Robot-Assisted Radical Prostatectomy by the Hugo Robotic-Assisted Surgery (RAS) System and the da Vinci System: A Comparison between the Two Platforms.

OBJECTIVE: In a previous study, we proved that an experienced urologist is more likely to adapt to the Hugo RAS system. Based on this, we further examine various parameters in this study. Parameters included in this study consisted of console time, functional outcomes, and oncological outcomes. MATERIALS AND METHODS: A total of 60 patients who underwent robot-assisted radical prostatectomy (RARP) performed by a single surgeon using the da Vinci (DV) system (n = 30) or the Hugo RAS system (n = 30) between March 2023 and August 2023 were included in the analysis. The intraoperative operative time was categorized into vesicourethral anastomosis time and overall console time. Functional and oncological outcomes were documented at the 1st and 3rd postoperative months. Parametric and non-parametric methods were adopted after checking skewness and kurtosis, and an α value of 5% was used to determine the significance. RESULTS: The vesicourethral anastomosis time was significantly lengthened (Hedge's g: 0.87; 95% confidence interval (CI): 0.34-1.39; J factor = 0.987). However, the overall console time was not affected. The functional (postoperative 3rd month: p = 0.130) and oncological outcomes (postoperative 3rd month: p = 0.103) were not significantly different. We also found that the adverse effect on surgical specimens and positive surgical margins was not affected (p = 0.552). CONCLUSION: During the process of adaptation, although intricate motions (such as the vesicourethral anastomosis time) would be lengthened, the overall console time would not change remarkably. In this process, the functional and oncological outcomes would not be compromised. This encourages urologists to adopt the Hugo RAS system in RARP if they have previous experiences of using the DV system, since their trifecta advantage would not be compromised.

[Formononetin enhances the antitumor effect of H22 hepatoma transplanted mice].

Objective To explore the effect of formononetin on immunity of mice with transplanted H22 hepatocarcinoma. Methods Male C57BL/6 mice were subcutaneously inoculated with H22 cells (4×105) to establish a tumor-bearing mouse model. The mice were treated with formononetin [10 mg/(kg.d)] or [50 mg/(kg.d)] for 28 days, and then the tumor inhibition rate was calculated. Carrilizumab was used as a positive control drug. The expressions of CD8, granzyme B and forkbox transcription factor 3 (FOXP3) in HCC tissues were analyzed by immunohistochemical staining. The mRNA and protein expression of programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) in HCC tissues were detected by real-time PCR or Western blot analysis, respectively. The serum levels of interleukin-10 (IL-10) and transforming growth factor-ß (TGF-ß) were detected by ELISA. Results Formononetin increased the tumor inhibition rate and the positive rate of CD8 and granzyme B staining in tumor-bearing mice. There was no significant difference in the positive rate of FOXP3 staining in tumor tissues of mice in each group. Formononetin decreased the levels of IL-10 and TGF-ß in serum of tumor-bearing mice, and decreased the relative expression of mRNA and protein of PD-1 and PD-L1 in tumor tissue of tumor-bearing mice. Conclusion Formononetin can activate CD8+ T cells and reduce the release of immunosuppressive factors in regulatory T cells by blocking PD-1/PD-L1 pathway and play an antitumor role.

Hesperetin ameliorates spinal cord injury by inhibiting NLRP3 inflammasome activation and pyroptosis through enhancing Nrf2 signaling.

