The Effect of Topical Vancomycin Powder Application on the Rate of Intervertebral Fusion Following Lumbar Fusion: A Retrospective Study.

PURPOSE: The occurrence of surgical site infection (SSI) after lumbar spinal fusion is a serious complication. Therefore, an increasing number of clinicians are applying vancomycin powder topically in the surgical field to reduce the incidence of SSI. However, there is concern that topical vancomycin powder application may affect intervertebral fusion. The purpose of this study was to analyse the effect of clinically relevant topical vancomycin doses on the rate of intervertebral fusion after lumbar fusion and to further investigate the effect of vancomycin powder on the prevention of SSI. METHODS: The clinical data of 192 patients with degenerative lumbar spine disease admitted from January 2019 to June 2022, all of whom underwent posterior lumbar fusion, were retrospectively analysed. According to the infection prevention protocol, they were divided into a vancomycin group and a control group (no vancomycin), and the vancomycin group was sub-divided into 0.5 g, 1.0 g, and 1.5 g vancomycin groups. General information and surgical evaluation indexes were compared between the control and vancomycin groups and intervertebral fusion was compared between the vancomycin groups at 6 months and 12 months, postoperatively. RESULTS: The rate of SSI in the vancomycin group was 0.0%, which was significantly lower than that in the control group (5.3%, P < 0.05), and intervertebral fusion was good in all 3 vancomycin groups at 6 months and 12 months postoperatively, with no statistically-significant differences (P > 0.05). CONCLUSIONS: Topical application of 0.5 g, 1.0 g, or 1.5 g vancomycin powder did not affect the rates of intervertebral fusion after lumbar fusion. In addition, topical application of vancomycin powder significantly reduced the rates of SSI.

Malic enzyme 2 promotes the progression of hepatocellular carcinoma via increasing triglyceride production.

The incidence and mortality of hepatocellular carcinoma (HCC) are gradually increasing during the past years. Recently, some studies have reported that malic enzyme (ME) plays an important role in cancer development, while the involvement of ME2 in HCC remains still undetermined. Here, we demonstrated that ME2 played an oncogenic role in HCC. ME2 was overexpressed in HCC tissues. TCGA database showed that the ME2 transcript level was inversely associated with the survival of HCC patients. Loss-of-function and gain-of-function assays showed that ME2 promoted HCC cell growth and migration. Furthermore, the xenografted tumorigenesis of MHCC97H cells was retarded by ME2 knockdown. ME2 silencing also suppressed the cell cycle process and induced apoptosis. Mechanistically, ME2 potentiated triglyceride synthesis, inhibition of which suppressed the proliferation and migration. We propose that ME2 promotes HCC progression by increasing triglyceride production.

AEB-071 Ameliorates Muscle Weakness by Altering Helper T Lymphocytes in an Experimental Autoimmune Myasthenia Gravis Rat Model.

BACKGROUND Myasthenia gravis (MG) is an autoimmune neurological disorder of neuromuscular junctions. In this study we established experimental autoimmune myasthenia gravis (EAMG) rat models to investigate the effects of AEB-071 (AEB), which is a specific inhibitor of protein kinase C that prevents T lymphocyte activation. MATERIAL AND METHODS We utilized animals divided into 4 groups: (1) control rats, (2) EAMG, (3) AEB-071+EAMG, and (4) AZP+EAMG. Drug treatment was continued for 10 days. Ten weeks after immunization we measured body weights, assessed mortality rates, and used Lennon scores to evaluate EAMG grades. We also assessed the proportions of Treg, Th1, Th2, Th17, and lymphocytes using flow cytometry. RESULTS In the absence of drug treatment, we found a significant decline in body weights in the EAMG group in comparison to control rats, and EAMG group rats also had higher Lennon scores (P<0.05). Interestingly, we found that AEB-071 restored the body weight of EAMG rats and the decreased mortality rate compared to AZP treatment. Although a decrease in the number of Treg cells was observed, the proportion of Th lymphocytes was significantly increased in the EAMG group, and AEB-071 treatment decreased the proportion of Th lymphocytes. CONCLUSIONS We concluded that AEB-071 treatment imparts beneficial effects in EAMG rat models by reducing mortality rate and restoring Th lymphocyte balance, and thus may be an attractive candidate for use in MG treatment.

Green Tea Polyphenol Epigallocatechin-3-Gallate Promotes Reendothelialization in Carotid Artery of Diabetic Rabbits by Reactivating Akt/eNOS Pathway.

