Clot removAl with or without decompRessive craniectomy under ICP monitoring for supratentorial IntraCerebral Hemorrhage (CARICH): a randomized controlled trial.

BACKGROUND: Decompressive craniectomy, a surgery to remove part of the skull and open the dura mater, maybe an effective treatment for controlling intracranial hypertension. It remains great interest to elucidate whether decompressive craniectomy is beneficial to intracerebral hemorrhage patients who warrant clot removal to prevent intracranial hypertension. METHODS: The trial was a prospective, pragmatic, controlled trial involving adult patients with intracerebral hemorrhage who were undergoing removal of hematoma. Intracerebral hemorrhage patients were randomly assigned at a 1:1 ratioto undergo clot removal with or without decompressive craniectomy under the monitoring of intracranial pressure. The primary outcome was the proportion of unfavorable functional outcome (modified Rankin Scale 3-6) at 3 months. Secondary outcomes included the mortality at 3 months and the occurrence of re-operation. RESULTS: A total of 102 patients were assigned to the clot removal with decompressive craniectomy group and 102 to the clot removal group. Median hematoma volume was 54.0 mL (range 30-80 mL) and median preoperative Glasgow Coma Scale was 10 (range 5-15). At 3 months, 94 patients (92.2%) in clot removal with decompressive craniectomy group and 83 patients (81.4%) in the clot removal group had unfavorable functional outcome (P=0.023). Fourteen patients (13.7%) in the clot removal with decompressive craniectomy group died versus five patients (4.9%) in the clot removal group (P=0.030). The number of patients with re-operation was similar between the clot removal with decompressive craniectomy group and clot removal group (5.9% vs. 3.9%; P=0.517). Postoperative intracranial pressure values were not significantly different between two groups and the mean values were less than 20 mmHg. CONCLUSIONS: Clot removal without decompressive craniectomy decreased the rate of modified Rankin Scale score of 3-6 and mortality in patients with intracerebral hemorrhage, compared with clot removal with decompressive craniectomy.

High ANO1 expression is a prognostic factor and correlated with an immunosuppressive tumor microenvironment in pancreatic cancer.

Background: Aminooctylamine (ANO1) plays an oncogenic role in various cancers. However. its role in pancreatic cancer (PC) has rarely been studied. This study investigated the prognostic value of ANO1 and its correlation with the tumor microenvironment (TME) in PC. Methods: Consecutive patients with PC (n = 119) were enrolled. The expression of ANO1 in cancer cells, the expression of fibroblast activation protein (FAP) and alpha smooth muscle actin in cancer-associated fibroblasts (CAFs), and the numbers of CD8- and FOXP3-positive tumor-infiltrating lymphocytes (TILs) were evaluated using immunohistochemistry. The prognostic value of ANO1 and its correlation with CAF subgroups and TILs were analyzed. The possible mechanism of ANO1 in the TME of PC was predicted using the the Cancer Genome Atlas (TCGA) dataset. Results: The expression of AN01 was correlated with overall survival (OS) and disease-free survival. Multi-factor analysis showed that high ANO1 expression was an independent adverse prognostic factor for OS (hazard ratio, 4.137; P = 0.001). ANO1 expression was positively correlated with the expression of FAP in CAFs (P < 0.001) and negatively correlated with the number of CD8-positive TILs (P = 0.005), which was also validated by bioinformatics analysis in the TCGA dataset. Moreover, bioinformatic analysis of the TCGA dataset revealed that ANO1 may induce an immunosuppressive tumor microenvironment in pancreatic cancer in a paracrine manner. Conclusion: ANO1 is a prognostic factor in patients with PC after radical resection. ANO1 may induce an immunosuppressive tumor microenvironment in PC in a paracrine manner, suggesting that ANO1 may be a novel therapeutic target.

The Prognostic Role of Serine Racemase in Patients With Pancreatic Cancer: A New Marker in Cancer Metabolism.

