Precise Differentiation of Wobble-Type Allele via Ratiometric Design of a Ligase Chain Reaction-Based Electrochemical Biosensor for CYP2C19*2 Genotyping of Clinical Samples.

Due to the comparable stability between the perfect-base pair and the wobble-base pair, a precise differentiation of the wobble-type allele has remained a challenge, often leading to false results. Herein, we proposed a ligase chain reaction (LCR)-based ratiometric electrochemical DNA sensor, namely, R-eLCR, for a precise typing of the wobble-type allele, in which the traditionally recognized "negative" signal of wobble-base pair-mediated amplification was fully utilized as a "positive" one and a ratiometric readout mode was employed to ameliorated the underlying potential external influence and improved its detection accuracy in the typing of the wobble-type allele. The results showed that the ratio between current of methylene blue (IMB) and current of ferrocene (IFc) was partitioned in three regions and three types of wobble-type allele were thus precisely differentiated (AA homozygote: IMB/IFc > 2; GG homozygote: IMB/IFc < 1; GA heterozygote: 1 < IMB/IFc < 2); the proposed R-eLCR successfully discriminated the three types of CYP2C19*2 allele in nine cases of human whole blood samples, which was consistent with those of the sequencing method. These results evidence that the proposed R-eLCR can serve as an accurate and robust alternative for the identification of wobble-type allele, which lays a solid foundation and holds great potential for precision medicine.

Nucleic Acid Amplification by Template-Dominated Click Chemistry for Ultrasensitive DNA/RNA Detection on an Electrochemical Readout Platform.

As an enzyme-free exponential nucleic acid amplification method, the click chemistry-mediated ligation chain reaction (ccLCR) has shown great prospects in the molecular diagnosis. However, the current optics-based ccLCR is challenged by remarkable nonspecific amplification, severely hindering its future application. This study demonstrated that the severe nonspecific amplification was generated probably due to high random collision in the high DNA probe concentration (µM level). To solve this hurdle, a nucleic acid template-dominated ccLCR was constructed using nM-level DNA probes and read on an electrochemical platform (cc-eLCR). Under the optimal conditions, the proposed cc-eLCR detected a low-level nucleic acid target (1 fM) with a single-base resolution. Furthermore, this assay was applied to detect the target of interest in cell extracts with a satisfactory result. The proposed cc-eLCR offers huge possibility for click chemistry-mediated enzyme-free exponential nucleic acid amplification in the application of medical diagnosis and biomedical research.

Multimodal Ochratoxin A-Aptasensor Using 3'-FAM-Enhanced Exonuclease I Tool and Magnetic Microbead Carrier.

Thanks to its preparatory ease, close affinity, and low cost, the aptasensor can serve as a promising substitute for antibody-dependent biosensors. However, the available aptasensors are mostly subject to a single-mode readout and the interference of unbound aptamers in solution and non-target-induced transition events. Herein, we proposed a multimodal aptasensor for multimode detection of ochratoxin A (OTA) with cross-validation using the 3'-6-carboxyfluorescein (FAM)-enhanced exonuclease I (Exo I) tool and magnetic microbead carrier. Specifically, the 3'-FAM-labeled aptamer/biotinylated-cDNA hybrids were immobilized onto streptavidin-magnetic microbeads via streptavidin-biotin interaction. With the presence of OTA, an antiparallel G-quadruplex conformation was formed, protecting the 3'-FAM labels from Exo I digestion, and then anti-FAM-horseradish peroxidase (HRP) was bound via specific antigen-antibody affinity; for the aptamers without the protection of OTA, the distal ssDNA was hydrolyzed from 3' → 5', releasing 3'-FAM labels to the solution. Therefore, the OTA was detected by analyzing the "signal-off" fluorescence of the supernatant and two "signal-on" signals in electrochemistry and colorimetry through the detection of the coating magnetic microbeads in HRP's substrate. The results showed that the 3'-FAM labels increased the activity of Exo I, producing a low background due to a more thorough digestion of unbound aptamers. The proposed multimodal aptasensor successfully detected the OTA in actual samples. This work first provides a novel strategy for the development of aptasensors with Exo I and 3'-FAM labels, broadening the application of aptamer in the multimode detection of small molecules.

