Unilateral hemilaminectomy vs. laminoplasty for the resection of spinal schwannomas: an analysis of 100 patients.

Objective: Spinal schwannomas are the most common intradural extramedullary tumors, and their complete removal is recommended to avoid tumor recurrence. Although laminoplasty provides a sufficient window for tumor resection, this approach may increase tissue trauma and cause postoperative instability compared with unilateral hemilaminectomy. This study aimed to compare the efficacy and clinical outcomes of the two approaches. Materials and methods: We included 100 consecutive patients who underwent unilateral hemilaminectomy or laminoplasty for resection of spinal schwannomas between January 2015 and February 2023. The patients' baseline characteristics, including sex, age, tumor location, percentage of tumor occupying the intradural space, operative time, postoperative length of hospital stay, intraoperative bleeding volume, visual analog scale score, and neurologic results, were retrospectively analyzed. Results: Hemilaminectomy patients who underwent unilateral hemilaminectomy had smaller intraoperative bleeding (p = 0.020) volume, shorter operative time (p = 0.012), and shorter postoperative length of hospital stay (p = 0.044). The mean VAS scores at the last follow-up were similar between the two groups (p = 0.658). Although the postoperative McCormick and Karnofsky Performance scores were not significantly different between the laminoplasty and unilateral hemilaminectomy groups (p = 0.687 and p = 0.649, respectively), there was a statistically significant improvement based on postoperative neurological results compared to preoperative neurological results for both groups. The incidence of postoperative complications was 5% and 11.7% in the unilateral hemilaminectomy and laminoplasty groups, respectively (p = 0.308). Conclusions: For spinal schwannoma resection, unilateral hemilaminectomy has more advantages than laminoplasty, including a shorter postoperative hospital stay, faster procedure, and less intraoperative blood loss while achieving the same desired result.

Effect of Intraoperative Opioid Dose on Perioperative Neutrophil-to-Lymphocyte Ratio and Lymphocyte-to-Monocyte Ratio in Glioma.

Background: The neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) are inflammatory biomarkers. Until now, it is unknown the impact of opioid dosage on perioperative immunity in glioma patients. The aim of this study was to explore the effect of intraoperative opioid dosage on perioperative immune perturbations using NLR and LMR as inflammatory biomarkers and evaluate the correlation between inflammatory biomarkers and pathological grade of glioma. Methods: The study included 208 patients with primary glioma who underwent glioma resection from February 2012 to November 2019 at Harbin Medical University Cancer Hospital. Complete blood count (CBC) was collected at 3 time points: one week before surgery, and 24 hours and one week after surgery. Patients were divided into high-dose and low-dose groups, based on the median value of intraoperative opioid dose. The relationships between perioperative NLR, LMR and intraoperative opioid dosage were analyzed using repeated measurement analysis of variance (ANOVA). Correlations between preoperative various factors and pathological grade were analyzed by Spearman analysis. Receiver operating characteristic (ROC) curves were performed to assess the predictive performance of the NLR and LMR for pathological grade. Results: The NLR (P=0.020) and lower LMR (P=0.037) were statistically significant different between high-dose and low-dose groups one week after surgery. The area under the curve (AUC) of the NLR to identify poor diagnosis was 0.685, which was superior to the LMR (AUC: 0.607) and indicated a correlation between the NLR with pathological grade. The preoperative NLR (P=0.000), LMR (P=0.009), age (P=0.000) and tumor size (P=0.001) exhibited a significant correlation with the pathological grade of glioma. Conclusion: Intraoperative opioids in the high-dose group were associated with higher NLR and lower LMR in postoperative glioma patients. The preoperative NLR and LMR demonstrated predictive value for distinguishing between high-grade and low-grade gliomas.

Negative Impact of Intra-Operative Blood Transfusion on Survival Outcomes of Hepatocellular Carcinoma Patients.