OBJECTIVES: Serine racemase (SRR) participates in serine metabolism in central nervous systems. Serine racemase is only studied in colorectal cancer, and its role in pancreatic cancer (PC) is unknown. This study aims to investigate the role of SRR in PC. METHODS: Totally 182 patients with PC were enrolled in this study. Slices from patients were stained for SRR and CD8+ T cells. Kaplan-Meier methods were used to do survival analysis according to SRR expression from immunohistochemical staining. Univariate and multivariate Cox regression analysis was performed to clarify the independent prognostic value of SRR. Bioinformatic tools were used to explore and validate the expression, prognostic value, possible mechanism, and immune interaction of SRR in PC. RESULTS: The expression of SRR was lower in tumor tissue than normal tissue, also potentially decreased with the increasing tumor grade. Low SRR expression was an independent risk factor for overall survival (hazards ratio, 1.875; 95% confidence interval, 1.175-2.990; P = 0.008) in patients with PC. Serine racemase was positively correlated with CD8+ T cells infiltration and possibly associated with CCL14 and CXCL12 expression. CONCLUSIONS: Serine racemase plays a prognostic role in PC and may be a potentially therapeutic target.

Significance of a Tumor Mutation Burden Gene Signature with Prognosis and Immune Feature of Gastric Cancer Patients.

Gastric cancer (GC) is a common digestive tumor which ranks the fourth most common malignancy worldwide. Immunotherapy is a promising treatment for GC, especially for advanced gastric cancer (AGC). However, in clinical practice, not all patients are sensitive to immunotherapy. Recent studies showed that tumor mutation burden (TMB) is closely correlated with the response of immunotherapy. The current study identified a TMB-related genes' signature to predict the prognosis and immune feature of GC patients. Firstly, we acquired the TMB data and expression data from The Cancer Genome Atlas (TCGA) and the National Center for Biotechnology Information (NCBI) GEO databases. Then, we extracted TMB-related genes from the expression data of TCGA and two GEO cohorts. By using univariate Cox analysis, we identified that the 429 genes were correlated to GC patients' overall survival. Subsequently, an immune prognostic signature was constructed by using the least absolute shrinkage and selection operator analysis (LASSO) and multivariate Cox regression analysis. The signature could be utilized to predict the prognosis of GC patients. In addition, the signature showed a closed correlation with immune feature of GC patients. In conclusion, our risk signature could offer hints for the prognosis of GC patients and might provide insights to formulate new immunotherapy strategies for GC patients.

High Expression of Bloom Syndrome Helicase is a Key Factor for Poor Prognosis and Advanced Malignancy in Patients with Pancreatic Cancer: A Retrospective Study.

BACKGROUND: Bloom syndrome helicase (BLM) is overexpressed in multiple types of cancers and its overexpression may induce genomic instability. This study aimed to determine the function of BLM expression in pancreatic cancer. METHODS: BLM messenger RNA (mRNA) expression was analyzed using public datasets to determine its relationship with pancreatic cancer prognosis. Overall, 182 patients with pancreatic cancer who underwent radical resection at our institution were enrolled. BLM expression was evaluated by immunohistochemistry (IHC). We explored the effect of BLM on the proliferation, invasion, migration, and chemoresistance of pancreatic cancer cells via small-interfering RNAs and performed pathway analysis using gene set enrichment analysis. RESULTS: BLM mRNA expression was higher in tumor tissue than in normal tissue and had a prognostic effect on overall survival (OS) and recurrence-free survival. The same results were validated by IHC. Multivariate analysis showed that high BLM expression was an independent poor prognostic factor for OS (hazard ratio [HR] 1.678, p = 0.029). In subgroup analysis, the effect of high BLM expression was more significant on OS in patients with younger age (HR 2.27, p = 0.006), male sex (HR 2.39, p = 0.002), high cancer antigen 19-9 level (HR 2.44, p = 0.001), advanced tumor stage (HR 2.25, p = 0.001), lymph node metastasis (HR 2.51, p = 0.001), nerve invasion (HR 2.07, p = 0.002), and adjuvant chemotherapy (HR 2.66, p < 0.001). In vitro, BLM suppression resulted in reduced tumor proliferation, invasion, migration, and chemoresistance. Mechanistically, BLM expression may be associated with E2F1 and E2F2. CONCLUSION: BLM expression is a prognostic factor for patients with pancreatic cancer, especially in those with advanced malignancies and receiving chemotherapy.

Cancer-associated fibroblast senescence and its relation with tumour-infiltrating lymphocytes and PD-L1 expressions in intrahepatic cholangiocarcinoma.

