High-grade transformation of head and neck adenoid cystic carcinoma demonstrates distinctive clinicopathological features and an unfavorable prognosis: a matched case-control study of the largest series in China.

PURPOSE: Amidst the rarity of High-grade transformation (HGT) in adenoid cystic carcinoma (ACC), this study offers unprecedented insights into its aggressive nature and clinical implications. METHODS: A 1:1 match comparison between 23 HGT patients and non-HGT counterparts was extracted from 412 ACC cases, focusing on dissecting distinctive clinicopathological features and prognostic outcomes. RESULTS: The predominant sites of HGT were the sinonasal and lacrimal glands (30.4% each). Notably, the solid subtype was the most prevalent pattern within HGT, accounting for 69.6% of cases. Compared to non-HGT, the HGT cohort exhibited significantly higher rates of lymph node metastasis (39.1% vs. 8.7%; P < 0.05), perineural invasion (60.9% vs. 26.1%; P < 0.05), and increased Ki-67 proliferation index (35.0% vs. 10.0%; P < 0.05). Moreover, HGT regions typically showed reduced or absent p63 expression, along with high-grade pathomorphology. HGT was associated with increased recurrence (55.0%) and distant metastasis (78.3%), leading to an average survival of 35.9 months and a 3-years mortality rate of 35.0%. Overall and progression-free survival rates were significantly decreased in the HGT group. CONCLUSION: This study represents the largest single-center cohort of HGT cases to our knowledge, highlighting its frequent occurrence in the sinonasal and lacrimal glands and association with poorer outcomes. The findings support classifying HGT in ACC as Grade 4, reflecting its severity.

The effect of influenza A (H1N1) pdm09 virus infection on cytokine production and gene expression in BV2 microglial cells.

Acute influenza infection has been reported to be associated with neurological symptoms such as influenza-associated encephalopathy (IAE). Although the pathophysiology of this condition remain unclear, neuroinflammation and associated alterations in the central nervous system (CNS) are usually induced. Microglia (MGs), CNS-resident macrophages, are generally the first cells to be activated in response to brain infection or damage. We performed reverse transcriptase droplet digital PCR (RT-ddPCR) and luminex assays to investigate virus proliferation and immune reactions in BV2 MGs infected with influenza A(H1N1)pdm09 virus. Furthermore, isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics methods were used to investigate the dynamic change in the protein expression profile in BV2 MGs to gain insight into the CNS response to influenza A (H1N1) pdm09 infection. Our results showed that the influenza A(H1N1)pdm09 virus was replicative and productive in BV2 MG cells, which produced cytokines such as interleukin (IL)-1ß, IL-6, tumour necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1. The expression of osteopontin (OPN) in the influenza A (H1N1) pdm09-infected BV2 MGs was upregulated at 16 and 32 h post-infection (hpi) compared to that in the control group, resulting in aggravated brain damage and inflammation. Our study indicates that OPN signalling might provide new insights into the treatment of CNS injury and neurodegenerative diseases in IAE.

Evaluating the higher education productivity of Chinese and European "elite" universities using a meta-frontier approach.

This research focuses on a sample of European and Chinese elite universities for the period 2011-2015. We adopt a meta-frontier methodology to decompose their overall productivity in three main determinants: (1) technical efficiency compared with contemporaneous technology, (2) change in technical efficiency and (3) technology relative superiority of the two groups of universities. The results reveal different patterns of evolution: Chinese institutions' productivity grows faster than that of their European counterparts (+ 7.15%/year vs 4.51%/year), however the latter maintain a higher level of technology in efficient production as a group.

[A method for reliable detection of genomic point mutations based on single-cell target-sequencing].

