SIRT2 promotes base excision repair by transcriptionally activating OGG1 in an ATM/ATR-dependent manner.

Sirtuin 2 (SIRT2) regulates the maintenance of genome integrity by targeting pathways of DNA damage response and homologous recombination repair. However, whether and how SIRT2 promotes base excision repair (BER) remain to be determined. Here, we found that independent of its catalytic activity SIRT2 interacted with the critical glycosylase OGG1 to promote OGG1 recruitment to its own promoter upon oxidative stress, thereby enhancing OGG1 promoter activity and increasing BER efficiency. Further studies revealed that SIRT2 was phosphorylated on S46 and S53 by ATM/ATR upon oxidative stress, and SIRT2 phosphorylation enhanced the SIRT2-OGG1 interaction and mediated the stimulatory effect of SIRT2 on OGG1 promoter activity. We also characterized 37 cancer-derived SIRT2 mutants and found that 5 exhibited the loss of the stimulatory effects on OGG1 transcription. Together, our data reveal that SIRT2 acts as a tumor suppressor by promoting OGG1 transcription and increasing BER efficiency in an ATM/ATR-dependent manner.

The chromosome-scale assembly of the Salvia rosmarinus genome provides insight into carnosic acid biosynthesis.

Rosemary (Salvia rosmarinus) is considered a sacred plant because of its special fragrance and is commonly used in cooking and traditional medicine. Here, we report a high-quality chromosome-level assembly of the S. rosmarinus genome of 1.11 Gb in size; the genome has a scaffold N50 value of 95.5 Mb and contains 40 701 protein-coding genes. In contrast to other diploid Labiataceae, an independent whole-genome duplication event occurred in S. rosmarinus at approximately 15 million years ago. Transcriptomic comparison of two S. rosmarinus cultivars with contrasting carnosic acid (CA) content revealed 842 genes significantly positively associated with CA biosynthesis in S. rosmarinus. Many of these genes have been reported to be involved in CA biosynthesis previously, such as genes involved in the mevalonate/methylerythritol phosphate pathways and CYP71-coding genes. Based on the genomes and these genes, we propose a model of CA biosynthesis in S. rosmarinus. Further, comparative genome analysis of the congeneric species revealed the species-specific evolution of CA biosynthesis genes. The genes encoding diterpene synthase and the cytochrome P450 (CYP450) family of CA synthesis-associated genes form a biosynthetic gene cluster (CPSs-KSLs-CYP76AHs) responsible for the synthesis of leaf and root diterpenoids, which are located on S. rosmarinus chromosomes 1 and 2, respectively. Such clustering is also observed in other sage (Salvia) plants, thus suggesting that genes involved in diterpenoid synthesis are conserved in the Labiataceae family. These findings provide new insights into the synthesis of aromatic terpenoids and their regulation.

Detection and complete genome sequence analysis of human adenovirus in children with acute diarrhea in Yunnan, China, 2015-2021.

The aims of this study were to determine the distribution and prevalence of gastroenteritis caused by human adenovirus (HAdV) in children in Yunnan province, China, in 2015-2021 and to identify preventive measures that can be taken to reduce morbidity and mortality in children.HAdV is a significant agent of diarrhea in children, but limited data are available regarding the epidemiology and genetic diversity of HAdV in children with diarrhea in Yunnan province, China. A total of 1754 fecal samples were subjected to real-time RT-PCR to detect and quantify HAdV. Positive samples were further analyzed using next-generation sequencing (NGS), and epidemiological data were analyzed as well.1754 patients with diarrhea were enrolled, of which 1041 were male and 713 were female (M:F ratio: 1.46). Seventy-two stool samples out of 1754 (4.10%) were positive for HAdV. The detection rates of all age groups varied from 2.50-4.78%. The highest incidence of HAdV was observed in children under 2 years of age, especially in children 12-24 months-old. From 2015-2021, the annual detection rate ranged from 1.62-12.26%. HAdV was detected throughout the year, but with marked seasonality. Children were most likely to be positive for HAdV in June and November. We detected HAdV in 15.53% (16/103) of samples collected in June and in 8.19% (14/171) of those collected in November. The entire viral genome was successfully sequenced for 13 of the 72 HAdV-positive samples, and 76.92% (10/13) of these were classified as genotype F41 and 23.08% (3/13) were classified as genotype C2.ConclusionsIn Yunnan province, children of all ages are susceptible to HAdV infection, but there has been marked variation in the yearly prevalence. The highest rate of HAdV detection was in June, followed by November. Priority should be given to disease prevention over the development of targeted antiviral therapies, and effective vaccines for preventing HAdV diarrhea are needed. It is also important to establish a surveillance system to collect relevant clinical and epidemiological data quickly in order to assess the potential risk of HAdV infection in children and to identify epidemic strains for the development of effective vaccines.