Neuroinflammation is a prominent feature of traumatic spinal cord injuries (SCIs). Hesperetin exhibits anti-inflammatory effects in neurological disorders; however, the potential neuroprotective effects of hesperetin in cases of SCI remain unclear. Sprague-Dawley rats with C5 hemi-contusion injuries were used as an SCI model. Hesperetin was administered to the experimental rats in order to investigate its neuroprotective effects after SCI, and BV2 cells were pretreated with hesperetin or silencing of nuclear factor erythroid 2-related factor 2 (siNrf2), and then stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP). The therapeutic impact and molecular mechanism of hesperetin were elucidated in a series of in vivo and in vitro investigations conducted using a combination of experiments. The results of the present in vivo experiment indicated that hesperetin improved functional recovery and protected spinal cord tissue after SCI. Hesperetin attenuated oxidative stress and microglial activation, lowered malondialdehyde (MDA) levels, and elevated catalase (CAT), glutathione (GSH)-Px, and superoxide dismutase (SOD) levels. Moreover, hesperetin downregulated the expression of advanced oxygenation protein products (AOPPs), ionized calcium-binding adapter molecule 1 (Iba-1), NOD-like receptor protein 3 (NLRP3), and interleukin-1 beta (IL-1ß), but increased the expression of Nrf2. In vitro studies have shown that hesperetin inhibits the generation of reactive oxygen species (ROS), as well as the neuroinflammation associated with the upregulation of Nrf2 and heme oxygenase-1 (HO-1) in BV2 cells. The results of the present study indicated that hesperetin inhibited BV2 cell pyroptosis and significantly blocked the expression of NLRP3 inflammasome proteins (NLRP3 Caspase-1 p10 apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain [ASC]) and pro-inflammatory mediators (IL-18, IL-1ß). Furthermore, the silencing of Nrf2 by small interfering ribonucleic acid (siRNA) partially abolished its antioxidant effect in the aforementioned cell experiments. Collectively, these findings illustrate that through an increase in Nrf2 signaling hesperetin reduces oxidative stress and neuroinflammation by suppressing NLRP3 inflammasome activation and pyroptosis.

Long-Term Surveillance and Management of Urological Complications in Chronic Spinal Cord-Injured Patients.

Bladder dysfunction is a common complication after chronic spinal cord injury (SCI). Patients may experience renal function loss, urinary tract infection (UTI), urolithiasis, bladder cancer, and even life-threatening events such as severe sepsis or renal failure. Suitable patient care may prevent UTI and urinary incontinence, decrease medication use, and preserve renal function. As the primary goal is to preserve renal function, management should be focused on facilitating bladder drainage, the avoidance of UTI, and the maintenance of a low intravesical pressure for continence and complete bladder emptying. Currently, several bladder management options are available to SCI patients: (1) reflex voiding; (2) clean intermittent catheterization; (3) indwelling catheterization. The target organ may be the bladder or the bladder outlet. The purposes of intervention include the following: (1) increasing bladder capacity and/or decreasing intravesical pressure; (2) increasing bladder outlet resistance; (3) decreasing bladder outlet resistance; (4) producing detrusor contractility; (5) urinary diversion. Different bladder management methods and interventions may have different results depending on the patient's lower urinary tract dysfunction. This review aims to report the current management options for long-term bladder dysfunction in chronic SCI patients. Furthermore, we summarize the most suitable care plans for improving the clinical outcome of SCI patients.

Minimizing complications following transinguinal preperitoneal modified Kugel mesh herniorrhaphy: a double blind prospective randomized clinical trial.

Transinguinal preperitoneal (TIPP) single-layer mesh herniorrhaphy has been proven effective. Mesh manufacturers make either a single-unit, two-layer mesh design or a separate optional onlay with the pre-peritoneal mesh. For peace of mind, most surgeons still incorporate the optional onlay. This study evaluated any counterproductive effects of adding the onlay to single-layer TIPP mesh herniorrhaphy and compared the long-term efficacy. This prospective, single-surgeon, single-center, randomized trial compared two groups of 50 consecutive patients at a 1 to 1 ratio. The control group received a single-layer modified Kugel mesh in the preperitoneal space, while the study group received the optional onlay mesh in the inguinal canal with preperitoneal mesh placement. A single surgeon performed the same operation to place the preperitoneal mesh in both groups, the only difference being the placement of the optional onlay mesh in the study group. A blinded researcher performed post-operative interviews using a series of questions at 1, 3, 6, and 12 months after surgery, and another unblinded researcher organized and performed statistical analysis of the peri-operative and post-operative data. The primary endpoints included foreign body sensation, pain, and any other discomfort in the inguinal region following surgery; and the secondary endpoints included recurrence and any complications related to surgery. The patient demographics were similar between the two groups. The average follow-up period was 29 months. Two patients in the 1-layer group and one patient in the 2-layer group were lost to follow-up. Postoperative pain, numbness and soreness were similar between groups. No patients experienced a foreign body sensation after 3 months in the 1-layer group, while five patients still had a foreign body sensation at 12 months in the 2-layer group. No recurrence was noted in either group during the follow-up period. Adequate dissection of the preperitoneal space is the key to a successful single-layer TIPP herniorrhaphy. With decreased materials in the inguinal canal, single-layer TIPP has a lower rate of long-term postoperative discomfort without increasing the risk of future recurrence.Trial registration: ISRCTN 47111213.

