Predictive Value of the Neutrophil-to-Lymphocyte Ratio and C-Reactive Protein in Patients with Idiopathic Facial Nerve Palsy.

Objective: This study aims to investigate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) in patients with idiopathic facial nerve palsy. Methods: The clinical data of patients with idiopathic facial nerve palsy were retrospectively analyzed. After three months of follow-up, patients were divided into good prognosis and poor prognosis, and the correlation between NLR, CRP and idiopathic facial nerve palsy was analyzed. Results: Negative correlation of NLR with Portmann score in idiopathic facial nerve palsy (r=-0.788, P<0.05); In contrast to the group with poor prognosis, patients in good prognosis group had low levels of body mass index (BMI), NLR, and C-reactive protein (CRP), and high Portmann score (P<0.05); Multivariate logistic regression analysis showed Portmann score (OR=1.268, 95% CI (1.005-1.616)), NLR (OR=0.262, 95% CI (0.128-0.533)) and CRP levels (OR=0.949, 95% CI (0.895-0.989)) were risk factors of poor prognosis for patients with idiopathic facial nerve palsy. The area under the receiver operator characteristic (ROC) curve of NLR and CRP levels in predicting poor facial nerve function was 0.764 and 0.697, the specificity was 85.5% and 75.0%, and the sensitivity was 74. 0% and 76.0%, respectively. The ROC curve of the combined diagnosis was 0.829, the specificity was 80.7%, and the sensitivity was 82.0%. Conclusion: Elevated NLR and CRP are associated with a poor prognosis of idiopathic facial nerve palsy and can serve as an indicator for clinical prognosis, and can be widely used in clinical.

Matrilin-3 supports neuroprotection in ischemic stroke by suppressing astrocyte-mediated neuroinflammation.

In the brain, the role of matrilin-3, an extracellular matrix component in cartilage, is unknown. Here, we identify that matrilin-3 decreased in reactive astrocytes but was unchanged in neurons after ischemic stroke in animals. Importantly, it declined in serum of patients with acute ischemic stroke. Genetic or pharmacological inhibition or supplementation of matrilin-3 aggravates or reduces brain injury, astrocytic cell death, and glial scar, respectively, but has no direct effect on neuronal cell death. RNA sequencing demonstrates that Matn3-/- mice display an increased inflammatory response profile in the ischemic brain, including the nuclear factor κB (NF-κB) signaling pathway. Both endogenous and exogenous matrilin-3 reduce inflammatory mediators. Mechanistically, extracellular matrilin-3 enters astrocytes via caveolin-1-mediated endocytosis. Cytoplasmic matrilin-3 translocates into the nucleus by binding to NF-κB p65, suppressing inflammatory cytokine transcription. Extracellular matrilin-3 binds to BMP-2, blocking the BMP-2/Smads pathway. Thus, matrilin-3 is required for astrocytes to exert neuroprotection, at least partially, by suppressing astrocyte-mediated neuroinflammation.

Expression of the immune checkpoint molecules PD­L1 and PD­1 in EBV­associated lymphoproliferative disorders: A meta­analysis.

Epstein-Barr virus (EBV) has been implicated in the development of a wide range of lymphoproliferative disorders. In this process, the role of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) has remained to be clarified. A meta-analysis of 20 studies was performed and risk ratios (RRs) with 95% confidence intervals (CIs) were used to evaluate the association between PD-L1/PD-1 expression and the status of EBV infection. The results showed that the expression level of PD-L1 in tumor cells was significantly higher in EBV+ cases with a pooled RR of 2.26 (95% CI, 1.63-3.14; P<0.01), particularly in subtypes of diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma. Similarly, EBV infection increased the expression of PD-L1 in immune cells with a pooled RR of 2.20 (95% CI, 1.55-3.12; P<0.01). In subtypes of DLBCL and post-transplant lymphoproliferative disorder, the expression of PD-L1 in immune cells is increased in EBV+ cases. Regarding the expression level of PD-1 in tumor-infiltrating lymphocytes (TILs), no significance was found between EBV infection and PD-1 expression, with a pooled RR of 1.10 (95% CI, 0.81-1.48; P>0.05). The present meta-analysis demonstrated that in EBV-associated lymphoproliferative disorders, EBV infection was associated with the expression level of PD-L1 in tumor cells and immune cells but was not associated with the expression of PD-1 in TILs.

