Microvascular decompression as a second step treatment for trigeminal neuralgia in patients with failed two-isocentre gamma knife radiosurgery.

OBJECTIVE: Subsequent microvascular decompression (MVD) might be affected by the previous two-isocentre gamma knife radiosurgery (GKS) due to the tissue changes caused by its higher dose radiation and larger treatment volume. This study aimed to evaluate the safety and efficacy of MVD as a second step treatment after two-isocentre GKS. METHODS: Between December 2016 and May 2019, data from 19 consecutive trigeminal neuralgia (TN) patients who experienced MVD after failed two-isocentre GKS were collected. The clinical characteristics, intraoperative findings, surgical outcomes and complications were reviewed and compared with 158 patients who underwent MVD as an initial treatment. RESULTS: Fifteen patients (78.9%) achieved complete pain relief (Barrow Neurological Institute, BNI class I) immediately after surgery and nine patients (47.4%) maintained complete pain relief at the last follow-up, which was similar to patients who underwent initial MVD. The median follow-up period was 36 months. The incidence of new or worsened facial numbness showed no statistical significance between the groups. During surgery, trigeminal nerve atrophy was noted in 9 patients (47.4%), thickened arachnoid in 3 patients (15.8%), atherosclerotic plaque in 3 patients (15.8%) and neurovascular adhesion in 1 patient (5.3%). CONCLUSIONS: MVD remains an effective and safe rescue therapy for patients who elect the minimally invasive treatment with two-isocentre GKS for the first time, without an increased risk of facial numbness.

CNN3 in glioma: The prognostic factor and a potential immunotherapeutic target.

BACKGROUND: Gliomas are the most intrinsic type of primary intracranial tumors. The protein encoded by The calponin 3 (CNN3) has been proven to be a member of the calponin family. Its relationships with cervical cancer, colorectal cancer, gastric cancer, and colon cancer have been emphasized by several studies. Our research aims to explore the prognosis value and immunotherapeutic targetability of CNN3 in glioma patients using bioinformatics approach. METHODS: CNN3 expression in glioma was analyzed based on GEO and TCGA datasets. Gene expression profiling with clinical information was employed to investigate the correlation between clinicopathological features of glioma patients and relative CNN3 expression levels. Survival analysis was conducted using Kaplan-Meier analysis and the Cox proportional-hazards regression model. Gene set enrichment analysis was conducted to select the pathways significantly enriched for CNN3 associations. Correlations between inflammatory activities, immune checkpoint molecules and CNN3 were probed by gene set variation analysis, correlograms, and correlation analysis. RESULTS: CNN3 was enriched in gliomas, and high expression of CNN3 correlated with worse clinicopathological features and prognosis. Associations between CNN3 and several immune-related pathways were confirmed using a bioinformatics approach. Correlation analysis revealed that CNN3 was associated with inflammatory and immune activities, tumor microenvironment, and immune checkpoint molecules. CONCLUSION: Our results indicate that high CNN3 expression levels predict poor prognosis, and CNN3 may be a promising immunotherapy target.

The impact of bile leakage on long-term prognosis in primary liver cancers after hepatectomy: A propensity-score-matched study.

BACKGROUND: The impact of bile leakage (BL) on the long-term prognosis in patients with primary liver cancers after hepatectomy remains unclear. METHODS: One thousand nine hundred and seventy-one consecutive patients with primary liver cancers who underwent curative hepatectomy were enrolled. 75 patients encountered BL, including 34 long-time BL (LTBL) and 41 short-time BL (STBL) according to 4-weeks demarcation. Variables associated with BL were identified using multiple logistic regression analysis. 75 patients without BL were enrolled into the Non-BL group using a one-to-one propensity score matched analysis before assessing the impact of BL on the long-term prognosis. The levels of interleukin-6 (IL-6) and C-reactive protein (CRP) in the serum and drain fluid were detected and compared. RESULTS: The tumor size, type of liver cancer, operation time, blood loss and blood transfusion were independent risk factors for BL. The long-term survival showed no difference between the patients with and without BL (p > 0.05), while the LTBL was a significant predictor of poor long-term prognosis (p < 0.001). Compared with the patients without BL, the patients with BL had a higher level of IL-6 from postoperative day (POD) 1 to POD 60, and a higher level of CRP from POD 7 to POD 60. By POD 60, the levels of IL-6 and CRP hadn't restored to the normal level in the LTBL group. CONCLUSIONS: The LTBL has a negative impact on the long-term prognosis of patients with primary liver cancers after hepatectomy, in which the inflammatory responses may play a pivotal role.