Autologous blood transfusion promotes autophagy and inhibits hepatocellular carcinoma progression through HIF-1α signalling pathway.

To explore the molecular mechanism of autologous blood transfusion promoting autophagy of hepatocellular carcinoma (HCC) cells and inhibiting the HCC progression through HIF-1α signalling pathway. This is a research paper. Rat hepatocellular carcinoma model and HepG2 cell model were built. The rats with HCC were conducted a surgery, and their blood was collected for detection to detect the recurrence and metastasis of the rats. Western blot was used to analysed the expression of HIF-1α, TP53, MDM2, ATG5 and ATG14 protein. The apoptosis rate of HepG2 cells was detected by flow cytometry, and autophagosomes were observed by transmission electron microscopy. HIF-1α expression was measured by immunofluorescence assay. The expressions of HIF-1α, TP53, MDM2, ATG5 and ATG14 protein were highest in model + autoblood group compared with the model group. HIF-1α content of model group was higher, but content of TP53, MDM2, ATG5 and ATG14 in the model group is the second. The highest apoptosis rate was found in HepG2 + autoblood group. The number of autophagosomes in HepG2 + autoblood was obviously larger than that of HepG2 + autoblood + inhibitor. HIF-1α expression of immunofluorescence assay showed that high expression of HIF-1α was clearly observed in HepG2 and HepG2 + autoblood group from confocal observation. However, there was no HIF-1α protein expression in HepG2 + autoblood + inhibitor group. The migration rate in HepG2 group, HepG2 + autoblood group and HepG2 + autoblood + inhibitor group was 85.71 ± 7.38%, 14.36 ± 6.54% and 61.25 ± 5.39%, respectively. Autologous blood transfusion promotes autophagy of HCC cells through HIF-1α signalling pathway, which further inhibits HCC migration and erosion.

Circulating small extracellular vesicles microRNAs plus CA-125 for treatment stratification in advanced ovarian cancer.

BACKGROUND: No residual disease (R0 resection) after debulking surgery is the most critical independent prognostic factor for advanced ovarian cancer (AOC). There is an unmet clinical need for selecting primary or interval debulking surgery in AOC patients using existing prediction models. METHODS: RNA sequencing of circulating small extracellular vesicles (sEVs) was used to discover the differential expression microRNAs (DEMs) profile between any residual disease (R0, n = 17) and no residual disease (non-R0, n = 20) in AOC patients. We further analyzed plasma samples of AOC patients collected before surgery or neoadjuvant chemotherapy via TaqMan qRT-PCR. The combined risk model of residual disease was developed by logistic regression analysis based on the discovery-validation sets. RESULTS: Using a comprehensive plasma small extracellular vesicles (sEVs) microRNAs (miRNAs) profile in AOC, we identified and optimized a risk prediction model consisting of plasma sEVs-derived 4-miRNA and CA-125 with better performance in predicting R0 resection. Based on 360 clinical human samples, this model was constructed using least absolute shrinkage and selection operator (LASSO) and logistic regression analysis, and it has favorable calibration and discrimination ability (AUC:0.903; sensitivity:0.897; specificity:0.910; PPV:0.926; NPV:0.871). The quantitative evaluation of Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) suggested that the additional predictive power of the combined model was significantly improved contrasted with CA-125 or 4-miRNA alone (NRI = 0.471, IDI = 0.538, p < 0.001; NRI = 0.122, IDI = 0.185, p < 0.01). CONCLUSION: Overall, we established a reliable, non-invasive, and objective detection method composed of circulating tumor-derived sEVs 4-miRNA plus CA-125 to preoperatively anticipate the high-risk AOC patients of residual disease to optimize clinical therapy.

