Identification of an immune-related gene-based signature to predict prognosis of patients with gastric cancer.

BACKGROUND: Gastric cancer (GC) is the most commonly diagnosed malignancy worldwide. Increasing evidence suggests that it is necessary to further explore genetic and immunological characteristics of GC. AIM: To construct an immune-related gene (IRG) signature for accurately predicting the prognosis of patients with GC. METHODS: Differentially expressed genes (DEGs) between 375 gastric cancer tissues and 32 normal adjacent tissues were obtained from The Cancer Genome Atlas (TCGA) GDC data portal. Then, differentially expressed IRGs from the ImmPort database were identified for GC. Cox univariate survival analysis was used to screen survival-related IRGs. Differentially expressed survival-related IRGs were considered as hub IRGs. Genetic mutations of hub IRGs were analyzed. Then, hub IRGs were selected to conduct a prognostic signature. Receiver operating characteristic (ROC) curve analysis was used to evaluate the prognostic performance of the signature. The correlation of the signature with clinical features and tumor-infiltrating immune cells was analyzed. RESULTS: Among all DEGs, 70 hub IRGs were obtained for GC. The deletions and amplifications were the two most common types of genetic mutations of hub IRGs. A prognostic signature was identified, consisting of ten hub IRGs (including S100A12, DEFB126, KAL1, APOH, CGB5, GRP, GLP2R, LGR6, PTGER3, and CTLA4). This prognostic signature could accurately distinguish patients into high- and low- risk groups, and overall survival analysis showed that high risk patients had shortened survival time than low risk patients (P < 0.0001). The area under curve of the ROC of the signature was 0.761, suggesting that the prognostic signature had a high sensitivity and accuracy. Multivariate regression analysis demonstrated that the prognostic signature could become an independent prognostic predictor for GC after adjustment for other clinical features. Furthermore, we found that the prognostic signature was significantly correlated with macrophage infiltration. CONCLUSION: Our study proposed an immune-related prognostic signature for GC, which could help develop treatment strategies for patients with GC in the future.

Down-regulation of FOXR2 inhibits non-small cell lung cancer cell proliferation and invasion through the Wnt/ß-catenin signaling pathway.

Forkhead box R2 (FOXR2), a new member of the FOX family, is an important player in a wide range of cellular processes such as proliferation, migration, differentiation and apoptosis. Recently, FOXR2 has been reported to be implicated in cancer development. However, the biological functions of FOXR2 in non-small cell lung cancer (NSCLC) remain unclear. In this study, we investigated the specific role of FOXR2 in NSCLC. The results showed that down-regulation of FOXR2 significantly inhibited NSCLC cell proliferation and invasion in vitro and suppressed NSCLC cell growth and metastasis in vivo. In addition, the decrease in FOXR2 expression markedly reduced the protein levels of ß-catenin, cyclinD1 and c-Myc and hence inactivated the Wnt/ß-catenin pathway in NSCLC cells. Taken together, we concluded that FOXR2 might be considered as a promising therapeutic target for NSCLC treatment.

SLCO1B1 Variants and Angiotensin Converting Enzyme Inhibitor (Enalapril)-Induced Cough: a Pharmacogenetic Study.

Clinical observations suggest that incidence of cough in Chinese taking angiotensin converting enzyme inhibitors is much higher than other racial groups. Cough is the most common adverse reaction of enalapril. We investigate whether SLCO1B1 genetic polymorphisms, previously reported to be important determinants of inter-individual variability in enalapril pharmacokinetics, are associated with the enalapril-induced cough. A cohort of 450 patients with essential hypertension taking 10 mg enalapril maleate were genotyped for the functional SLCO1B1 variants, 388A > G (Asn130Asp, rs2306283) and 521T > C (Val174Ala, rs4149056). The primary endpoint was cough, which was recorded when participants were bothered by cough and respiratory symptoms during enalapril treatment without an identifiable cause. SLCO1B1 521C allele conferred a 2-fold relative risk of enalapril-induced cough (95% confidence interval [CI] = 1.34-3.04, P = 6.2 × 10(-4)), and haplotype analysis suggested the relative risk of cough was 6.94-fold (95% CI = 1.30-37.07, P = 0.020) in SLCO1B1*15/*15 carriers. Furthermore, there was strong evidence for a gene-dose effect (percent with cough in those with 0, 1, or 2 copy of the 521C allele: 28.2%, 42.5%, and 71.4%, trend P = 6.6 × 10(-4)). Our study highlights, for the first time, SLCO1B1 variants are strongly associated with an increased risk of enalapril-induced cough. The findings will be useful to provide pharmacogenetic markers for enalapril treatment.

Auditory Rehabilitation in Rhesus Macaque Monkeys (Macaca mulatta) with Auditory Brainstem Implants.

BACKGROUND: The auditory brainstem implants (ABIs) have been used to treat deafness for patients with neurofibromatosis Type 2 and nontumor patients. The lack of an appropriate animal model has limited the study of improving hearing rehabilitation by the device. This study aimed to establish an animal model of ABI in adult rhesus macaque monkey (Macaca mulatta). METHODS: Six adult rhesus macaque monkeys (M. mulatta) were included. Under general anesthesia, a multichannel ABI was implanted into the lateral recess of the fourth ventricle through the modified suboccipital-retrosigmoid (RS) approach. The electrical auditory brainstem response (EABR) waves were tested to ensure the optimal implant site. After the operation, the EABR and computed tomography (CT) were used to test and verify the effectiveness via electrophysiology and anatomy, respectively. The subjects underwent behavioral observation for 6 months, and the postoperative EABR was tested every two weeks from the 1 st month after implant surgery. RESULT: The implant surgery lasted an average of 5.2 h, and no monkey died or sacrificed. The averaged latencies of peaks I, II and IV were 1.27, 2.34 and 3.98 ms, respectively in the ABR. One-peak EABR wave was elicited in the operation, and one- or two-peak waves were elicited during the postoperative period. The EABR wave latencies appeared to be constant under different stimulus intensities; however, the amplitudes increased as the stimulus increased within a certain scope. CONCLUSIONS: It is feasible and safe to implant ABIs in rhesus macaque monkeys (M. mulatta) through a modified suboccipital RS approach, and EABR and CT are valid tools for animal model establishment. In addition, this model should be an appropriate animal model for the electrophysiological and behavioral study of rhesus macaque monkey with ABI.

