Stem Cell Therapies for Restorative Treatments of Central Nervous System Ischemia-Reperfusion Injury.

Ischemic damage to the central nervous system (CNS) is a catastrophic postoperative complication of aortic occlusion subsequent to cardiovascular surgery that can cause brain impairment and sometimes even paraplegia. Over recent years, numerous studies have investigated techniques for protecting and revascularizing the nervous system during intraoperative ischemia; however, owing to a lack of knowledge of the physiological distinctions between the brain and spinal cord, as well as the limited availability of testing techniques and treatments for ischemia-reperfusion injury, the cause of brain and spinal cord ischemia-reperfusion injury remains poorly understood, and no adequate response steps are currently available in the clinic. Given the limited ability of the CNS to repair itself, it is of great clinical value to make full use of the proliferative and differentiation potential of stem cells to repair nerves in degenerated and necrotic regions by stem cell transplantation or mobilization, thereby introducing a novel concept for the treatment of severe CNS ischemia-reperfusion injury. This review summarizes the most recent advances in stem cell therapy for ischemia-reperfusion injury in the brain and spinal cord, aiming to advance basic research and the clinical use of stem cell therapy as a promising treatment for this condition.

In silico analysis of the immune microenvironment in bladder cancer.

BACKGROUND: Infiltrating immune and stromal cells are vital components of the bladder cancer (BC) microenvironment, which can significantly affect BC progression and outcome. However, the contribution of each subset of tumour-infiltrating immune cells is unclear. The objective of this study was to perform cell phenotyping and transcriptional profiling of the tumour immune microenvironment and analyse the association of distinct cell subsets and genes with BC prognosis. METHODS: Clinical data of 412 patients with BC and 433 transcription files for normal and cancer tissues were downloaded from The Cancer Genome Atlas. The CIBERSORT algorithm was used to determine the relative abundance of 22 immune cell types in each sample and the ESTIMATE algorithm was used to identify differentially expressed genes within the tumour microenvironment of BC, which were subjected to functional enrichment and protein-protein interaction (PPI) analyses. The association of cell subsets and differentially expressed genes with patient survival and clinical parameters was examined by Cox regression analysis and the Kaplan-Meier method. RESULTS: Resting natural killer cells and activated memory CD4+ and CD8+ T cells were associated with favourable patient outcome, whereas resting memory CD4+ T cells were associated with poor outcome. Differential expression analysis revealed 1334 genes influencing both immune and stromal cell scores; of them, 97 were predictive of overall survival in patients with BC. Among the top 10 statistically significant hub genes in the PPI network, CXCL12, FN1, LCK, and CXCR4 were found to be associated with BC prognosis. CONCLUSION: Tumour-infiltrating immune cells and cancer microenvironment-related genes can affect the outcomes of patients and are likely to be important determinants of both prognosis and response to immunotherapy in BC.

Localizing hand motor area using resting-state fMRI: validated with direct cortical stimulation.

BACKGROUND: Resting-state functional magnetic resonance imaging (R-fMRI) is a promising tool in clinical application, especially in presurgical mapping for neurosurgery. This study aimed to investigate the sensitivity and specificity of R-fMRI in the localization of hand motor area in patients with brain tumors validated by direct cortical stimulation (DCS). We also compared this technique to task-based blood oxygenation level-dependent (BOLD) fMRI (T-fMRI). METHODS: R-fMRI and T-fMRI were acquired from 17 patients with brain tumors. The cortex sites of the hand motor area were recorded by DCS. Site-by-site comparisons between R-fMRI/T-fMRI and DCS were performed to calculate R-fMRI and T-fMRI sensitivity and specificity using DCS as a "gold standard". R-fMRI and T-fMRI performances were compared statistically RESULTS: A total of 609 cortex sites were tested with DCS and compared with R-fMRI findings in 17 patients. For hand motor area localization, R-fMRI sensitivity and specificity were 90.91 and 89.41 %, respectively. Given that two subjects could not comply with T-fMRI, 520 DCS sites were compared with T-fMRI findings in 15 patients. The sensitivity and specificity of T-fMRI were 78.57 and 84.76 %, respectively. In the 15 patients who successfully underwent both R-fMRI and T-fMRI, there was no statistical difference in sensitivity or specificity between the two methods (p = 0.3198 and p = 0.1431, respectively) CONCLUSIONS: R-fMRI sensitivity and specificity are high for localizing hand motor area and even equivalent or slightly higher compared with T-fMRI. Given its convenience for patients, R-fMRI is a promising substitute for T-fMRI for presurgical mapping.