The Mechanism of SNHG8/Microrna-421-3p/Sorting Nexin 8 Axis on Dopaminergic Neurons in Substantia Nigra in a Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease affecting the aging population. Particularly, long non-coding RNAs (lncRNAs) have been demonstrated to play vital roles in PD, while the role of lncRNA SNHG8 in PD remains to be further explored. C57BL/6 mice were induced by rotenone to establish a PD model in vivo, and then the dopaminergic (DA) neuronal damage and locomotor dysfunction in rotenone-treated mice were evaluated. Murine DA cell line MN9D was treated with rotenone to establish a cellular PD model in vitro. Then, the viability, apoptosis, mitochondrial dysfunction, endoplasmic reticulum stress, and autophagy in rotenone-treated MN9D cells were assessed. Expression levels of SNHG8, microRNA-421-3p (miR-421-3p), and sorting nexin 8 (SNX8) in the substantia nigra (SN) of PD mice and rotenone-treated MN9D cells were detected. The interaction between SNHG8 and miR-421-3p, and the targeting relationship between SNX8 and miR-421-3p were confirmed. SNHG8 and SNX8 expression levels were decreased while miR-421-3p expression level was increased in the SN of PD mice and rotenone-treated MN9D cells. Upregulated SNHG8 ameliorated dopaminergic neuron damage and locomotor dysfunction in PD mice. Meanwhile, upregulated SNHG8 enhanced viability, diminished apoptosis, and alleviated mitochondrial dysfunction, endoplasmic reticulum stress, and autophagy in rotenone-treated MN9D cells. Mechanistically, SNHG8 bound to miR-421-3p, and miR-421-3p targeted SNX8. Overexpressed SNHG8 downregulates miR-421-3p to alleviate rotenone-induced dopaminergic neuron injury in PD via upregulating SNX8.

Improved performance of non-preloaded and high flip-angle dynamic susceptibility contrast perfusion-weighted imaging sequences in the presurgical differentiation of brain lymphoma and glioblastoma.