Ultrasensitive Detection of RNA with Single-Base Resolution by Coupling Electrochemical Sensing Strategy with Chimeric DNA Probe-Aided Ligase Chain Reaction.

Accurate and sensitive detection of single-base mutations in RNAs is of great value in basic studies of life science and medical diagnostics. However, the current available RNA detection methods are challenged by heterogeneous clinical samples in which trace RNA mutants usually existed in a large pool of normal wild sequences. Thus, there is still great need for developing the highly sensitive and highly specific methods in detecting single-base mutations of RNAs in heterogeneous clinical samples. In the present study, a new chimeric DNA probe-aided ligase chain reaction-based electrochemical method (cmDNA-eLCR) was developed for RNA mutation detection through the BSA-based carrier platform and the horseradish peroxidase-hydrogen peroxide-tetramethylbenzidine (HRP-H2O2-TMB) system. The denaturing polyacrylamide gel electrophoresis and a fluorophore-labeled probe was ingeniously designed to demonstrate the advantage of cmDNA in ligation to normal DNA templated by RNA with the catalysis of T4 RNA ligase 2 as well as its higher selectivity than DNA ligase system. Finally, the proposed cmDNA-eLCR, compared with the traditional eLCR, showed excellent performance in discriminating single base-mismatched sequences, where the signal response for mismatched targets at a high concentration could overlap completely with that for the blank control. Besides, this cmDNA-eLCR assay had a wide linear range crossing six orders of magnitude from 1.0 × 10-15 to1.0 × 10-10 M with a limit of detection as low as 0.6 fM. Furthermore, this assay was applied to detect RNA in real sample with a satisfactory result, thereby demonstrating its great potential in diagnosis of RNA-related diseases.

Relationship Between Pituitary Adenoma Consistency and Extent of Resection Based on Tumor/Cerebellar Peduncle T2-Weighted Imaging Intensity (TCTI) Ratio of the Point on Preoperative Magnetic Resonance Imaging (MRI) Corresponding to the Residual Point on Postoperative MRI.

BACKGROUND Controversies exist in imaging modalities for predicting adenoma consistency. In this study, we proposed a method of predicting consistency by magnetic resonance T2-sequence imaging based on adenoma to cerebellar peduncle signal (TCTI) ratio. MATERIAL AND METHODS Between January 2013 and May 2017, 191 consecutive patients with pituitary adenoma diagnosed at our institution were retrospectively studied. The consistency grade for each lesion was assigned. And the TCTI ratio based on preoperative and postoperative T2-weighted imaging was calculated. RESULTS The median TCTI ratio was 1.55, 1.28, and 1.25 for soft, fibrous, and hard adenomas, respectively. The differences were significant for all groups (p<0.001). A cutoff value of 1.38 for soft adenomas was found to be 80.2% sensitive and 88.7% specific. The median ratio of the outermost layer of residual tumor was 1.25 (SD±0.408, 95% CI 1.27-1.42). It was less than that ratio of the upper, lower quarter, and middle region of adenoma, respectively, and the inter-group differences were all statistically significant with p≤0.001. The extent of resection for the soft group was significantly greater than that of the hard group (85.3% vs. 70.6%, p=0.011). Analysis of Variance (ANOVA) revealed that the consistency grade was the influencing factor of degree of resection. p=0.003. CONCLUSIONS The TCTI ratio showed a good correlation with pituitary adenoma consistency. We also determined the optimal ratio of the residual adenoma.

Ultrasensitive Electrochemical Biosensor Developed by Probe Lengthening for Detection of Genomic DNA in Human Serum.

