Correlation between genetic alterations and clinicopathological features of papillary thyroid carcinomas.

OBJECTIVE: To investigate the correlations between multigene alterations and clinicopathological features in papillary thyroid carcinoma (PTC) samples. METHODS: In this retrospective study, 111 cytological specimens of thyroid nodules, including 74 PTC samples and 37 benign samples, were analyzed using a 22-gene mutation assay employing next-generation sequencing. Clinicopathological information was retrospectively collected and analyzed. RESULTS: Gene alterations were associated with a higher rate of lymph node metastasis (LNM) and thyroid capsular invasion, a lower rate of coexisting Hashimoto's thyroiditis, the classical PTC subtype, and younger age (<45 years). Among the 22 genes tested, the BRAF mutation rates showed a significant difference between the PTC and benign groups. In the subgroup analysis, younger age (odds ratio = 12.512, 95% confidence interval: 3.126-50.087) was an independent risk factor for LNM. In further analyses, BRAF mutation was significantly associated with LNM in the older subgroup (age ≥ 45 years), suggesting that the BRAF mutation test has greater value for determining PTC prognosis in the older age group. CONCLUSIONS: Our findings will provide a more comprehensive understanding of the relationship between gene mutations and PTC and may contribute to improved PTC management.

Predictive model for epileptogenic tubers from all tubers in patients with tuberous sclerosis complex based on 18F-FDG PET: an 8-year single-centre study.

BACKGROUND: More than half of patients with tuberous sclerosis complex (TSC) suffer from drug-resistant epilepsy (DRE), and resection surgery is the most effective way to control intractable epilepsy. Precise preoperative localization of epileptogenic tubers among all cortical tubers determines the surgical outcomes and patient prognosis. Models for preoperatively predicting epileptogenic tubers using 18F-FDG PET images are still lacking, however. We developed noninvasive predictive models for clinicians to predict the epileptogenic tubers and the outcome (seizure freedom or no seizure freedom) of cortical tubers based on 18F-FDG PET images. METHODS: Forty-three consecutive TSC patients with DRE were enrolled, and 235 cortical tubers were selected as the training set. Quantitative indices of cortical tubers on 18F-FDG PET were extracted, and logistic regression analysis was performed to select those with the most important predictive capacity. Machine learning models, including logistic regression (LR), linear discriminant analysis (LDA), and artificial neural network (ANN) models, were established based on the selected predictive indices to identify epileptogenic tubers from multiple cortical tubers. A discriminating nomogram was constructed and found to be clinically practical according to decision curve analysis (DCA) and clinical impact curve (CIC). Furthermore, testing sets were created based on new PET images of 32 tubers from 7 patients, and follow-up outcome data from the cortical tubers were collected 1, 3, and 5 years after the operation to verify the reliability of the predictive model. The predictive performance was determined by using receiver operating characteristic (ROC) analysis. RESULTS: PET quantitative indices including SUVmean, SUVmax, volume, total lesion glycolysis (TLG), third quartile, upper adjacent and standard added metabolism activity (SAM) were associated with the epileptogenic tubers. The SUVmean, SUVmax, volume and TLG values were different between epileptogenic and non-epileptogenic tubers and were associated with the clinical characteristics of epileptogenic tubers. The LR model achieved the better performance in predicting epileptogenic tubers (AUC = 0.7706; 95% CI 0.70-0.83) than the LDA (AUC = 0.7506; 95% CI 0.68-0.82) and ANN models (AUC = 0.7425; 95% CI 0.67-0.82) and also demonstrated good calibration (Hosmer‒Lemeshow goodness-of-fit p value = 0.7). In addition, DCA and CIC confirmed the clinical utility of the nomogram constructed to predict epileptogenic tubers based on quantitative indices. Intriguingly, the LR model exhibited good performance in predicting epileptogenic tubers in the testing set (AUC = 0.8502; 95% CI 0.71-0.99) and the long-term outcomes of cortical tubers (1-year outcomes: AUC = 0.7805, 95% CI 0.71-0.85; 3-year outcomes: AUC = 0.8066, 95% CI 0.74-0.87; 5-year outcomes: AUC = 0.8172, 95% CI 0.75-0.87). CONCLUSIONS: The 18F-FDG PET image-based LR model can be used to noninvasively identify epileptogenic tubers and predict the long-term outcomes of cortical tubers in TSC patients.