DNA methylation profiling identifies potentially significant epigenetically-regulated genes in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is one of the most lethal and damaging types of human cancer. The current study was conducted to identify differentially methylated genes (DMGs) between GBM and normal controls, and to improve our understanding of GBM at the epigenetic level. The DNA methylation profile of GBM was downloaded from the Gene Expression Omnibus (GEO) database using the accession number GSE50923. The MethyAnalysis package was applied to identify DMGs between GBM and controls, which were then analyzed by functional enrichment analysis. Protein-protein interaction (PPI) networks were constructed using the hypermethylated and hypomethylated genes. Finally, transcription factors (TFs) that can regulate the hypermethylated and hypomethylated genes were predicted, followed by construction of transcriptional regulatory networks. Furthermore, another relevant dataset, GSE22867, was downloaded from the GEO database for data validation. A total of 476 hypermethylated and 850 hypomethylated genes were identified, which were mainly associated with the functions of 'G-protein-coupled receptors ligand binding', 'cytokine activity', 'cytokine-cytokine receptor interaction', and 'D-glutamine and D-glutamate metabolism'. The hypermethylated gene neuropeptide Y (NPY) and the hypomethylated gene tumor necrosis factor (TNF) demonstrated high degrees in the PPI network. Forkhead box protein A1 (FOXA1), potassium voltage-gated channel subfamily C member 3 (KCNC3) and caspase-8 (CASP8) exhibited high degrees in the transcriptional regulatory networks. In addition, the methylation profiles of NPY, TNF, FOXA1, KCNC3 and CASP8 were confirmed by another dataset. In summary, the present study systematically analyzed the DNA methylation profile of GBM using bioinformatics approaches and identified several abnormally methylated genes, providing insight into the molecular mechanism underlying GBM.

Laparoscopic Anatomic Spiegel Lobectomy With the Extrahepatic Glissonean Approach.

BACKGROUND: Laparoscopic Spiegel lobectomy is difficult due to its deep location and being surrounded by gross vessels. Extrahepatic Glissonean pedicle transection method has been proposed by Takasaki during open liver resections. This approach can be successfully performed during laparoscopic anatomic hepatectomy. Here we describe pure laparoscopic Spiegel lobectomy using the extrahepatic Glissonean approach. METHODS: The patient was a 25-year-old male with a background of hepatitis B. A 1.5 cm×1.7 cm mass was detected in liver Spiegel lobe and highly suspected to be an hepatocellular carcinoma. The liver function was normal (Child-pugh 5), and alpha-fetoprotein was within the normal ranges. Laparoscopic Spiegel lobectomy using extrahepatic Glissonean approach was proposed. The hilar plate was partly detached from liver parenchyma, and 2 Glissonean pedicles of the Spiegel lobe were dissected, clamped and divided. Liver parenchymal transection was performed using the harmonic scalpel. RESULTS: The operation time was 196 minutes without Pringle's maneuver. Estimated blood loss was <50 mL, and no blood transfusion was required. The patient recovered well and was discharged on postoperative day 6. There was no complication. Pathologic findings support the diagnosis of hepatocellular carcinoma. CONCLUSIONS: Laparoscopic Spiegel lobectomy using the extrahepatic Glissonean approach is safe and feasible.

Fabricating polydopamine-coated MoSe2-wrapped hollow mesoporous silica nanoplatform for controlled drug release and chemo-photothermal therapy.

BACKGROUND: Integration of several types of therapeutic agents into one nanoplatform to enhance treatment efficacy is being more widely used for cancer therapy. METHODS: Herein, a biocompatible polydopamine (PDA)-coated MoSe2-wrapped doxorubicin (DOX)-loaded hollow mesoporous silica nanoparticles (HMSNs) nanoplatform (PM@HMSNs-DOX) was fabricated for dual-sensitive drug release and chemo-photothermal therapy for enhancing the therapeutic effects on breast cancer. The HMSNs were obtained by a "structural difference-based selective etching" strategy and served as the drug carrier, exhibiting a high DOX loading capacity of 427 mg/g HMSNs-NH2, and then wrapped with PDA-coated MoSe2 layer to form PM@HMSNs-DOX. Various techniques proved the successful fabrication of the nanocomposites. RESULTS: The formed PM@HMSNs-DOX nanocomposites exhibited good biocompatibility, good stability, and super-additive photothermal conversion efficiency due to the cooperation of MoSe2 and PDA. Simultaneously, the pH/near-infrared-responsive drug release profile was observed, which could enhance the synergistic therapeutic anticancer effect. The antitumor effects of PM@HMSNs-DOX were evaluated both in vitro and in vivo, demonstrating that the synergistic therapeutic efficacy was significantly superior to any monotherapy. Also, in vivo pharmacokinetics studies showed that PM@HMSNs-DOX had a much longer circulation time than free DOX. In addition, in vitro and in vivo toxicity studies certified that PM@HMSNs are suitable as biocompatible agents. CONCLUSION: Our nanoplatform loaded with DOX displays pH/near-infrared-induced chemotherapy and excellent photothermal therapy, which hold great potential for cancer treatment.