Two polymorphs of tris(ethylenediamine)cobalt(III) tetrathioantimonate(V).

Details of the structures of two polymorphs of tris(ethylenediamine)cobalt(III) tetrathioantimonate(V), [Co(C2H8N2)3][SbS4], are reported. The first polymorph crystallizes in the orthorhombic space group Pna21, whereas the second polymorph belongs to the tetragonal space group P42bc. Both structures contain octahedral [Co(en)3]³âº cations (en is ethylenediamine) and tetrahedral [SbS4]³â» anions, which are interconnected via various N-H∙∙∙S hydrogen bonds to form two different types of three-dimensional network.

Elusive workers are more likely to differentiate into replacement reproductives than aggressive workers in a lower termite.

One of the most intriguing questions in eusocial insects is to understand how the overt reproductive conflict in the colony appears limited when queens or kings are senescent or lost because the morphologically similar individuals in the colony are reproductively totipotent. Whether there are some individuals who preferentially differentiate into replacement reproductives or not has received little attention. The consistent individual behavioral differences (also termed "animal personality") of individuals from the colony can shape cunningly their task and consequently affect the colony fitness but have been rarely investigated in eusocial insects. Here, we used the termite Reticulitermes labralis to investigate if variations in individual personalities (elusiveness and aggressiveness) may predict which individuals will perform reproductive differentiation within colonies. We observed that when we separately reared elusive and aggressive workers, elusive workers differentiate into reproductives significantly earlier than aggressive workers. When we reared them together in the proportions 12:3, 10:5, and 8:7 (aggressive workers: elusive workers), the first reproductives mostly differentiated from the elusive workers, and the reproductives differentiated from the elusive workers significantly earlier than from aggressive workers. Furthermore, we found that the number of workers participating in reproductive differentiation was significantly lower in the groups of both types of workers than in groups containing only elusive workers. Our results demonstrate that the elusiveness trait was a strong predictor of workers' differentiation into replacement reproductives in R. labralis. Moreover, our results suggest that individual personalities within the insect society could play a key role in resolving the overt reproductive conflict.

(2-Hy-droxy-acetato-κO)bis-(1,10-phenan-throline-κN,N')copper(II) nitrate.

In the title compound, [Cu(C(2)H(3)O(3))(C(12)H(8)N(2))(2)]NO(3), the Cu(II) atom is coordinated by two phenanthroline (phen) ligands and one carboxyl-O atom of a hy-droxy-acetate anion in a distorted square-pyramidal geometry. The hy-droxy group of the hy-droxy-acetate ligand links with the counter NO(3) (-) anion via a pair of bifurcated O-H⋯O hydrogen bonds. The centroid-centroid distance of 3.5676 (14) Šbetween benzene rings of parallel phen ligands of adjacent mol-ecules suggests the existence of π-π stacking. Weak inter-molecular C-H⋯O hydrogen bonding is also present in the crystal structure.

[Preliminary application of 3.0 T intraoperative magnetic resonance imaging neuronavigation system in China].

OBJECTIVE: To report the preliminary experience in clinical application of 3.0 T intraoperative magnetic resonance imaging (iMRI) neuronavigation system in China. METHODS: From September 2010 to March 2011, a consecutive series of 122 patients with intracranial lesions underwent operations in guidance with 3.0 T iMRI. A retrospective analysis was conducted regarding clinical efficiency. RESULTS: Among 122 procedures, the numbers of intraoperative scanning were 2 - 4 times with an average of 2.6. The qualities of images were excellent. Due to the discovery and further possibility of resection of residual tumors, the ratio of gross total resection was increased from 71.7% to 90.0% in cerebral gliomas (n = 60), while from 75.9% to 93.1% in macroadenomas (n = 29). There were 6.7% of all patients occurred postoperative paralysis, but only 3.3% of patients had persistent paralysis at 1 - 2 months follow-up. There was no iMRI-related adverse event occurred. During the same period, more than 2500 patients underwent diagnostic MRI scanning. CONCLUSIONS: 3.0 T iMRI neuronavigation system provides high-quality intraoperative structural, functional and metabolic images for real time tumor resection control and accurate functional preservation, resulting in an improvement in maximal safe brain surgery. The system is cost-effective.