The analysis of genomic point mutations is one of the research strategies to explore the clonal evolution of tumor cells. At present, clonal evolution of tumor cells is mainly determined by bulk sampling and sequencing of different sections of the tumor. Since this approach analyzes a mixture of different cell types, it may not accurately represent the clonal evolution of specific tumor cell populations and likely miss low frequency mutations, especially when the sequencing depths are not sufficient. To address this issue, we have developed a strategy to analyze genomic point mutations from prostate basal cell carcinoma (BCC) tissues at single-cell resolution. Firstly, we optimized the single-cell whole genome amplification procedure with HepG2 cells. Then the single cells from BCC tissue were captured by a microfluidic chip of Fluidigm and processed for whole-genome amplification. Both SCUBE3 and MST1L genomic mutations were obtained by whole exome sequencing. Finally, we examined the genomic mutations through single-cell targeted amplification and Sanger sequencing. The established method successfully reconfirmed the mutations of SCUBE3 and MST1L in BCC at single cell level. The strategy established in this study could provide a useful tool for determining the clonal evolution of tumor cells based on genomic mutations at single-cell resolution.

Investigating industrial water-use efficiency in mainland China: An improved SBM-DEA model.

Improving water-use efficiency (WUE) is a crucial way of achieving green industrial production and sustainable development. Applying an improved Super-slacks-based measure model with undesirable outputs, this paper investigates industrial WUE in mainland China. The results show that: (1) Industrial WUE in China is improving with the efficiency value increasing from 0.9874 to 0.9962 in 2012-2015. (2) The regions of water absolute scarcity and the vulnerability show the highest industry-related WUE, whereas the water stressed region, water scarce region, and water abundant region failed to achieve efficiency during the observation period. (3) The overall index value using the conventional model was higher than that of the improved model, indicating the need for a more reasonable water-use structure and environmentally friendly discharge structure. This study provides a new perspective for measuring industrial WUE and advances related studies by (1) incorporating the actual structure of water used and wastewater discharged with weights assigned to input and output slacks according to marginal use cost of water and marginal treatment cost of wastewater; and (2) adding realistic constraints on the amount of water used and wastewater discharged to the model. The estimated provinces in mainland China can adjust their industrial water-use structures and wastewater-discharge structures based on the results of this study, and thus improve the industrial WUE.

Association between serum angiopoietin-2 concentrations and periprocedural myocardial injury in patients undergoing elective percutaneous coronary intervention.

Angiopoietin-2 (Ang-2) is a proangiogenic factor that mediates inflammation and atherosclerosis. We evaluated the predictive value of circulating Ang-2 levels for periprocedural myocardial injury (PMI) in 145 patients undergoing elective percutaneous coronary intervention (PCI), and investigated whether post-PCI Ang-2 levels are influenced by PMI. PMI was defined as a post-procedural troponin elevation above the 5×99th percentile upper reference limit. Blood samples for Ang-2 analysis were collected at admission and on postoperative days 1 and 3. PMI occurred in 40 patients (28%). At baseline, there was no difference in Ang-2 levels between PMI and non-PMI patients (P=0.554). However, a significant interaction effect between PMI occurrence and time on Ang-2 levels was observed (interaction P=0.036). Although serum Ang-2 levels in non-PMI patients gradually decreased, Ang-2 levels in PMI patients did not change between different time-points. Multiple logistic regression analysis revealed that age, total stent length, and serum levels of N-terminal pro-brain natriuretic peptide were independent PMI predictors. These findings indicate that pre-procedural Ang-2 levels do not impact PMI occurrence after elective PCI. However, changes in Ang-2 levels after the procedure are closely related to PMI.

SKA3 promotes lung adenocarcinoma metastasis through the EGFR-PI3K-Akt axis.

The processes that lead to lung adenocarcinoma (LUAD) metastasis are poorly characterized. Spindle and kinetochore associated complex subunit 3 (SKA3) plays a key role in cervical cancer development, but its contribution to LUAD is unknown. Here, we found that SKA3 is overexpressed in LUAD and its expression correlates with lymph node metastasis and poor prognosis. SKA3 silencing experiments identified SKA3 as an oncogene that promotes the metastasis of LUAD cell lines and tissues. SKA3 was found to induce the expression of matrix metalloproteinase (MMP)-2, -7, and -9, which activate PI3K-AKT. SKA3 was also found to bind and activate EGFR to activate PI3K-AKT. In summary, we identify a role for SKA3 in LUAD metastasis through its ability to bind EFGR and activate PI3K-AKT signaling.

