Integration of single-cell RNA-seq and bulk RNA-seq to construct liver hepatocellular carcinoma stem cell signatures to explore their impact on patient prognosis and treatment.

BACKGROUND: Liver hepatocellular carcinoma (LIHC) is a prevalent form of primary liver cancer. Research has demonstrated the contribution of tumor stem cells in facilitating tumor recurrence, metastasis, and treatment resistance. Despite this, there remains a lack of established cancer stem cells (CSCs)-associated genes signatures for effectively predicting the prognosis and guiding the treatment strategies for patients diagnosed with LIHC. METHODS: The single-cell RNA sequencing (scRNA-seq) and bulk RNA transcriptome data were obtained based on public datasets and computerized firstly using CytoTRACE package and One Class Linear Regression (OCLR) algorithm to evaluate stemness level, respectively. Then, we explored the association of stemness indicators (CytoTRACE score and stemness index, mRNAsi) with survival outcomes and clinical characteristics by combining clinical information and survival analyses. Subsequently, weighted co-expression network analysis (WGCNA) and Cox were applied to assess mRNAsi-related genes in bulk LIHC data and construct a prognostic model for LIHC patients. Single-sample gene-set enrichment analysis (ssGSEA), Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and Tumor Immune Estimation Resource (TIMER) analysis were employed for immune infiltration assessment. Finally, the potential immunotherapeutic response was predicted by the Tumor Immune Dysfunction and Exclusion (TIDE), and the tumor mutation burden (TMB). Additionally, pRRophetic package was applied to evaluate the sensitivity of high and low-risk groups to common chemotherapeutic drugs. RESULTS: A total of four genes (including STIP1, H2AFZ, BRIX1, and TUBB) associated with stemness score (CytoTRACE score and mRNAsi) were identified and constructed a risk model that could predict prognosis in LIHC patients. It was observed that high stemness cells occurred predominantly in the late stages of LIHC and that poor overall survival in LIHC patients was also associated with high mRNAsi scores. In addition, pathway analysis confirmed the biological uniqueness of the two risk groups. Personalized treatment predictions suggest that patients with a low risk benefited more from immunotherapy, while those with a high risk group may be conducive to chemotherapeutic drugs. CONCLUSION: The current study developed a novel prognostic risk signature with genes related to CSCs, which provides novel ideas for the diagnosis, prognosis and treatment of LIHC.

[Inhibition of Ferulic Acid on U937 Cell Growth and Its Related Mechanism].

OBJECTIVE: To investigate the effects of ferulic acid (FA) on proliferation, apoptosis and Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway of human acute myeloid leukemia (AML) U937 cells. METHODS: Different concentrations of FA (0、10、25、50、100、200 µmol/L) was used to treat human AML cell lines Kasumi-1, HL-60, and U937 cells respectively for 24 h. The cell survival rate was detected by cell counting kit-8 method, and the 50% inhibitory concentration (IC50) of each cell line was calculated. The U937 cells were divided into control group, FA group (50 µmol/L FA), FA+pcDNA group (50 µmol/L FA+transfected with empty plasmid), FA+pcDNA-TLR4 group (50 µmol/L FA+transfected with TLR4 overexpression plasmid). Flow cytometry was used to detect U937 cell cycle and cell apoptosis; plate clone formation test was used to detect U937 cell clone formation ability; fluorescence quantitative PCR was used to detect the TLR4, NF-κB p65 mRNA levels in U937 cells; Western blot was used to detect the expression levels of CyclinD1, CyclinE, Bcl-2 related X protein (Bax), B cell lymphoma-2 (Bcl-2), Caspase-3, TLR4, and NF-κB p65 protein in U937 cells. RESULTS: With the increase of FA concentration, the survival rates of Kasumi-1, HL-60 and U937 cells gradually decreased(r=-0.919, r=-0.909, r=-0.900), the IC50 of U937 cells was 50.25±2.23 µmol/L. Compared with the control group, after drug treatment of U937 cells, the ratio of G0/G1 phase cells, apoptosis rate, expression levels of Bax and Caspase-3 proteins in FA group were significantly increased (P<0.05), the number of cell clones, the ratios of S phase and G2/M phase cells, expression levels of CyclinD1, CyclinE and Bcl-2 proteins, and TLR4, NF-κB p65 mRNA and protein were significantly decreased (P<0.05); compared with FA group and FA+pcDNA group, the ratio of G0/G1 phase cells, apoptosis rate, expression levels of Bax and Caspase-3 proteins in FA+pcDNA-TLR4 group were significantly decreased (P<0.05), the number of cell clones, the ratios of S phase and G2/M phase cells, expression levels of expression levels of CyclinD1, CyclinE and Bcl-2 proteins, and TLR4, NF-κB p65 mRNA and proteins were significantly increased (P<0.05). CONCLUSION: FA inhibits U937 cell proliferation and promotes cell apoptosis by inhibiting the TLR4/NF-κB signaling pathway.