[Awake craniotomy and intraoperative language cortical mapping for eloquent cerebral glioma resection: preliminary clinical practice in 3.0 T intraoperative magnetic resonance imaging integrated surgical suite].

OBJECTIVES: To evaluate preliminary clinical experience for combining awake craniotomy and intraoperative language brain mapping within the integrated 3.0 T intraoperative magnetic resonance imaging (iMRI) suite. METHODS: From December 2010 to April 2011, 11 right hand-dominant patients with left glioma were involved in, or adjacent to, eloquent cortex was carried out awake craniotomies with cortical stimulation within an integrated 3.0 T iMRI suite. Aphasia battery of Chinese was used to test the language function before the operation. During the procedure, after the occipital, temporal, and supraorbital nerves were blocked by the anesthesiologists, the head was fixed with a custom high-field MRI-compatible head holder. The skull and dura was opened as usual and language brain mapping was then performed. Language testing followed a set protocol: counting numbers from 1 to 50, naming objects, reading single words. Resection of the tumor was guided by neuronavigation system and continued until eloquent areas were encountered or the margin of assessment was reached. An interdissection MRI was acquired to evaluate the glioma removal in a movable MRI scanner after minimal draping. Meanwhile, adverse effects caused by electrical stimulation and iMRI were recorded. The follow-up speech tests were assessed on 7th day and 1 month at least after the operation. RESULTS: The combined use of 3.0 T iMRI and awake craniotomy was performed safely in all patients. No adverse effects were reported. The duration of surgery was prolonged by 2 to 4 h. The patients' perception of iMRI during surgery was favorable. First-look MRI studies led to further resection attempts in 6/11 cases as well as a 3/11 increase in the number of gross-total resections. One week after surgery, baseline language function worsened in 4 cases. However, no patients had a persistent language deficit one month after surgery. CONCLUSIONS: Awake craniotomy and direct cortical electrical stimulation can be performed safely and effectively within a 3.0 T iMRI suite. The combination of high-field iMRI and awake craniotomy may facilitate safe removal of eloquent glioma.

Malignant pheochromocytoma with cerebral and skull metastasis: A case report and literature review.

BACKGROUND: Malignant pheochromocytoma with cerebral and skull metastasis is a very rare disease. Combining our case with 16 previously reported cases identified from a PubMed search, an analysis of 17 cases of malignant cerebral pheochromocytoma was conducted. This literature review aimed to provide information on clinical manifestations, radiographic and histopathological features, and treatment strategies of this condition. CASE SUMMARY: A 60-year-old man was admitted with a progressive headache and enlarging scalp mass lasting for 3 mo. Radiographic images revealed a left temporal biconvex-shaped epidural mass and multiple lytic lesions. The patient underwent a left temporal craniotomy for resection of the temporal tumor. Histopathological analysis led to identification of the mass as malignant pheochromocytoma. The patient's symptoms were alleviated at the postoperative 3-mo clinical follow-up. However, metastatic pheochromocytoma lesions were found on the right 6th rib and the 6th to 9th thoracic vertebrae on a 1-year clinical follow-up computed tomography scan. CONCLUSION: Magnetic resonance spectroscopy and histopathological examination are necessary to make an accurate differential diagnosis between malignant cerebral pheochromocytoma and meningioma. Surgery is regarded as the first choice of treatment.

Femoral artery cannulation as a safe alternative for aortic dissection arch repair in the era of axillary artery cannulation.

BACKGROUND: To evaluate the safety and efficacy of femoral artery cannulation as an alternative to axillary artery cannulation, we retrospectively compared outcomes between patients with axillary or femoral artery cannulation during open aortic arch repair for type A aortic dissection (TAAD). METHODS: Between January 2014 and January 2019, 646 patients underwent open aortic arch repair with circulatory arrest for TAAD using antegrade selective cerebral perfusion (SACP) and were divided into two groups according to the site of arterial cannulation: an axillary artery group (axillary group, n=558) or a femoral artery group (femoral group, n=88). The axillary artery was considered as the primary cannulation site, and the femoral artery was used as an alternative when axillary artery cannulation was deemed unsuitable or had failed. Propensity score matching was performed to correct baseline differences. RESULTS: After propensity score matching, the patients' characteristics were comparable between groups (n=85 in each). The incidence of in-hospital mortality (10.6% vs. 14.1%; P=0.642) and stroke (3.5% vs. 5.9%; P=0.720) were comparable between the axillary and femoral groups. The incidence of newly required dialysis was lower in the femoral group, but the difference was not statistically significant (34.1% vs. 20.0%; P=0.050). Other outcomes and major adverse events were comparable. CONCLUSIONS: Femoral artery cannulation produced similar perioperative outcomes to axillary cannulation after open arch repair for TAAD. The femoral artery can be used as a safe and effective alternative to the axillary artery for arterial cannulation in TAAD patients undergoing open arch repair.