Hippocampal ripples correlate with memory performance in humans.

Memory performance evaluation has generally been based on behavioral tests in the past decades. However, its neural correlates remain largely unknown, particularly in humans. Here we addressed this question using intracranial electroencephalography in patients with refractory epilepsy, performing an episodic memory test. We used the presurgical Wechsler Memory Scale (WMS) test to assess the memory performance of each patient. We found that hippocampal ripples significantly exhibited a transient increase during visual stimulation or before verbal recall. This increase in hippocampal ripples positively correlated with memory performance. By contrast, memory performance is negatively correlated with hippocampal interictal epileptic discharges (IEDs) or epileptic ripples in the memory task. However, these correlations were not present during quiet wakefulness. Thus, our findings uncover the neural correlates of memory performance in addition to traditional behavioral tests.

Inversion of soil salinity in China's Yellow River Delta using unmanned aerial vehicle multispectral technique.

The rapid and accurate acquisition of soil property information, especially the soil salinity (SS), is required for saline soil management in the Yellow River Delta (YRD). In this study, Lijin County and Kenli District were selected as study area. Unmanned aerial vehicle (UAV) multispectral data and soil sample data were acquired from March 25 to 28, 2019. Pearson correlation and gray correlation analyses were first used to screen sensitive spectral bands/indices, which were used for model parameters construction. Three machine learning and one statistical analysis methods were used to construct the SS inversion models. The results found that the gray correlation coefficient value were greater than the Pearson coefficient value for all bands and indices. Based on the gray correlation coefficient, nine sensitive bands and indices were selected to construct 18 model parameters. By comparing the 4 models, it was concluded that the BPNN model had the highest inversion accuracy, and its calibration coefficient of determination (R2) and root mean square error (RMSE) were 0.769 and 1.342, respectively. The validation R2 and RMSE were 0.774 and 1.975, respectively, and the relative prediction deviation (RPD) was 2.963. The SS estimation results based on BPNN model were consistent with those of the field investigation. Rapid and accurate inversion of SS based on UAV multispectral technique was achieved in this study, which provides technical support for regional management.

Ubiquitin-Like Protein UBD Promotes Cell Proliferation in Colorectal Cancer by Facilitating p53 Degradation.

PURPOSE: Ubiquitin D (UBD) is a member of the ubiquitin-like modifier (UBL) family and is highly expressed in a variety of cancers including colorectal cancer (CRC). However, the mechanisms of its regulatory roles in CRC are largely elusive. In this study, we revealed the effect of UBD on the proliferation of CRC. METHODS: The expression of UBD in clinical tissue samples of CRC and seven CRC cell lines was detected using qRT-PCR, immunohistochemistry (IHC) and Western blotting. CCK-8, colony formation, EdU and flow cytometry assays were used to detect the functional changes of CRC cells transfected with UBD stable expression plasmids in vitro. A xenograft model was constructed to assess the effect of UBD on the growth of CRC cells in vivo. The connection between UBD and p53 was analyzed using Western blotting, immunoprecipitation, proteasome inhibition assay and Cycloheximide (CHX) chase assay. RESULTS: UBD was overexpressed in CRC tumor tissues compared with nontumor tissues, and its overexpression was positively associated with the tumor size and TNM stage of CRC patients. Functionally, UBD significantly accelerated CRC cell viability and proliferation in vitro and promoted tumorigenesis in vivo. Mechanistically, UBD interacted with p53 in CRC cells, downregulated the expression of p53 by regulating its degradation, shortened the p53 half-life, thereby further affecting the decrease in p21 and the increase in Cyclin D1, Cyclin E, CDK2, CDK4 and CDK6. Moreover, in vivo experiments showed that UBD-induced tumor growth in nude mice was dependent on a decrease in p53. CONCLUSIONS: Our study proved that UBD mediates the degradation of p53, thereby facilitating the growth of CRC cells and ultimately promoting the progression of CRC. Therefore, UBD may be a potential therapeutic target and a promising prognostic biomarker for CRC.