Albumin-Globulin Ratio and Common Carotid Artery Intima-Media Thickness in Patients with Ischemic Stroke.

BACKGROUND: The relationships between serum albumin, albumin-globulin (A/G) ratio, globulin and atherosclerosis in acute ischemic stroke (AIS) remain uncertain. We investigated the associations between serum albumin, A/G ratio, globulin levels and carotid atherosclerosis in patients with AIS. METHODS: A total of 1,339 AIS patients were enrolled. Admission A/G ratio was divided into quartiles, and serum albumin and globulin levels were also categorized. Carotid atherosclerosis was detected through the assessment of common carotid artery intima-media thickness (cIMT), and abnormal cIMT was characterized by mean and maximum cIMT values of ≥1 mm. We evaluated the relationships between A/G ratio, albumin, globulin and abnormal cIMT, using multivariable logistic regression models. RESULTS: In the multivariable-adjusted analysis, the highest A/G ratio quartile (Q4) was linked to a 59% decreased risk of abnormal mean cIMT (OR 0.41; 95% CI 0.29-0.60) and a 58% decreased risk of abnormal maximum cIMT (OR 0.42; 95% CI 0.30-0.60) when compared to the lowest quartile (Q1), respectively. Moreover, decreased albumin and elevated globulin levels were also associated with abnormal mean cIMT and maximum cIMT. In addition, the A/G ratio provided supplementary predictive capability beyond the already established risk factors, and the C-statistic of the A/G ratio for abnormal cIMT is larger than globulin (P <0.01). CONCLUSION: Decreased serum A/G ratio, albumin and elevated serum globulin were independently associated with abnormal cIMT in AIS patients. Moreover, the A/G ratio appeared to be a better predictor of abnormal cIMT.

Prognostic significance of serum globulin in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: We investigated the association between serum globulin levels upon hospital admission and in-hospital short-term outcomes in acute ischemic stroke (AIS) patients. METHODS: A total of 3,127 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included in the present study. We divided patients into 4 groups according to their level of admission serum globulin: Q1 (<23.5 g/L), Q2 (23.5-26.4 g/L), Q3 (26.4-29.9 g/L), and Q4 (≥29.9 g/L). Logistic regression models were used to estimate the effect of serum globulin on the short-term outcomes, including all cause in-hospital mortality, poor outcome upon discharge (modified Rankin Scale score ≥3) and in-hospital pneumonia in AIS patients. RESULTS: The median National Institutes of Health Stroke Scale (NIHSS) score was 4.0 (IQR, 2.0-7.0). The risk of in-hospital mortality was significantly higher in patients with highest serum globulin level (Q4) compared to those with lowest (Q1) (adjusted odds ratio [OR] 2.30; 95% confidence interval [CI], 1.12-4.70; P-trend =0.026). The highest serum globulin level (Q4) was associated with a 1.32-fold and 1.62-fold increase in the risk of poor outcome upon discharge (adjusted OR 1.32; 95% CI, 1.00-1.75; P-trend = 0.070) and in-hospital pneumonia (adjusted OR 1.62; 95% CI, 1.18-2.23; P-trend = 0.001) in comparison to Q1 after adjustment for potential covariates. CONCLUSIONS: A high level of serum globulin upon hospital admission was independently associated with all cause in-hospital mortality, poor outcome upon discharge and in-hospital pneumonia in relative mild AIS patients.

The association between serum phosphorus and common carotid artery intima-media thickness in ischemic stroke patients.