Transcriptome-wide profiling of A-to-I RNA editing by Slic-seq.

Adenosine-to-inosine (A-to-I) RNA editing is a post-transcriptional processing event involved in diversifying the transcriptome and is responsible for various biological processes. In this context, we developed a new method based on the highly selective cleavage activity of Endonuclease V against Inosine and the universal activity of sodium periodate against all RNAs to enrich the inosine-containing RNA and accurately identify the editing sites. We validated the reliability of our method in human brain in both Alu and non-Alu elements. The conserved sites of A-to-I editing in human cells (HEK293T, HeLa, HepG2, K562 and MCF-7) primarily occurs in the 3'UTR of the RNA, which are highly correlated with RNA binding and protein binding. Analysis of the editing sites between the human brain and mouse brain revealed that the editing of exons is more conserved than that in other regions. This method was applied to three neurological diseases (Alzheimer's, epilepsy and ageing) of mouse brain, reflecting that A-to-I editing sites significantly decreased in neuronal activity genes.

New Indole Diketopiperazine Alkaloids from Soft Coral-Associated Epiphytic Fungus Aspergillus versicolor CGF 9-1-2.

Two new indole diketopiperazine alkaloids (IDAs), (+)19-epi-sclerotiamide (1) and (-)19-epi-sclerotiamide (2), along with 13 known analogs (3-15), were isolated from a soft coral-associated epiphytic fungus Aspergillus versicolor CGF 9-1-2. The structures of two new compounds were established based on the combination of HR-ESI-MS, 1D and 2D NMR spectroscopy, optical rotation measurements and quantum chemical 13 C-NMR, the absolute configurations were determined by experimental and electronic circular dichroism (ECD) calculations. The results of molecular docking showed that all the compounds had a good binding with TDP1, TDP2, TOP1, TOP2, Ache, NLRP3, EGFR, EGFR L858R, EGFR T790M and EGFR T790/L858. Biological evaluation of compounds 3, 6, 8, 11 showed that 3 exerted a strong inhibitory effect on TDP2 with a rate of 81.72 %.

Correlation between direction of pedicle screw and restoration of lumbar degenerative scoliosis in degenerative lumbar spondylolisthesis: a retrospective study.

Background: Inferior clinical outcomes have been reported in patients with degenerative lumbar spondylolisthesis (DLS) accompanied by lumbar degenerative scoliosis, but little attention has been paid to its radiologic assessment or preoperative planning. The aim of this study was to analyze the effect of transforaminal lumbar interbody fusion on patients with DLS and lumbar degenerative scoliosis and explore the surgical aspects benefiting the restoration of lumbar degenerative scoliosis. Methods: All patients with DLS and lumbar degenerative scoliosis undergoing single-level unilateral transforaminal lumbar interbody fusion surgery between July 1, 2015, and April 30, 2021, were screened in this retrospective cohort study. Clinical outcomes including visual analog scale (VAS), Oswestry disability index (ODI), and radiographic parameters of sagittal and coronal alignment, cage spatial locations, and angle of pedicle screw (parallel, cranial, and caudad angle) were assessed. Coronal asymmetry was demonstrated by the intervertebral height difference between the medial and lateral margins of indexed intersegmental space. The correlations between Δintervertebral height difference (postoperative intervertebral height difference-preoperative intervertebral height difference) and radiographic parameters and clinical outcomes were analyzed by univariable, multivariable, mediation, and correlation analyses. Significance was set at a bilateral P<0.05. Results: A total of 57 included patients were followed up for a minimum of 1 year. Reduction of VAS, ODI, and improvement of radiographic parameters were found after surgery. The cranial angle of the lower pedicle screw positively correlated with Δintervertebral height difference restoration (b=0.54; standard error=0.11; P<0.001). Conclusions: Transforaminal lumbar interbody fusion surgery appears to be an effective approach to improving the radiographic and clinical outcomes of patients with DLS and lumbar degenerative scoliosis. The cranial direction of the lower pedicle screws in single-level unilateral transforaminal lumbar interbody fusion surgery may be associated with a better postoperative restoration of lumbar degenerative scoliosis.