The Association of Hypoglycemia Assessed by Continuous Glucose Monitoring With Cardiovascular Outcomes and Mortality in Patients With Type 2 Diabetes.

Objective: Hypoglycemia has been shown to promote inflammation, a common pathogenic process, in many chronic health conditions including diabetes and cardiovascular disease. The aim of this study was to investigate the association of hypoglycemia, assessed by continuous glucose monitoring (CGM) with major adverse cardiovascular event (MACE) outcomes and all-cause mortality. Methods: A retrospective cohort study was conducted with 1,520 patients with type 2 diabetes mellitus (T2DM). The severity of hypoglycemia event was assessed by CGM system. Results: Three hundred and forty-seven participants experienced hypoglycemia events (323 with mild hypoglycemia and 24 with severe hypoglycemia). A fraction of 72.62% hypoglycemia was asymptomatic. During a median follow-up of 31 months, 380 participants reached the primary outcome of MACE (61 cardiovascular death, 50 non-fatal myocardial infarction [MI], 116 non-fatal stroke, 153 unstable angina requiring hospitalization), 80 participants died before the end of the study. In multivariate Cox regression models, hypoglycemia was associated with cardiovascular death (HR 2.642[95CI% 1.398-4.994]), non-fatal stroke (HR 1.813 [95CI% 1.110-2.960]) and all-cause mortality (HR 1.960 [95 CI% 1.124- 3.418]) after the full adjustment. Hypoglycemia was not associated with non-fatal MI and unstable angina. The HR of severe hypoglycemia was higher than mild hypoglycemia for cardiovascular death. Patients with symptomatic and asymptomatic hypoglycemia had similar MACE outcomes and all-cause mortality. Conclusions: CGM is effective to detect asymptomatic and nocturnal hypoglycemia. Hypoglycemia is associated with an increased risk of non-fatal stroke, cardiovascular related death, and total mortality. The cardiovascular mortality is dose-dependent on the severity of hypoglycemia.

Angiopoietin-2 provides no incremental predictive value for the presence of obstructive coronary artery disease over N-terminal pro-brain natriuretic peptide.

BACKGROUND: Using circulating biomarkers as a noninvasive method to assist the evaluation of coronary artery disease (CAD) is beneficial for reducing the unnecessary diagnostic cardiac catheterization. This study aimed to assess the predictive role of angiopoietin-2 (Ang-2) for the presence of obstructive coronary stenosis as compared with N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with symptoms of CAD. METHODS: The study enrolled 222 consecutive symptomatic patients who underwent elective diagnostic cardiac catheterization from July to December 2018. Blood samples were collected in the first morning after admission. The severity of coronary stenosis was assessed by coronary angiography. The obstructive CAD was defined as stenosis ≥50% of the left main coronary artery or stenosis ≥70% of a major epicardial vessel (left anterior descending artery, left circumflex artery and right coronary artery). RESULTS: Patients with obstructive CAD (n = 120) had significantly higher levels of Ang-2 and NT-proBNP compared with those without. In multivariable regression analysis, only NT-proBNP levels were independently associated with Ang-2 levels. NT-proBNP was superior to Ang-2 as a predictor for the presence of obstructive CAD (NT-proBNP, area under curve [AUC] = 0.733, vs Ang-2, AUC = 0.626, P = 0.004). In multiple logistic regression analysis, NT-proBNP, but not Ang-2, was the independent predictor of obstructive CAD. The combination of Ang-2 with NT-proBNP did not provide the incremental value over NT-proBNP alone. CONCLUSION: Serum Ang-2 levels are associated with NT-proBNP levels in patients suspected for CAD. NT-proBNP is superior to Ang-2 as a predictor for the presence of obstructive CAD. However, Ang-2 does not further increase diagnostic accuracy on top of NT-proBNP.