The role of voltage-gated chloride channels in the epileptogenesis of temporal lobe epilepsy.

BACKGROUND: Temporal lobe epilepsy (TLE) is the most common intractable epilepsy in adults, and elucidation of the underlying pathological mechanisms is needed. Voltage-gated chloride channels (ClC) play diverse physiological roles in neurons. However, less is known regarding their functions in the epilepogenesis of TLE. METHODS: ClC-mediated current and the spontaneous inhibitory synaptic currents (sIPSC) in hippocampal neurons of epileptic lesions were investigated by electrophysiological recording. The EEG data were analyzed by Z-scored wavelet and Fourier transformations. The expression of ClC-3, a member of ClC gene family, was detected by immunostaining and western blot. FINDINGS: ClC-mediated current was increased in the hippocampal neurons of chronic TLE mice. Application of chloride channel blockers, NPPB (5-Nitro-2- [3-phenylpropylamino] benzoic acid) and DIDS (4,4'-Diisothiocyanato-2,2'-stilbenedisulfonic acid disodium salt) reduced ClC-mediated current and increased inhibitory synaptic transmission in TLE mice. NPPB and DIDS reduced the seizure frequency and the average absolute power of ictal high-frequency oscillations (HFOs, 80-500 Hz) in TLE mice. In addition, both drugs induced outwardly rectified currents, which might be tonic inhibitory currents in the hippocampal neurons of TLE patients. Furthermore, the expression of ClC-3 was increased in the hippocampus of TLE mice and patients and positively correlated with both the absolute power and number of ictal HFOs per seizure in the sclerotic hippocampus. INTERPRETATION: These data suggest that ClC participate in the epilepogenetic process of TLE and the inhibition of ClC may have anti-epileptic effect. FUNDING: This work was supported by National Natural Science Foundation of China (No. 81601143, No. 81771217).

Downregulated GPR30 expression in the epileptogenic foci of female patients with focal cortical dysplasia type IIb and tuberous sclerosis complex is correlated with 18 F-FDG PET-CT values.

Focal cortical dysplasia type IIb (FCDIIb) and tuberous sclerosis complex (TSC) are typical causes of developmental delay and refractory epilepsy. G-protein-coupled receptor 30 (GPR30) is a specific estrogen receptor that is critical in neurodevelopment, neuroinflammation, and neuronal excitability, suggesting that it plays a potential role in the epilepsy of patients with FCDIIb and TSC. Therefore, we investigated the role of GPR30 in patients with FCDIIb and TSC. We found that the expression of GPR30 and its downstream protein kinase A (PKA) pathway were decreased and negatively correlated with seizure frequency in female patients with FCDIIb and TSC, but not in male patients. GPR30 was widely distributed in neurons, astrocytes, and microglia, and its downregulation was especially notable in microglia. The GPR30 agonist G-1 increased the expression of PKA and p-PKA in cultured cortical neurons, and the GPR30 antagonist G-15 exhibited the opposite effects of G-1. The NF-κB signaling pathway was also activated in the specimens of female patients with FCDIIb and TSC, and was regulated by G-1 and G-15 in cultured cortical neurons. We also found that GPR30 regulated cortical neuronal excitability by altering the frequency of spontaneous excitatory postsynaptic currents and the expression of NR2A/B. Further, the relationship between GPR30 and glycometabolism was evaluated by analyzing the correlations between GPR30 and 18 F-FDG PET-CT values (standardized uptake values, SUVs). Positive correlations between GPR30 and SUVs were found in female patients, but not in male patients. Intriguingly, GPR30 expression and SUVs were significantly decreased in the epileptogenic tubers of female TSC patients, and ROC curves indicated that SUVs could predict the localization of epileptogenic tubers. Taken together, our results suggest a potential protective effect of GPR30 in the epileptogenesis of female patients with FCDIIb and TSC.