BACKGROUND: Caveolin-1 (CAV1) in cancer-associated fibroblasts (CAFs) has pro- or anti-tumourigenic effect depending on the cancer type. However, its effect in intrahepatic carcinoma (ICC) remains unknown. Therefore, this study aimed to investigate the relationship between CAV1 in CAFs and tumour-infiltrating lymphocyte (TIL) numbers or PD-L1 levels in ICC patients. METHODS: Consecutive ICC patients (n = 158) were enrolled in this study. The levels of CAV1 in CAFs, CD8 + TILs, Foxp3+ TILs and PD-L1 in cancer cells were analysed using immunohistochemistry. Their association with the clinicopathological factors and prognosis were evaluated. The correlation between these factors was evaluated. RESULTS: CAV1 upregulation in CAFs was associated with a poor overall survival (OS) (P < 0.001) and recurrence-free survival (P = 0.008). Clinicopathological factors were associated with high CA19-9 levels (P < 0.001), advanced tumour stage (P = 0.046) and lymph node metastasis (P = 0.004). CAV1 level was positively correlated with Foxp3+ TIL numbers (P = 0.01). There were no significant correlations between CAV1 levels and CD8 + TIL numbers (P = 0.80) and PD-L1 levels (P = 0.97). An increased CD8 + TIL number and decreased Foxp3+ TIL number were associated with an increased OS. In multivariate analysis, positive CAV1 expression in CAFs (P = 0.013) and decreased CD8 + TIL numbers (P = 0.021) were independent poor prognostic factors. CONCLUSION: Cellular senescence, represented by CAV1 levels, may be a marker of CAFs and a prognostic indicator of ICC through Foxp3+ TIL regulation. CAV1 expression in CAFs can be a therapeutic target for ICC.

Combination of the Distance From Tumor Edge to Subventricular Zone and IDH Mutation Predicts Prognosis of Patients With Glioma.

Both subventricular zone (SVZ) contact and isocitrate dehydrogenase 1 (IDH1) mutation have been reported to be related to the outcome of glioma, respectively. However, far too little attention has been paid to the role of tumor edge-SVZ distance in the outcome of glioma. We aim to assess the value of tumor-SVZ distance, as well as combined tumor-SVZ distance and IDH status, in predicting the outcome of gliomas (WHO grade II-IV). Here, the MR images and clinical data from 146 patients were included in the current study. The relationship between survival and the tumor-SVZ distance as well as survival and combination of tumor-SVZ distance and IDH status were determined via univariate and multivariate analyses. In univariate analysis of tumor-SVZ distance, the patients were divided into three types (SVZ involvement, tumor-SVZ distance from 0 to 10 mm, and tumor-SVZ distance >10 mm). The results showed that the OS (p = 0.02) and PFS (p = 0.002) for the patients had a positive correlation with the tumor-SVZ distance. In addition, simple linear correlation found a significant relationship between the two parameters (OS and PFS) and tumor-SVZ distance in patients with non-SVZ-contacting glioma. Combination analysis of the tumor-SVZ distance and IDH status showed that IDH1 mutation and SVZ non-involvement enable favorable outcomes, whereas IDH1 wild type with SVZ involvement indicates a significantly worse prognosis in all patients. Moreover, in patients with non-SVZ-contacting glioma, IDH1 mutation concurrent with tumor-SVZ distance >10 mm has better OS and PFS. IDH1 wild type and tumor-SVZ distance from 0 to 10 mm suggest poorer OS and PFS. Multivariate analysis showed WHO grade IV, SVZ involvement, tumor-SVZ distance from 0 to 10 mm, IDH1 mutation, gross total resection, and chemotherapy serve as independent predictors of OS. WHO grade IV, SVZ involvement, tumor-SVZ distance from 0 to 10 mm, IDH1 mutation, and chemotherapy serve as independent predictors of PFS of patients with glioma. In conclusion, tumor-SVZ distance and IDH1 mutation status are the determinants affecting patient outcome.

Hematoma Evacuation via Image-Guided Para-Corticospinal Tract Approach in Patients with Spontaneous Intracerebral Hemorrhage.