Serum angiopoietin-2 concentrations of post-PCI are correlated with the parameters of renal function in patients with coronary artery disease.

Patients with coronary artery disease (CAD) frequently have comorbidity of chronic kidney disease (CKD). Their renal function may deteriorate because of the use of contrast agent after percutaneous coronary intervention (PCI). Angiopoietin-2 (Ang-2), which is highly expressed in the site of angiogenesis, plays an important role in both CAD and CKD. This study aimed to investigate the relation of serum Ang-2 concentrations with the renal function after PCI.This study enrolled 57 patients with CAD undergoing PCI. Blood samples for Ang-2 were collected in the first morning after admission and within 24 to 48 h after PCI. The parameters of renal function (serum creatinine, cystatin C and eGFR) were tested on the first day after admission and within 72 h after PCI.Overall, serum Ang-2 levels of post-PCI were significantly lower than those of pre-PCI [median, 1733 (IQR, 1100-2568) vs median, 2523 (IQR, 1702-3640) pg/mL; P < .001]. However, in patients with CKD (eGFR < 60 mL/min/1.73 m), there was no significant difference between serum Ang-2 levels of post-PCI and those of pre-PCI [median, 2851 (IQR, 1720-4286) vs. median, 2492 (IQR, 1434-4994) pg/mL; P = .925]. In addition, serum Ang-2 levels of post-PCI, but not pre-PCI, were significantly correlated with the post-PCI parameters of renal function.Serum Ang-2 concentrations of post-PCI are closely related to renal function in patients with CAD. It may have potential to be the early biomarker of contrast-induced nephropathy in the future.

An unusual intragenic promoter of PIWIL2 contributes to aberrant activation of oncogenic PL2L60.

PIWIL2-like (PL2L) protein 60 (PL2L60), a product of aberrantly activated PIWIL2 gene, is widely expressed in various types of tumors and may promote tumorigenesis. However, the mechanisms underlying the activation of expression of PL2L60 remain unknown. In this study, an intragenic promoter responsible for the activation of PL2L60 within the human PIWIL2 gene has been identified, cloned and characterized. The promoter of PL2L60 is located in the intron 10 of the host gene PIWIL2. Bioinformatic and mutagenic analysis reveals that this intragenic promoter within the sequence of 50 nucleotides contains two closely arranged cis-acting elements specific for the hepatic leukemia factor (HLF) in the positive strand and signal transducer and activator of transcription 3 (STAT3) in the negative strand. Chromatin immunoprecipitation analysis demonstrates that both the HLF and polymerase II (Pol II), a hallmark of active promoters, directly bind to the sequence, although STAT3 does not. Knockdown of HLF and STAT3 alone or both by RNA interference significantly reduced both promoter activity and the PL2L60 protein expression, although there is no additive effect. The expression of PL2L60 proteins was enhanced when host gene Piwil2 was genetically disrupted in a murine cell model. Taken together, we have identified a PL2L60-specific intragenic promoter in the host gene of PIWIL2, which is interdependently activated by HLF and STAT3 through steric interaction. This activation is dependent on cellular milieu rather than the integrity of host gene PIWIL2, highlighting a novel, important mechanism for a cancer-causing gene to be activated during tumorigenesis.

A novel treatment strategy for newly diagnosed high-grade T1 bladder cancer: Gemcitabine and cisplatin adjuvant chemotherapy-A single-institution experience.