Background: Epigallocatechin gallate (EGCG) is the most abundant catechin in green tea and has proven benefits on endothelial cells in diabetes. However, it remains unclear whether EGCG could improve function of late endothelial progenitor cells (L-EPCs) in diabetes. Methods: Thirty-six rabbits were randomized into six groups. Thirty diabetic rabbits were induced by a single dose of alloxan (100 mg/kg injection intraperitoneally). All of them were given intragastrically EGCG (50 mg/kg/day) or saline for 7 days after carotid injury. In autotransfusion experiment, L-EPCs were cultured with pre-treated EGCG (40 µM for 72 h) and then were injected into the site of injured vascular. Proliferation and migration of EGCG pre-treated L-EPCs in high glucose condition were assessed by EDU incorporation assay and modified Boyden chamber assay, respectively. The mRNA and protein expression of Akt-eNOS pathway were detected by real-time PCR and western blot. Results: Reendothelialization rate in injured carotid artery of diabetic rabbits was augmented in the EGCG group (50 mg/kg/d for 7 days) compared with the non-EGCG group (74.2 ± 4.6% vs. 25.6 ± 5.9%, P < 0.001). EGCG pre-treated L-EPCs autologous transfusion also accelerated the diabetic rabbits' carotid reendothelialization compared with the diabetic sham-operated group (65.6 ± 8.5% vs. 32.9 ± 5.0%, P = 0.011). In vitro studies showed, 40 µM EGCG treatment for 72 h recovered L-EPCs' proliferation and migration, as well as restored the phosphorylation level of Akt and eNOS blocked by high glucose condition. Conclusion: EGCG accelerated reendothelialization in diabetic rabbits after carotid injury in part by reactivating the Akt/eNOS pathway, which might contribute to recovering proliferation and migration of L-EPCs impaired by high glucose.

A Twisted Thieno[3,4-b]thiophene-Based Electron Acceptor Featuring a 14-π-Electron Indenoindene Core for High-Performance Organic Photovoltaics.

With an indenoindene core, a new thieno[3,4-b]thiophene-based small-molecule electron acceptor, 2,2'-((2Z,2'Z)-((6,6'-(5,5,10,10-tetrakis(2-ethylhexyl)-5,10-dihydroindeno[2,1-a]indene-2,7-diyl)bis(2-octylthieno[3,4-b]thiophene-6,4-diyl))bis(methanylylidene))bis(5,6-difluoro-3-oxo-2,3-dihydro-1H-indene-2,1-diylidene))dimalononitrile (NITI), is successfully designed and synthesized. Compared with 12-π-electron fluorene, a carbon-bridged biphenylene with an axial symmetry, indenoindene, a carbon-bridged E-stilbene with a centrosymmetry, shows elongated π-conjugation with 14 π-electrons and one more sp3 carbon bridge, which may increase the tunability of electronic structure and film morphology. Despite its twisted molecular framework, NITI shows a low optical bandgap of 1.49 eV in thin film and a high molar extinction coefficient of 1.90 × 105 m-1 cm-1 in solution. By matching NITI with a large-bandgap polymer donor, an extraordinary power conversion efficiency of 12.74% is achieved, which is among the best performance so far reported for fullerene-free organic photovoltaics and is inspiring for the design of new electron acceptors.

Interleukin-8 prevents oxidative stress-induced human endothelial cell senescence via telomerase activation.

Senescence is an irreversible growth arrest which can be triggered by stresses such as oxidative reaction, telomere shortening, DNA damage, or oncogene signaling. Oxidative stress accelerates vascular endothelial cell senescence, and may promote atherosclerosis in humans. Interleukin-8 (IL-8) has been shown to play an important role in tumor growth, angiogenesis, and metastasis, and has close relationship with oxidative stress. The objective of this study was to determine if IL-8 might be able to prevent oxidative stress-induced senescence of endothelial cells and the mechanisms. Human umbilical vein endothelial cells (HUVECs) were cultured and stimulated with hydrogen peroxide in the absence or presence of IL-8. After ex vivo cultivation, HUVECs became senescent as determined by acidic beta-galactosidase staining. IL-8 dose-dependently inhibited the onset of HUVEC senescence. Western blots indicated that IL-8 attenuated the oxidative stress induced high-expression of cell cycle regulation protein and inhibited the activation of p38 and NF-κB pathway. IL-8 also increased telomerase activity which was accompanied with upregulation of the catalytic subunit, telomerase reverse transcriptase (TERT), whereas these effects were significantly attenuated by SB 225002 (selective non-peptide CXCR2 antagonist). In conclusion, IL-8 exerted protective effects against endothelial senescence, which may be related to the activation of telomerase.