INTRODUCTION: Corticospinal tract injury caused by direct hematoma compression and secondary damage induced from blood toxic substances might influence the outcomes in patients with intracerebral hemorrhage (ICH). This study aimed to evaluate the safety and efficacy of hematoma evacuation via image-guided para-corticospinal tract approach based on the protection of compressed or residual corticospinal tract. METHODS: Seventy-five patients with ICH who underwent the image-guided para-corticospinal tract approach were retrospectively collected into the surgery group. Diffusion tensor imaging or computed tomography angiography was performed to identify the relationship between important white matter tracts and hematoma. The neuronavigation system for the preoperative imaging data loaded was used to identify the location of the burr hole, insertion trajectory, and depth of insertion. Cortical entry points and insertion trajectories were kept parallel to the corticospinal tract route into the hematoma based on the protection of compressed or residual corticospinal tract. Hematoma was removed under the image-guided para-corticospinal tract approach. Seventy-five age-, sex-, hematoma site-, and volume-matched patients with ICH who underwent conservative treatment were selected as controls. Demographical, clinical, radiological, and treatment-related data were retrospectively analyzed. Functional outcome was evaluated by modified Rankin scale on day 90. RESULTS: A total of 150 patients with ICH were retrospectively enrolled. The median Glasgow coma scale (GCS) score on admission was 11 (IQR 8-13). Deep hematoma (thalamus and basal ganglion) was present in 86.7% (130 patients). The mean hematoma volume on admission was 47 ± 19 mL, and the postoperative hematoma volume was 11 ± 10 mL. A higher proportion of favorable outcome was observed in the surgery group than in conservative treatment group (32.0% versus 17.4%; p = 0.037). CONCLUSION: Hematoma evacuation via image-guided para-corticospinal tract approach based on the protection of compressed or residual corticospinal tract seems to be safer in patients with ICH with a relatively higher functional independence.

Long-Term Mortality Related to Acute Kidney Injury Following Intracerebral Hemorrhage: A 10-Year (2010-2019) Retrospective Study.

OBJECTIVES: Acute kidney injury (AKI) following intracerebral hemorrhage (ICH) is an intractable medical complication and an independent predictor of short-term mortality. However, the correlation between AKI and long-term mortality has not been fully investigated. The aim of the present study was to determine the relationship between AKI following ICH and long-term mortality in a 10-year (2010-2019) retrospective cohort. MATERIALS AND METHODS: A total of 1449 ICH patients were screened and enrolled at the Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University) from January 2010 to December 2016. The endpoint for follow-up was May 31, 2019. The estimated all-cause mortality was determined using Cox proportional hazard regression models. RESULTS: Among 1449 ICH patients, 136 (9.4%) suffered from AKI, and the duration of follow-up was a median of 5.1 years (IQR 3.2-7.2). The results indicated that the risk factors for AKI without preexisting chronic kidney disease (CKD) in the multivariable analysis were age (p = 0.002), nephrotoxic antibiotics (p = 0.000), diabetes mellitus (p = 0.005), sepsis (p = 0.000), antiplatelet therapy (p = 0.002), infratentorial hemorrhage (p = 0.000) and ICH volume (p = 0.003). Age (p = 0.008), ACEIs/ARBs (p = 0.010), nephrotoxic antibiotics (p = 0.014), coronary artery disease (p = 0.009), diabetes mellitus (p = 0.014), hypertension (p = 0.000) and anticoagulant therapy (p = 0.000) were independent predictors of AKI with preexisting CKD. Meanwhile, the data demonstrated that the estimated all-cause mortality was significantly higher in ICH patients with AKI without preexisting CKD (HR 4.208, 95% CI 2.946-6.011; p = 0.000) and in ICH patients with AKI with preexisting CKD (HR 2.470, 95% CI 1.747-3.492; p = 0.000) than in those without AKI. CONCLUSIONS: AKI is a long-term independent predictor of mortality in ICH patients. Thus, renal function needs to be routinely determined in ICH patients during clinical practice.

Usage of Angiotensin-Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker in Hypertension Intracerebral Hemorrhage.