BACKGROUND: Management of high-grade T1 (formerly T1G3) bladder cancer continues to be controversial. Should patients with T1G3 bladder cancer have an immediate radical cystectomy or should they receive intravesical bacillus Calmette-Guérin-preserving bladder? Gemcitabine and cisplatin (GC) adjuvant chemotherapy may help to strike a balance between intravesical and early cystectomy. For purposes of this study, we continue to refer high-grade T1 lesion as "T1G3." OBJECTIVE: To evaluate the characteristics and the long-term outcome of GC adjuvant chemotherapy in T1G3 bladder cancer after transurethral resection of bladder tumor (TURBT). MATERIALS AND METHODS: We retrospectively reviewed 48 patients who were newly diagnosed with T1G3 bladder cancer between January 2009 and December 2012. A total of 48 patients received 4 cycles of GC adjuvant chemotherapy after TURBT. One month after 4 cycles of GC adjuvant chemotherapy, response was evaluated by re-TURBT. Median follow-up was 59.5 (range: 18-70) months, all patients have been observed for more than 3 years. Salvage cystectomy was recommended for patients with persistent disease and for tumor progression after initial complete response. RESULT: Complete response was achieved in 44 (91.7%) patients. Of complete responders, 5 patients experienced recurrence and 5 patients showed progression. The progression rate and disease-specific survival rate were 10.4% and 91.7% at 3 years, respectively. More than 80% of survivors preserved their bladder. Kaplan-Meier curves showed that concomitant carcinoma in situ (CIS) was the only factor that had an influence on progression-free survival (P = 0.022) and disease-specific survival (P = 0.017). Concomitant CIS was the prognostic factor for progression rate and disease-specific survival rate at 3 years (P = 0.008 and P = 0.035). CONCLUSION: GC adjuvant chemotherapy is a safe conservative treatment for T1G3 bladder cancer, but effective is really a phase II study. Patients with T1G3 bladder cancer with concomitant CIS should be treated more aggressively because of the high risk of progression.

Chinese expert consensus on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancies.

Locoregional spread of abdominopelvic malignant tumors frequently results in peritoneal carcinomatosis (PC). The prognosis of PC patients treated by conventional systemic chemotherapy is poor, with a median survival of < 6 mo. However, over the past three decades, an integrated treatment strategy of cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) has been developed by the pioneering oncologists, with proved efficacy and safety in selected patients. Supported by several lines of clinical evidence from phases I, II and III clinical trials, CRS + HIPEC has been regarded as the standard treatment for selected patients with PC in many established cancer centers worldwide. In China, an expert consensus on CRS + HIPEC has been reached by the leading surgical and medical oncologists, under the framework of the China Anti-Cancer Association. This expert consensus has summarized the progress in PC clinical studies and systematically evaluated the CRS + HIPEC procedures in China as well as across the world, so as to lay the foundation for formulating PC treatment guidelines specific to the national conditions of China.

Metformin can block precancerous progression to invasive tumors of bladder through inhibiting STAT3-mediated signaling pathways.

BACKGROUND: Metformin is the first line of oral antidiabetic drug in the biguanide class for treatment of type 2 diabetes. Increasing evidence has suggested that it is a potential anti-tumor drug. However, the mechanisms underlying inhibiting tumor development remain elusive, especially in bladder tumors. METHODS: T24 and J82 cell lines were used as an in vitro model, and 24 female SD rats were used to build an N-methyl-N-nitrosourea (MNU)-induced orthotopic rat bladder cancer model. Transfection of lentivirus-based shRNA was used to construct the STAT3-KNOCKDOWN T24 cell line. After metformin treatment, the viability of bladde cancer cells was determined by CCK8. Cell cycle distribution and apoptosis were assessed by flow cytometry. The migration and invasion abilities of cells were evaluated by wound healing and transwell asssays. The inactivation of stat3 pahtway was examined by qRTPCR, western blot and Immunofluorescence. RESULTS: Metformin can effectively inhibit precancerous progression to invasive cancer in an MNU-induced rat orthotopic bladder tumor model, although it could not completely suppress normal cells transforming into tumor cells. While the MNU could induce 50 % rats (4/8) to develop invasive bladder cancers, the rats co-administrated with metformin failed to develop invasive tumors but retained at precancerous or non-invasive stages, exhibiting as dysplasia, papillary tumor and/or carcinoma in situ (CIS). Accordingly, phosphorylation of signal transducer and activator of transcription 3 (STAT3), which is a well known oncogene, was significantly inhibited in the tumors of rats treated with metformin. In vitro experiments revealed that the metformin could efficiently inhibit STAT3 activation, which was associated with the cell cycle arrest, reduction of cell proliferation, migration and invasiveness, and increase in apoptotic cell death of bladder cancer cell lines. CONCLUSIONS: These findings provide for the first time the evidence that metformin can block precancerous lesions progressing to invasive tumors through inhibiting the activation of STAT3 pathway, and may be used for treatment of the non-invasive bladder cancers to prevent them from progression to invasive tumors.