Background: Studies have reported that blood transfusion may have an association with survival outcomes of cancer patients. This study was aimed at finding the effect of intra-operative blood transfusion on the prognosis of patients of hepatocellular carcinoma (HCC). Methods: This was a retrospective study. HCC patients who underwent tumor resection from January 2013 to November 2018 at Harbin Medical University Cancer Hospital were included. The survival time of patients receiving or not receiving blood transfusion during the operation were compared. Results: Of HCC patients, 21.1% (102/484) received intra-operative blood transfusion. After propensity score matching, 87 pairs of patients were included in the study. In the subset of patients with a tumor size of >4 cm, univariable analysis found that there were significant differences in recurrence-free survival (RFS; P=0.004) and overall survival (OS; P=0.028) between blood transfusion and non-blood transfusion groups. After multivariable Cox regression analysis, intra-operative blood transfusion was an independent risk factor for RFS (HR: 2.011, 95% CI: 1.146-3.529, P=0.015), but not for OS (HR: 1.862, 95% CI: 0.933-3.715, P=0.078) in the subset of patients with a tumor size of >4 cm. Conclusion: Intra-operative blood transfusion was associated with worse RFS in HCC patients with a tumor size of >4 cm.

Clinical Significance of Mean Platelet Volume Combined with Neutrophil-Lymphocyte Ratio in Predicting the Therapeutic Effect of Splanchnic Neurolysis.

Introduction: In most cases of pain related to abdominal tumors, increasing the dosage of analgesics still makes the pain difficult to alleviate. Splanchnic neurolysis is a new treatment option. However, not all patients receiving splanchnic neurolysis treatment will achieve satisfactory results. The aim of this study is to retrospectively analyze the predictive value of preoperative serum immune indicators (white blood cells, neutrophils, lymphocytes, and platelets) for the efficacy of splanchnic neurolysis. Methods: The abdominal cancer patients (pancreatic cancer, liver cancer, gastric cancer, colorectal cancer, cholangiocarcinoma, and renal cancer) admitted to the Department of Pain Medicine, Harbin Medical University Cancer Hospital from January 2017 to October 2020 were collected. We evaluate the efficacy of splanchnic neurolysis by assessing the dosage of opioids and Numerical Rating Scale (NRS) scores of patients 24 to 48 hr before and after splanchnic neurolysis. The predictive value of preoperative serum immune indicators on the efficacy of splanchnic neurolysis was analyzed using Receiver Operating Characteristic (ROC). Contract the Nomogram prediction model by R software. Results: We found that Mean Platelet Volume (MPV) has statistical significance for predicting splanchnic neurolysis efficacy in digestive system tumors. MPV and Neutrophil-Lymphocyte Ratio (NLR) are independent predictors and have statistical significance in predicting splanchnic neurolysis efficacy in pancreatic cancer. The combination of MPV and NLR had satisfactory predictive value in pancreatic cancer (AUC = 0.715) and the nomogram model was constructed. Furthermore, there was a negative correlation between lymphocyte count and NRS score, and a positive correlation between Platelet-Lymphocyte Ratio (PLR) and NRS score. Discussion: The combined detection of MPV and NLR has important clinical predictive value for the postoperative efficacy of splanchnic neurolysis in pancreatic cancer.

Epoxied SiO2 nanoparticles and polyethyleneimine (PEI) coated polyvinylidene fluoride (PVDF) membrane for improved oil water separation, anti-fouling, dye and heavy metal ions removal capabilities.

Epoxied SiO2 nanoparticles and polyethyleneimine (PEI) was used to coating polyvinylidene fluoride (PVDF) membrane for improved anti-fouling, oil water separation, dye and heavy metal ions removal capabilities. Characterization of the modified membrane revealed that the hydrophilic coating layer was applied onto the PVDF substrate successfully. The modified membrane can exhibit a high degree of superhydrophilicity and underwater superoleophobicity. Consequently over 98% of the oil was retained when this membrane was used in oil water separation. The hydrophilic coating layer enhanced the membrane antifouling performance, and its flux recovery rate reached 96.3% after filtration and washing with bovine serum protein solution (BSA). In addition, the modified membrane presented the ability to adsorb organic dyes and heavy metal ions in water and reject them via filtration. Most importantly, the crosslinking reaction between the epoxied SiO2 nanoparticles and PEI imparts a high degree of stability to the coating layer. Thanks to the simple fabrication method and multifunctional performances of the coating layer described in this report, it may be used to modify other substrates.