Bootstrap confidence intervals for the optimal cutoff point to bisect estimated probabilities from logistic regression.

To classify estimated probabilities from a logistic regression model into two groups (e.g., yes or no, disease or no disease), the optimal cutoff point or threshold is crucial. While various methods have been proposed for estimating such a threshold, statistical inference is not generally available. To tackle this issue, we put forward several bootstrap based methods, including the conventional nonparametric bootstrap standard errors and the quantile interval. Special emphasis is placed on a more precise bagging estimator of the optimal cutoff point, for which a confidence interval can be obtained via the recently proposed infinitesimal jackknife method. We investigate the empirical performance of the proposed methods by simulation and illustrate their use via the analysis of a fertility data set concerning seminal quality prediction.

Activation of leukocyte immunoglobulin-like receptor B2 signaling pathway in cortical lesions of pediatric patients with focal cortical dysplasia type IIb and tuberous sclerosis complex.

BACKGROUNDS: Focal cortical dysplasia type IIb (FCD IIb) and tuberous sclerosis complex (TSC) are very frequently associated with epilepsy in pediatric patients. Human leukocyte immunoglobulin-like receptor B2 (LILRB2) participates in the process of neurite growth, synaptic plasticity, and inflammatory reaction, suggesting a potential role of LILRB2 in epilepsy. However, little is known about the distribution and expression of LILRB2 in cortical lesions of FCD IIb and cortical tubers of TSC. METHODS: In this study, we have described the distribution and expression of LILRB2 signaling pathway in cortical lesions of pediatric patients with FCD IIb (n = 15) and TSC (n = 12) relative to age-matched autopsy control samples (CTX, n = 10), respectively. The protein levels of LILRB2 pathway molecules were assessed by western blotting and immunohistochemistry. The expression pattern was investigated by immunohistochemistry and double labeling experiment. Spearman correlation analysis to explore the correlation between LILRB2 protein level and seizure frequency. RESULTS: The protein levels of LILRB2 and its downstream molecules POSH, SHROOM3, ROCK1, ROCK2 were increased in cortices of patients compared to CTX. Protein levels of LILRB2 negatively correlated with the frequency of seizures in FCD IIb and TSC patients, respectively. Moreover, all LILRB2 pathway molecules were strongly expressed in dysmorphic neurons, balloon cells, and giant cells, LILRB2 co-localized with neuron marker and astrocyte marker. CONCLUSION: Taken together, the special expression patterns of LILRB2 signaling pathway in cortical lesions of FCD IIb and TSC implies that it may be involved in the process of epilepsy.

A Retrospective Analysis of Stereoelectroencephalography and Subdural Electroencephalography for Preoperative Evaluation of Intractable Epilepsy.

BACKGROUND: Different methods for intracranial electrode recording have various advantages and disadvantages, and controversy exists regarding the complications of stereoelectroencephalography (SEEG) and subdural EEG. OBJECTIVE: The purpose of this study was to determine the efficacy and safety of SEEG by comparing it with subdural EEG. METHODS: Data from 100 patients who underwent SEEG (n = 48) and subdural EEG (n = 52) to evaluate the epileptogenic zone were collected from June 2011 to June 2015. The evaluation results, surgical outcomes, and complications were compared. RESULTS: No significant differences were noted between the SEEG and subdural EEG groups in identifying the epileptogenic zone or undergoing epileptic surgery. Of the 88 patients who underwent epilepsy surgery after assessment, 59.5% in the SEEG group and 52.2% in the subdural EEG group became seizure free. No significant differences in postoperative seizure control or intelligence improvement were noted. The overall complication rate in SEEG patients (8/48; 16.7%) was lower than that in subdural EEG patients (13/52; 25%), particularly for hemorrhage and infection (4.2 vs. 17.3%, p < 0.05). CONCLUSIONS: This retrospective review indicates that SEEG has low associated complications, particularly regarding hemorrhage and infection. SEEG is a safe and effective method for intracranial monitoring.

Comparison of Neuronavigation and Frame-Based Stereotactic Systems in Implanting Epileptic Depth Electrodes.