[Qingli shengjing pills decrease apoptosis of germ cells and expressions of fas and fasL in male mice infected with Escherichia coli].

OBJECTIVE: To study the effects of Qingli Shengjing Pills (QSP) on the apoptosis of germ cells and expressions of Fas and FasL in male mice infected with Escherichia coli (E. coli), and to clarify the molecular mechanism of QSP in the treatment of male infertility induced by E. coli infection. METHODS: Fifty male mice were injected with E. coli via the bladder to make infection models, and at 15 dpi equally randomized into five groups: an untreated, a high-dose QSP (22.5 g/ml), a medium-dose QSP (13.5 g/ml), a low-dose QSP (4.50 g/ml) and a Furadantin treatment group, which were coded as MN, MTa, MTb, MTc and MTd, respectively. Another 10 mice were injected with saline and included in the control group coded as CT. After 10 days of oral medication, the apoptosis of germ cells in the testis of the mice was detected by flow cytometry, the expressions of Fas and FasL determined by immunohistochemistry and the histopathological changes observed simultaneously. RESULTS: After the treatment, the apoptosis of germ cells was observed in all the infected groups, and the apoptosis level in MN (57.44%) was significantly higher than that in CT (28.54%), MTb (28.59%) or MTa (30.11%) (P < 0.01) but had no significant difference from that in MTc (46.54%) or MTd (43.41%) (P > 0.05). The expressions of Fas and FasL proteins were significantly higher in MN than in CT, MTa, MTb, MTc and MTd (P < 0.01). Histopathological changes of the testis tissue were observed in MN, but not in other groups. CONCLUSION: E. coli infection could increase the apoptosis rate of germ cells and the expressions of Fas and FasL proteins. Qingli Shengjing Pills, capable of enhancing reproductivity by reducing the expressions of Fas and FasL and apoptosis of germ cells, can be used as one of the effective drugs for infertility induced by E. coli infection.

Biological, clinical and epidemiological features of COVID-19, SARS and MERS and AutoDock simulation of ACE2.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has caused a public catastrophe and global concern. The main symptoms of COVID-19 are fever, cough, myalgia, fatigue and lower respiratory tract infection signs. Almost all populations are susceptible to the virus, and the basic reproduction number (R0) is 2.8-3.9. The fight against COVID-19 should have two aspects: one is the treatment of infected patients, and the other is the mobilization of the society to avoid the spread of the virus. The treatment of patients includes supportive treatment, antiviral treatment, and oxygen therapy. For patients with severe acute respiratory distress syndrome (ARDS), extracorporeal membrane oxygenation (ECMO) and circulatory support are recommended. Plasma therapy and traditional Chinese medicine have also achieved good outcomes. This review is intended to summarize the research on this new coronavirus, to analyze the similarities and differences between COVID-19 and previous outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and to provide guidance regarding new methods of prevention, diagnosis and clinical treatment based on autodock simulations. METHODS: This review compares the multifaceted characteristics of the three coronaviruses including COVID-19, SARS and MERS. Our researchers take the COVID-19, SARS, and MERS as key words and search literatures in the Pubmed database. We compare them horizontally and vertically which respectively means concluding the individual characteristics of each coronavirus and comparing the similarities and differences between the three coronaviruses. RESULTS: We searched for studies on each outbreak and their solutions and found that the main biological differences among SARS-CoV-2, SARS-CoV and MERS-CoV are in ORF1a and the sequence of gene spike coding protein-S. We also found that the types and severity of clinical symptoms vary, which means that the diagnosis and nursing measures also require differentiation. In addition to the common route of transmission including airborne transmission, these three viruses have their own unique routes of transmission such as fecal-oral route of transmission COVID-19. CONCLUSIONS: In evolutionary history, these three coronaviruses have some similar biological features as well as some different mutational characteristics. Their receptors and routes of transmission are not all the same, which makes them different in clinical features and treatments. We discovered through the autodock simulations that Met124 plays a key role in the efficiency of drugs targeting ACE2, such as remdesivir, chloroquine, ciclesonide and niclosamide, and may be a potential target in COVID-19.