Antioxidant, AChE inhibitory, and anticancer effects of Verbascum thapsus extract.

Verbascum thapsus (VT) is a medicinal plant that is used in folk medicine to treat a variety of ailments. For this study, the biological functions of VT methanol extract were determined in vitro. The plant's methanol extract was created through the maceration process. The phytochemical composition of plant extracts was investigated using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The antioxidant capacity of the extract was determined using the DPPH (2,2-diphenyl-1-picrylhydrazil) and ABTS (2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) tests and its cytotoxicity was assessed using the MTT ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole)) assay on the Caco-2 (human colorectal adenocarcinoma cells), LNCaP (Lymph Node Carcinoma of the Prostate), and HEK293 cell lines (Human embryonic kidney 293 cells) used to model colon, prostate, and non-cancerous cells. VT extract showed low DPPH and ABTS radical scavenging activities compared to standard antioxidants at 30 mg/ml concentration. In addition, it was determined that VT extract inhibited acetylcholinesterase enzyme.

Phase I/II trial of local interstitial chemotherapy with arsenic trioxide in patients with newly diagnosed glioma.

Background: Glioma is the most common primary brain tumor in adults with poor prognosis. The glioma patients benefit from STUPP strategy, including maximum and safe resection and adjuvant radiotherapy and chemotherapy. Arsenic trioxide could inhibit various tumors. However, it is a challenge to evaluate the efficiency and safety of srsenic trioxide in glioma patients. Objective: The arsenic trioxide has the potent therapeutic effect on glioma. However, the safety and efficacy of local interstitial chemotherapy with arsenic trioxide in newly diagnosed glioma patients is unclear. Methods: All patients received partial or complete tumor resection and intraoperative implantation of Ommaya reservoirs followed by standard radiotherapy. Arsenic trioxide with the starting dose 0.3 mg was administered via an Ommaya reservoir catheter inserted into the tumor cavity for 5 consecutive days every 3 months for a total of eight cycles unless tumor progression or excessive toxicity was observed. Results: No hematological or grade 4 non-hematological toxicity was observed in any patient during arsenic trioxide treatment. The maximum tolerated dose of 1.5 mg of arsenic trioxide was safe and well tolerated. The median overall survival for WHO grade 3 glioma was 33.6 months, and for glioblastoma was 13.9 months. The median progression-free survival for WHO grade 2 glioma was 40.3 months, for grade 3 glioma was 21.5 months, and for glioblastoma was 9.5 months. Conclusion: These results suggest that arsenic trioxide is safe and well tolerated with local delivery into the tumor cavity of the brain, and the dose recommended for a phase II trial is 1.5 mg.

Calcaneous interlocking nail treatment for calcaneous fracture: a multiple center retrospective study.