As an alternative to most of the reported nucleic acid amplification-based electrochemical DNA biosensors used for detection of trace levels of genomic DNA, we herein present a novel detection concept. The proposed system involves the conversion of two short double-stranded DNAs (dsDNAs), labeled with a thiol-tag or biotin-tag, into a single integrated dsDNA containing thiol and biotin at both terminals in the presence of target DNA through ligase chain reaction (LCR) and followed by the immobilization of these integrated dsDNAs on a bovine serum albumin (BSA)-modified gold electrode surface. Owing to rapid depletion of the two short dsDNAs via LCR, the integrated dsDNAs were generated in an exponential manner so that this sensoring approach offered a limit of detection of 25 yoctomoles (15 copies in 50 µL sample volumes), a high discrimination of single-base mismatch and a wide linear concentration range (across 6 orders of magnitude) for target DNA. Significantly, the proposed sensor, which has simplicity in operation and ease of miniaturization, detected the target of interest in total nucleic acid extracts derived from clinical serum samples with excellent results, thereby demonstrating its considerable diagnostic potential in fields ranging from virus detection to the diagnosis of genetic diseases.

UV/TiO2 photocatalytic oxidation of recalcitrant organic matter: effect of salinity and pH.

Photocatalytic oxidation processes have interest for water treatment since these processes can remove recalcitrant organic compounds and operate at mild conditions of temperature and pressure. However, performance under saline conditions present in many water resources is not well known. This study aims to explore the basic effects of photocatalysis on the removal of organic matter in the presence of salt. A laboratory-scale photocatalytic reactor system, employing ultraviolet (UV)/titanium dioxide (TiO2) photocatalysis was evaluated for its ability to remove the humic acid (HA) from saline water. The particle size and zeta potential of TiO2 under different conditions including solution pH and sodium chloride (NaCl) concentrations were characterized. The overall degradation of organics over the NaCl concentration range of 500-2,000 mg/L was found to be 80% of the non-saline equivalent after 180 min of the treatment. The results demonstrated that the adsorption of HA onto the TiO2 particles was dependent on both the pH and salinity due to electrostatic interaction and highly unstable agglomerated dispersion. This result supports UV/TiO2 as a viable means to remove organic compounds, but the presence of salt in waters to be treated will influence the performance of the photocatalytic oxidation process.

[Amyloid ß protein suppresses hippocampal theta rhythm and induces behavioral disinhibition and spatial memory deficit in rats].

Hippocampal neuronal network oscillation is closely related to the memory, anxiety and behavioral inhibition of mammalian. The cognitive decline and behavioral disinhibition in the patients with Alzheimer's disease (AD) may be relevant to amyloid ß protein (Aß)-induced impairment in hippocampal neuronal cooperative activity. However, it is not well known whether intrahippocampal injection of Aß could induce behavioral disinhibition and neuronal network disorder, as well as cognition decline in animals. In the present study, we observed the effects of intracerebral injection of Aß(1-42) on the spatial memory and behavioral inhibition of rats by using Morris water maze and elevated plus-maze tests. Further, we analyzed hippocampal theta rhythm by recording hippocampal local field potential. The results showed that: (1) bilateral hippocampal injection of Aß(1-42) reduced the anxious behavior of rats, with a significant behavioral disinhibition in the elevated plus-maze test, representing as an increase in the mean entering times and mean residence time in the open arm; (2) Aß(1-42) injection resulted in a significant impairment of spatial memory in rats, with significantly increased mean escape latencies in hidden platform test; (3) Aß(1-42) disrupted the induction of theta rhythm induced by tail pinch, with a significant reduction in the peak power, not the peak power frequency of the theta rhythm. These experimental results indicate that intrahippocampal injection of Aß(1-42) can induce behavioral disinhibition and theta rhythm suppression, as well as spatial memory impairment in rats, which suggests that the cognition deficits and behavior impairments in AD are probably associated with the Aß-induced disruption of hippocampal theta rhythm and consequent down-regulation of synaptic plasticity.

Increased expression of microRNA-221 inhibits PAK1 in endothelial progenitor cells and impairs its function via c-Raf/MEK/ERK pathway.