Bioinformatics analysis identified apolipoprotein E as a hub gene regulating neuroinflammation in macrophages and microglia following spinal cord injury.

Macrophages and microglia play important roles in chronic neuroinflammation following spinal cord injury (SCI). Although macrophages and microglia have similar functions, their phagocytic and homeostatic abilities differ. It is difficult to distinguish between these two populations in vivo, but single-cell analysis can improve our understanding of their identity and heterogeneity. We conducted bioinformatics analysis of the single-cell RNA sequencing dataset GSE159638, identifying apolipoprotein E (APOE) as a hub gene in both macrophages and microglia in the subacute and chronic phases of SCI. We then validated these transcriptomic changes in a mouse model of cervical spinal cord hemi-contusion and observed myelin uptake, lipid droplets, and lysosome accumulation in macrophages and microglia following SCI. Finally, we observed that knocking out APOE aggravated neurological dysfunction, increased neuroinflammation, and exacerbated the loss of white matter. Targeting APOE and the related cholesterol efflux represents a promising strategy for reducing neuroinflammation and promoting recovery following SCI.

Id2 exerts tumor suppressor properties in lung cancer through its effects on cancer cell invasion and migration.

Background: Despite advances in prognosis and treatment of lung adenocarcinoma (LADC), a notable non-small cell lung cancer subtype, patient outcomes are still unsatisfactory. New insight on novel therapeutic strategies for LADC may be gained from a more comprehensive understanding of cancer progression mechanisms. Such strategies could reduce the mortality and morbidity of patients with LADC. In our previous study, we performed cDNA microarray screening and found an inverse relationship between inhibitor of DNA binding 2 (Id2) expression levels and the invasiveness of LADC cells. Materials and Methods: To identify the functional roles of Id2 and its action mechanisms in LADC progression, we successfully established several Id2-overexpressing and Id2-silenced LADC cell clones. Subsequently, we examined in vitro the effects exerted by Id2 on cell morphology, proliferation, colony formation, invasive, and migratory activities and examined in vivo those exerted by Id2 on cell metastasis. The mechanisms underlying the action of Id2 were investigated using RNA-seq and pathway analyses. Furthermore, the correlations of Id2 with its target gene expression and clinical outcomes were calculated. Results: Our data revealed that Id2 overexpression could inhibit LADC cells' migratory, invasive, proliferation, and colony formation capabilities. Silencing Id2 expression in LADC cells reversed the aforementioned inhibitory effects, and knockdown of Id2 increased LADC cells' metastatic abilities in vivo. Bioinformatics analysis revealed that these effects of Id2 on cancer progression might be regulated by focal adhesion kinase (FAK) signaling and CD44/Twist expression. Furthermore, in online clinical database analysis, patients with LADC whose Id2 expression levels were high and FAK/Twist expression levels were low had superior clinical outcomes.Conclusion: Our data indicate that the Id2 gene may act as a metastasis suppressor and provide new insights into LADC progression and therapy.

Advanced oxidation protein products induce annulus fibrosus cell senescence through a NOX4-dependent, MAPK-mediated pathway and accelerate intervertebral disc degeneration.