OBJECTIVE: This study aimed to compare the accuracy of relative cerebral blood volume (rCBV) and percentage signal recovery (PSR) obtained from high flip-angle dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) sequences with and without contrast agent (CA) preload for presurgical discrimination of brain glioblastoma and lymphoma. METHODS: Consecutive 336 patients (glioblastoma, 236; PCNSL, 100) were included. All the patients underwent DSC-PWI on 3.0-T magnetic resonance units before surgery. The rCBV and PSR with preloaded and non-preloaded CA were measured. The means of the continuous variables were compared using Welch's t-test. The diagnostic accuracies of the individual parameters were compared using the receiver operating characteristic curve analysis. RESULTS: The rCBV was higher with preloaded CA than with non-preloaded CA (glioblastoma, 10.20 vs. 8.90, p = 0.020; PCNSL, 3.88 vs. 3.27, p = 0.020). The PSR was lower with preloaded CA than with non-preloaded CA (glioblastoma, 0.59 vs. 0.90; PCNSL, 0.70 vs. 1.63; all p < 0.001). Regarding the differentiation of glioblastoma and PCNSL, the AUC of rCBV with preloaded CA was indistinguishable from that of non-preloaded CA (0.940 vs. 0.949, p = 0.703), whereas the area under the curve of PSR with preloaded CA was lower than non-preloaded CA (0.529 vs. 0.884, p < 0.001). CONCLUSION: With preloaded CA, diagnostic performance in differentiating glioblastoma and PCNSL did not improve for rCBV and it was decreased for PSR. Therefore, high flip-angle non-preload DSC-PWI sequences offer excellent accuracy and may be of choice sequence for presurgical discrimination of brain lymphoma and glioblastoma. CLINICAL RELEVANCE STATEMENT: High flip-angle DSC-PWI using non-preloaded CA may be an excellent diagnostic method for distinguishing glioblastoma from PCNSL. KEY POINTS: • Differentiating primary central nervous system lymphoma and glioblastoma accurately is critical for their management. • DSC-PWI sequences optimised for the most accurate CBV calculations may not be the optimal sequences for presurgical brain tumour diagnosis as they could be masquerading leakage phenomena that may provide interesting information in terms of differential diagnosis. • High flip-angle non-preloaded DSC-PWI sequences render the best accuracy in the presurgical differentiation of brain lymphoma and glioblastoma.

Chronic stress induces platinum and Niraparib resistance in mouse models of ovarian cancer.

Resistance to platinum and PARP inhibitors represents a major barrier to the long-term survival of ovarian cancer patients. We aim to explore the potential role of chronic stress in drug resistance in ovarian cancer. Leveraging four ovarian cancer with chronic stress (OCCS) mouse models, we explore the therapeutic efficacy of platinum, Niraparib, and Docetaxel treatment in vivo, and compare the efficacy of these anti-tumor drugs in vitro using cell viability assays. Comparing the transcriptional characteristics in RNA-Seq of OCCS mice with public databases, we analyze the molecular mechanism of chronic stress promoting drug resistance in ovarian cancer. We find that chronic stress is positively correlated with platinum-resistant recurrence in ovarian cancer patients. Chronic stress can induce platinum and Niraparib resistance of ovarian cancer, but it does not affect the therapeutic efficacy of Docetaxel treatment in vivo. And the platinum-resistant cell lines are not sensitive to these anti-tumor drugs, which is different from the result in vivo. Then, we identify several gene networks and their constituent genes that are most significantly associated with chronic stress and drug resistance in ovarian cancer, including the glycolysis pathway and DNA damage. This study develops Niraparib and platinum-resistant in vivo models, reflecting the ability of OCCS mice to reproduce different aspects of human ovarian cancer molecular mechanism, and provides a new theoretical basis for overcoming the double drug resistance of ovarian cancer.

Dermoscopy and reflection confocal microscope features of pigmented prurigo.

BACKGROUND: Pigmented prurigo (PP) is a chronic and recurrent inflammatory skin disease. PP is not common clinically, but it is easily misdiagnosed because of its diversified clinical manifestations in different stages. MATERIALS AND METHODS: We retrospectively analyzed the clinical, histopathological, dermoscopy, and reflectance confocal microscopy (RCM) features of 20 patients diagnosed as PP. RESULTS: The female predominance ratio was revealed with male to female of 1:4. Seven female patients were on a diet (without staple food) and one patient had a history of diabetes. Eight cases were suffered in spring, six cases in winter, three cases in summer, and three cases in autumn. Multiple sites were involved in 13 cases. Four patients had urticarial papules and plaques. Nineteen patients had erythematous papules with reticular distribution, of which 14 cases accompanied reticulate hyperpigmentation, four cases with papulovesicle, and two cases accompanied with pustules. One patient only showed reticulate hyperpigmentation. In the early lesions, dermatoscopy showed pink oval lesions, punctate or linear vessels, and pale yellow rings around the skin lesions. RCM is characterized by spongiosis, spongy vesicle, neutrophils scattered in the epidermis, which was consistent with epidermis spongiosis, neutrophils infiltrating into the upper epidermis and necrotic keratinocytes in histopathology. In the fully developed lesions, dermatoscopy showed pink lesions with brown pigment granules in the center and linear vessels in the edge. RCM showed that demarcation of epidermis and dermis is not clear, and inflammatory cells can be seen in the upper dermis and histopathologically lesions assumed a patchy lichenoid pattern, and the inflammatory cells infiltrating the dermis were dominated by lymphocytes. In the late lesions, dermatoscopy showed grainy grayish-brown or yellowish-brown pigmentation surrounding the hair follicle merging with each other. RCM showed that pigment granules were increased on the ring of basal cells, inflammatory cells were sparsely infiltrated in the dermal papilla and superficial layer, and epidermis slightly hyperplastic, with melanophages and a few lymphocytes infiltrating the superficial dermis in histopathology. CONCLUSION: PP is easily misdiagnosed and not always occurs in those on a restrictive diet. A combination of dermatoscopy and RCM is helpful for its diagnosis of PP.

Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression.

The COVID-19 has emerged as an epidemic, causing severe pneumonia with a high infection rate globally. To better understand the pathogenesis caused by SARS-CoV-2, we developed a rhesus macaque model to mimic natural infection via the nasal route, resulting in the SARS-CoV-2 virus shedding in the nose and stool up to 27 days. Importantly, we observed the pathological progression of marked interstitial pneumonia in the infected animals on 5-7 dpi, with virus dissemination widely occurring in the lower respiratory tract and lymph nodes, and viral RNA was consistently detected from 5 to 21 dpi. During the infection period, the kinetics response of T cells was revealed to contribute to COVID-19 progression. Our findings implied that the antiviral response of T cells was suppressed after 3 days post infection, which might be related to increases in the Treg cell population in PBMCs. Moreover, two waves of the enhanced production of cytokines (TGF-α, IL-4, IL-6, GM-CSF, IL-10, IL-15, IL-1ß), chemokines (MCP-1/CCL2, IL-8/CXCL8, and MIP-1ß/CCL4) were detected in lung tissue. Our data collected from this model suggested that T cell response and cytokine/chemokine changes in lung should be considered as evaluation parameters for COVID-19 treatment and vaccine development, besides of observation of virus shedding and pathological analysis.

Guaiane-type sesquiterpenoids with various ring skeletons from Daphne bholua uncovered by molecular networking and structural revisions of previously reported analogues.

The genus Daphne is a treasure-house of secondary metabolites with various biological effects, which inspired Daphne bholua being fully investigated phytochemically and biologically for the first time. Here, seven undescribed guaiane-type sesquiterpenoids (1-7) along with thirteen known analogues (8-20) were targeted and isolated from D. bholua using molecular networking. Their chemical structure and configurations were established via NMR spectroscopy analysis, NMR and ECD calculations, Snatzke's method, along with single-crystal X-ray diffraction technique. Moreover, two pairs of sesquiterpene isomers, either with prominent biological properties or with unprecedented skeleton, were revised by means of computer-assisted structure elucidation, chemical shift calculator using deep learning, etc. The inhibitory potentials of all isolates against acetylcholinesterase were evaluated in vitro and in silico.

Differentiation between supratentorial pilocytic astrocytoma and extraventricular ependymoma using multiparametric MRI.