Dynamic evaluation of the cervical spine by kinematic MRI in patients with cervical spinal cord injury without fracture and dislocation.

BACKGROUND: The pattern of changes in the cervical spine and the spinal cord and their dynamic characteristics in patients with cervical spinal cord injury without fracture and dislocation remain unclear. This study aimed to evaluate the dynamic changes in the cervical spine and spinal cord from C2/3 to C7/T1 in different positions by using kinematic magnetic resonance imaging in patients with cervical spinal cord injury without fracture and dislocation. This study was approved by the ethics committee of Yuebei People's Hospital. METHODS: Using median sagittal T2-weighted images for 16 patients with cervical spinal cord injury without fracture and dislocation who underwent cervical kinematic MRI, the anterior space available for the cord, spinal cord diameter, posterior space available for the cord from C2/3 to C7/T1, and Muhle's grade were determined. The spinal canal diameter was calculated by adding the anterior space available for the cord, spinal cord diameter, and posterior space available for the cord. RESULTS: The anterior space available for the cord, posterior space available for the cord, and spinal canal diameters at C2/3 and C7/T1 were significantly higher than those from C3/4 to C6/7. Muhle's grades at C2/3 and C7/T1 were significantly lower than those at the other levels. Spinal canal diameter was lower in extension than in the neutral and flexion positions. In the operated segments, significantly lesser space was available for the cord (anterior space available for the cord + posterior space available for the cord), and the spinal cord diameter/spinal canal diameter ratio was higher than those in the C2/3, C7/T1, and non-operated segments. CONCLUSION: Kinematic MRI demonstrated dynamic pathoanatomical changes, such as canal stenosis in different positions, in patients with cervical spinal cord injury without fracture and dislocation. The injured segment had a small canal diameter, high Muhle's grade, low space available for the cord, and high spinal cord diameter/spinal canal diameter ratio.

PD-1 inhibitor-based adverse events in solid tumors: A retrospective real-world study.

Background & Aims: Immune checkpoint inhibitors (ICIs) have transformed the landscape of cancer treatment, and ICI-related toxicities (i.e., immune-related adverse events (irAEs) have been reported in many clinical studies. However, the toxicity data of real-world have not been fully assessed. Methods: Patients with histologically confirmed solid tumors who had been treated with PD-1 inhibitors were included in the study. Patient data were collected from electronic medical records, including basic characteristics, data of irAEs, management and outcome. Incidences of irAEs were pooled and compared, and the risk of irAEs was also analyzed. Results: A total of 362 solid tumor patients treated with sintilimab (n = 171), camrelizumab (n = 60), toripalimab (n = 72), and pembrolizumab (n = 59) were included. In total, any grade irAEs, grade 1-2 irAEs, and grade ≥3 irAEs accounted for 47.24%, 38.67% and 8.56% of cases, reapectively. Further, 29.24% of patients discontinued immunotherapy due to irAEs, with pneumonitis being the main reason for discontinuation. By comparing the toxicity profiles between different ICIs, we found that reactive capillary haemangiomas were camrelizumab-specific. Additionally, the frequency of irAEs was association with ICIs type, the pooled incidence (standardized rate) of irAEs related to sintilimab, camrelizumab, toripalimab and pembrolizumab were 55.56% (52.81%), 48.33% (55.55%), 33.33% (29.23%) and 38.98% (38.29%), respectively. Sintilimab and camrelizumab had higher incidences of any grade and grade 1-2 than toripalimab (55.56% vs. 33.33%, p = 0.002; 48.54% vs. 25.00%, p = 0.0001) and pembrolizumab (55.56% vs. 38.98%, p = 0.0028; 48.54% vs. 25.42%, p = 0.002), while the grade ≥3 irAEs of pembrolizumab (13.56%) were approximately 1.63- to 1.93-fold higher than other ICIs, and the standardized grade ≥3 of pembrolizumab was significantly higher than that of sintilimab (13.21% vs. 7.12%, p = 0.026), especially for grade ≥3 pneumonitis. Multivariate analysis found that cumulative cycles of ICI (OR = 1.081; 95% CI: 1.023-1.142; p = 0.006), and lung cancer (OR = 1.765; 95% CI: 1.105-2.820; p = 0.017) were independent risk factors for irAEs. Conclusion: The frequency of irAEs is associated with ICI type. The pooled incidence of irAEs related to sintilimab and pneumonitis caused by pembrolizumab were higher. These data indicate the importance of having different monitoring priorities for different PD-1 inhibitors.