Bladder cancer survival nomogram: Development and validation of a prediction tool, using the SEER and TCGA databases.

Bladder cancer (BC) is a common malignancy associated with high morbidity and mortality, however, accurate and convenient risk assessment tools applicable to BC patients are currently lacking. Previous studies using nomograms to evaluate bladder cancer (BC) survival have been based on small samples. Using a large dataset, this study aimed to construct more precise clinical nomograms to effectively predict bladder cancer survival.Data on patients with pathologically-confirmed bladder cancer were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Additional BC patient data for an external validation cohort were extracted from the Cancer Genome Atlas (TCGA) database. Clinical parameters that constituted potential risk factors were reviewed and analyzed using univariate and multivariate Cox proportional hazards regression. A nomogram was constructed with parameters that significantly correlated with the overall survival (OS). Prognostic performance of a nomogram was assessed using the concordance index (c-index), area under the receiver operating characteristic curve (AUC), and a calibration curve. The model was then tested with data from an internal and external validation cohort. Patients' survival was analyzed and compared with the Kaplan-Meier (KM) method.Multivariate Cox regression showed that age, sex, race, stage_T1, stage_T2a, stage_T2b, stage_T3a, stage_Ta, stage_Tis, stage_N, stage_M were independent predictors of BC survival. A nomogram was constructed based on these factors. The c-index of the nomogram was 0.7916 (95% confidence interval CI, 0.79-0.80). The calibration curve showed excellent agreement between the predicted and observed values. The c-index for the internal validation cohort was 0.7917 (95% CI 0.79-0.80), which was higher than for the training cohort, suggesting robustness of the model. For the training cohort, the AUC for the 3- and the 5-year survival was 0.82 and 0.813, respectively. The c-index for the TNM-based model was superior to that for the AJCC-TNM classification.The models presented in this study might be suitable for clinical use, supporting clinicians in their individualized assessment of expected survival in BC patients. They might also be used as a layered tool for clinical research.

Screening of housekeeping genes in Gelsemium elegans and expression patterns of genes involved in its alkaloid biosynthesis / 生物工程学报

Gelsemium elegans is a traditional Chinese herb of medicinal importance, with indole terpene alkaloids as its main active components. To study the expression of the most suitable housekeeping reference genes in G. elegans, the root bark, stem segments, leaves and inflorescences of four different parts of G. elegans were used as materials in this study. The expression stability of 10 candidate housekeeping reference genes (18S, GAPDH, Actin, TUA, TUB, SAND, EF-1α, UBC, UBQ, and cdc25) was assessed through real-time fluorescence quantitative PCR, GeNorm, NormFinder, BestKeeper, ΔCT, and RefFinder. The results showed that EF-1α was stably expressed in all four parts of G. elegans and was the most suitable housekeeping gene. Based on the coexpression pattern of genome, full-length transcriptome and metabolome, the key candidate targets of 18 related genes (AS, AnPRT, PRAI, IGPS, TSA, TSB, TDC, GES, G8H, 8-HGO, IS, 7-DLS, 7-DLGT, 7-DLH, LAMT, SLS, STR, and SGD) involved in the Gelsemium alkaloid biosynthesis were obtained. The expression of 18 related enzyme genes were analyzed by qRT-PCR using the housekeeping gene EF-1α as a reference. The results showed that these genes' expression and gelsenicine content trends were correlated and were likely to be involved in the biosynthesis of the Gelsemium alkaloid, gelsenicine.

Gastrointestinal toxicity induced by microcystins.