Coronary artery disease (CAD) is associated with high mortality and occurs via endothelial injury. Endothelial progenitor cells (EPCs) restore the integrity of the endothelium and protect it from atherosclerosis. In this study, we compared the expression of microRNAs (miRNAs) in EPCs in atherosclerosis patients and normal controls. We found that miR-221 expression was significantly up-regulated in patients compared with controls. We predicted and identified p21/Cdc42/Rac1-activated kinase 1 (PAK1) as a novel target of miR-221 in EPCs. We also demonstrated that miR-221 targeted a putative binding site in the 3'UTR of PAK1, and absence of this site was inversely associated with miR-221 expression in EPCs. We confirmed this relationship using a luciferase reporter assay. Furthermore, overexpression of miR-221 in EPCs significantly decreased EPC proliferation, in accordance with the inhibitory effects induced by decreased PAK1. Overall, these findings demonstrate that miR-221 affects the MEK/ERK pathway by targeting PAK1 to inhibit the proliferation of EPCs.

Time-dependent movement and distribution of chlorothalonil and chlorpyrifos in tomatoes.

Determining the distribution of pesticides in fruits is essential to eliminate pesticide residues during food processing. In this study, the dynamic distribution of two pesticides, chlorothalonil (CHT) and chlorpyrifos (CHP), were determined in different tomato parts following immersion in pesticide solutions. The concentrations of CHT and CHP in tomato followed an order of cuticle>plasma>pulp. However, the plasma initially accumulated the highest pesticide concentration. And the ratio of CHT concentration to that of CHP in plasma was about 2.1:1, similar to the ratio in solution, which suggested carpopodium as the entry site for the pesticides tested. The ratio in the cuticle was 0.02:1-0.06:1. This was consistent with the ratio of Kow for the two pesticides, manifesting the direct pesticide transfer from solution to cuticle. Following pesticide injection into tomato, the degradation of CHT over 96h was described by a first-order decay equation, Ctomato(t)CHT=C0×e(-0.0239t). The CHP concentration in tomato remained nearly constant with little degradation detected. Deducting the amount of degradation and migration, volatilization appeared to contribute the most amount of migration of CHT and CHP in tomato.

Adaptive radiation in Orinus, an endemic alpine grass of the Qinghai-Tibet Plateau, based on comparative transcriptomic analysis.

The species of Orinus (Poaceae) are important alpine plants with a variety of phenotypic traits and potential usages in molecular breeding toward drought-tolerant forage crops. However, the genetic basis of evolutionary adaption and diversification in the genus is still unclear. In the present study, we obtained transcriptomes for the two most divergent species, O. thoroldii and O. kokonoricus, using the Illumina platform and de novo assembly. In total, we generated 23,029 and 24,086 unigenes with N50 values of 1188 and 1203 for O. thoroldii and O. kokonoricus respectively, and identified 19,005 pairs of putative orthologs between the two species of Orinus. For these orthologs, estimations of non-synonymous/synonymous substitution rate ratios indicated that 568 pairs may be under strongly positive selection (Ka/Ks > 1), and Gene Ontogeny (GO) enrichment analysis revealed that significantly enriched pathways were in DNA repair and resistance to abiotic stress. Meanwhile, the divergence times of species between O. thoroldii and O. kokonoricus occurred 3.2 million years ago (Mya), and the recent evolutionary branch is an allotetraploid species, Cleistogenes songorica. We also detected a Ks peak of ∼0.60 for Orinus. Additionally, we identified 188 pairs of differentially expressed genes (DEGs) between the two species of Orinus, which were significantly enrich in stress resistance and lateral root development. Thus, we considered that the species diversification and evolutionary adaption of this genus was initiated by environmental selection, followed by phenotypic differentiation, finally leading to niche separation in the Qinghai-Tibet Plateau.

[Pollution Characteristics and Health Risk Assessment of Perfluorinated Compounds in PM2.5 in Zhejiang Province].