What Is Different about Teratoma-Associated Anti-LGI1 Encephalitis? A Long-Term Clinical and Neuroimaging Case Series.

INTRODUCTION: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is clinically heterogeneous, especially at presentation, and though it is sometimes found in association with tumor, this is by no means the rule. METHODS: Clinical data for 10 patients with anti-LGI1 encephalitis were collected including one case with teratoma and nine cases without and compared for clinical characteristics. Microscopic pathological examination and immunohistochemical assay of the LGI1 antibody were performed on teratoma tissue obtained by laparoscopic oophorocystectomy. RESULTS: In our teratoma-associated anti-LGI1 encephalitis case, teratoma pathology was characterized by mostly thyroid tissue and immunohistochemical assay confirmed positive nuclear staining of LGI1 in some tumor cells. The anti-LGl1 patient with teratoma was similar to the non-teratoma cases in many ways: age at onset (average 47.3 in non-teratoma cases); percent presenting with rapidly progressive dementia (67% of non-teratoma cases) and psychiatric symptoms (33%); hyponatremia (78%); normal cerebrospinal fluid results except for positive LGI1 antibody (78%); bilateral hippocampal hyperintensity on magnetic resonance imaging (44%); diffuse slow waves on electroencephalography (33%); good response to immunotherapy (67%); and mild residual cognitive deficit (22%). Her chronic anxiety and presentation with status epilepticus were the biggest differences compared with the non-teratoma cases. CONCLUSION: In our series, anti-LGI1 encephalitis included common clinical features in our series: rapidly progressive dementia, faciobrachial dystonic seizures, behavioral disorders, hyponatremia, hippocampal hyperintensity on magnetic resonance imaging, and residual cognitive deficit. We observed some differences (chronic anxiety and status epilepticus) in our case with teratoma, but a larger accumulation of cases is needed to improve our knowledge base.

Predictive value of prognostic nutritional index on infection after radical gastrectomy: a retrospective study.

Background: The prognostic nutritional index (PNI) is a useful tool to evaluate nutritional status, which is associated with postoperative complications and prognosis of patients with cancer. Recent studies have shown that PNI has important predictive value for postoperative infection in cancer patients. However, the role and clinical value of PNI in infection after radical gastrectomy remains unclear. This study investigated the relationship between PNI and infection after radical surgery for gastric cancer (GC), focusing on the predictive value of PNI. Methods: A total of 1,111 patients with primary gastric cancer who underwent radical surgery in our hospital from December 2010 to December 2020 were included in this retrospective study. The demographic and clinicopathological data of all patients were acquired through hospital information system (HIS). Preoperative serum albumin (ALB) level and peripheral blood lymphocyte count were obtained for PNI calculation. We selected 812 patients by propensity score matching to reduce biases due to the different distributions of co-variables among the comparable groups. The factors influencing postoperative infection in the matched patients were explored using univariate and multivariate analyses. Results: Baseline characteristics significantly differed among patients with different PNI scores. After one-to-one matching, the clinicopathological data of the 2 groups were comparable, and 812 patients were included for further analysis. Among these patients, 101 developed infections, with an infection rate of 12.4%, which were mainly caused by gram-negative bacteria. The incidence of infection was significantly higher in the low PNI group than in the high PNI group. Univariate and multivariate analyses identified body mass index (BMI) ≥25 kg/m2 [odds ratio (OR) =2.314, P=0.004], diabetes mellitus (OR =1.827, P=0.042), PNI score <45 (OR =2.138, P=0.037), combined multi-organ resection (OR =2.946, P<0.001), operation time ≥240 minutes (OR =2.744, P=0.023), and perioperative blood transfusion (OR =2.595, P=0.025) as risk factors for infection after radical surgery for GC. Conclusions: Infection is the most common complication after radical gastrectomy for GC, and a low preoperative PNI score is a risk factor for postoperative infection.

The role of microRNA-4723-5p regulated by c-myc in triple-negative breast cancer.