BACKGROUND: Minimally invasive treatments for calcaneous fractures have the same outcomes and fewer complications. However, they are technically demanding, and there are a lack reduction tools. To overcome these problems, a calcaneous interlocking nail system was developed that can make reduction and fixation minimally invasive and effective. We retrospectively studied the calcaneous fracture variables intraoperatively and followed up to evaluate the outcomes of patients treated with the calcaneous interlocking nail system. METHODS: All patients in 7 institutions between October 2020 and May 2021 who had calcaneous fractures treated with calcaneous interlocking nails were retrospectively analyzed. The patient characteristics, including age, sex, injury mechanism, Sanders type classification, smoking status, and diabetes were recorded. The calcaneous interlocking nail and standard surgical technique were introduced. The intraoperative variables, including days waiting for surgery, surgery time, blood loss, incision length, and fluoroscopy time, were recorded. The outcomes of complications, AOFAS scores and VAS scores were recorded and compared with other similar studies. RESULTS: Fifty-nine patients were involved in this study; 54 were male; 5 were female; and they had an average age of 47.5 ± 9.2 years (range 25-70). 2 of these fractures were Sanders type I, 28 of these fractures were Sanders type II, 27 of these fractures were Sanders type III, and 2 of these were Sanders type IV. The surgery time was 131.9 ± 50.5 (30-240) minutes on average. The blood loss was 36.9 ± 41.1 (1-250) ml. The average incision length was 3.5 ± 1.8 (1-8) cm; 57 were sinus tarsi incisions; and 2 were closed fixations without incisions. The average fluoroscopy time was 12.3 ± 3.6 (10-25) seconds during the surgery. The VAS score of patients on the day after surgery was 2.4 ± 0.7 (1-3). The AOFAS ankle-hindfoot score in patients who had a follow-up of at 12 months was 93.3 ± 3.6(85-99). During the follow-up, all patients' functional outcomes were good. One patient had a superficial infection. The rate of complications of the 59 patients was 1.7% (1/59). CONCLUSION: The calcaneous interlocking nail system can have satisfactory reduction and fixation in calcaneous fractures, even in Sanders type IV. The outcomes of follow-up showed good function. The calcaneous interlocking nail could be an alternative method for minimally invasive calcaneous fracture fixation.

Therapeutic effect of natural polyphenols against glioblastoma.

Glioblastoma (GBM) is the most common and aggressive tumor of the central nervous system, which has a highly invasive growth pattern, which creates poor prospects for patient survival. Chemotherapy and tumor surgery are limited by anticancer drug resistance and tumor invasion. Evidence suggests that combinations of treatments may be more effective than single drugs alone. Natural polyphenolic compounds have potential as drugs for the treatment of glioblastoma and are considered as potential anticancer drugs. Although these beneficial effects are promising, the efficacy of natural polyphenolic compounds in GBM is limited by their bioavailability and blood-brain barrier permeability. Many of them have a significant effect on reducing the progression of glioblastoma through mechanisms such as reduced migration and cell invasion or chemosensitization. Various chemical formulations have been proposed to improve their pharmacological properties. This review summarizes natural polyphenolic compounds and their physiological effects in glioblastoma models by modulating signaling pathways involved in angiogenesis, apoptosis, chemoresistance, and cell invasion. Polyphenolic compounds are emerging as promising agents for combating the progression of glioblastoma. However, clinical trials are still needed to confirm the properties of these compounds in vitro and in vivo.

Cd248a and Cd248b in zebrafish participate in innate immune responses.

CD248, also known as endosialin or tumor endothelial marker 1, is a type I single transmembrane glycoprotein. CD248 has been demonstrated to be upregulated in cancers, tumors and many fibrotic diseases in human and mice, such as liver damage, pulmonary fibrosis, renal fibrosis, arthritis and tumor neovascularization. However, no definite CD248 orthologs in fish have been documented so far. In this study, we report the identification of cd248a and cd248b in the zebrafish. Both the phylogenetic analysis and the conserved synteny strongly suggested that zebrafish cd248a and cd248b are orthologs of the human CD248. Both cd248a and cd248b exhibited similar and dynamic expression pattern in early development, both genes had weak maternal expression, the zygotic transcripts were first seen in anterior somites and head mesenchyme, then shifted to eyes and head mesenchyme, later expanded to branchial arches, and gradually declined with development. The expression profiles of cd248a and cd248b were upregulated upon LPS (Lipopolysaccharide) challenge. Both Cd248a protein and Cd248b protein were localized on the cell membrane and cytoplasm, and overexpression of cd248a and cd248b induced the expression of pro-inflammatory cytokines, in vitro and in vivo. Moreover, deficiency of cd248a or cd248b both downregulated the expression of pro-inflammatory cytokines and upregulated anti-inflammatory cytokine. Additionally, loss of cd248a or cd248b both downregulated the expression of pro-inflammatory cytokines after LPS treatment. Taken together, these results indicated that cd248a and cd248b in zebrafish were involved in immune response and would provide further information to understand functions of Cd248 protein in innate immunity of fish.