Purpose: An elevated concentration of phosphorus is associated with an increased risk of atherosclerosis and cardiovascular diseases. Common carotid artery intima-media thickness (cIMT) is an imaging marker of atherosclerosis. However, data on the relationship between phosphorus and cIMT in ischemic stroke are scarce. We aimed to evaluate the association between serum phosphorus levels and cIMT in patients who had experienced ischemic stroke. Patients and methods: A total of 1,450 ischemic stroke patients were enrolled. Participants were divided into four groups (quartiles) according to baseline serum phosphorus level. Carotid atherosclerosis was identified by measurement of cIMT; abnormal cIMT was defined as a maximum cIMT or mean cIMT ≥ 1 mm. Multivariable logistic regression models were used to assess the association between serum phosphorus level and the presence of abnormal cIMT. Results: In the multivariable adjusted analysis, falling into the highest quartile for serum phosphorus (Q4) was associated with a 2.00-fold increased risk of having abnormal maximum cIMT [adjusted odds ratio (OR) 2.00; 95% confidence interval (CI) 1.44-2.79] and a 1.76-fold increased risk of having abnormal mean cIMT (adjusted OR 1.76; 95% CI 1.22-2.53) in comparison to Q1. Furthermore, the association between serum phosphorus and abnormal cIMT was confirmed in analyses treating serum phosphorus as a continuous variable and in subgroup analyses. Conclusion: In acute ischemic stroke patients, baseline elevated serum phosphorus level was found to be independently associated with carotid atherosclerosis, as measured by cIMT.

Prognostic significance of international normalised ratio and prothrombin time in Chinese acute ischaemic stroke patients.

BACKGROUND: We investigated the association between international normalised ratio (INR) and prothrombin time (PT) levels on hospital admission and in-hospital outcomes in acute ischaemic stroke (AIS) patients. METHODS: A total of 3175 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included. We divided patients into four groups according to their level of admission INR: (<0.92), Q2 (0.92-0.98), Q3 (0.98-1.04) and Q4 (≥1.04) and PT. Logistic regression models were used to estimate the effect of INR and PT on death or major disability (modified Rankin Scale score (mRS)>3), death and major disability (mRS scores 4-5) separately on discharge in AIS patients. RESULTS: Having an INR level in the highest quartile (Q4) was associated with an increased risk of death or major disability (OR 1.69; 95% CI 1.23 to 2.31; P-trend = 0.001), death (OR, 2.64; 95% CI 1.12 to 6.19; P-trend = 0.002) and major disability on discharge (OR, 1.56; 95% CI 1.13 to 2.15; P-trend = 0.008) in comparison to Q1 after adjusting for potential covariates. Moreover, in multivariable logistic regression models, having a PT level in the highest quartile also significantly increased the risk of death (OR, 2.38; 95% CI 1.06 to 5.32; P-trend = 0.006) but not death or major disability (P-trend = 0.240), major disability (P-trend = 0.606) on discharge. CONCLUSIONS: High INR at admission was independently associated with death or major disability, death and major disability at hospital discharge in AIS patients and increased PT was also associated with death at hospital discharge.

RIPK1 inhibition contributes to lysosomal membrane stabilization in ischemic astrocytes via a lysosomal Hsp70.1B-dependent mechanism.