The aim of this study was to investigate the expression of miRNA regulated by c-myc and its mechanism in three negative breast cancer (TNBC). We constructed MDA-MB-231 cell line with low expression of c-myc by lentivirus short hairpin RNA (shRNA), analyzed the miRNA expression profile of MDA-MB-231 cell line with different expression levels of c-myc by high-throughput sequencing technology, obtained differential miRNA by bioinformatics analysis and statistical analysis, and verified hsa-mir-4723-5p by Quantitative Real-time polymerase chain reaction(QRT-PCR). The target gene of hsa-mir-4723-5p was analyzed by miRDB and miRWalk database. The results showed that there were significant differences in 126 miRNAs in c-myc knockdown cell lines compared with the control group, of which 84 were significantly up-regulated and 42 were significantly down regulated. According to the results of miRNA sequencing, the miRNA closely related to the expression of c-myc was hsa-mir-4723-5p. QRT PCR showed that the expression of hsa-mir-4723-5p was down regulated in TNBC cell line MDA-MB-231 with low expression of c-myc, which was positively correlated with the expression. The target genes of hsa-mir-4723-5p were predicted according to mirdb and mirwalk database. A total of 112 target genes were obtained, and 107 target genes were related to hsa-mir-4723-5p. Through mirdb and mirwalk databases, it was found that the target gene TRAF4 of hsa-mir-4723-5p may be related to cancer pathway and affect tumor metastasis. In conclusion, the hsa-miR-4723-5p regulated by c-myc may be involved.

Thyroidectomy Using the Lateral Cervical Small Incision Approach for Early Thyroid Cancer.

Objective: Surgical resection is the main treatment for thyroid cancer, but while traditional open thyroidectomy improves prognosis, it also results in poor cosmetic outcomes. Therefore, we devised the lateral cervical small incision approach to thyroidectomy and will evaluate its efficacy. Methods: The clinicopathological data of 191 patients who underwent unilateral thyroidectomy and isthmusectomy for early thyroid cancer were collected retrospectively. Of these, 100 patients underwent a traditional thyroidectomy using the median cervical approach (control group), and 91 patients underwent a thyroidectomy using the lateral cervical small incision approach (experimental group). The differences in perioperative prognosis, postoperative complications, and cosmetic outcomes between the two groups were evaluated. Results: There was no significant difference in sex, age, tumor size, lymph node dissection, number of metastases, or postoperative complications between the experimental group and the control group (P > 0.05). There were significant differences in the duration of the operation; postoperative blood loss, drainage, and hospital stay; and scar color, blood circulation, hardness, and thickness between the groups (P < 0.05). The cosmetic outcomes of the incisions in the experimental group were more satisfactory than in the control group (P < 0.05). Conclusion: When compared with traditional open thyroidectomy, the lateral cervical small incision approach has a lower incidence of complications, a better perioperative prognosis, and an improved cosmetic outcome.

Probing Indole Diketopiperazine-Based Hybrids as Environmental-Induced Products from Aspergillus sp. EGF 15-0-3.

Comprehensive analyses of the metabolite spectra of Aspergillus sp. EGF 15-0-3 under different culture conditions revealed the presence of unique environmental-induced metabolites exclusively from the rice medium. Subsequent target isolation afforded four unprecedented indole diketopiperazine-based hybrids with a pyrano[3',2':7,8]isochromeno[4,3-b]pyrazino[2,1-i]indole core (1 and 2) or a spiro[piperazine-2,2'-pyrano[3,4,5-de]chromene] scaffold (3 and 4). Putative biosynthetic pathways for 1-4, with Diels-Alder cycloadditions as key steps, were proposed. 1-4 exhibited selective cytotoxicities among several human cancer cells.

Is obstructive sleep apnoea associated with hypoxaemia and prolonged ICU stay after type A aortic dissection repair? A retrospective study in Chinese population.

BACKGROUND: Although obstructive sleep apnoea (OSA) is prevalent among patients with aortic dissection, its prognostic impact is not yet determined in patients undergoing major vascular surgery. We aimed to investigate the association of OSA with hypoxaemia and with prolonged intensive care unit (ICU) stay after type A aortic dissection (TAAD) repair. METHODS: This retrospective study continuously enrolled 83 patients who underwent TAAD repair from January 1 to December 31, 2018. OSA was diagnosed by sleep test and defined as an apnoea hypopnea index (AHI) of ≥ 15/h, while an AHI of > 30/h was defined severe OSA. Hypoxaemia was defined as an oxygenation index (OI) of < 200 mmHg. Prolonged ICU stay referred to an ICU stay of > 72 h. Receiver operating characteristic curve analysis was performed to evaluate the predictive value of postoperative OI for prolonged ICU stay. Multivariate logistic regression was performed to assess the association of OSA with hypoxaemia and prolonged ICU stay. RESULTS: A total of 41 (49.4%) patients were diagnosed with OSA using the sleep test. Hypoxaemia occurred postoperatively in 56 patients (67.5%). Postoperatively hypoxaemia developed mostly in patients with OSA (52.4% vs. 83.0%, p = 0.003), and particularly in those with severe OSA (52.4% vs. 90.5%, p = 0.003). The postoperative OI could fairly predict a prolonged ICU stay (area under the receiver-operating characteristic curve, 0.72; 95% confidence intervals [CI] 0.60-0.84; p = 0.002). Severe OSA was associated with both postoperative hypoxaemia (odds ratio [OR] 6.65; 95% CI 1.56-46.26, p = 0.008) and prolonged ICU stay (OR 5.58; 95% CI 1.54-20.24, p = 0.009). CONCLUSIONS: OSA was common in patients with TAAD. Severe OSA was associated with postoperative hypoxaemia and prolonged ICU stay following TAAD repair.