Evolutionary and Expression Analysis of MOV10 and MOV10L1 Reveals Their Origin, Duplication and Divergence.

MOV10 and MOV10L1 both encode ATP-dependent RNA helicases. In mammals, MOV10 and MOV10L1 participate in various kinds of biological contexts, such as defense of RNA virus invasion, neuron system, germ cell and early development. However, mov10 and mov10l1 in zebrafish are obscure and the evolutionary relationships of mov10 among different species remain unclear. In this study, we found MOV10 and MOV10L1 had some variations despite they possessed the conserved feature of RNA helicase, however, they may originate from a single ancestor although they shared limited homology. A single MOV10L1 gene existed among all species, while MOV10 gene experienced lineage-specific intra-chromosomal gene duplication in several species. Interestingly, the mov10 gene expanded to three in zebrafish, which originating from a duplication by whole genome specific duplication of teleost lineage followed by a specific intra-chromosome tandem duplication. The mov10 and mov10l1 showed distinct expression profiles in early stages, however, in adult zebrafish, three mov10 genes exhibited similar diverse expression patterns in almost all tissues. We also demonstrated mov10 genes were upregulated upon virus challenge, highlighting they had redundant conserved roles in virus infection. These results provide valuable data for the evolution of MOV10 and MOV10L1 and they are important to the further functional exploration.

Dose of intra-operative opioids has no impact on recurrence or survival in primary liver cancer.

BACKGROUND: Intra-operative use of opioid analgesics might have an impact on cancer recurrence and survival after surgery. The objective of this study was to investigate the association between the intra-operative fentanyl equivalents and survival outcomes in patients with primary liver cancer after receiving hepatectomy. METHODS: This was a retrospective single-center cohort study, and clinical data of 700 patients with primary liver cancer who underwent hepatectomy in Harbin Medical University Cancer Hospital from September 2013 to August 2018 were reviewed. After propensity matching, 376 patients were included. Patients were divided into high-dose and low-dose groups according to the median intra-operative fentanyl equivalents (1.500 mg). Kaplan Meier curve and Cox proportional hazards regression model were used. RESULTS: Results of univariable analysis showed there were no significant differences in recurrence-free survival (RFS) (p = 0.136) and overall survival (OS) (p = 0.444) between high-dose fentanyl equivalents and low-dose fentanyl equivalents group. The multivariable Cox regression analysis found that the dose of intra-operative fentanyl equivalents was not associated with RFS (HR: 1.119, 95%CI: 0.851-1.472, p = 0.422) or OS (HR: 0.939, 95%CI: 0.668-1.319, p = 0.715). CONCLUSIONS: The amounts of intra-operative fentanyl equivalents had no impact on recurrence-free or overall survival in patients with primary liver cancer after curative hepatectomy.

Protective effect of C-phycocyanin and apo-phycocyanin subunit on programmed necrosis of GC-1 spg cells induced by H2 O2.

C-phycocyanin (C-PC) is an effective antioxidant and has an important value in medical research. Oxidative stress is considered to be one of the main underlying mechanisms of cell death, and reducing oxidative stress is one of the strategies to enhance germ cell viability. Herein, we investigated the protective effect and the mechanism of C-PC and apo-phycocyanin subunit on oxidative stress damage induced by H2 O2 in GC-1 spg cells. C-PC genes were cloned into the pGEX-4T-1 vectorand transformed into Escherichia coli BL21 to achieve the efficient expression of C-PC subunit. GC-1 spg cells were treated with 600 µM H2 O2 for 24 h to establish the oxidative stress damage model. Cell viability was detected by CCK-8. The degree of oxidative stress was detected by testing Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and glutathione (GSH) and Malondialdehyde (MDA) levels. Reactive oxygen species (ROS) was evaluated utilizingby 2', 7'-dichlorofluorescent-diacetate (DCFH-DA). Mitochondrial membrane potential was determined by JC-1. Cell necrosis rate was detected by Annexin V-FITC/PI. Expression of protein was detected by western blot. We found that C-PC and GST-CPC ß significantly inhibited H2 O2 -induced oxidative damage of GC-1 spg cells, improved the ability of antioxidation, reduced ROS overproduction, and mitochondrial membrane potential loss, and inhibited the RIP-1/RIP-3/ p-MLKL signaling pathway to reduce the necrosis rate. The results demonstrated that C-PC played a protective role against H2 O2 -induced cell damage, especially its ß subunit. This study provides a theoretical basis for C-PC as a potential protective agent of reproductive system.