Background: Intervertebral disc degeneration (IVDD) is closely associated with senescence. Annulus fibrosus (AF) cell senescence is a crucial driver of AF tissue tearing and fissures, thereby exacerbating IVDD. Increased advanced oxidative protein products (AOPPs) were found in human degenerative discs and aged rat discs and may be involved in IVDD. This study aimed to explore the mechanism of AOPPs-induced senescence in AF cells. Methods: The pathological effects of AOPPs in vivo were investigated using a rat lumbar disc persistent degeneration model and a rat caudal disc puncture model. Rat primary AF cells were selected as in vitro models, and AOPPs were used as direct stimulation to observe their pathological effects. Setanaxb (NOX1/4 inhibitor), apocynin (NADPH oxidase inhibitor) and adenovirus (ADV) packed NADPH oxidase 4 (NOX4) specific shRNAs were used for pathway inhibition, respectively. Finally, adeno-associated viruses (AAVs) packed with NOX4-specific blocking sequences were used to inhibit the in vivo pathway. Results: AOPPs accumulated in the rat lumbar and caudal degenerative discs. Intra-discal loading of AOPPs up-regulated the expression of NOX4, p53, p21, p16, IL-1ß, and TNF-α, ultimately accelerating IVDD. Exposure of AOPPs to AF primary cells up-regulated NOX4 expression, induced phosphorylation of mitogen-activated protein kinases (MAPK), triggered senescence and increased IL-1ß and TNF-α. Apocynin, setanaxib, and ADV pre-cultured AF cells abrogated AOPPs-induced senescence. AAV-mediated inhibition of NOX4 expression in vivo reduced the expression of p53, p21, p16, IL-1ß and TNF-α in vivo and delayed IVDD. Conclusions: AOPPs induced AF cell senescence through a NOX4-dependent and MAPK-mediated pathway.

Insulin sensitizer and antihyperlipidemic effects of Cajanus cajan (L.) millsp. root in methylglyoxal-induced diabetic rats.

Cajanus cajan (L.) Millsp., known as pigeon pea, is one of the major grain legume crops of the tropical world. It recognizes as an ethnomedicine to possess various functions, such as helping in healing wound and cancer therapy. We investigated whether 95% ethanol extracts from C. cajan root (EECR) protect against methylglyoxal (MGO)-induced insulin resistance (IR) and hyperlipidemia in male Wistar rats and explored its possible mechanisms. The hypoglycemic potential of EECR was evaluated using α-amylase, α-glucosidase activities, and advanced glycation end products (AGEs) formation. For in vivo study, the rats were divided into six groups and orally supplemented with MGO except for Group 1 (controls). Group 2 was supplemented with MGO only, Group 3: MGO + metformin, Group 4: MGO + Low dose-EECR (L-EECR; 10 mg/kg bw), Group 5: MGO + Middle dose-EECR (M-EECR; 50 mg/kg bw), and Group 6: MGO + High dose-EECR (H-EECR; 100 mg/kg bw). EECR possessed good inhibition of α-glucosidase, α-amylase activities, and AGEs formation (IC50 = 0.12, 0.32, and 0.50 mg/mL), respectively. MGO significantly increased serum levels of blood glucose (GLU), glycosylated hemoglobin, homeostasis model assessment of IR, AGEs, lipid biochemical values, and atherogenic index, whereas EECR decreased these levels in a dose-dependent manner. EECR can also act as an insulin sensitizer, which significantly decreased (47%, P < 0.05) the blood GLU levels after intraperitoneal injection of insulin in the insulin tolerance tests. The hypoglycemic and antihyperlipidemic mechanisms of EECR are likely through several possible pathways including the inhibition of carbohydrate-hydrolyzing enzymes (α-glucosidase and α-amylase) and the enhancement of MGO-trapping effects on inhibition of AGEs formation.

NPS-1034 Induce Cell Death with Suppression of TNFR1/NF-κB Signaling in Testicular Cancer.