As typical new pollutants, perfluorinated compounds (PFCs) have been widely concerned by environmental workers in recent years. This study was carried out to investigate the pollution characteristics of perfluorinated compounds in atmospheric particulate matter (PM2.5) in Zhejiang Province. The chemical extraction of PM2.5 was performed using the accelerated solvent extraction (ASE) method with mixed dichloromethane and acetone (2:1). The chemical analysis was implemented by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The results showed that the daily average concentration of the sum of 12 PFCs (Σ12 PFCs) ranged from 131.63 pg·m-3 to 578.53 pg·m-3, which was slightly higher in winter compared to that in autumn. The concentrations of perfluorosulfonic acids (PFSAs) were much lower than those of perfluorocarboxylic acids (PFCAs). PFOS was the primary contaminant among PFASs, with an average concentration of 12.90 pg·m-3. The content of PFCAs exhibited a trend of PFOA>PFHxA>PFHpA, and the detection rate of long-chain PFCs was much lower than that of short-chain PFCs. The hysplit-4 model was used to calculate the QZ air mass transport trajectory. The results indicated that the backward trajectory of this point was significantly different along time, and the source of air mass rarely affected the concentration. The forward trajectory confirmed that PFCs can be transmitted over long distances in the atmosphere in a short time. The correlation coefficient between PFUdA and PFTeDA was evaluated to be 0.68, and that between PFHxS and PFOS was 0.66, suggesting the same sources of these chemicals. The content of PFCs was positively correlated with PM2.5, indicating that people might suffer from higher health risks on haze days. The risk quotient estimation implied no health risk of PFCs in PM2.5 in Zhejiang Province.

[Effects of biochar combined with nitrification/urease inhibitors on soil active nitrogen emissions from subtropical paddy soils]. / ç”Ÿç‰©ç‚­é æ–½ç¡åŒ–/è„²é ¶æŠ‘åˆ¶å‰‚å¯¹äºšçƒ­å¸¦æ°´ç¨»åœŸæ´»æ€§æ°®æ°”ä½“æŽ’æ”¾çš„å½±å“.

We examined the effects of biochar and urease inhibitors/nitrification inhibitors on nitrification process, ammonia and N2O emission in subtropical soil, and determined the best combination of biochar with nitrification and urease inhibitors. This work could provide a theoretical basis for the mitigation of the negative environmental risk caused by reactive nitrogen gas in the application of nitrogen fertilizer. A indoor aerobic culture test was conducted with seven treatments [urea+biochar (NB), urea+nitrification inhibitor (N+NI), urea+urease inhibitor (N+UI), urea+nitrification inhibitor+urease inhibitor (N+NIUI), urea+nitrification inhibitor+biochar (NB+NI), urea+urease inhibitor+biochar (NB+UI), urea+nitrification inhibitor+urease inhibitor+biochar (NB+NIUI)] and urea (N) as the control. The dynamics of soil inorganic nitrogen content, N2O emission and the volatility of ammonia volatilization were observed under combined application of biochar with urease inhibitor (NBPT)/nitrification inhibitor (DMPP). The results showed that:1)Compared to the control (5.11 mg N·kg-1·d-1) during the incubation period, NB treatment significantly increased therate constant of nitrification by 33.9%, and N+NI treatment significantly reduced the nitrification rate constant by 22.9%. NB treatment significantly increased the abundance of ammonia oxidizing bacteria (AOB) by 56.0%. 2) Compared with N treatment, N+NI and NB+NI treatments signi-ficantly enhanced the cumulative emission of NH3 by 49%. The N+UI treatment reduced the cumulative loss of NH3. The inhibition effect of NB+UI treatment was more significant. 3) The emission rate of N2O was highest in the first 10 days after fertilization. The N2O emission under NB treatment was the earliest, and that of N treatment was the highest (5.87 µg·kg-1·h-1). The combined application of DMPP and NBPT performed the best in reducing soil N2O emission. We estimated global warming potential (GWP) of the direct N2O and indirect N2O (NH3) emissions. Compared with N treatments, N+NI and NB+NI treatments increased the GWP by 34.8% and 40.9%, respectively. While the NB and NB+UI treatments significantly reduced the GWP by 45.9% and 60.5%, the combination of biochar and urease inhibitor had the best effect on reduction of GWP of soil active nitrogen emissions.