Do the positioning variables of the cage contribute to adjacent facet joint degeneration? Radiological and clinical analysis following intervertebral fusion.

BACKGROUND: Compared to other risk factors, adjacent facet joint degeneration (AFD) is the main contributor to adjacent segment disease (ASD). The interbody cage may be a potential indirect risk of AFD. This study investigated the correlations among the lumbar sagittal balance parameters, the inter-body cage's intraoperative positioning variables, and adjacent facet joint degeneration following the transforaminal lumbar interbody fusion (TLIF) technique. METHODS: Patients who accepted single-level TLIF for symptomatic lumbar degenerative disease and were followed up for at least six months were enrolled in this study. According to the inclusive and exclusive criteria, 93 patients were included (44 males and 49 females). X-ray and computed tomography (CT) images were obtained before and six months after surgery. The vertebral contour and the center of the marker mass in the cage were calculated using a geometric algorithm. Orthopedic surgeons measured the disc height, lordosis angle, and facet joint degeneration. Patient-reported outcomes, including the Oswestry Disability Index (ODI) and the visual analog scale (VAS), were used to assess the clinical outcomes. The Student's t-test, Wilcoxon rank-sum test, and Chi-square test were used for the statistical analyses. RESULTS: The average age was 53.7 years old (range, 27-84 years). The average functional disability outcome assessed by the ODI was 61.2, and the average back and leg pain assessed by the VAS was 6.2 and 6.9, respectively. The patients were categorized into a normal group and an abnormal (AFD) group according to whether the facet joint degeneration was aggravated. The abnormal group had a higher back pain VAS score (P=0.031) and lower sagittal vertical position (P=0.027). The other parameters were similar at baseline (P>0.05). The cage's sagittal vertical position decreased significantly with AFD aggravation (OR, 0.737; 95% CI, 0.561-0.969). CONCLUSIONS: In patients with AFD aggravation, the preoperative VAS and postoperative ODI scores were significantly higher. The cage position parameters were related to AFD. A lower cage center was associated with a greater incidence of AFD.

Solution-processed perylene diimide-ethylene diamine cathodes for aqueous zinc ion batteries.

Organic electroactive compounds can be applied as alternative cathodes in rechargeable zinc ion batteries (ZIBs) instead of using inorganic cathode materials with low stability or high toxicity. However, many reported organic ZIB cathodes have some limitations, which are their tedious synthesis processes and low yields. In this work, perylene diimide-ethylenediamine/carbon black (PDI-EDA/CB) composites are prepared with a high yield of over 88% under mild conditions via a solution-based processing method. As the organic cathodes in aqueous ZIBs, the PDI-EDA/CB composites have a high specific capacity of 118.0 mA h g-1 at 0.05 A g-1; this capacity can be maintained as 95.0 mA h g-1 even at a high current density of 5.00 A g-1. Also, PDI-EDA/CB has good cycling stability by reserving 70.5% of its initial capacity after 1500 charge-discharge cycles at 1.00 A g-1, outperforming many recently reported ZIB cathodes. As disclosed by the structural and electrochemical characterization of PDI-EDA/CB, its excellent electrochemical performance is due to the zinc ion storage mechanism of PDI-EDA and the solution-based fabrication method.

Eriodictyol inhibits glioblastoma migration and invasion by reversing EMT via downregulation of the P38 MAPK/GSK-3ß/ZEB1 pathway.