Background and objectives: NPS-1034 with a dual inhibitory effect on Met and Axl kinase receptors has exhibited therapeutic potential in previous models. However, no study on treating testicular cancer (TC) cell lines with NPS-1034 has been established. Materials and Methods: In this study, a series of in vitro examinations of the apoptotic effect induced by NPS-1034 in TC cell lines was conducted to clarify the molecular interactions involved. Results: A decrease in cell viability rate was observed following NPS-1034 treatment, as shown in the MTT assay. Induction of the apoptotic effect was observed in TC cells as the sub-G1 and Annexin-PI populations increased in a dose-dependent manner. The involvement of the tumor receptor necrosis factor receptor 1 (TNFR1) pathway was later determined by the proteome array and western blotting. A reduction in TNFR1 and NF-κB downstream protein expressions, an upregulation of cleaved caspase-3 and -7, and a downregulation of survivin and claspin all reassured the underlying mechanism of the TNFR1 involved in the apoptotic pathway induced by NPS-1034. Conclusions: Our findings provide evidence for a potential underlying TNFR1 pathway involved in NPS-1034 treatment. This study should offer new insights into targeted therapy for TC.

miR-25 Regulates Gastric Cancer Cell Growth and Apoptosis by Targeting EGR2.

Gastric cancer is one of the most common malignancies harmful to human health. The search for effective drugs or gene therapy has aroused the attention of scientists. So far, microRNAs, as small non-coding RNAs, have the potential to be therapeutic targets for cancer. Herein, we found a highly expressed miR-25 in gastric cancer cell. However, the function of miR-25 for gastric cancer cell growth and apoptosis was unknown. Functionally, we used RT-qPCR, western blot, CCK-8, and flow cytometry to detect gastric cancer cell growth and apoptosis. The results indicated that miR-25 promoted gastric cancer cell growth and inhibited their apoptosis. Mechanistically, we found that a gene EGR2 was a potential target gene of miR-25. Further dual-luciferase results supported this prediction. Moreover, knockdown of EGR2 promoted gastric cancer cell growth and inhibited their apoptosis by flow cytometry detection. Altogether, these findings revealed miR-25 as a regulator of gastric cancer cell growth and apoptosis through targeting EGR2.

Proteomics and bioinformatics reveal insights into neuroinflammation in the acute to subacute phases in rat models of spinal cord contusion injury.

Neuroinflammation is recognized as a hallmark of spinal cord injury (SCI). Although neuroinflammation is an important pathogenic factor that leads to secondary injuries after SCI, neuroprotective anti-inflammatory treatments remain ineffective in the management of SCI. Moreover, the molecular signatures involved in the pathophysiological changes that occur during the course of SCI remain ambiguous. The current study investigated the proteins and pathways involved in C5 spinal cord hemi-contusion injury using a rat model by means of 4-D label-free proteomic analysis. Furthermore, two Gene Expression Omnibus (GEO) transcriptomic datasets, Western blot assays, and immunofluorescent staining were used to validate the expression levels and localization of dysregulated proteins. The present study observed that the rat models of SCI were associated with the enrichment of proteins related to the complement and coagulation cascades, cholesterol metabolism, and lysosome pathway throughout the acute and subacute phases of injury. Intriguingly, the current study also observed that 75 genes were significantly altered in both the GEO datasets, including ANXA1, C1QC, CTSZ, GM2A, GPNMB, and PYCARD. Further temporal clustering analysis revealed that the continuously upregulated protein cluster was associated with immune response, lipid regulation, lysosome pathway, and myeloid cells. Additionally, five proteins were further validated by means of Western blot assays and the immunofluorescent staining showed that these proteins coexisted with the F4/80+ reactive microglia and infiltrating macrophages. In conclusion, the proteomic data pertaining to the current study indicate the notable proteins and pathways that may be novel therapeutic targets for the treatment of SCI.

Advanced oxidation protein products aggravate age­related bone loss by increasing sclerostin expression in osteocytes via ROS­dependent downregulation of Sirt1.