BACKGROUND: Inflammation plays an essential role in secondary brain injury after intracerebral hemorrhage (ICH). Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) have been suggested to suppress neuroinflammation after central nervous system (CNS) damage in animal models. However, the role of ACEIs and ARBs in ICH patients with hypertension remains unresolved in clinic. The aim of the present study is to evaluate the effect of ACEIs/ARBs on ICH patients with hypertension using a retrospective, single-center data analysis. METHODS: ICH patients diagnosed by computerized tomographic (CT) at Southwest Hospital, Third Military Medical University were included in the present research from January 2015 to December 2019. According to the medical history for the usage of antihypertensive drugs, patients were assigned into either ACEIs/ARBs group or non-ACEIs/ARBs group. Demographics, clinical baseline, radiological documents and treatments were collected and these data were statistically analyzed between the two groups. RESULTS: A total of 635 ICH patients with hypertension were included and allocated into 2 groups according to the usage of antihypertensive drugs: 281 in the ACEIs/ARBs group and 354 in the non-ACEIs/ARBs group. The results presented that the 3-months mortality and prevalence of ICH-associated pneumonia were lower in ACEIs/ARBs group than that in non-ACEIs/ARBs group (5.0% vs 11.9%, p=0.002; 58.4% vs 66.7%, p=0.031). While, there was no significant difference in favorable outcome (40.2% vs 33.9%, p=0.101) between the two groups. Furthermore, patients in ACEIs/ARBs group exhibited significantly less perihematomal edema volume on days 3 (23.5 ± 14.4 versus 28.7 ± 20.1 mL, p=0.045) and 7 (21.0 ± 13.7 versus 25.7 ± 17.6 mL, p=0.044), compared to that in non- ACEIs/ARBs group. CONCLUSION: The usage of ACEIs/ARBs helps decrease mortality, perihematomal edema volume, and prevalence of ICH-associated pneumonia in ICH patients with hypertension.

Long-term Outcomes and Risk Factors Related to Hydrocephalus After Intracerebral Hemorrhage.

Hydrocephalus after intracerebral hemorrhage (ICH) is a common and treatable complication. However, the long-term outcomes and factors for predicting hydrocephalus have seldom been studied. The goal of this study was to determine the long-term outcomes and analyze the risk factors of hydrocephalus after ICH. A consecutive series of 1342 patients with ICH were reviewed from 2010 to 2016 to identify significant risk factors for hydrocephalus. Patients with a first-ever ICH without any prior diagnosis of hydrocephalus after ICH were followed up for survival status and cause of death. Risk factors for hydrocephalus were evaluated by using logistic regression analysis. Out of a total of 1342 ICH patients, 120 patients (8.9%) had hydrocephalus. The risk factors for hydrocephalus (≤ 3 days) were infratentorial hemorrhage (p = 0.000), extension to ventricles (p = 0.000), greater ICH volume (p = 0.09), and hematoma expansion (p = 0.01). Extension to ventricles (p = 0.022) was the only independent risk factor for hydrocephalus (4-13 days), while extension to ventricles (p = 0.028), decompressive craniotomy (p = 0.032), and intracranial infection (p = 0.001) were independent predictors of hydrocephalus (≥ 14 days). Patients were followed up for a median of 5.2 years (IQR 3.3-7.3 years). Estimated all-cause mortality was significantly higher in the ICH patients with hydrocephalus than that without hydrocephalus (HR 3.22, 95% CI 2.42-4.28; p = 0.000). Fifty-nine (49.2%) died and 40 (33.3%) had a favorable outcome in patients with hydrocephalus. Of all deaths, 30.5% were from ICH and 64.4% from infection. Hydrocephalus is a frequent complication of ICH and most commonly occurs at the onset of ICH. Patients with hydrocephalus show relatively higher mortality. ClinicalTrials.gov Identifier: NCT02135783 (May 7, 2014).

Comprehensive analysis of prognostic value and immune infiltration of calpains in pancreatic cancer.