Inflammation & apoptosis in spinal cord injury.

Spinal cord injury (SCI) consists of a two-steps process involving a primary mechanical injury followed by an inflammatory process and apoptosis. Secondary insult is characterized by further destruction of neuronal and glial cells, and leads to expansion of the damage, so that the paralysis can extend to higher segments. With the identification of mechanisms that either promote or prevent neuronal inflammation and apoptosis come new approaches for preventing and treating neurodegenerative disorders. From a clinical perspective, this article discusses novel targets for the development of therapeutic agents that have the potential to protect the spinal cord from irreversible damage and promote functional recovery.

Osteoporosis as a potential contributor to the bone metastases.

Bone metastasis is a serious complication of patients with tumor, and most primary tumors can metastasize to bone. And the main threat and the reason for most cancer deaths are not the primary neoplasias, but secondary tumors, the metastases. To minimize the morbidity and economic expenditure associated with bone metastases, it is important to decrease the etiological factors of bone metastasis. Although current evidence suggested that the therapies to the underlying malignancy bone metastasis might result in bone loss leading to osteoporosis, no studies have shown direct evidence the successful seeding of bone metastases of cancer cells is the part played by osteoporosis. In the state of osteoporosis, for the enhancement of the osteolysis, the increased inflammatory factors could make blood vessels leakier, resulting in the easier hematogenous metastasis to bone and bone marrow. Moreover, leptin, which was positive correlation with osteoporosis, has been showed to exert angiogenic effects and could regulate VEGF expression, promoting the proliferation of the cancer blood vessel. In addition, the increased growth factors in osteoporosis could enrich the local microenvironment, promoting the growth of the metastasis mass. Given the above background, we hypothesize that osteoporosis may be a potential contributor to the bone metastases.

Determination of benzalkonium chloride in viscous ophthalmic drops of azithromycin by high-performance liquid chromatography.

A high-performance liquid chromatography (HPLC) system was used in the reversed phase mode for the determination of benzalkonium chloride (BKC) in azithromycin viscous ophthalmic drops. A Venusil-XBP(L)-C(18) (150 mmx4.6 mm, 5 microm) column was used at 50 degrees C. The mobile phase consisted of a mixture of methanol-potassium phosphate (16:5, v/v). Two sample preparation methods were compared. The results suggested that, compared with an extraction procedure, a deproteinization procedure was much quicker and more convenient. Using the deproteinization procedure for sample preparation, calibration curves were linear in the range 5.0 to approximately 50 microg/ml. The within-day and inter-day coefficients of variation were less than 10%. The average recoveries were determined as 96.70%, 98.52%, and 97.96% at concentrations of 10.0, 30.0, and 50.0 microg/ml, respectively. Variability in precision did not exceed 5%. In conclusion, this HPLC method using a simple sample treatment procedure appears suitable for monitoring BKC content in azithromycin viscous ophthalmic drops.

5-Fluorouracil: mechanisms of resistance and reversal strategies.

The purpose of this work is to review the published studies on the mechanisms of action and resistance of 5-fluorouracil. The review is divided into three main sections: mechanisms of anti-tumor action, studies of the resistance to the drug, and procedures for the identification of new genes involved in resistance with microarray techniques. The details of the induction and reversal of the drug resistance are also described.

Moderate alcohol consumption may decrease risk of intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a serious health problem worldwide. Unfortunately, efforts to control IDD are largely unsuccessful. It is therefore important to get better understanding of risks. Various evidences indicate that moderate alcohol consumption has protective effect on IDD. Here, we review the clinical evidence on alcohol consumption and IDD, and propose a possible mechanism. There is increasing evidence indicating that moderate alcohol consumption keeps the feeding arteries smooth. Furthermore, strong evidence indicates that some inflammatory factors are very important in the pathophysiology of IDD, while moderate alcohol consumption can decrease the expression of these inflammatory factors. Moreover, experimental studies show that alcohol exposure could increase the type II collagen and aggrecan, the major constituents of nucleus pulposus matrix. Given the above background, we hypothesize that moderate alcohol consumption may reduce the risk of IDD.