Receptor-interacting protein kinase 1 (RIPK1) contributes to necroptosis. Our previous study showed that pharmacological or genetic inhibition of RIPK1 protects against ischemic stroke-induced astrocyte injury. In this study, we investigated the molecular mechanisms underlying RIPK1-mediated astrocyte injury in vitro and in vivo. Primary cultured astrocytes were transfected with lentiviruses and then subjected to oxygen and glucose deprivation (OGD). In a rat model of permanent middle cerebral artery occlusion (pMCAO), lentiviruses carrying shRNA targeting RIPK1 or shRNA targeting heat shock protein 70.1B (Hsp70.1B) were injected into the lateral ventricles 5 days before pMCAO was established. We showed that RIPK1 knockdown protected against OGD-induced astrocyte damage, blocked the OGD-mediated increase in lysosomal membrane permeability in astrocytes, and inhibited the pMCAO-induced increase in astrocyte lysosome numbers in the ischemic cerebral cortex; these results suggested that RIPK1 contributed to the lysosomal injury in ischemic astrocytes. We revealed that RIPK1 knockdown upregulated the protein levels of Hsp70.1B and increased the colocalization of Lamp1 and Hsp70.1B in ischemic astrocytes. Hsp70.1B knockdown exacerbated pMCAO-induced brain injury, decreased lysosomal membrane integrity and blocked the protective effects of the RIPK1-specific inhibitor necrostatin-1 on lysosomal membranes. On the other hand, RIPK1 knockdown further exacerbated the pMCAO- or OGD-induced decreases in the levels of Hsp90 and the binding of Hsp90 to heat shock transcription factor-1 (Hsf1) in the cytoplasm, and RIPK1 knockdown promoted the nuclear translocation of Hsf1 in ischemic astrocytes, resulting in increased Hsp70.1B mRNA expression. These results suggest that inhibition of RIPK1 protects ischemic astrocytes by stabilizing lysosomal membranes via the upregulation of lysosomal Hsp70.1B; the mechanism underlying these effects involves decreased Hsp90 protein levels, increased Hsf1 nuclear translocation and increased Hsp70.1B mRNA expression.

Triglyceride-glucose index and short-term functional outcome and in-hospital mortality in patients with ischemic stroke.

BACKGROUND AND AIMS: The triglyceride-glucose (TyG) index has been demonstrated as an independent marker of ischemic stroke. Whether TyG index predicts short-term outcomes in patients with ischemic stroke remains uncertain. The aim of the study was to investigate the early prognosis value of TyG index in ischemic stroke patients. METHODS AND RESULTS: A total of 3216 acute ischemic stroke patients from 22 hospitals were included in this analysis. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). Logistic regression model was performed to estimate the relationship between TyG index and unfavorable functional outcome of death or disability (modified Rankin Scale score of 4-6) at discharge. Risk reclassification with TyG index to predict unfavorable functional outcome was analyzed. During hospitalization, 748 patients (23.3%) experienced poor functional outcome and 105 patients (3.3%) died from all causes. The multivariable adjusted odds ratios for the highest versus lowest quartile of TyG index was 1.62 (95% CI 1.15-2.29) for unfavorable functional outcome at discharge. The addition of TyG index to the conventional model improved the risk reclassification (net reclassification improvement 10.37%; integrated discrimination improvement 0.27%; both p < 0.05) for poor functional outcome. Moreover, TyG index was associated with an odds ratio (95% CI) of 1.26 (1.02-1.55) for an ordinal shift in mRS score and 2.49 (1.21-5.12) for in-hospital mortality. CONCLUSIONS: Higher TyG index was associated with higher risk of unfavorable functional outcome at discharge and in-hospital mortality, implicating the significant short-term prognostic effect of TyG index in patients with ischemic stroke.

Prognostic Value of the Neutrophil-to-Lymphocyte Ratio in Patients with Chronic Internal Carotid Artery Occlusion Complicated by Cerebral Infarction.

Purpose: This study aims to investigate the prognostic value of the peripheral neutrophil-to-lymphocyte ratio (NLR) in patients with chronic internal carotid artery occlusion (CICAO) complicated by cerebral infarction. Patients and Methods: The clinical data of 99 CICAO patients complicated by cerebral infarction were retrospectively analyzed. The modified Rankin Scale (mRS) was used to assess their 3-month prognosis, and a multivariate logistic regression model was established to explore risk factors for poor prognosis. Results: Multivariate logistic regression analysis demonstrated that NLR (OR=2.114; 95% CI: 1.129-3.959) and baseline National Institute of Health Stroke Scale (NIHSS; OR=1.288, 95% CI: 1.053-1.574) score were risk factors of poor prognosis. The area under the receiver operator characteristic (ROC) curve of NLR in predicting the 3-month outcome after onset was 0.717 (95% CI: 0.606-0.828, P<0.000). The optimal cut-off value was 3.22, with a sensitivity of 0.743 and a specificity of 0.791. Conclusion: NLR is an independent risk factor for the poor prognosis of CICAO patients complicated by cerebral infarction and can serve as an indicator for clinical prognosis.