Establishment of reference (housekeeping) genes via quantitative real-time PCR for investigation of the genomic basis of abiotic stress resistance in Psammochloa villosa (Poaceae).

Psammochloa villosa is a desert plant growing in Northwest China with considerable resistance to abiotic stress, including drought, cold, and salt. To facilitate future studies of stress resistance in Psammochloa villosa, we sought to establish a suite of reference (or housekeeping) genes for utilization within future gene expression studies. Specifically, we selected nine candidate genes based on prior studies and new transcriptomic data for P. villosa, and we evaluated their expression stability in three different tissues of P. villosa under different treatments simulating abiotic stress conditions using four different bioinformatics assessments. Our results showed that TIP41 (TIP41-like family protein) was the most stable reference gene in drought- and salt-stressed leaves and salt-stressed stems, ELF-1α (elongation factor 1-α) was the most stable in cold-stressed leaves and drought- and salt-stressed roots, ACT (actin) was the most stable in drought-stressed stems, TUA (α-tubulin) was the most stable in cold-stressed stems, and 18S rRNA (18S ribosomal RNA) was the most stable in cold-stressed roots. Additionally, we tested the utility of these candidate reference genes to detect the expression pattern of P5CS (Δ1-pyrroline-5-carboxylate synthetase), which is a drought-related gene. This study is the first report on selecting and validating reference genes of P. villosa under various stress conditions and will benefit future investigations of the genomic mechanisms of stress resistance in this ecologically important species.

The Relationship Between Peritumoral Brain Edema and the Expression of Vascular Endothelial Growth Factor in Vestibular Schwannoma.

Objective: This study aimed to explore the potential mechanism of peritumoral brain edema (PTBE) formation in vestibular schwannoma (VS) by detecting intra-tumoral vascular endothelial growth factor (VEGF) expression. Methods: Between January 2018 and May 2021, 15 patients with PTBE and 25 patients without PTBE were included in the analysis. All patients enrolled in our study underwent surgery in our institution. Expression level of VEGF and microvessel density (MVD) between the two groups were analyzed. Edema index (EI) of each patient with PTBE was calculated. Results: In the PTBE group, the average of EI was 1.53 ± 0.22. VEGF expression levels were significantly enhanced in the PTBE group compared with the non-PTBE group (p < 0.001). The expression level of VEGF in the PTBE group and non-PTBE group was 1.14 ± 0.21 and 0.52 ± 0.09, respectively. Similarly, there were significantly different amounts of MVD in the two groups (p < 0.001). The amount of MVD in the PTBE group and non-PTBE group was 11.33 ± 1.59 and 6.28 ± 1.77, respectively. Correlation analysis showed a highly significant positive correlation between VEGF and MVD (r = 0.883, p < 0.001) and VEGF and EI (r = 0.876, p < 0.001). Conclusion: Our study confirmed the close relationship among VEGF expression, tumor angiogenesis, and formation of PTBE in VS patients. It may be possible to develop new effective therapies to attenuate PTBE in VS for alleviation of symptoms and reduction of postoperative complication.

New lymphatic cell formation is associated with damaged brain tissue clearance after penetrating traumatic brain injury.

We characterized the tissue repair response after penetrating traumatic brain injury (pTBI) in this study. Seventy specific pathogen-free Kunming mice were randomly divided into the following groups: normal control, 1, 3, 7, 15, 21, and 30 days after pTBI. Hematoxylin and eosin (H&E) staining, immunohistochemistry, and immunofluorescence were performed to examine and monitor brain tissue morphology, and the distribution and expression of lymphatic-specific markers lymphatic vessel endothelial receptor-1 (LYVE-1), hematopoietic precursor cluster of differentiation 34 (CD34) antigen, and Prospero-related homeobox-1 (PROX1) protein. H&E staining revealed that damaged and necrotic tissues observed on day 1 at and around the injury site disappeared on day 7, and there was gradual shrinkage and disappearance of the lesion on day 30, suggesting a clearance mechanism. We explored the possibility of lymphangiogenesis causing this clearance as part of the post-injury response. Notably, expression of lymphangiogenesis markers LYVE-1, CD34, and PROX1 was detected in damaged mouse brain tissue but not in normal tissue. Moreover, new lymphatic cells and colocalization of LYVE-1/CD34 and LYVE-1/PROX1 were also observed. Our findings of the formation of new lymphatic cells following pTBI provide preliminary insights into a post-injury clearance mechanism in the brain. Although we showed that lymphatic cells are implicated in brain tissue repair, further research is required to clarify the origin of these cells.