BACKGROUND: Calpains (CAPNs) are intracellular calcium-activated neutral cysteine proteinases involved in cancer initiation, progression, and metastasis. However, its role in pancreatic cancer (PC) is still unclear. This study aims to identify the prognostic value and immune infiltration of CAPNs for PC patients using comprehensive bioinformatics analyzes. METHODS: We analyzed the transcription levels of CAPNs in different cancers from Oncomine, differential gene expression in tumor/normal tissues and pathological stage through GEPIA database, the prognostic value of the mRNA expression of CAPNs by Kaplan-Meier plotter, the protein expression comparison of different CAPNs in human tumor/normal tissues from The Human Protein Atla, the CAPNs gene alterations through cBioPortal, the prediction of protein-protein interactions by STRING and GeneMANIA, the functional enrichment of discrepant CAPNs by GO and KEGG, and the immune infiltration of CAPNs by ssGSEA. RESULTS: Our results showed that CAPN1, 2, 4, 5, 6, 8, 9, 10, and 12 were highly expressed in PC. CAPN1, 5, 8, and 12 expression levels were positively correlated with individual cancer stages. Furthermore, CAPN1, 2, 5, and 8 expression levels were negatively correlated with overall survival (OS) and recurrence-free survival (RFS), while CAPN10 was positively correlated with OS and RFS. We found that CAPN1, 2, 5, and 8 were correlated with tumor-infiltrating T follicular helper cells and CAPN10 with tumor-infiltrating T helper 2 cells. Functional enrichment analysis showed that differentially expressed CAPNs (CAPN1, 2, 5, 8, and 10) are involved in axonogenesis, cell-substrate adhesion, immune response-activating cell surface receptor signaling pathway, and cell junction organization in PC. CONCLUSIONS: These results suggested that CAPN1, 2, 5, 8, and 10 could be used as prognostic biomarkers in PC and improve individualized treatment strategies.

Magnetic resonance imaging for preoperative staging of pancreatic cancer based on the 8th edition of AJCC guidelines.

BACKGROUND: Preoperative staging of pancreatic cancer determines the choice of treatment. Magnetic resonance imaging (MRI) plays an important role in preoperative staging of pancreatic cancer. The American Joint Committee on Cancer (AJCC) TNM staging system was revised to its 8th version in 2016, there has been no report correlating the 8th edition of the AJCC TNM staging with preoperative MRI examinations and pathological findings. The purpose of our study is to determine the staging accuracy and evaluate the resectability by using MRI about pancreatic cancer compared with intraoperative or pathological findings according to the 8th edition of the AJCC TNM staging system. METHODS: One hundred thirty-two patients with a pathological diagnosis of pancreatic cancer who underwent preoperative MRI were identified. The clinical data, MRI findings and pathological findings were analyzed. Preoperative MRI staging and resectability evaluation were compared with pathological findings. The accuracy of MRI for preoperative T and N staging was evaluated, and the sensitivity, specificity and accuracy of MRI in evaluating the resectability were assessed. All the staging and resectability assessments were according to the 8th edition of the AJCC TNM staging system. RESULTS: Analysis showed that the accuracy of MRI for evaluation of the T and N stages was 82.6% (109/132) and 74.2% (98/132), respectively. The sensitivity and specificity of MRI in assessing the resectability were 94.2% and 71.4%, respectively. Integrating the 8th edition of the AJCC TNM stage, no significant differences were identified between the preoperative MRI and pathological results for the staging of pancreatic cancer (P=0.805). CONCLUSIONS: MRI is highly accurate for T staging and moderately accurate for N staging. MRI provides important preoperative evaluation of the stage and resectability of pancreatic cancer based on the 8th edition of the AJCC TNM staging system.

Extrapancreatic Inflammation on Magnetic Resonance Imaging for the Early Prediction of Acute Pancreatitis Severity.

OBJECTIVES: This work aimed to study the early predictive value of extrapancreatic inflammation on magnetic resonance imaging (EPIM) for acute pancreatitis (AP) severity. METHODS: The EPIM score, magnetic resonance severity index, Acute Physiology and Chronic Health Evaluation (APACHE II) score, bedside index of severity in AP, and high-sensitivity C-reactive protein levels were evaluated for 337 AP patients. The extrapancreatic inflammation on computed tomography (EPIC) was also assessed for 86 patients undergoing computed tomography. The predictive values of these scores for severe AP and organ failure were evaluated using receiver operating characteristic curve analyses. RESULTS: Of the 337 AP patients, 55 (16.3%) had organ failure and 17 (5.0%) had severe AP. The EPIM showed a strong correlation with the EPIC (r = 0.794, P < 0.001) and had a higher correlation with the APACHE II and hospital stay compared with the EPIC. The accuracy of the EPIM in predicting severe AP and organ failure (areas under the curve, 0.844 and 0.817) was consistent with that of the APACHE II and bedside index of severity in AP, and higher than that of the magnetic resonance severity index. CONCLUSION: The EPIM is more helpful in assessing AP severity than the EPIC and can indicate the occurrence of severe AP and organ failure early.