Role of Semaphorins in Ischemic Stroke.

Ischemic stroke is one of the major causes of neurological morbidity and mortality in the world. Although the management of ischemic stroke has been improved significantly, it still imposes a huge burden on the health and property. The integrity of the neurovascular unit (NVU) is closely related with the prognosis of ischemic stroke. Growing evidence has shown that semaphorins, a family of axon guidance cues, play a pivotal role in multiple pathophysiological processes in NVU after ischemia, such as regulating the immune system, angiogenesis, and neuroprotection. Modulating the NVU function via semaphorin signaling has a potential to develop a novel therapeutic strategy for ischemic stroke. We, therefore, review recent progresses on the role of semphorin family members in neurons, glial cells and vasculature after ischemic stroke.

Triglyceride-glucose index and common carotid artery intima-media thickness in patients with ischemic stroke.

BACKGROUND: Triglyceride glucose (TyG) index was recently reported to be associated with an increased risk of the development and recurrence of cardiovascular events, and atherosclerosis is a main speculative mechanism. However, data on the relationship between TyG index and atherosclerosis, especially in the setting of ischemic stroke, is rare. We aimed to explore the association between TyG index and carotid atherosclerosis in patients with ischemic stroke. METHODS: A total of 1523 ischemic stroke patients with TyG index and carotid artery imaging data were enrolled in this analysis. The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Carotid atherosclerosis was measured by common carotid artery intima-media thickness (cIMT), and abnormal cIMT was defined as a mean cIMT and maximum cIMT value ≥ 1 mm. Multivariable logistic regression models and restricted cubic spline models were used to assess the relationships between TyG index and abnormal cIMT. Risk reclassification and calibration of models with TyG index were analyzed. RESULTS: The multivariable-adjusted odds ratios (95% CIs) in quartile 4 versus quartile 1 of TyG index were 1.56 (1.06-2.28) for abnormal mean cIMT and 1.46 (1.02-2.08) for abnormal maximum cIMT, respectively. There were linear relationships between TyG index and abnormal mean cIMT (P for linearity = 0.005) and abnormal maximum cIMT (P for linearity = 0.027). In addition, the TyG index provided incremental predictive capacity beyond established risk factors, shown by an increase in net reclassification improvement and integrated discrimination improvement (all P < 0.05). CONCLUSIONS: A higher TyG index was associated with carotid atherosclerosis measured by cIMT in patients with ischemic stroke, suggesting that TyG could be a promising atherosclerotic marker.

Prognostic significance of international normalised ratio and prothrombin time in Chinese acute ischaemic stroke patients.

BACKGROUND: We investigated the association between international normalised ratio (INR) and prothrombin time (PT) levels on hospital admission and in-hospital outcomes in acute ischaemic stroke (AIS) patients. METHODS: A total of 3175 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included. We divided patients into four groups according to their level of admission INR: (<0.92), Q2 (0.92-0.98), Q3 (0.98-1.04) and Q4 (≥1.04) and PT. Logistic regression models were used to estimate the effect of INR and PT on death or major disability (modified Rankin Scale score (mRS)>3), death and major disability (mRS scores 4-5) separately on discharge in AIS patients. RESULTS: Having an INR level in the highest quartile (Q4) was associated with an increased risk of death or major disability (OR 1.69; 95% CI 1.23 to 2.31; P-trend = 0.001), death (OR, 2.64; 95% CI 1.12 to 6.19; P-trend = 0.002) and major disability on discharge (OR, 1.56; 95% CI 1.13 to 2.15; P-trend = 0.008) in comparison to Q1 after adjusting for potential covariates. Moreover, in multivariable logistic regression models, having a PT level in the highest quartile also significantly increased the risk of death (OR, 2.38; 95% CI 1.06 to 5.32; P-trend = 0.006) but not death or major disability (P-trend = 0.240), major disability (P-trend = 0.606) on discharge. CONCLUSIONS: High INR at admission was independently associated with death or major disability, death and major disability at hospital discharge in AIS patients and increased PT was also associated with death at hospital discharge.