BACKGROUND: The differentiation of supratentorial pilocytic astrocytomas (STPAs) and supratentorial extraventricular ependymomas (STEEs) is clinically pivotal because of distinct therapeutic management and prognosis, which is sometimes challenging to both neuroradiologists and pathologists. PURPOSE: To explore and compare the conventional and advanced magnetic resonance imaging (MRI) features between STPA and STEE. MATERIAL AND METHODS: A total of 23 patients with STPAs and 23 patients with STEEs were reviewed in this study. All patients performed conventional MRI, susceptibility-weighted imaging (SWI), and diffusion-weighted imaging (DWI), and 34 patients (17 with STPAs and 17 with STEEs) examined dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI) in addition. Clinical data, conventional MRI features, minimum relative apparent diffusion coefficient ratio (rADCmin), and maximum relative cerebral blood volume ratio (rCBVmax) were compared between the two groups and subgroups. The optimal cutoff values of rADCmin and rCBVmax with sensitivity and specificity were calculated. RESULTS: STPA manifested similar to STEE as a solid-cystic mass but more frequently presented with a marked enhancing deep nodule (P = 0.02), no peritumoral edema (P = 0.036), higher rADCmin value (2.0 ± 0.5 vs. 0.9 ± 0.2; P < 0.001), and lower rCBVmax value (2.1 ± 0.4 vs. 14.4 ± 5.5; P < 0.001). The cutoff value of >1.39 for rADCmin and ≤ 2.81 for rCBVmax produced a high sensitivity of 95.65% and 100.0%, respectively, and all produced a specificity of 100.0% in differentiating STPAs from STEEs. CONCLUSION: Multiparametric MRI techniques including conventional MRI, DWI, and DSC-PWI contribute to the differential diagnosis of STPA and STEE.

Undocumented Migrants Reintroducing COVID-19, Yunnan Province, China.

To limit the spread of severe acute respiratory syndrome coronavirus 2, the government of China has been monitoring infected travelers and minimizing cold-chain contamination. However, other factors might contribute to recurring outbreaks. We analyze the role of undocumented migrants as potential transmitters of severe acute respiratory syndrome coronavirus 2 in China.

Distinct infection process of SARS-CoV-2 in human bronchial epithelial cell lines.

Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leads to a series of clinical symptoms of respiratory and pulmonary inflammatory reactions via unknown pathologic mechanisms related to the viral infection process in tracheal or bronchial epithelial cells. Investigation of this viral infection in the human bronchial epithelial cell line (16HBE) suggests that SARS-CoV-2 can enter these cells through interaction between its membrane-localized S protein with the angiotensin-converting enzyme 2 molecule on the host cell membrane. Further observation indicates distinct viral replication with a dynamic and moderate increase, whereby viral replication does not lead to a specific cytopathic effect but maintains a continuous release of progeny virions from infected cells. Although messenger RNA expression of various innate immune signaling molecules is altered in the cells, transcription of interferons-α (IFN-α), IFN-ß, and IFN-γ is unchanged. Furthermore, expression of some interleukins (IL) related to inflammatory reactions, such as IL-6, IL-2, and IL-8, is maintained at low levels, whereas that of ILs involved in immune regulation is upregulated. Interestingly, IL-22, an IL that functions mainly in tissue repair, shows very high expression. Collectively, these data suggest a distinct infection process for this virus in respiratory epithelial cells, which may be linked to its clinicopathological mechanism.

High expression of ESRP1 regulated by circ-0005585 promotes cell colonization in ovarian cancer.

BACKGROUND: Ovarian cancer is the third most common gynecological cancer in the world but the leading cause of death among gynecological malignancies. Epithelial splicing regulatory protein-1 (ESRP1), a key negative splicing regulator in epithelial-mesenchymal transition (EMT), has been proven to be overexpressed and may plays a role in epithelial ovarian cancer (EOC) progression. However, the functional roles of ESRP1 and the underlying mechanisms in this process still remain unclear. METHODS: Tumor invasion, migration, colony formation and animal experiments were used to study the malignant biological behavior of ESRP1. A vector-based system expressing circ-0005585 was established to investigate circRNA as a microRNAs sponge. RNA-Seq and cytoskeleton staining explored underlying mechanisms of ESRP1. RESULTS: Our results demonstrated that circ-0005585 regulates ESRP1 overexpression via sponging miR-23a/b and miR-15a/15b/16. Overexpression of ESRP1 suppresses EOC cell migration, but promotes colonization and drives a switch from mesenchymal to epithelial phenotype (MET) in association with actin cytoskeleton reorganization, mainly by alternative splicing EPB41L5 and RAC1. Furthermore, we have shown that high ESRP1 expression may be associated with immune-suppression in tumor immune microenvironment in vivo. CONCLUSIONS: ESRP1 overexpression promotes MET status and correlates with actin cytoskeleton reorganization in EOC. ESRP1 plays an important role in EOC colonization. In addition, a miRs panel from two miR families can inhibit ESRP1, may provide an innovative approach for cancer theranostics.