Advanced oxidation protein products (AOPPs) induce intracellular oxidative stress (OS) and are involved in numerous diseases. AOPPs accumulate with age, and our previous study revealed that AOPPs accelerated bone deterioration in aged rats. However, the underlying mechanism remains unknown. The present study demonstrated that AOPPs aggravated bone loss in aging male mice by increasing the resorptive activity and decreasing the formative activity of bone tissues. In addition, SOST mRNA (encoding sclerostin) and sclerostin protein levels were increased in the bone tissues of AOPP­treated mice, which was associated with enhanced OS status as well as decreased Sirtuin 1 (SIRT1) mRNA and protein expression levels. Incubation of MLO­Y4 cells with AOPPs induced the accumulation of reactive oxygen species (ROS) via the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. The accumulated ROS then upregulated sclerostin expression in MLO­Y4 cells by decreasing Sirt1 expression. In vivo, AOPP­challenged mice co­treated with apocynin (an inhibitor of NADPH oxidases), N­acetyl­L­cysteine (a ROS scavenger) or SRT3025 (a Sirt1 activator) displayed improved bone mass and microstructure. Moreover, sclerostin expression in the bone tissues of the co­treated groups was significantly lower compared with that in groups treated with AOPPs alone. Collectively, these data suggested that AOPPs aggravated age­related bone loss by increasing the expression of sclerostin in osteocytes via ROS­dependent downregulation of Sirt1. The present findings provide novel insights into the pathogenesis of senile osteoporosis.

[Biomechanical study of polymethyl methacrylate bone cement and allogeneic bone for strengthening sheep vertebrae].

OBJECTIVE: To investigate the feasibility and mechanical properties of polymethyl methacrylate (PMMA) bone cement and allogeneic bone mixture to strengthen sheep vertebrae with osteoporotic compression fracture. METHODS: A total of 75 lumbar vertebrae (L 1-L 5) of adult goats was harvested to prepare the osteoporotic vertebral body model by decalcification. The volume of vertebral body and the weight and bone density before and after decalcification were measured. And the failure strength, failure displacement, and stiffness were tested by using a mechanical tester. Then the vertebral compression fracture models were prepared and divided into 3 groups ( n=25). The vertebral bodies were injected with allogeneic bone in group A, PMMA bone cement in group B, and mixture of allogeneic bone and PMMA bone cement in a ratio of 1∶1 in group C. After CT observation of the implant distribution in the vertebral body, the failure strength, failure displacement, and stiffness of the vertebral body were measured again. RESULTS: There was no significant difference in weight, bone density, and volume of vertebral bodies before decalcification between groups ( P>0.05). After decalcification, there was no significant difference in bone density, decreasing rate, and weight between groups ( P>0.05). There were significant differences in vertebral body weight and bone mineral density between pre- and post-decalcification in 3 groups ( P<0.05). CT showed that the implants in each group were evenly distributed in the vertebral body with no leakage. Before fracture, the differences in vertebral body failure strength, failure displacement, and stiffness between groups were not significant ( P>0.05). After augmentation, the failure displacement of group A was significantly greater than that of groups B and C, and the failure strength and stiffness were less than those of groups B and C, the failure displacement of group C was greater than that of group B, and the failure strength and stiffness were less than those of group B, the differences between groups were significant ( P<0.05). Except for the failure strength of group A ( P>0.05), the differences in the failure strength, failure displacement, and stiffness before fracture and after augmentation in the other groups were significant ( P<0.05). CONCLUSION: The mixture of allogeneic bone and PMMA bone cement in a ratio of 1∶1 can improve the strength of the vertebral body of sheep osteoporotic compression fractures and restore the initial stiffness of the vertebral body. It has good mechanical properties and can be used as one of the filling materials in percutaneous vertebroplasty.

A bone substitute composed of polymethyl-methacrylate bone cement and Bio-Gene allogeneic bone promotes osteoblast viability, adhesion and differentiation.