Necroptotic kinases are involved in the reduction of depression-induced astrocytes and fluoxetine's inhibitory effects on necroptotic kinases.

The role of astrocytes in major depressive disorder has received great attention. Increasing evidence indicates that decreased astrocyte numbers in the hippocampus may be associated with depression, but the role of necroptosis in depression is unknown. Here, in a chronic unpredictable mild stress (CUMS) mouse model and a corticosterone (Cort)-induced human astrocyte injury model in vitro, we found that mice treated with chronic unpredictable mild stress for 3-5 weeks presented depressive-like behaviors and reduced body weight gain, accompanied by a reduction in astrocytes and a decrease in astrocytic brain-derived neurotropic factors (BDNF), by activation of necroptotic kinases, including RIPK1 (receptor-interacting protein kinase 1)/p-RIPK1, RIPK3 (receptor-interacting protein kinase 3)/p-RIPK3 and MLKL (mixed lineage kinase domain-like protein)/p-MLKL, and by upregulation of inflammatory cytokines in astrocytes of the mouse hippocampus. In contrast, necroptotic kinase inhibitors suppressed Cort-induced necroptotic kinase activation, reduced astrocytes, astrocytic necroptosis and dysfunction, and decreased Cort-mediated inflammatory cytokines in astrocytes. Treatment with fluoxetine (FLX) for 5 weeks improved chronic unpredictable mild stress-induced mouse depressive-like behaviors; simultaneously, fluoxetine inhibited depression-induced necroptotic kinase activation, reversed the reduction in astrocytes and astrocytic necroptosis and dysfunction, decreased inflammatory cytokines and upregulated brain-derived neurotropic factors and 5-HT1A levels. Furthermore, fluoxetine had no direct inhibitory effect on receptor-interacting protein kinase 1 phosphorylation. The combined administration of fluoxetine and necroptotic kinase inhibitors further reduced corticosterone-induced astrocyte injury. In conclusion, the reduction in astrocytes caused by depressive-like models in vivo and in vitro may be associated with the activation of necroptotic kinases and astrocytic necroptosis, and fluoxetine exerts an antidepressive effect by indirectly inhibiting receptor-interacting protein kinase 1-mediated astrocytic necroptosis.

Decreased Serum Total Bilirubin Level Predicts Early Neurological Deterioration in Patients with Acute Ischemic Stroke.

OBJECTIVE: This study aimed to investigate the relationship between serum total bilirubin (TBil) level and early neurological deterioration (END) in patients with acute ischemic stroke of large artery atherosclerosis. PATIENTS AND METHODS: In this retrospective study, a total of 291 patients with acute ischemic stroke were enrolled. The demographic and laboratory dates were collected. Stroke severity had been assessed using the National Institutes of Health Stroke Scale (NIHSS). Multivariable logistic regression was used to examine the independent association between TBil and END. RESULTS: Approximately 63 (21.6%) of the patients were diagnosed with END within the first seven days. The proportion of hypertension, diabetes mellitus (DM) and previous stroke/transient ischemic attack (TIA) was significant greater in the lowest quartile (<9.8 µmol/l) of TBil. The proportion of patients with an elevated TBil levels was significantly lower in the END group than in the non-END group. After controlling for covariates, the first quartiles (<9.8 µmol/l) of TBil were still associated with END. In addition, an increased level of CRP and age were also associated with an increased risk of END. CONCLUSION: The TBil levels in patients with acute cerebral infarction may be a useful biomarker for the prediction of END.

Cyclin-dependent kinase 1 shows to be a potential genetic target for chemical cystitis.