Comparison of Conventional, Diffusion, and Perfusion MRI Between Low-Grade and Anaplastic Extraventricular Ependymoma.

OBJECTIVE. The purpose of this study was to investigate and compare conventional MRI, DWI, and dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI) characteristics between low-grade and anaplastic extraventricular ependymomas. MATERIALS AND METHODS. Twenty-six patients with extraventricular ependymomas (19 anaplastic and seven low-grade) who underwent preoperative MRI were enrolled in this retrospective study. Conventional MRI and DWI were performed in all patients; DSCPWI was performed in 15 patients (11 with anaplastic ependymoma and four with low-grade ependymoma). Demographics, conventional MRI features, minimum relative apparent diffusion coefficient (rADCmin), and maximum relative cerebral blood volume (rCBVmax) of the low-grade and anaplastic ependymomas were compared. Diagnostic performance with optimal cutoff values was determined. RESULTS. Anaplastic extraventricular ependymomas were more likely to be located in the superficial supratentorial cerebral hemisphere (p = 0.026) and to present with pial and cortical involvement (p = 0.028 and 0.013, respectively) and necrotic degeneration (p = 0.014). The mean rADCmin ± SD of anaplastic ependymoma was significantly lower than that of low-grade ependymoma (0.8 ± 0.2 vs 1.2 ± 0.3, p = 0.002). The mean rCBVmax of anaplastic ependymoma was significantly higher than that of low-grade ependymoma (15.7 ± 5.3 vs 9.0 ± 4.4, p = 0.042). The cutoff values in grading extraventricular ependymoma were 1.02 for rADCmin and 10.43 for rCBVmax. Combining conventional MRI, DWI, and DSC-PWI allowed the best differentiation of low-grade and anaplastic ependymoma (AUC = 1.00). CONCLUSION. Conventional MRI, DWI, and DSC-PWI techniques may aid in assessing and grading extraventricular ependymomas.

Performance of diffusion and perfusion MRI in evaluating primary central nervous system lymphomas of different locations.

BACKGROUND: Diffusion and perfusion MRI can invasively define physical properties and angiogenic features of tumors, and guide the individual treatment. The purpose of this study was to investigate whether the diffusion and perfusion MRI parameters of primary central nervous system lymphomas (PCNSLs) are related to the tumor locations. METHODS: We retrospectively reviewed the diffusion, perfusion, and conventional MRI of 68 patients with PCNSLs at different locations (group 1: cortical gray matter, group 2: white matter, group 3: deep gray matter). Relative maximum cerebral blood volume (rCBVmax) from perfusion MRI, minimum apparent diffusion coefficients (ADCmin) from DWI of each group were calculated and compared by one-way ANOVA test. In addition, we compared the mean apparent diffusion coefficients (ADCmean) in three different regions of control group. RESULTS: The rCBVmax of PCNSLs yielded the lowest value in the white matter group, and the highest value in the cortical gray matter group (P < 0.001). However, the ADCmin of each subgroup was not statistically different. The ADCmean of each subgroup in control group was not statistically different. CONCLUSION: Our study confirms that rCBVmax of PCNSLs are related to the tumor location, and provide simple but effective information for guiding the clinical practice of PCNSLs.