Targeting neutrophil extracellular traps enhanced tPA fibrinolysis for experimental intracerebral hemorrhage.

The minimally invasive surgery plus fibrinolysis has been identified as a promising treatment for spontaneous intracerebral hemorrhage (ICH). However, the fibrinolytic efficacy is not satisfactory. Neutrophil extracellular traps (NETs) have been demonstrated to impair fibrinolysis in sepsis and acute ischemic stroke. Therefore, we decided to explore the presence and potential effect of NETs in ICH fibrinolysis. Intracerebral hemorrhage was induced by autologous arterial blood injection into the basal ganglia in rats. First, at 0.5 hour, 1 hour, and 1.5 hours after blood injection, the brains were collected for NETs detection by immune-staining. Second, ICH rats were given intrahematoma fibrinolysis: rats were randomized to receive the equal amount of saline, DNAse 1, tissue-plasminogen activator (tPA), and tPA + DNAse 1 at 1 hour after hematoma placement. On day 3, animals were sacrificed for terminal deoxynucleotidyl transferase-mediated dUTP Nick-end labeling staining following MRI and behavioral tests. Third, on day 3 after ICH, the hematoma within brain were collected for ex vivo fibrinolysis assay to further evaluate the effect of NETs in ICH fibrinolysis. Co-staining of DAPI, H3, and MPO confirmed the presence of NETs in ICH. Disintegration of NETs using DNAse 1 enhanced tPA-induced hematoma fibrinolysis, relieved brain swelling, reduced cell death, and improved the functional outcome in ICH rats. Therefore, we concluded that NETs impaired the efficacy of tPA for ICH fibrinolysis in rats. Targeting NETs may be a new alternative to improve the fibrinolytic therapy following ICH.

Surgery combined with post-operative trancatheter arterial chemoembolization improves survival of intermediate hepatocellular carcinoma.

AIM: To investigate the efficacy of surgery combined with post-operative trancatheter arterial chemoembolization (TACE) for intermediate hepatocellular carcinoma (HCC). METHODS: A total of 102 patients were divided into two groups: Radical liver resection only (LR group, 52 patients) and radical liver resection combined with post-operative TACE (combined group, 50 patients). Survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate analysis were performed using Cox proportional analysis to detect prognostic factors of survival outcomes. RESULTS: The 1-, 3- and 5-year survival rate in the LR group were significantly lower compared with those in combined group (p = .019). The 1-, 3- and 5-year progression-free survival rate in the LR group were also lower than those in the combined group (p = .048). Multivariate analysis detected that tumor number (multiple vs single), tumor distribution (both lobes vs semi-liver), treatment strategy (surgery + TACE vs surgery) were independent factors for OS (HR values were 2.307, 3.155 and 0.526, respectively) and PFS (HR values were 1.938, 3.425 and 0.633, respectively; p < .05). CONCLUSION: In conclusion, surgery combined with post-operative TACE may improve survival outcomes for patients with intermediate HCC. Tumor number, tumor distribution and treatment strategy (surgery + TACE) were significantly associated with the prognosis of patients with intermediate HCC.

Chondroitin sulfate proteoglycan represses neural stem/progenitor cells migration via PTPσ/α-actinin4 signaling pathway.