The protective effect of C-phycocyanin in male mouse reproductive system.

C-phycocyanin from Spirulina platensis has pharmacological effects such as anti-oxidation, anti-cancer, anti-inflammatory and anti-atherosclerosis activities as well as liver and kidney protection. However, there is little research on C-phycocyanin applied in the field of reproductive medicine, and it is therefore the focus of the current study. In this study, a GC-1 spg cell model and male mouse reproductive injury model were constructed by TNF α + Smac mimetic + zVAD-fmk (TSZ) and cyclophosphamide (Cy), respectively. It has been proved that C-phycocyanin can increase cell viability and reduce cell death in GC-1 spg cells induced by TSZ. C-phycocyanin could protect the reproductive system of male mice from cyclophosphamide, improve spermatogenesis, sperm quality and fertility, increase the release of testosterone, stabilize the feedback regulation mechanism, and ensure the spermatogenic ability of mice. It could also improve the ability of anti-oxidation. In addition, C-phycocyanin could play a protective role by down-regulating RIPK1, RIPK3, and p-MLKL to inhibit the necroptotic signaling pathway. These results suggest that C-phycocyanin could protect GC-1 spg cells and the reproductive system of male mice from TSZ and cyclophosphamide, and the protective mechanism may be achieved by inhibiting the signal pathway of necroptosis. Therefore, C-phycocyanin could serve as a promising reproductive system protective agent. C-phycocyanin may enter public life as a health product in the future.

Surgical Resection of Dorsal Spinal Meningiomas with the Inner Dura Layer-An Improved Preservation Technique of Spinal Dura in 40 Cases.

BACKGROUND: Spinal meningiomas are the common benign tumors in intradural extramedullary spinal tumors. Simpson grade I resection is recommended to avoid tumor recurrence. However, the dura reconstruction increases a risk of cerebrospinal fluid leakage after this surgical resection. To address this concern, the inner dura layer resection and long-term surgical outcomes of this technique were designed and examined after total tumor resection to preserve the outer dura layer. METHODS: This study included 40 spinal meningioma patients undergoing the outer dura layer resection between 2002 and 2019. Clinical characteristics, radiologic features, preoperative and postoperative functional states, tumor recurrence, and perioperative complications were described and evaluated. RESULTS: A total of 40 spinal meningioma cases with the median age of 63 years (36-81 years) were enrolled in this study. The median postoperative follow-up period of all 40 cases was 96 months (34-193 months). About 82.5% of cases were located in the thoracic spine, while 16.5% of cases were located in the cervical spine. Of the symptomatic cases, 87.5% of cases follow with satisfactory outcomes and 12.5% of cases follow with unexpected outcomes. The local spinal meningioma recurrence rate was 2.5% (1 of 40 cases). No postoperative cerebrospinal fluid leak occurred in the 40 spinal meningioma cases. CONCLUSIONS: A long-term postoperative follow-up indicated that this modified spinal dura preservation technique caused good neurologic improvement with rare recurrence. Therefore we recommend this improved technique may be an alternative surgical option for total resection of spinal meningiomas with favorable prognosis.

Bone pain from spinal metastases: Iodine-125 brachytherapy.