Eriodictyol (ERD) is a natural flavonoid that exists in many vegetables and fruits, especially citrus fruits. It has been proven to have many pharmacological effects, such as antioxidative, anti-inflammatory and neuroprotective effects. Our previous study showed that eriodictyol could inhibit the proliferation and induce the apoptosis of glioblastoma cells by downregulating the PI3K/Akt/NF-κB pathway and restraining its migration and invasion. However, the mechanism by which eriodictyol prevents glioblastoma metastasis is still unknown. Epithelial-mesenchymal transition (EMT) is a key process for many cancer metastases; it also confers locomotivity to tumor cells, including glioblastoma. In this study, we found that eriodictyol can suppress the migration and invasion of glioblastoma A172 and U87 MG cell lines by suppressing the EMT markers - N-cadherin and E-cadherin through Wound healing and Transwell assays, Western blot, RT-qPCR, immunofluorescence and immunohistochemistry. Further research revealed that the mechanism could be connected with downregulation of the P38 MAPK/GSK-3ß/ZEB1 signaling pathway. These findings can provide a new idea for the treatment of glioblastoma.

Distinct fusion intersegmental parameters regarding local sagittal balance provide similar clinical outcomes: a comparative study of minimally invasive versus open transforaminal lumbar interbody fusion.

BACKGROUND: Most contemporary studies suggested that intersegmental parameters including disc height and local lordosis contribute to the sagittal balance of fused lumbar. Although similar clinical outcomes following MIS- and Open-TLIF were reported essentially at the early postoperative time, the comparison of local balance variables after these two different techniques was lack. The radiological differences maybe not relevant to the postoperative efficacy at an earlier post-operation stage. But during the long-term follow-up, the complications with regards to the sagittal imbalance might occur due to the distinct biomechanical properties of fusion level after MIS- and Open-TLIF. METHODS: The patients who underwent a single-level MIS- and Open-TLIF were reviewed retrospectively. The anterior disc height (ADH), posterior disc height (PDH), and segmental lordosis (SL) of the fusion segment were measured using recognition technical fluoroscopy. The mean disc height (MDH) was calculated by (ADH + PDH)/2. The relative DH was normalized by the anterior height of the upper vertebrae. The body mass index (BMI), the pain score of low back and leg visual analogue scale (VAS), Oswestry disability index (ODI), estimated blood loss, and hospital stay length was collected. RESULTS: A total of 88 patients undergoing a single-level TLIF (MIS and Open) were included. The pre- and post-operative ADH, PDH, MDH, and SL of MIS-TLIF group were 1.57 ± 0.33 cm, 0.79 ± 0.20 cm, 1.18 ± 0.21 cm, 7.36 ± 3.07 and 1.63 ± 0.30 cm, 1.02 ± 0.28 cm, 1.32 ± 0.24 cm, 10.24 ± 4.79 respectively. Whereas, the pre- and post-operative ADH, PDH, MDH, and SL of Open-TLIF group were 1.61 ± 0.40 cm, 0.77 ± 0.21 cm, 1.19 ± 0.24 cm, 9.05 ± 5.48 and 1.81 ± 0.33 cm, 0.98 ± 0.24 cm, 1.39 ± 0.24 cm, 12.34 ± 4,74 respectively. MIS- and Open-TLIF group showed no significant differences in low back VAS, leg VAS, and ODI both in pre-operation and post-operation (P > 0.05). The estimated blood loss and hospital stay length in the MIS-TLIF group were significantly lower than those in the Open-TLIF group (P < 0.05). CONCLUSION: MIS- and Open-TLIF provided similar clinical outcomes as the respect of low back VAS, leg VAS, and ODI. MIS-TLIF significantly reduced the blood loss and length of hospital stay though. The intervertebral parameters of DH and SL were both increased significantly, Open-TLIF group presented better sagittal balance in term of ADH and SL variables. The contrast investigation of intersegmental parameters may help the surgeons to figure out the further advantages of MIS-TLIF technique, and then better manage the rehabilitation and prevent the reoperation.

An improved LC-MS/MS method for determination of docetaxel and its application to population pharmacokinetic study in Chinese cancer patients.

Because of its unpredictable side effects and efficacy, the anticancer drug docetaxel (DTX) requires improved characterisation of its pharmacokinetic profiles through population pharmacokinetic studies. A sensitive and rugged LC-MS/MS method for the detection of DTX in human plasma was developed and optimised using paclitaxel as an internal standard (IS). The plasma samples underwent rapid extraction using hybrid solid-phase extraction-protein precipitation. The analyte and IS were separated with an isocratic system on a Zorbax Eclipse Plus C18 column using water containing 0.05% acetic acid along with 20 µM of sodium acetate and methanol (30/70, v/v) as the mobile phase. Quantification was performed using a triple quadrupole mass spectrometer through multiple reaction monitoring in positive mode, using the m/z 830.3 → 548.8 and m/z 876.3 → 307.7 transitions for DTX and paclitaxel, respectively. The range of the calibration curve was 1-500 ng/mL for DTX, and the linear correlation coefficient was >0.99. The accuracies ranged from -4.6 to 4.2%, and the precision was no higher than 7.0% for the analytes. No significant matrix effect was observed. Both DTX and the IS showed considerable recovery. This method was finally applied to the establishment of a population pharmacokinetic model to optimise the clinical use of DTX.