Microcystins (MCs) are produced by certain bloom-forming cyanobacteria that can induce toxicity in various organs, including renal toxicity, reproductive toxicity, cardiotoxicity, and immunosuppressive effects. It has been a significant global environmental issue due to its harm to the aquatic environment and human health. Numerous investigators have demonstrated that MC exposure can induce a widespread epidemic of enterogastritis with symptoms similar to food poisoning in areas close to lakes. Both in vivo and in vitro studies have provided evidence of positive associations between MC exposure and gastrointestinal toxicity. The toxicity of MCs on the gastrointestinal tract is multidimensional. MCs can affect gastrointestinal barrier function and shift the structure of gut microbiota in different gut regions. Furthermore, MCs can inhibit the secretion of gastrointestinal digestive enzymes and the release of inflammatory cytokines, which affects the expression of immune-related genes in the intestine. The damage of the intestine is closely correlated to MC exposure because the intestine is the main site for the digestion and absorption of nutrients. The damage to the gastrointestinal tract due to MCs was summarized from different aspects, which can be used as a foundation for further exploration of molecular damage mechanisms.

[Investigation of algae pollution in Xiliu Lake and identification of toxic cyanobacteria by whole-cell PCR].

OBJECTIVE: To investigate the contaminative condition of the floating algae (especially toxic cyanobacteria) in Xiliu Lake, and establish a whole-cell PCR method for identifying the toxic cyanobacteria. METHODS: The surface water of Xiliu Lake was sampled by plastic sampler from March, 2004, and the number of algae was counted by using blood cell counter. The phycocyanin intergenic spacer region (PC-IGS) and microcystin synthetase gene B (mcyB) were identified by whole-cell PCR in water samples, and the amplified product of mcyB was inserted into T vector and sequenced. RESULTS: Cyanobacteria, Chlorophyta, Bacillariophyta and Euglenophyta were main algae, and cyanobacteria was the dominant algae in summer and autumn. From July 7 to September 27,2 004, PC-IGS was detected positively in 11 samples, and from July 29 to September 27, mcyB was-detieted positively in 9 samples. Compared with the reported mcyB of Microcystis aeruginosa in Genbank, the homology of gene sequence was more than 97 t he homology of amino acid sequence was more than 94%. CONCLUSION: In summer and autumn toxic cyanobacteria could be detected in Xiliu Lake. Toxic cyanobacteria could be identified successfully by whole-cell PCR.

[Research in the relation between telomerase reverse transcriptase expression in spermatogenic cells and serum levels of estradiol of fluorotic rats].

OBJECTIVE: To study the relation between telomerase reverse transcriptase (TERT) activity expression in spermatogenic cells and serum levels of estradiol of fluorotic rats. METHODS: We randomly divided thirty SD male rats into control group, low-dose group and high-dose group, then inject sodium fluoride (0, 10, 20 mg/kg bw) into celiac of rats. We respectively observed changes of estrogen and TERT using methods of radioimmunoassay, in situ hybridization. In addition, we observed the quality of spermatozoa. RESULTS: The level of estrogen, the expression of telomerase and the number and the livability of the spermatozoon in low-dose and high-dose fluorotic rats were lower than those of control rats (P < 0.05). Therefore,the above indexes decreased with the increase of dosage. In addition, sperm aberration of each fluorotic group was higher than control group (P < 0.05). And it increased with the increase of dosage. The content of E2 in serum of different fluoride treatment groups was positively correlated with the expression of telomerase in seminiferous tubule significantly, respectively (low-dose fluoride treatment groups, r = 0.941, P < 0.01, high-dose fluoride treatment groups, r = 0.929, P < 0.01). CONCLUSION: NaF possibly damaged the male reproductive system by the approach of E2/ER-TERT-spermatozoon, relation between TERT expression in spermatogenic cells and serum levels of estradiol is positive correlation.

Alleviation of Lead-Induced Apoptosis by Puerarin via Inhibiting Mitochondrial Permeability Transition Pore Opening in Primary Cultures of Rat Proximal Tubular Cells.

Previous study has demonstrated that mitochondrial-dependent apoptotic pathway is involved in the nephroprotective effect of puerarin (PU) against lead-induced cytotoxicity in primary cultures of rat proximal tubular (rPT) cells. To further clarify how PU exerts its antiapoptotic effects, this study was designed to investigate the role of mitochondrial permeability transition (MPT) and subsequent apoptotic events in the process of PU against Pb-induced cytotoxicity in rPT cells. The results showed that Pb-mediated mitochondrial permeability transition pore (MPTP) opening together with mitochondrial cytochrome c release, activations of caspase-9 and caspase-3, and subsequent poly-ADP-ribose polymerase (PARP) cleavage can be effectively blocked by the addition of PU. Simultaneously, upregulation and downregulation of Bcl-2 and Bax with increased Bcl-2/Bax ratio due to PU administration further alleviated Pb-induced mitochondrial apoptosis. Moreover, PU can reverse Pb-induced ATP depletion by restoring mitochondrial fragmentation to affect ATP production and by regulating expression levels of ANT-1 and ANT-2 to improve ATP transport. In summary, PU produced a significant protection against Pb-induced mitochondrial apoptosis in rPT cells by inhibiting MPTP opening to ameliorate the mitochondrial dysfunction.

