFβ1, TGFβ3, and TGFβ receptor type II (TGFβRII) by means of real-time PCR. Patient clinical data was also analyzed. Results: Both PRL level and tumor volume of the male patient group were higher than that of the female patient group. There was a significant correlation between PRL level and tumor volume in the total patient group. Expression of ERα, bFGF, TGFα, and TGFβ3 mRNA levels of the patient group were significantly different from that of the control group. A significant correlation between ERα mRNA levels and PRL levels, tumor volume, TGFβ1 mRNA levels in the total patient group were found. Conclusions: PRL level and tumor volume have a significant difference between genders in prolactinoma patients. ERα and some growth factors may be involved in the tumorigenesis of prolactinoma. ERα could potentially be an effective therapy target for treating prolactinoma.

Reversion of multidrug resistance in human glioma by RNA interference

Abstract Objective: To explore whether the vector construction of short hairpin in vivo could make human glioma cell line BT325 produce RNA interference (RNAi) duplexes and reverse the expression of the MDR1 gene. Methods: Three 62nt oligonucleotide fragments (shRNA) were constructed according to GeneBank MDR1 sequence and were cloned to the retrovirus-delivered vectors. After these vectors were transfected directly to the BT325 cell by Lipofectamine 2000 with enhanced green fluorescent protein (EGFP) co-transfection, the MDR1 gene silence effects were detected by the changing levels of mRNA and P-glycoprotein (P-gp) including real-time PCR (RT-PCR), Northern blot and Western blot analysis. For assessing multidrug resistance against doxorubicin (DOX) and vincristine (VCR), cell proliferation assays were performed by cell counting kit-8 and IC50 was calculated. Results: The RNAi plasmid vectors were constructed successfully. The gene silence became the strongest after 48 hour transfection from Northern blot; Western blot analysis demonstrated that P-gp expression reduced to 12.9, 30.3 and 4.8%. The chemosensitivity assays showed that the transfected cell could increase the sensitivity of DOX and VCR. Based on the value of IC50, BT325 cells increased sensitivity to drugs obviously. The sequence specific RNAi could inhibit MDR1 mRNA and P-gp expression of the glioma cell line. And it may reverse multidrug resistance phenotype, which may provide promising therapeutic modalities in the treatment of human glioma.

Reversal of multidrug resistance by magnetic chitosan-Fe3O4 nanoparticle-encapsulated MDR1 siRNA in glioblastoma cell line

Abstract Objective: To investigate the reversal effects of MDR1 gene on multidrug resistance in the glioblastoma cell line BT325 by magnetic chitosan-Fe3O4 nanoparticle-encapsulated MDR1 siRNA. Methods: The shRNA expression vector was constructed and the recombinant plasmids were cloned. Magnetic chitosan-Fe3O4 nanoparticles were prepared and the encapsulation rate was determined. After transfection, the BT325 cells were cultured to assay the transfection efficiency. The changing of MDR1 mRNA level and P-gp protein was evaluated. And the sensitivity to different chemotherapeutic drugs was assessed in BT325-siRNA transfected cell and untransfected cell by IC50 values. Results: The MDR1 RNAi plasmid was successfully designed and preparation. The encapsulation efficiency of the magnetic chitosan-Fe3O4 nanoparticle was 98–99%. The transfection efficiency of the siRNA-nanoparticles in BT325 cells was 70–80%. And the MDR1 mRNA levels were downregulated by reverse transcription (RT)-PCR assay. Furthermore, the results of P-gp protein expression decreased on immunocytochemical assay, Western blot and flow cytometry compared with control group. The IC50 values of DOX and VCR were decreased between the transfected cell and normal BT325 cell. Conclusion: After targeted transfection of the glioblastoma cell line with magnetic chitosan-Fe3O4 nanoparticle-encapsulated MDR1 siRNA, the expression of MDR1 at both the mRNA and protein level decreased, which increased sensitivity to chemotherapy in vitro. It might provide a basis for investigation of the mechanism involved in multidrug resistance in glioma.

The role of FSCN1 in migration and invasion of pituitary adenomas.

The prediction of invasion or malignant behavior in PAs remains challenging. FSCN1, an actin-bundling protein, is associated with increased risk of mortality and metastasis in various cancer types. The objective of the study was to evaluate the expression of FSCN1 in 312 PAs cases, and to analyze its association with clinicopathologic features and invasion of PAs, thus serving as a promoter of cancer invasion. In non-function PAs (NFPA), FSCN1 nuclear-positive cases were 53/97 in the invasive group (IPA), and 21/115 in the noninvasive group (nIPA) (ⅹ(2) = 30.65, p = 0.004). FSCN1 cytoplasm-positive cases were 36/97 in IPA, and 8/107 in nIPA (ⅹ(2) = 29.09, p = 0.000). In growth hormone adenomas (GHomas), FSCN1 nuclear-positive were 10/13 in IPA, and 3/37 in nIPA (ⅹ(2) = 23.67, p = 0.000). FSCN1 cytoplasm-positive were 8/13 in IPA, and 2/37 in nIPA (Table 3 ⅹ(2) = 18.94, p = 0.000). Overall, a significant difference was found between FSCN1 expression and tumor size (ⅹ(2) = 46.21, p = 0.000), not age (ⅹ(2) = 2.09, p = 0.148). In the high FSCN1 expression group, 27/137 cases (19.7%) had tumor recurrence, and 10/175 cases (5.7%) in low FSCN1 level (ⅹ(2) = 14.40 p = 0.000). Reduction of FSCN1 suppressed the invasion level of GH3 cells through transwells test. In addition, reduction of FSCN1 can obviously down-regulate the level of Notch1 and DLL3. Our data may help in deciding whether FSCN1 can be a predictor for invasion and recurrence of PAs.