[Comparison of intervertebral height and lordosis of fusion segment between open- and minimally invasive-transforaminal lumbar interbody fusions].

OBJECTIVE: To analyze the restoration of intervertebral height and lordosis of fusion segment after open-transforaminal lumbar interbody fusion (Open-TLIF) and minimally invasive-TLIF (MIS-TLIF). METHODS: Between January 2013 and February 2016, patients who treated with TLIF due to lumbar degenerative diseases and met the selection criteria were selected as the study objects. Among them, 41 patients were treated with open-TLIF (Open-TLIF group), 34 patients were treated with MIS-TLIF (MIS-TLIF group). There was no significant difference between the two groups ( P>0.05) in gender, age, body mass index, disease type, disease duration, pathological segment, and other general data. The intraoperative bleeding volume, hospital stay, visual analogue scale (VAS) score of waist and leg, and Oswestry disability index (ODI) were recorded before and after operation. The anterior disc height (ADH), posterior disc height (ADH), and segmental lordosis (SL) of fusion segment were measured by X-ray film before and at 6 months after operation. The differences of ADH, PDH, and SL between pre- and post-operation were calculated. RESULTS: The intraoperative bleeding volume and hospital stay in Open-TLIF group were significantly higher than those in MIS-TLIF group ( t=14.619, P=0.000; t=10.021, P=0.000). All incisions healed by first intention without early complications. All patients were followed up 6-24 months (mean, 12.6 months) in Open-TLIF group and 6-24 months (mean, 11.5 months) in MIS-TLIF group. The preoperative VAS scores of waist and leg and ODI of the two groups significantly improved ( P<0.05). There was no significant difference in VAS scores and ODI between the two groups before operation and at 2 weeks and 6 months after operation ( P>0.05). Imaging examination showed the good intervertebral fusion. There was no significant difference in ADH, PDH, and SL between the two groups before operation and at 6 months after operation ( P>0.05). The differences of ADH, PDH, and SL between the two groups were not significant ( P>0.05). The ADH, PDH, and SL after operation significantly increased in the two groups ( P<0.05). CONCLUSION: Open-TLIF and MIS-TLIF show similar effectiveness and radiological change in the treatment of single lumbar degenerative diseases and the improved intervertebral height and lordosis, but MIS-TLIF can significantly reduce hospital stay and intraoperative blood loss.

Eriodictyol Inhibits Proliferation, Metastasis and Induces Apoptosis of Glioma Cells via PI3K/Akt/NF-κB Signaling Pathway.

Glioma is the most common type of malignant brain tumor. Due to its highly aggressive and metastatic features, glioma is associated with poor prognosis and a lack of effective treatments. Eriodictyol, a natural flavonoid compound, has been reported to possess anti-inflammatory and antioxidant effects. However, the anti-tumor effects of eriodictyol and the underlying mechanisms have rarely been reported. In this study, we found that eriodictyol has anti-tumor activity in lung, colon, breast, pancreas, and liver cancer, and most significantly in glioma cell lines. Eriodictyol dose- and time-dependently suppresses cell proliferation, migration, and invasion in U87MG and CHG-5 glioma cells. In addition, eriodictyol induces apoptosis in U87MG and CHG-5 cells, as evaluated by flow cytometry, immunofluorescence, and Western blot. Furthermore, eriodictyol downregulates the phosphoinositide 3-kinase (PI3K)/Akt/NF-κB signaling pathway in a concentration-dependent manner. Moreover, the effects of eriodictyol on the apoptosis of glioma cells are enhanced by LY294002 (a PI3K inhibitor) and reversed by 740 Y-P (a PI3K agonist). In a mouse xenograft model, eriodictyol not only dramatically suppressed tumor growth but also induced apoptosis in tumor cells. In summary, our data illustrate that eriodictyol effectively inhibits proliferation and metastasis and induces apoptosis of glioma cell lines, which might be a result of the blockade of the PI3K/Akt/NF-κB signaling pathway.