AKAP4 mediated tumor malignancy in esophageal cancer.

AKAP4 as a new Cancer/Testis (CT) antigen is expressed not only in human germ cells, but also expressed in various tumor cells. AKAP4 is correlated with tumor malignancy; however, the role of AKAP4 in esophageal cancer remains unknown. Here we explored the function of AKAP4 in esophageal cancer. We found that AKAP4 mRNA and protein levels were up-regulated in the esophageal cancer tissues compared to normal control. In KYSE150 cell line, inhibition of AKAP4 suppressed cell growth and invasiveness. Overexpression of AKAP4 promoted cell growth and invasiveness. In addition, expression of epithelial markers (E-cadherin and ZO-1) was up-regulated or down-regulated and expression of mesenchymal markers (vimentin and N-cadherin) was down-regulated or up-regulated after knockdown or overexpression of AKAP4 in vitro. In vivo in a xenograft model silencing AKAP4 suppressed tumor growth. We also found that NF-κB p65 bound to AKAP4 promoter and regulated expression of AKAP4. In conclusion, overexpression of AKAP4 is associated with esophageal cancer progression. Inhibition of AKAP4 leads to suppressed growth and invasion of esophageal cancer.

Modulation of E-cadherin expression promotes migration ability of esophageal cancer cells.

Losing the E-cadherin plays an important role in the metastasis of cancer. The regulation of the expression of E-cadherin is unclear. Circadian rhythm alteration is associated with the pathogenesis of a number of cancers. This study aims to investigate the role of one of the circadian proteins, period-2 (Per2) in repressing the expression of E-cadherin in esophageal cancer (esophageal cancer). We observed that the levels of circadian protein Per2 were significantly increased and E-cadherin was significantly decreased in the tissue of human esophageal cancer with metastasis as compared with non-metastatic esophageal cancer. Overexpression of Per2 in the esophageal cancer cells markedly repressed the expression of E-cadherin. The pHDAC1 was detected in human esophageal cancer with metastasis, which was much less in the esophageal cancer tissue without metastasis. Overexpression of Per2 increased the levels of pHDAC1 as well as the E-cadherin repressors at the E-cadherin promoter locus. Overexpression of Per2 markedly increased the migratory capacity of esophageal cancer cells, which was abolished by the inhibition of HDAC1. We conclude that Per-2 plays an important role in the esophageal cancer cell metastasis, which may be a novel therapeutic target for the treatment of esophageal cancer.

[Effect of Long Non-coding RNA SPRY4-IT1 on Invasion and Migration of A549 Cells].

BACKGROUND AND OBJECTIVE: The abnormal expression of human long chain non encoding RNA gene is related to many kinds of tumors. The aim of this study is to investigate the expression of long non-coding RNA maternally expressed gene 3 (SPRY4-IT1) in lung cancer (A549) cells, and to observe the effect of SPRY4-IT1 on the invasion and migration of A549 cells. METHODS: The levels of SPRY4-IT1 in A549 was detected by Real-time PCR. The effects of SPRY4-IT1 on the invasion and migration of A549 cell were analyzed by MTT and Transwell assay. The expression of matrix metalloproteinase (MMP) family proteins was determined by Western blot. RESULTS: The invasion and migration of A549 cells were increased after SPRY4-IT1 over-expression. The cell spaces were narrower after SPRY4-IT1 over expression in the wound healing assay. Transwell assays showed that the numbers of transmembrane A549 cells were significantly higher in SPRY4-IT1 over expression group than that in control group (P<0.05). Meanwhile, over expression of SPRY4-IT1 reduced the expression of MMP-2 and MMP-9. CONCLUSIONS: Over expression of SPRY4-IT1 enhanced the invasion and migration of A549 cells. MMP-2 and MMP-9 might play an important role in this regulation.
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Porous liquids: a promising class of media for gas separation.

A porous liquid containing empty cavities has been successfully fabricated by surface engineering of hollow structures with suitable corona and canopy species. By taking advantage of the liquid-like polymeric matrices as a separation medium and the empty cavities as gas transport pathway, this unique porous liquid can function as a promising candidate for gas separation. Moreover, such a facile synthetic strategy can be further extended to the fabrication of other types of nanostructure-based porous liquid, opening up new opportunities for preparation of porous liquids with attractive properties for specific tasks.

Bio-Oss(®) for delayed osseointegration of implants in dogs: a histological study.