Changes in the Vision-related Resting-state Network in Pituitary Adenoma Patients After Vision Improvement.

BACKGROUND: The aim of this research was to investigate the changes in the vision-related resting-state network (V-RSN) in pituitary adenoma (PA) patients after vision improvement, which was induced by operative treatment. METHODS: Ten PA patients with an improved visual acuity or/and visual field after transsphenoidal pituitary tumor resection were recruited and underwent a complete neuro-ophthalmologic evaluation, as well as an magnetic resonance imaging (MRI) protocol, including structural and resting-state functional MRI sequences before and after the operation. The regional homogeneity (ReHo) of the V-RSN was evaluated. Two sample t-test was performed to identify the significant differences in the V-RSN in the PA patients before and after transsphenoidal pituitary tumor resection. RESULTS: Compared with the preoperation counterparts, the PA patients with improved vision after the operation exhibited reduced ReHo in the bilateral thalamus, globus pallidus, caudate nucleus, putamen nucleus, supplementary motor area, and left hippocampal formation, and increased ReHo in the bilateral cuneus gyrus, calcarine gyrus, right lingual gyrus, and fusiform gyrus. CONCLUSIONS: PA patients with improved vision exhibit increased neural activity within the visual cortex, but decreased neural activity in subareas of the multisensory and multimodal systems beyond the vision cortex.

Effect of basic fibroblast growth factor and transforming growth factor ß1 on the healing of reconstructed dura by carbon dioxide laser soldering in minipigs.

BACKGROUND: Carbon dioxide (CO2) laser soldering is an alternative technique for tissue bonding. Basic fibroblast growth factor (bFGF) and transforming growth factor ß(1) (TGFß(1)) are two key factors for wound healing. This study was performed to demonstrate the efficacy of CO2 laser soldering for dural reconstruction and the effect of bFGF and TGFß(1) on healing. METHODS: In Part I, 10 minipigs were randomized into two equal groups. Dural defects were reconstructed by conventional fibrin glue bonding (group I(a)) or CO2 laser soldering (group I(b)). The reconstructed dura was subjected to burst pressure (BP) measurement and immunohistochemical staining after 1 week. In Part II, 36 minipigs were randomized into three equal groups. Dural reconstruction was achieved by CO2 laser soldering. Exogenous bFGF (group II(b)) or TGFß(1) (group II(c)) was administered while group II(a) served as a control group. The specimens were subjected to BP measurement after 1, 2, 3, and 4 weeks, respectively. RESULTS: In Part I, the dura specimens displayed positive staining of only bFGF in group I(a) and of both bFGF and TGFß(1) in group I(b). Group I(b) showed higher BP than group I(a) ((98.00 ± 21.41) mmHg vs. (70.80 ± 15.09) mmHg, respectively; P < 0.05). In Part II, BP of group II(c) was significantly higher than that of group II(a) (P < 0.01). The BP of group II(a) trended toward stabilization after 3 weeks of growth, while that of groups II(b) and II(c) trended toward stabilization after 2 weeks of growth. CONCLUSIONS: CO2 laser soldering is a reliable technique for dural reconstruction. The superior healing of dural reconstruction by CO2 laser soldering may be related to higher expression of bFGF and TGFß(1), and CO2 lasers may stimulate their secretion. Exogenous bFGF or TGFß(1) may improve healing by shortening the wound healing time, and exogenous TGFß(1) may improve the tensile strength.

Prevention of postoperative intracranial infection in patients with cerebrospinal fluid rhinorrhea.

BACKGROUND: Intracranial infection is a common postoperative complication of neurosurgery. This study aimed to identify risk factors of postoperative intracranial infection in patients with cerebrospinal fluid rhinorrhea and to suggest proposals for the prevention. METHODS: A total of 167 patients (113 males and 54 males, average age of 34.4 years) with cerebrospinal fluid rhinorrhea operated on by the senior author were retrospectively reviewed. The data collected included etiology, previous history, clinical manifestation, site of bone defect, operative approach, and postoperative complications. Risk factor(s) for postoperative infection were analyzed using the stepwise multiple Logistic regression. RESULTS: Eighteen (10.8%) patients were infected post-operatively. The independent risk factors for infection were the site of defect (RR = 0.508, 95%CI 0.306 - 0.843, P = 0.009) and historical meningitis (RR = 0.290, 95%CI 0.094 - 0.893, P = 0.031). Patients with multiple defects and saddle floor defects had a higher infection rate. The germiculture was positive in 11 patients, and vancomycin was sensitive to all the pathogenesis. Nine infected patients needed lumbar drainage. Ten patients had hyponatremia, and hydrocephalus occurred in two patients with serious trauma. CONCLUSIONS: To prevent the infection, we should pay closer attention to the high-risk patients pre-operation. During the operation, the methods those can improve wound healing, such as using blood-supply materials, reliable fixation, and eliminating dead space are all helpful. Conducting lumbar drainage and choosing effective prophylactic antibiotics in the early postoperative stage for the high-risk patients are methods of postoperative management.