OBJECTIVES: This study evaluated the analgesic efficacy and safety of CT-guided iodine-125 (125I) brachytherapy in patients with spinal metastasis-induced pain who were not suitable to receive radiotherapy. METHODS: A cohort of 68 patients with spinal metastasis induced pain not fully relieved by opioids and did not receive external beam radiation therapy due to poor general status were enrolled and underwent CT-guided 125I brachytherapy for analgesic treatment. RESULTS: Patients were followed for 8 weeks after brachytherapy. Mean Numerical Rating Scale score before brachytherapy was 7.3±1.3 and decreased to 3.3±0.9, 2.6±0.8, 2.7±0.8, 2.9±0.9 and 3.3±1.1 at weeks 1, 2, 4, 6 and 8, respectively, after brachytherapy. Daily dose of morphine equivalent was 105.1±28.0 mg before brachytherapy and decreased to 45.3±13.7, 39.9±14.2, 40.4±14.9, 48.5±18.0 and 62.4±17.5 mg at weeks 1, 2, 4, 6 and 8, respectively, after brachytherapy. Patients had fewer daily episodes of breakthrough pain after brachytherapy (p<0.001). Patients had improvement in pain-related functional interference and in hospital anxiety and depression score after brachytherapy. CONCLUSIONS: CT-guided 125I brachytherapy is an effective and safe intervention for patients with spinal metastasis-induced pain who are not able to receive radiation therapy.

Gabapentin enhances the antinociceptive effect of intrathecal morphine in refractory cancer pain patients.

PURPOSE: Morphine infusion through Intrathecal Drug Delivery System (IDDS) is widely used to relieve refractory cancer pain. However, continuous escalation of morphine dose caused by opioid tolerance and/or progress of cancer was commonly observed. Combining morphine with medications of different analgesic mechanisms is applied to blunt the rate of morphine increase. The purpose of this study was to determine the analgesic efficacy and safety of combining gabapentin with morphine after IDDS implantation. METHODS: This study compared patients that received IDDS implantation from January 1, 2017 to November 10, 2018 in our institute. Key outcomes included change in mean pain score, dose of morphine used in patients, percentage of patients with 30% and 50% reduction in mean pain score, Patient Global Impression of Change scores, breakthrough pain characters and side effects. RESULTS: 34 patients in the combination group (morphine + gabapentin) and 40 patients in the monotherapy group(morphine)were analyzed. The results showed that both therapy groups achieved similar analgesic efficacy, demonstrated by Numerical rating scale (2.42 ± 0.88 vs 2.57 ± 0.85; Combination vs Monotherapy), PGIC and responder status. Mean daily dose of morphine was significantly lower in combination group compared to monotherapy group (3.54 ± 1.29 mg vs 4.64 ± 1.28 mg, P = 0.007). More patients experienced dizziness and somnolence after receiving combination therapy compared to morphine-alone treatment although no statistical significance was found (P = 0.49). CONCLUSION: Addition of gabapentin achieved similar analgesic efficacy with lower dose of morphine compared to morphine alone accompanying with higher incidence of dizziness and somnolence.

AKIP1 promotes glioblastoma viability, mobility and chemoradiation resistance via regulating CXCL1 and CXCL8 mediated NF-κB and AKT pathways.

This study aimed to investigate the interaction of A-kinase-interacting protein 1 (AKIP1) with C-X-C motif chemokine ligand (CXCL)1, CXCL2, CXCL8, and their effects on regulating glioblastoma multiforme (GBM) malignant behaviors. AKIP1 expression was modified by pcDNA and pGPH1 vectors in U-87 MG and U-251 MG cells. Subsequently, multiple compensative experiments were conducted via adding CXCL1, CXCL2 and CXCL8 in the pGPH1-AKIP1 (AKIP1 knockdown) transfected U-87 MG and U-251 MG cells, respectively. Furthermore, AKIP1, CXCL1/2/8 expressions in 10 GBM and 10 low-grade glioma (LGG) tumor samples were detected. AKIP1 was elevated in various GBM cell lines compared to normal human astrocytes. AKIP1 overexpression promoted U-87 MG and U-251 MG cell proliferation and invasion while inhibited apoptosis; and it enhanced chemoresistance to temozolomide (but not cisplatin) and radiation resistance; then AKIP1 knockdown showed the opposite effects. Meanwhile, AKIP1 positively regulated CXCL1/2/8, NF-κB pathway, AKT pathway and PD-L1 expression. Further multiple compensative experiments uncovered that CXCL1 and CXCL8 promoted proliferation, invasion, chemoradiation resistance, NF-κB pathway, AKT pathway and PD-L1 expression in U-87 MG and U-251 MG cells, also in pGPH1-AKIP1 (AKIP1 knockdown) transfected U-87 MG and U-251 MG cells; although CXCL2 exhibited similar treads, but its effect was much weaker. Besides, NF-κB pathway inhibitor and AKT pathway inhibitor attenuated the effect of CXCL1&CXCL8 on promoting GBM cell malignant behaviors. Clinically AKIP1 and CXCL1/8 were elevated in GBM compared to LGG tumor samples, and they were inter-correlated. AKIP1 promotes GBM viability, mobility and chemoradiation resistance via regulating CXCL1 and CXCL8 mediated NF-κB and AKT pathways.