Metabolic approach for tumor delineation in glioma surgery: 3D MR spectroscopy image-guided resection.

OBJECT The extent of resection is one of the most essential factors that influence the outcomes of glioma resection. However, conventional structural imaging has failed to accurately delineate glioma margins because of tumor cell infiltration. Three-dimensional proton MR spectroscopy ((1)H-MRS) can provide metabolic information and has been used in preoperative tumor differentiation, grading, and radiotherapy planning. Resection based on glioma metabolism information may provide for a more extensive resection and yield better outcomes for glioma patients. In this study, the authors attempt to integrate 3D (1)H-MRS into neuronavigation and assess the feasibility and validity of metabolically based glioma resection. METHODS Choline (Cho)-N-acetylaspartate (NAA) index (CNI) maps were calculated and integrated into neuronavigation. The CNI thresholds were quantitatively analyzed and compared with structural MRI studies. Glioma resections were performed under 3D (1)H-MRS guidance. Volumetric analyses were performed for metabolic and structural images from a low-grade glioma (LGG) group and high-grade glioma (HGG) group. Magnetic resonance imaging and neurological assessments were performed immediately after surgery and 1 year after tumor resection. RESULTS Fifteen eligible patients with primary cerebral gliomas were included in this study. Three-dimensional (1)H-MRS maps were successfully coregistered with structural images and integrated into navigational system. Volumetric analyses showed that the differences between the metabolic volumes with different CNI thresholds were statistically significant (p < 0.05). For the LGG group, the differences between the structural and the metabolic volumes with CNI thresholds of 0.5 and 1.5 were statistically significant (p = 0.0005 and 0.0129, respectively). For the HGG group, the differences between the structural and metabolic volumes with CNI thresholds of 0.5 and 1.0 were statistically significant (p = 0.0027 and 0.0497, respectively). All patients showed no tumor progression at the 1-year follow-up. CONCLUSIONS This study integrated 3D MRS maps and intraoperative navigation for glioma margin delineation. Optimum CNI thresholds were applied for both LGGs and HGGs to achieve resection. The results indicated that 3D (1)H-MRS can be integrated with structural imaging to provide better outcomes for glioma resection.

Intraoperative Multi-Information-Guided Resection of Dominant-Sided Insular Gliomas in a 3-T Intraoperative Magnetic Resonance Imaging Integrated Neurosurgical Suite.

OBJECTIVE: To evaluate the clinical application of 3-T intraoperative magnetic resonance imaging (iMRI), awake craniotomy, multimodal functional mapping, and intraoperative neurophysiologic monitoring (IONM) for resection of dominant-sided insular gliomas. METHODS: From March 2011 to June 2013, 30 gliomas involving the dominant insular lobe were resected in the IMRIS 3.0-T iMRI integrated neurosurgical suite. For 20 patients, awake craniotomy with cortical electrical stimulation mapping was performed to locate the language areas. For 10 patients who were not suitable for awake surgery, general anesthesia and functional navigation were performed. Diffusion tensor imaging tractography-based navigation, continuous motor evoked potential monitoring, and subcortical electrical stimulation mapping were applied to localize and monitor the motor pathway in all cases. iMRI was used to assess the extent of resection. The results of intraoperative imaging, IONM, and the surgical consequences were analyzed. RESULTS: Intraoperative imaging revealed residual tumor in 26 cases and led to further resection in 9 cases. As a result, the median extent of resection was increased from 90% to 93% (P = 0.008) in all cases, and from 88% to 92% (P = 0.018) in low-grade gliomas. The use of iMRI also resulted in an increase in the percentage of gross and near total resection from 53% to 77% (P = 0.016). The rates of permanent language and motor deficits resulting from tumor removal were 11% and 7.1%, respectively. CONCLUSIONS: The combination of iMRI, awake craniotomy, multimodal brain mapping, and IONM tailored for each patient permits the maximal safe resection of dominant-sided insular glioma.