AIM: To investigate the application of neuronavigation in the implantation of depth electrodes in patients with epilepsy. MATERIAL AND METHODS: Thirty-six patients with epilepsy who were implanted with depth electrodes using neuronavigation were assessed for accuracy of implantation and associated complications. RESULTS: In the imaging navigation group, patients were implanted with 2-14 depth electrodes. The average number of implantations was 4.8 electrodes/case. The average implantation error was 2.03 ± 0.98 mm, exhibiting no significant difference compared to the frame-based stereotactic group. In the imaging group, an average of 19.4 min was required to implant each electrode, which was significantly shorter than the time required in the frame group (34.5 min). The temporal lobe was elucidated as the factor that affects electrode implantation accuracy. One patient in the imaging group exhibited a small amount of bleeding, and one suffered from cerebrospinal fluid leakage; however, the overall complication rate in the imaging group was lower than that in the frame group. CONCLUSION: Imaging navigation provides better means of depth electrode implantation; its implantation accuracy is similar to that of the frame-based stereotactic method and it is less time consuming and causes less complications, and is especially suitable for stereoelectroencephalography, which requires multiple depth electrodes.

[Ligustrazine fought against cisplatin induced ototoxicity in guinea pigs].

OBJECTIVE: To study the protective effect of Ligustrazine Injection (LI) against cisplatin-induced ototoxicity and to explore its mechanism. METHODS: Thirty healthy adult guinea pigs were randomly divided into three groups, 10 in each group, i.e., the normal control group, the cisplatin group, and the LI group. Guinea pigs in the normal control group were intraperitoneally injected with normal saline at 3 mL/kg for 7 consecutive days. Those in the cisplatin group were intraperitoneally injected with cisplatin at 3 mg/kg for 7 consecutive days. Those in the LI group were intraperitoneally injected with LI at 140 mg/kg for 7 days, but cisplatin (3 mg/kg) was intraperitoneally injected from the opposite side starting from the 4th day. Brainstem auditory evoked potential (BAEP) was performed in all animals before and after injection. All animals were sacrificed after the final testing under anesthesia and their cochleas collected. Half the cochleas of each group were collected for silver nitrate staining of cochlear basilar membrane stretched. The other half the cochleas of each group made into paraffin sections to observe the apoptosis of cochlea cells by TUNEL method and the expression levels of c-Jun detected by immunohistochemistry. RESULTS: There was no statistical difference in the difference of BAEP threshold among the 3 groups before injection (P > 0.05), but the BAEP threshold increased in the cisplatin group and the LI group (P < 0.05). Besides, it was higher in the cisplatin group (P < 0.05). In the cisplatin group, most hair cells were missing, spiral ganglion cells obviously decreased, more TUNEL positive cells occurred, and the expression of c-Jun was stronger. But the aforesaid impairment in the LI group was obviously lessened (P < 0.05). CONCLUSIONS: LI showed certain antagonist effect on cisplatin-induced ototoxicity. Its mechanism might be associated with scavenging oxygen radicals of the cochlea tissue, improving the microcirculation, and fighting against apoptosis.

[Preventive effects of cerebro cellular growth peptide on gentamycin-induced inner ear damage in guinea pigs].

AIM: To investigate the preventive effects of the cerebro cellular growth peptide (CCGP) on gentamycin-induced inner ear damage in guinea pigs, and to clarify its mechanism. METHODS: The hypoacusis severity and enzymatic activity in the cochlear hair cells were examined by brainstem auditory evoked potential (BAEP) and histochemistry, respectively. The damaged hair cells was counted in three groups. RESULTS: CCGP reduced the elevated BAEP reaction thresholds. It protected activities of mitochondrial succinate dehydrogenase and lysosome acid phosphatase in the cochlear hair cells. The number of damaged hair cells in the CCGP group was less than that in the gentamycin (GM) group. CONCLUSION: CCGP can reduce GM ototoxicity. The mechanism may be associated with the protective activity of mitochondrial enzyme, the maintenance of lysosome intactness, energy metabolism of the cochlear hair cells, and reduction of autolysis of hair cells induced by hydrolase over flowing from lysosome.