CACNA1C genomewide supported psychosis genetic variation affects cortical brain white matter integrity in Chinese patients with schizophrenia.

OBJECTIVE: Recent genomewide association studies have implicated the calcium channel, voltage-dependent, L type, alpha 1C subunit (CACNA1C) genetic variant in schizophrenia, which is associated with functional brain changes and cognitive deficits in healthy individuals. However, the impact of CACNA1C on brain white matter integrity in schizophrenia remains unclear. On the basis of prior evidence of CACNA1C-mediated changes involving cortical brain regions, we hypothesize that CACNA1C risk variant rs1006737 is associated with reductions of white matter integrity in the frontal, parietal, and temporal regions and cingulate gyrus. METHOD: A total of 160 Chinese participants (96 DSM-IV-diagnosed patients with schizophrenia and 64 healthy controls) were genotyped by using blood samples and underwent structural magnetic resonance imaging and diffusion tensor imaging scans from 2008 to 2012. Two-way analysis of covariance was employed to examine CACNA1C-related genotype effects, diagnosis effects, and genotype × diagnosis interaction effects on fractional anisotropy (FA) of relevant brain regions. RESULTS: Significant diagnosis-genotype interactions were observed (left frontal lobe mean FA: F1,156 = 6.22, P = .014; left parietal lobe mean FA: F1,156 = 7.14, P = .008; left temporal lobe mean FA: F1,156 = 8.37, P = .004). Compared with patients who were A carriers, patients who were G homozygotes had lower mean FA in the left frontal lobe (F1,93 = 2.504, P = .014), left parietal lobe (F1,93 = 2.37, P = .020), and left temporal lobe (F1,93 = 3.01, P = .003), with standardized effect sizes of -1.43, -1.3, and -1.0, respectively. CONCLUSIONS: CACNA1C risk variant rs1006737 affects cortical white matter integrity in schizophrenia. Further imaging genetic investigations on the mediating effect of CACNA1C in schizophrenia can uncover brain circuitries involved in schizophrenia and suggest potential novel targets for intervention.

Corpus callosum morphology in first-episode and chronic schizophrenia: combined magnetic resonance and diffusion tensor imaging study of Chinese Singaporean patients.

BACKGROUND: Abnormalities in the corpus callosum have been reported in patients with schizophrenia for over 30 years but the influence of inter-individual differences and illness characteristics remains to be fully elucidated. AIMS: To examine the influence of individual and illness characteristics on the corpus callosum in Chinese Singaporean patients with schizophrenia. METHOD: Using magnetic resonance and diffusion tensor imaging, mean corpus callosum area, volume and fractional anisotropy were investigated in 120 Chinese Singaporean patients (52 with chronic and 68 with first-episode schizophrenia) and compared with data from 75 matched healthy controls. RESULTS: Both area and volume were significantly reduced in patients relative to controls but no significant differences in corpus callosum existed between genders in either patients or controls. Differences in area and volume of the corpus callosum were greatest in patients whose condition was chronic relative to patients with a first episode and controls. Anterior callosum in patients, regardless of chronicity, was no different to that of controls. CONCLUSIONS: Morphological abnormalities in the corpus callosum may increase with illness progression.

[Pathogenic spectrum of enteroviruses associated with hand, foot and mouth disease by a GeXP™-based multiplex reverse transcription-PCR assay in Jinan, China, 2009-2012].