We evaluated the effects of Bio-Oss® (a natural bone substitute derived from the mineral portion of bovine bone) on delayed osseointegration of implants. The bilateral third and fourth mandibular premolars of 4 adult, healthy, male and female dogs were extracted. We randomly selected 2 extraction sockets in each dog to be filled with Bio-Oss® (the experimental group); the other 2 extraction sockets, which were not treated, served as controls. Dental implants were inserted into the alveolar bone of the experimental group and the control group 3 months after insertion of the Bio-Oss®. The osteogenic activity in the bone around the implants was assessed by evaluating the histological morphology and estimating histomorphometric variables at 3 and 6 months after delayed implantation. After 3 months, Goldner's trichrome staining analysis showed that the rate of content between the bone and the implant and the mineralised area of bone around the implant were significantly higher in the experimental group (76%(9%) and 69.5% (9.6%), respectively) than those in the control group (56.1% (8.2%) and 52.8% (7.3%), respectively, p=0.003 and 0.000). However, the 2 groups did not differ significantly at 6 months. Fluorescence microscopy showed that the mean rates of mineralisation of the bony tissue around the implant in the experimental group at months 3 and 6 were 6.8 (0.4) µm and 8.4 (0.8) µm, respectively, which were significantly higher than those in the control group (p=0.000 and 0.03). These data indicate that putting Bio-Oss® into the extraction sockets can promote osseointegration after delayed implantation, and may be a promising option for clinical use.

Effects of xuesetong soft capsules on angiogenesis and VEGF mRNA expression in ischemic myocardium in rats with myocardial infarction.

OBJECTIVE: To observe the effects of Xuesetong Soft Capsules, Notoginseng total saponin) on angiogenesis and vascular endothelial growth factor (VEGF) mRNA expression in ischemic myocardium of rats with myocardial infarction. METHODS: The left coronary artery of rats was ligated to establish the animal model of acute myocardial infarction. Rats were randomly divided into Xuesetong Soft Capsule, Shexiangbaoxin Pill (positive control), model (negative control) and sham operation groups. After 6 weeks, microvessel count (MVC), microvessel density (MVD) and VEGF mRNA expression in ischemic myocardium were evaluated. RESULTS: MVC and MVD in the myocardial infarct border area in model, Shexiangbaoxin Pill and Xuesetong Soft Capsule groups significantly increased compared with those of the sham operation group (P < 0.05). MVC and MVD in the myocardial infarct border area in Xuesetong Soft Capsule and Shexiangbaoxin Pill groups significantly increased compared with those of the model group (P < 0.05). No significant differences between Xuesetong Soft Capsule and Shexiangbaoxin Pill groups were observed (P > 0.05). The model group showed significantly higher VEGF mRNA expression than that in the sham operation group (P < 0.05). Xuesetong Soft Capsule and Shexiangbaoxin Pill groups showed significantly higher VEGF mRNA expression than that of the model group (P < 0.05). No significant difference between Xuesetong Soft Capsule and the Shexiangbaoxin Pill groups was observed (P > 0.05). CONCLUSION: Xuesetong Soft Capsules promote angiogenesis in ischemic myocardium after myocardial infarction and the mechanism may be associated with VEGF mRNA expression.

Overexpression of hyaluronan in the tunica media promotes the development of atherosclerosis.

The arterial content of hyaluronan (HA) undergoes diffuse changes as part of the diabetic macroangiopathy. Because HA influences the phenotype of vascular cells in vitro such as proliferation, migration, and secretion, it is tempting to speculate that diabetes-induced hastened cardiovascular disease may be linked to the increased amount of HA. To explore the pathophysiological role of altered HA content in the arterial wall in vivo, we created transgenic (Tg) mice with HA overexpression in smooth muscle cells (SMCs) in large and small vessels, targeted by the alpha smooth-muscle-cell-actin (alphaSMA) promoter fused to the human hyaluronan synthase 2 (hHAS2) cDNA. RT-PCR demonstrated hHAS2 mRNA expression in the tunica media of large and small vessels. In situ hybridization confirmed that hHAS2 mRNA was targeted to the SMCs. The aortic HA content was elevated in the Tg mice, and by immunohistochemistry, it was seen that HA accumulated in the tunica media. The secretory profile of high- and low-molecular HA was similar in wild-type and Tg animals. Overproduction of HA in the aorta resulted in thinning of the elastic lamellae in Tg mice. Our data suggest that this may lead to increased mechanical stiffness and strength, as determined by controlled stretching until failure. Finally, overproduction of HA on the genetic background of the ApoE-deficient mouse strain promoted atherosclerosis development in the aorta. These results indicate that a single component of the diabetic macroangiopathy, diffuse accumulation of HA, accelerates the progression of atherosclerosis.