BACKGROUND: Increasing reports on new cement formulations that address the shortcomings of PMMA bone cements and various active components have been introduced to improve the biological activity of PMMA cement. OBJECTIVE: Evaluating the biological properties of PMMA cements reinforced with Bio-Gene allogeneic bone. METHODS: The MC3T3-E1 mouse osteoblast-like cells were utilized to determine the effects of Bio-Gene + PMMA on osteoblast viability, adhesion and differentiation. RESULTS: The combination of allogeneic bone and PMMA increased the number of adherent live cells compared to both control group and PMMA or Bio-Gene group. Scanning electron microscopy observed that the number of cells adhered to Bio-Gene + PMMA was larger than Bio-Gene and PMMA group. Compared with the control and PMMA or Bio-Gene group, the level of ALP and the number of calcium nodules after osteoinduction was remarkably enhanced in Bio-Gene + PMMA group. Additionally, the combination of Bio-Gene and PMMA induced the protein expression of osteocalcin, osterix and collagen I. CONCLUSION: The composition of PMMA and allogeneic bone could provide a more beneficial microenvironment for osteoblast proliferation, adhesion and differentiation. PMMA bone cement reinforced with Bio-Gene allogeneic bone may act as a novel bone substitute to improve the biological activity of PMMA cement.

In vitro evaluation of drug delivery behavior for inhalable amorphous nanoparticle formulations in a human lung epithelial cell model.

Respiratory tract infections caused by multidrug-resistant (MDR) Gram-negative bacteria such as Pseudomonas aeruginosa are serious burdens to public health, especially in cystic fibrosis patients. The combination of colistin, a cationic polypeptide antibiotic, and ivacaftor, a cystic fibrosis transmembrane regulator (CFTR) protein modulator, displays a synergistic antibacterial effect against P. aeruginosa. The primary aim of the present study is to investigate the transport, accumulation and toxicity of a novel nanoparticle formulation containing colistin and ivacaftor in lung epithelial Calu-3 cells. The cell viability results demonstrated that ivacaftor alone or in combination with colistin in the physical mixture showed significant toxicity at an ivacaftor concentration of 10 µg/mL or higher. However, the cellular toxicity was significantly reduced in the nanoparticle formulation. Ivacaftor transport into the cells reached a plateau rapidly as compared to colistin. Colistin transport across the Calu-3 cell monolayer was less than ivacaftor. A substantial amount (46-83%) of ivacaftor, independent of dose, was accumulated in the cell monolayer following transport from the apical into the basal chamber, whereas the intracellular accumulation of colistin was relatively low (2-15%). The nanoparticle formulation significantly reduced the toxicity of colistin and ivacaftor to Calu-3 cells by reducing the accumulation of both drugs in the cell and potential protective effects by bovine serum albumin (BSA), which could be a promising safer option for the treatment of respiratory infections caused by MDR P. aeruginosa.

Is anterior decompression and fusion superior to laminoplasty for cervical myelopathy due to ossification of posterior longitudinal ligament? A systematic review and meta-analysis.

Context: Considerable controversy exists over surgical procedures for ossification of the posterior longitudinal ligament (OPLL).Objective: The purpose of the meta-analysis was to compare the clinical outcome of anterior decompression and fusion (ADF) with laminoplasty (LAMP) in treatment of cervical myelopathy due to OPLL.Methods: PubMed, EMBASE and the Cochrane Register of Controlled Trials database were searched to identify potential clinical studies compared ADF with LAMP for cervical myelopathy owing to OPLL. We also manually searched the reference lists of articles and reviews for possible relevant studies. Thirteen studies with 1120 patients were included in our analysis. Subgroup analyses were performed by the canal occupying ratio of OPLL.Results: Overall, the mean preoperative Japanese Orthopaedic Association (JOA) score was similar between two groups. Compared with LAMP group, ADF group was higher at the mean postoperative JOA scores and mean recovery rate, reoperation rate, and longer at mean operation time. There was not significantly different in mean blood loss and complication rate between two groups. In subgroup analysis, ADF had a higher mean postoperative JOA score and recovery rate than LAMP in cases of OPLL with occupying ratios ≥ 50%, while those difference were not found in cases of OPLL with occupying ratios < 50%.Conclusion: ADF achieves better neurological improvement compared with LAMP in treatment of cervical myelopathy due to OPLL, especially in cases of OPLL with occupying ratios ≥ 50%. Complication rate is similar between two groups, but ADF can increase the risk of reoperation.