Interfering with hyaluronic acid metabolism suppresses glioma cell proliferation by regulating autophagy.

The tumor microenvironment plays an important role in tumor progression. Hyaluronic acid (HA), an important component of the extracellular matrix in the tumor microenvironment, abnormally accumulates in a variety of tumors. However, the role of abnormal HA accumulation in glioma remains unclear. The present study indicated that HA, hyaluronic acid synthase 3 (HAS3), and a receptor of HA named CD44 were expressed at high levels in human glioma tissues and negatively correlated with the prognosis of patients with glioma. Silencing HAS3 expression or blocking CD44 inhibited glioma cell proliferation in vitro and in vivo. The underlying mechanism was attributed to the inhibition of autophagy flux and maintaining glioma cell cycle arrest in G1 phase. More importantly, 4-methylumbelliferone (4-MU), a small competitive inhibitor of Uridine diphosphate (UDP) with the ability to penetrate the blood-brain barrier (BBB), also inhibited glioma cell proliferation in vitro and in vivo. Thus, approaches that interfere with HA metabolism by altering the expression of HAS3 and CD44 and the administration of 4-MU potentially represent effective strategies for glioma treatment.

The combined analgesic effect of pregabalin and morphine in the treatment of pancreatic cancer pain, a retrospective study.

BACKGROUND: Pregabalin is commonly used to relieve neuropathic pain. However, data are lacking on its efficacy for the treatment of chronic cancer pain. The purpose of this study was to determine the analgesic efficacy of pregabalin combined with morphine in the management of pancreatic cancer pain. METHODS: This study reviewed patients who were prescribed morphine and 150 mg/d pregabalin between 1 January 2017 and 10 November 2018 in our institute. The primary outcomes of this study were the average pain score and dose of morphine. Secondary outcomes included characters of breakthrough cancer pain, functional interference related to pain, anxiety/depression status, and incidence of treatment-related adverse events during the study. RESULTS: A total of 240 patients with pain related to pancreatic cancer were included in the study. The results showed that patients of both combination therapy group (pregabalin+morphine) and monotherapy group (morphine) achieved similar analgesic efficacy, demonstrated by NRS (2.4 ± 0.9 vs. 2.6 ± 0.9; combination vs. monotherapy) at the end of the study. Mean daily dose of morphine used in the combination group was significant lower compared to monotherapy group (39.5 ± 16.0 mg vs. 61.5 ± 19.3 mg, net difference 23.5, 95% CI: 18.4-28.6, p < â€Š0.001). The change of functional interference score related to pain was significantly different between combination and monotherapy group (12.0 ± 0.4 vs. 9.8 ± 4.9; net difference, 2.3; 95% CI: 1.1-3.3; p < 0.001). Patients in combination therapy group had experienced shorter duration of breakthrough cancer pain than those in monotherapy group (X2 p < 0.001, Cramer's V:0.36). The incidence of somnolence, dizziness, and cognitive dysfunction were significantly higher in the combination group compared to monotherapy group. No serious treatment-related side effects were observed. CONCLUSIONS: The findings of this study supported the use of pregabalin with morphine to relieve pain in patients of pancreatic cancer.