IDH genotypes differentiation in glioblastomas using DWI and DSC-PWI in the enhancing and peri-enhancing region.

BACKGROUND: Isocitrate dehydrogenase (IDH) mutation has diagnostic and prognostic values in glioblastomas. Peritumoral invasion of glioma cells is a cardinal feature of glioblastomas. PURPOSE: To evaluate the contribution of DWI and DSC-PWI in the enhancing and peri-enhancing region for discriminating glioblastomas IDH genotypes, and the diagnostic values of combining two techniques in the peri-enhancing region compared with those in the enhancing region. MATERIAL AND METHODS: We retrospectively reviewed the conventional MRI (cMRI), DWI and DSC-PWI obtained from 10 patients with IDH-mutated (IDH-m) glioblastomas and 65 patients with IDH wild-type (IDH-w) glioblastomas. Features of cMRI, relative minimum ADC in the enhancing region (rADCmin-t) and peri-enhancing area (rADCmin-p), and relative maximum CBV values in the enhancing region (rCBVmax-t) and peri-enhancing region (rCBVmax-p) were compared between two groups. Receiver operating characteristic curves and logistic regression analysis were used to assess diagnostic performance. RESULTS: IDH-m glioblastomas tended to present in frontal lobes and younger patients. The rADCmin-t (P = 0.042) were significantly lower in IDH-w than IDH-m. Both rCBVmax-t and rCBVmax-p showed significant differences between two subgroups (all P < 0.001). The optimal cutoff values in prediction of IDH-m were >0.98 for rADCmin-t, <7.27 for rCBVmax-t, and < 0.97 for rCBVmax-p. Multivariate logistic regression revealed that the combination of rADCmin-t and rCBVmax-t yielded the highest sensitivity and specificity. CONCLUSION: The rCBVmax-t or rCBVmax-p may serve as preferable and comparable imaging biomarkers for evaluation of glioblastomas IDH status. The combination of rADCmin-t and rCBVmax-t may yield the maximum predictive power for differentiating IDH status.

Retinal Nerve Fiber Layer Thickness Changes in the Pseudoexfoliation Syndrome: A Meta-Analysis of Case-Control Studies.

PURPOSE: To evaluate and compare changes in retinal nerve fiber layer (RNFL) thickness in patients with the pseudoexfoliation syndrome (PXS) and healthy controls. METHODS: Case-control studies were selected through an electronic search of the Cochrane Controlled Trials Register, PubMed, and Embase. Results were reviewed to ensure that the included studies met prespecified inclusion/exclusion criteria, and the quality of each study was assessed using the Newcastle-Ottawa Scale. All included studies measured average and 4-quadrant (temporal, superior, nasal, and inferior) RNFL thickness using optical coherence tomography (OCT). For the continuous outcomes, we calculated the weighted mean difference (WMD) and 95% confidence intervals (CIs). RESULTS: Eight case-control studies were included in this meta-analysis involving 225 eyes of PXS patients and 208 eyes of healthy controls in total. Statistical analysis revealed that the average RNFL thickness in PXS patients was significantly reduced compared to healthy controls (WMD = -6.91, 95% CI: -9.99 to -3.82, p < 0.0001). Additionally, differences in RNFL thickness in the superior quadrant (WMD = -10.68, 95% CI: -16.40 to -4.95, p = 0.0003), inferior quadrant (WMD = -8.20, 95% CI: -10.85 to -5.55, p < 0.00001), nasal quadrant (WMD = -3.05, 95% CI: -5.21 to -0.90, p = 0.005), and temporal quadrant (WMD = -6.39, 95% CI: -9.98 to -2.80, p = 0.0005) were all significant between the two groups. CONCLUSIONS: These results suggest that it is important to evaluate RNFL thickness and the optic nerve head through OCT in patients with PXS in order to determine early glaucomatous damage and start timely intervention prior to visual field loss.