We investigated the pathogenic spectrum of enteroviruses associated with hand, foot and mouth disease (HFMD) in Jinan, China. A total of 274 specimens with a clinical diagnosis of HFMD in Jinan from 2009 to June 2012 were used. A GenomeLab™ (GeXP)-based multiplex reverse transcription-polymerase chain reaction (RT-PCR) assay was employed to simultaneously detect 15 serotypes of human enteroviruses: human enterovirus (EV)71; coxsackievirus A (CVA)16, 4, 5, 6, 9, and 10; CVB1, 3 and 5; echovirus (Echo) 6, 7, 11, 13 and 19. Results showed that all samples were enterovirus-positive, with the most common serotypes being EV71 (25.18%) and CVA16 (16.06%), followed by CVA10 (14.23%), CVA6 (7.30%), CVB1 (1.09%), Echo6 (0.73%), CVA9 (0.36%), CVB3 (0.36%) and co-infections (5.11%). CVA10 and CVA6 had the third and fourth highest prevalence of pathogens for HFMD, respec- tively. The most prevalent season for CVA10 was from April to August, with a peak in April; for CVA6 it was from April to August, with a peak in June. This is the first report of the pathogenic spectrum of en- teroviruses associated with HFMD in Jinan using the GeXP-based multiplex RT-PCR assay. These data will provide the scientific evidence for the prevention and control of epidemics, as well as therapy for HFMD patients.

GRIN2B gene and associated brain cortical white matter changes in bipolar disorder: a preliminary combined platform investigation.

Abnormalities in glutamate signaling and glutamate toxicity are thought to be important in the pathophysiology of bipolar disorder (BD). Whilst previous studies have found brain white matter changes in BD, there is paucity of data about how glutamatergic genes affect brain white matter integrity in BD. Based on extant neuroimaging data, we hypothesized that GRIN2B risk allele is associated with reductions of brain white matter integrity in the frontal, parietal, temporal, and occipital regions and cingulate gyrus in BD. Fourteen patients with BD and 22 healthy controls matched in terms of age, gender and handedness were genotyped using blood samples and underwent diffusion tensor imaging. Compared to G allele, brain FA values were significantly lower in BD patients with risk T allele in left frontal region (P = 0.001), right frontal region (P = 0.002), left parietal region (P = 0.001), left occipital region (P = 0.001), right occipital region (P < 0.001), and left cingulate gyrus (P = 0.001). Further elucidation of the interactions between different glutamate genes and their relationships with such structural, functional brain substrates will enhance our understanding of the link between dysregulated glutamatergic neurotransmission and neuroimaging endophenotypes in BD.

Increased expression of HMGB1 is associated with poor prognosis in human bladder cancer.

BACKGROUND AND OBJECTIVE: High-mobility group box 1 (HMGB1) is a versatile protein with intranuclear and extracellular functions that is involved in numerous biological and pathological processes, such as transcription, DNA repair, and response to infection and inflammation. HMGB1 overexpression has been reported in a variety of human cancers. However, the clinical significance of HMGB1 expression in bladder cancer (BC) remains unclear. This study is aimed to investigate the correlations between HMGB1 expression and prognosis in patients with BC. METHODS: HMGB1 protein expression in 164 primary BC tissue specimens was analyzed by immunohistochemistry, and its association with clinicopathologic factors and prognosis was also analyzed. RESULTS: HMGB1 protein had high expression in 87 of 164 cases of BC (53%). HMGB1 overexpression was significantly associated with tumor grade (P < 0.001), and stage (P = 0.001). The Kaplan-Meier survival analysis demonstrated that HMGB1 expression was significantly associated with shorter disease-free survival and overall survival (both P < 0.001). Multivariate analysis further demonstrated that HMGB1 was an independent prognostic factor for patients with BC. CONCLUSIONS: HMGB1 might be a new molecular marker to predict the prognosis of patients with BC.