BACKGROUND: In the present study, we aimed to explore whether common genetic targets or signaling pathways existed in chemical cystitis. METHODS: Gene Expression Omnibus (GEO) database was used to search the related gene expression profiles. The differentially expressed genes (DEGs) were identified by using GEO2R. The DAVID 6.8 Beta and R software were used to perform Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology function analysis of DEGs. The protein-protein interaction network was constructed by STRING 11.0 to reveal the potential gene interactions. The expression of cyclin-dependent kinase 1 (Cdk1) at the messnger RNA (mRNA) and protein levels was examined by real-time polymerase chain reaction (PCR) and Western blot analysis analysis, respectively. RESULTS: The GEO database was searched, and the gene expression profiles of GSE55986 and GSE68539 were downloaded. A total of 262 DEGs and 356 DEGs were identified from GSE55986 and GSE68539, respectively. We found that the p53 signaling pathway might play a key role in the development of chemical cystitis, and Cdk1 acted as a crucial gene in the p53 signaling pathway. Moreover, the experimental results of real-time PCR and Western blot analysis analysis demonstrated that the expression of Cdk1 at the mRNA and protein levels in cystitis tissues was significantly increased in different animal models of chemical cystitis compared with the control group. CONCLUSION: Cdk1 might be a potential pathogenic genetic target for chemical cystitis.

Endovascular revascularization of symptomatic chronic total occlusions of the internal carotid artery using a proximal balloon protection device.

To investigate the feasibility, efficacy, and safety of endovascular recanalization for symptomatic chronic internal carotid artery occlusions (ICAO). Thirty patients with symptomatic chronic ICAO were treated using the endovascular recanalization method. Proximal balloon protection devices were used to prevent embolic migration by completely blocking the blood flow. The morphology of the internal carotid artery (ICA) at the occluded segment based on catheter angiography was analyzed. Recanalization of symptomatic chronic internal carotid artery occlusion (CICAO) was successful in 20 of the 30 patients (66.7%). The time required for successful revascularization ranged from 120 to 180 min (mean, 150 min). Of the 20 successful patients, 14 were at the cervical ICAs, and six were at the intracranial ICAs. No permanent complications occurred in our study. Ischemic symptoms related to chronic ICAO did not occur during the 18.3 month follow-up period (range, 12-24 months) in the 20 successful patients. Endovascular revascularization can improve hemodynamic compromise. The treated sites of all 20 successfully recanalized patients were patent on computed tomographic angiography or carotid duplex sonography, and no case with >50% restenosis was observed during the follow-up period. Three patients with failed recanalization had a stroke during the follow-up period. Endovascular revascularization of symptomatic CICAO using a proximal balloon protection device is technically feasible in selected patients, and the outcomes are favorable for patients who benefit from revascularization.

High-dose methotrexate-based regimens and post-remission consolidation for treatment of newly diagnosed primary CNS lymphoma: meta-analysis of clinical trials.

With the exception of high-dose methotrexate (HD-MTX), there is currently no defined standard treatment for newly diagnosed primary central nervous system lymphoma (PCNSL). This review focused on first-line induction and consolidation treatment of PCNSL and aimed to determine the optimal combination of HD-MTX and the long-term beneficial consolidation methods. A comprehensive literature search of MEDLINE identified 1407 studies, among which 31 studies met the inclusion criteria. The meta-analysis was performed by using Stata SE version 15. Forest plots were generated to report combined outcomes like the complete response rate (CRR), overall survival, and progression-free survival. We also conducted univariate regression analyses of the baseline characteristics to identify the source of heterogeneity. Pooled analysis showed a CRR of 41% across all HD-MTX-based regimens, and three- and four-drug regimens had better CRRs than HD-MTX monotherapy. In all combinations based on HD-MTX, the HD-MTX + procarbazine + vincristine (MPV) regimen showed pooled CRRs of 63% and 58% with and without rituximab, respectively, followed by the rituximab + HD-MTX + temozolomide regimen, which showed a pooled CRR of 60%. Pooled PFS and OS showed that post-remission consolidation with autologous stem cell transplantation (ASCT) was associated with the best survival outcome, with a pooled 2-year OS of 80%, a 2-year PFS of 74%, a 5-year OS of 77%, and a 5-year PFS of 63%. Next, whole-brain radiation therapy (WBRT) + chemotherapy showed a pooled 2-year OS of 72%, 2-year PFS of 56%, 5-year OS of 55%, and 5-year PFS of 41%, with no detectable CR heterogeneity throughout the entire treatment process. In HD-MTX-based therapy of newly diagnosed PCNSL, MPV with or without rituximab can be chosen as the inductive regimen, and the rituximab + HD-MTX + temozolomide regimen is also a practical choice. Based on our study, high-dose chemotherapy supported by ASCT is an efficacious approach for consolidation. Consolidation with WBRT + chemotherapy can be another feasible approach.