A Nomogram for Predicting the Need of Postoperative Tracheostomy in Patients With Aneurysmal Subarachnoid Hemorrhage.

Objective: Early identification for the need of tracheostomy (TT) in aneurysmal subarachnoid hemorrhage (aSAH) patients remains one of the main challenges in clinical practice. Our study aimed to establish and validate a nomogram model for predicting postoperative TT in aSAH patients. Methods: Patients with aSAH receiving active treatment (interventional embolization or clipping) in our institution between June 2012 and December 2018 were retrospectively included. The effects of patients' baseline information, aneurysm features, and surgical factors on the occurrence of postoperative TT were investigated for establishing a nomogram in the training cohort with 393 patients. External validation for the nomogram was performed in the validation cohort with 242 patients. Results: After multivariate analysis, higher age, high neutrophil-to-lymphocyte ratio (NLR), high World Federation of Neurological Surgeons Scale (WFNS), and high Barrow Neurological Institute (BNI) grade were left in the final logistic regression model. The predictive power of the model was excellent in both training cohort and validation cohort [area under the curve (AUC): 0.924, 95% confidence interval [CI]: 0.893-0.948; AUC: 0.881, 95% CI: 0.833-0.919]. A nomogram consisting of these factors had a C-index of 0.924 (95% CI: 0.869-0.979) in the training cohort and was validated in the validation cohort (C-index: 0.881, 95% CI: 0.812-0.950). The calibration curves suggested good match between prediction and observation in both training and validation cohorts. Conclusion: Our study established and validated a nomogram model for predicting postoperative TT in aSAH patients.

Glioblastoma in a female neurofibromatosis 1 patient without IDH1, BRAF V600E, and TERT promoter mutations: A case report.

RATIONALE: Glioblastoma is the most lethal and common malignant brain tumor but rare in patients with neurofibromatosis type 1. The clinical findings and pathological findings with gene signatures in female patients have not been well clarified. PATIENT CONCERNS: A 51-year-old female patient complained of headache and left limb weakness lasting for 20 days. The patient underwent a cesarean section 20 years ago and hysterectomy 1 year ago because of uterine leiomyomas. Multiple café-au-lait spots and neurofibromas were found over patient's chest, neck, back, and arms. The myodynamia of left distant and proximate epipodite were grade 0 and grade 1 respectively. The myodynamia of lower left limb was grade 3. DIAGNOSES: Magnetic resonance imaging revealed a malignant lesion which was most likely a glioblastoma in the right temporo-parietal lobe, approximately 5.6 × 5.9 × 6.9 cm in size with a rounded boundary. INTERVENTIONS: A right temporo-parietal craniotomy was performed to resect the space-occupying lesion for gross total removal. Then, the patient received concurrent chemoradiotherapy. Histological examination confirmed a glioblastoma without v-RAF murine sarcoma viral oncogene homolog B1 gene, isocitrate dehydrogenase 1 gene, and telomerase reverse transcriptase gene promoter mutations. OUTCOMES: After surgery, the headache was relieved and the muscular strength of left limbs did improve. After receiving the standard treatment regimen, the patient was alive at 13 months follow-up. LESSONS: This is the first reported glioblastoma in female neurofibromatosis type 1 patient without v-RAF murine sarcoma viral oncogene homolog B1 gene, isocitrate dehydrogenase 1 gene, and telomerase reverse transcriptase gene promoter mutations. Tumors in adult patients with these signatures were less aggressive with well-circumscribed border and had long-term survivals which strengthened the evidence that these patients may comprise a unique subset in glioblastoma.