Neural stem/progenitor cells (NSPCs) are a promising candidate for the cell-replacement therapy after central nervous system (CNS) injury. However, the short of sufficient NSPCs migration and integration into the lesions is an essential challenge for cell-based therapy after CNS injury due to the disturbance of local environmental homeostasis. Chondroitin sulfate proteoglycan (CSPG) is obviously accumulated at the lesions and destroyed local homeostasis after CNS injury. The previous study has demonstrated that the CSPG is a dominating ingredient inhibiting axonal regrowth of newly born neurons after CNS injury. NSPCs, a strain of special neural subtypes, hold the capacity of leading processes formation to regulate NSPCs migration, which has the same mechanism as axonal regrowth. Hence, it is worth investigating the effect of CSPG on NSPCs migration and its underlying mechanism. Here, different concentration of CSPG was used to evaluate its effect on NSPCs migration. The results showed that the CSPG suppressed NSPCs migration in a dose-dependent manner from 10 to 80 µg/mL with phase-contrast microscopy after 24 hours. Meanwhile, transwell assays were performed to certify the above results. Our data indicated that the 40 µg/mL CSPG obviously suppressed NSPCs migration via decreasing filopodia formation using immunofluorescence staining. Furthermore, data indicated that the 40 µg/mL CSPG upregulated protein tyrosine phosphatase receptor σ (PTPσ) expression and decreased α-actinin4 (ACTN4) expression through immunofluorescence, reverse transcription polymerase chain reaction, and Western blot assays. While the inhibitory effect was attenuated using PTPσ-specific small interfering RNA. In addition, data demonstrated that the 40 µg/mL CSPG facilitated NSPCs differentiation into glial fibrillary acidic protein-positive cells and inhibited NSPCs directing into MAP2- and MBP-positive cells. Collectively, these data demonstrated that the CSPG suppressed NSPCs migration through PTPσ/ACTN4 signaling pathway. Meanwhile, CSPG facilitated NSPCs differentiation into astrocytes and inhibited NSPCs directing into neurons and oligodendrocytes.

Hepatic resection combined with radiofrequency ablation versus hepatic resection alone for multifocal hepatocellular carcinomas: A meta-analysis.

This meta-analysis aimed to comprehensively assess the efficacy and safety of hepatic resection combined with radiofrequency ablation versus hepatic resection (HR) alone for the treatment of multifocal hepatocellular carcinomas (HCC). A literature search was conducted from the database including MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and China Biology Medicine (CBM) disc. The primary outcomes included the 1-, 3-, 5-year overall survival (OS) and disease-free survival (DFS) rate. The secondary outcomes contained the intraoperative parameters and postoperative adverse events (AEs). These parameters were all analyzed by RevMan 5.3 software. After carefully screening relevant studies, four retrospective studies of high quality involving 466 patients (197 in the combined group and 269 in the HR group) were included in this study. The pooled results showed that the 1-, 3-, 5-year OS rate in the combined group were comparable with those in the HR group (OR=0.77, 0.96, 0.88; P=0.33, 0.88, 0.70, respectively). Similarly, there was no significant difference in 1-, 3-, 5-year DFS rate between the combined group and the HR alone group (OR=0.57, 0.83, 0.72; P=0.17, 0.37, 0.32, respectively). And the intraoperative parameters and postoperative AEs were also comparable between the above two cohorts. However, two included studies reported that tumor often recurred in the ablation site in the combined group. The present meta-analysis indicated that the HR combined with RFA could reach a long-term survival outcome similar to curative HR for multifocal HCC patients. And this therapy may be a promising alternative for these patients with marginal liver function or complicated tumor distribution. Furthermore, high quality randomized controlled trials (RCTs) are imperative to verify this conclusion.

HIF1α regulates glioma chemosensitivity through the transformation between differentiation and dedifferentiation in various oxygen levels.

Chemotherapy plays a significant role in glioma treatment; however, it has limited effectiveness in extending the life expectancies of glioma patients. Traditional studies have attributed this lack of efficacy to glioma stem cells (GSCs) and their high resistance to chemotherapy, and hypoxia worsens this issue. In contrast, hyperoxia effectively alleviates hypoxia in glioma and sensitizes glioma cells to chemotherapy. In a summary of traditional studies, the majority of researchers overlooked the influence of hypoxia on differentiated cells because they only focused on the maintenance of GSCs stemness, which thus resulted in chemoresistance. Because of this background, we hypothesized that GSCs may be induced through dedifferentiation under hypoxic conditions, and hypoxia maintains GSCs stemness, which thus leads to resistance to chemotherapy. In contrast, hyperoxia inhibits the dedifferentiation process and promotes GSCs differentiation, which increases the sensitization of glioma cells to chemotherapy. Hypoxia-inducible factor-1α (HIF1α) contributes substantially to the stemness maintenance of GSCs and resistance of glioma to chemotherapy; thus, we investigated whether HIF1α regulates the resistance or sensitization of glioma cells to chemotherapy in different oxygen levels. It highlights a novel viewpoint on glioma chemosensitivity from the transformation between dedifferentiation and differentiation in different oxygen levels.