Primary myelofibrosis with concurrent CALR and MPL mutations: A case report.

BACKGROUND: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by recurrent mutations in the JAK2, CALR, and MPL genes. The CALR and MPL co-mutation is very rare. To our knowledge, no more than five cases have been reported. Here, we report a case of PMF in which a CALR and MPL co-mutation was detected by next-generation sequencing (NGS) technology, and a literature review was performed. CASE SUMMARY: A 73-year-old woman was admitted to our hospital in 2018 due to abdominal distension. The patient had splenomegaly, lymphadenopathy, leukopenia, anemia, and immature granulocytes in peripheral blood. There were dacrocytes and atypical megakaryocytes in bone marrow, and megakaryocytic proliferation was very active, accompanied by reticulin fibrosis grade 2. By NGS analysis of the bone marrow sample, we detected mutations in CALR, MPL, and PIK3RI, while JAK2 V617F and BCR-ABL were negative. Therefore, the patient was diagnosed with PMF and received oral ruxolitinib. However, the spleen and hematologic responses were poor. We review the literature, analyze previous reports of the mutation sites in our patient and differences between our patient and other reported cases of co-mutated CALR and MPL genes, and discuss the reason why the CALR and MPL co-mutations are rare and possible mechanisms and their impact on the prognosis of patients. CONCLUSION: CALR and MPL mutations can be concurrent in MPN, but they are rare. The use of NGS may help to identify more patients with co-mutated CALR and MPL genes. This will help to further explore the mechanism and its impact on these patients to develop appropriate treatment strategies.

Elevated Total Homocysteine Predicts In-Hospital Pneumonia and Poor Functional Outcomes in Acute Ischemic Stroke.

BACKGROUND: We investigated the association between elevated total homocysteine (tHcy) levels upon hospital admission and short-term in-hospital outcomes, including pneumonia in acute ischemic stroke (AIS) patients. METHODS: A total of 2,084 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included in the present study. We divided patients into four groups according to their level of admission tHcy: quartile (Q1) (<9.70 umol/L), Q2 (9.70-12.3 umol/L), Q3 (12.3-16.9 umol/L), and Q4 (≥16.9 umol/L). Logistic regression models were used to estimate the effect of tHcy on the short-term outcomes, including in-hospital pneumonia, all-cause in-hospital mortality, and poor outcome upon discharge (modified Rankin Scale score ≥3) in AIS patients. RESULTS: The risk of in-hospital pneumonia was significantly higher in patients with the highest tHcy level (Q4) compared to those with the lowest tHcy level (Q1) (adjusted odds ratio [OR] 1.55; 95% confidence interval [CI], 1.03-2.33; P-trend =0.019). The highest tHcy level (Q4) was associated with a 3.35-fold and 1.50-fold increase in the risk of in-hospital mortality (OR 3.35; 95% CI, 1.11-10.13; P-trend =0.015) and poor outcome upon discharge (OR 1.50; 95% CI, 1.06-2.12; Ptrend =0.044) in comparison to Q1 after adjustment for potential covariates including pneumonia. CONCLUSION: Having a high admission tHcy level was independently associated with in-hospital pneumonia, in-hospital mortality, and poor outcome upon discharge in AIS patients.