Serum Inflammatory Biomarkers Contribute to the Prognosis Prediction in High-Grade Glioma.

BACKGROUND: To evaluate the prognostic value of serum inflammatory biomarkers and develop a risk stratification model for high-grade glioma (HGG) patients based on clinical, laboratory, radiological, and pathological factors. MATERIALS AND METHODS: A retrospective study of 199 patients with HGG was conducted. Patients were divided into a training cohort (n = 120) and a validation cohort (n = 79). The effects of potential associated factors on the overall survival (OS) time were investigated and the benefits of serum inflammatory biomarkers in improving predictive performance was assessed. Univariable and multivariable Cox regression analyses, the least absolute shrinkage and selection operator (LASSO) regression analysis, and support vector machines (SVM) were used to select variables for the final nomogram model. RESULTS: After multivariable Cox, LASSO, and SVM analysis, in addition to 3 other clinico-pathologic factors, platelet-to-lymphocyte ratio (PLR) >144.4 (hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.25-3.38; P = 0.005) were left for constructing the predictive model. The model with PLR exhibited a better predictive performance than that without them in both cohorts. The nomogram based on the model showed an excellent ability of discrimination in the entire cohort (C-index, 0.747; 95%CI, 0.706-0.788). The calibration curves showed good consistency between the predicted and observed survival probability. CONCLUSION: Our study confirmed the prognostic value of serum inflammatory biomarkers including PLR and established a comprehensive scoring system for the OS prediction in HGG patients.

Preoperative serum lactate dehydrogenase level predicts progression and prognosis in patients with glioma.

BACKGROUND: To evaluate the value of serum Lactate Dehydrogenase (LDH) level in predicting recurrence and the overall survival (OS) of glioma patients. MATERIALS AND METHODS: A total number of 216 patients with glioma in our institution were retrospectively recruited to analyze the relationship between preoperative serum LDH level and prognosis. RESULTS: Overall, the median age of patients was 46.0 (31.0-57.0) years old; 53.7% (116 of 216) of the enrolled patients were male. Multivariate analysis revealed that serum LDH level (odds ratio [OR] = 0.97, 95% confidence interval [CI] = 0.96-0.98, P < 0.001) and World Health Organization (WHO) grade (grade II: OR = 19.64, 95%CI = 5.56-69.35, P < 0.001; grade III: OR =1 9.50, 95%CI = 7.08-53.73, P < 0.001; grade IV: OR = 15.23, 95%CI = 4.94-46.97, P < 0.001) were significant and independent of 1-year Progression-free survival (PFS) after adjusting for confounders. The predictive performance of serum LDH level was represented with area under curve (AUC) = 0.741, 95%CI = 0.677-0.798. Multivariate Cox analysis revealed that LDH level (hazard ratio [HR] = 2.56, 95%CI = 1.59-4.15, P < 0.001) and WHO grade (grade II: HR = 4.58, 95%CI = 0.56-37.23, P = 0.155; grade III: HR = 16.35, 95%CI = 2.16-123.80, P = 0.007; grade IV: HR = 42.13, 95%CI = 5.83-304.47, P < 0.001) remained associated with survival at 2-year follow-up. At 3-year follow-up, lymphocyte count (HR = 0.68, 95%CI = 0.51-0.91, P = 0.008), LDH level (HR = 2.21, 95%CI = 1.40-3.49, P = 0.001), and WHO grade (grade II: HR = 1.44, 95%CI = 0.44-4.68, P = 0.543; grade III: HR = 4.99, 95%CI = 1.68-14.87, P = 0.004; grade IV: HR = 16.96, 95%CI = 6.13-46.93, P < 0.001) remained associated with survival in multivariate Cox analysis. CONCLUSION: Our study demonstrated that preoperative serum LDH level could serve as a reliable indicator for predicting prognosis of glioma patients. Further multicenter studies are still required to verify our findings.