Evaluation of a new spinal surgical robotic system of Kirschner wire placement for lumbar fusion: A multi-centre, randomised controlled clinical study.

BACKGROUND: To introduce a novel robotic system 'Orthbot' that has been developed and tested as a surgical assistant for auto-placement of the K-wire in lumbar fusion. METHODS: This is a multi-centre, randomized controlled clinical study that includes 56 patients (robot group, RG: 27, free-hand group, FG: 29). Following the pre-operative planning and intra-operative fluoroscopic images, the 'Orthbot' automatically completed registration and K-wire placement under the supervision of the surgeon. Deviation distance (DD) and deviation angle (DA) were used as the primary parameters to evaluate the accuracy of the robotic system. RESULTS: The average DD was 0.95 ± 0.377 mm and 4.35 ± 2.01 mm, respectively in the RG and FG (p < 0.001). The average DA of the K-wire in the coronal plane and the sagittal plane in X-Ray was respectively 6.80 ± 7.79° and 1.27 ± 2.32° in the RG (p < 0.001), and 22.22 ± 16.85° and 4.57 ± 3.86° in the FG (p < 0.001), which showed a higher accuracy rate in the robotic-assisted cases compared to the free-hand cases. CONCLUSIONS: The novel robotic system could achieve accurate K-wire insertions as indicated by the radiological results.

Posterior unilateral exposure and stability reconstruction with pedicle and lamina screw fixation for the cervical dumbbell tumorectomy: a case report and biomechanical study.

PURPOSE: Cervical dumbbell tumor is usually removed via a posterior approach and may require the spinal fixation sometimes. However, the present surgical methods involved either more trauma or a higher risk of instability of the cervical spine. A new technique of unilateral exposure and stability reconstruction with pedicle and lamina screws fixation for posterior cervical dumbbell tumorectomy was described and compared with conventional techniques. METHODS: Posterior unilateral exposure, hemi-laminectomy and facetectomy were performed in one patient with the cervical dumbbell tumor between C3 and C4. The stability was reconstructed by the unilateral pedicle and lamina screws fixation (UPLS), and a strip of shaped allograft bone was also implanted between the superior and inferior lateral mass. Biomechanical stability test of this new technique was investigated using seven fresh-frozen human cervical spine specimens (C4-C7) and compared with unilateral pedicle screw (UPS) and bilateral pedicle screw fixation (BPS) techniques. A continuous pure moment of ± 2.0 Nm was applied to the specimen in flexion, extension, lateral bending and axial rotation. RESULTS: The cervical dumbbell tumor was removed completely, and bone fusion with continuous bone trabecula was maintained in the patient on the final follow-up examination at 18 months postoperatively. Biomechanical stability tests revealed that the range of motion of the UPLS fixation plus graft bone implant was the same as the BPS fixation in flexion (1.8°vs. 1.5°, p = 0.58) and extension (2.3°vs. 2.2°, p = 0.73), but significantly bigger in lateral bending (3.9° vs. 1.0°, p < 0.001) and axial rotation (6.8° vs. 3.8°, p = 0.002), which were significantly smaller than the UPS fixation in all directions (all p < 0.001). CONCLUSIONS: For the treatment of cervical dumbbell tumor, posterior unilateral exposure and stability reconstruction with pedicle and lamina screws fixation following hemi-laminectomy and facetectomy appear to be a more stable and lesser trauma technique. LEVEL OF EVIDENCE: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Inhalable Nanocomposite Microparticles with Enhanced Dissolution and Superior Aerosol Performance.

Previous studies have shown that combining colistin (Col), a cationic polypeptide antibiotic, with ivacaftor (Iva), a cystic fibrosis (CF) drug, could achieve synergistic antibacterial effects against Pseudomonas aeruginosa. The purpose of this study was to develop dry powder inhaler formulations for co-delivery of Col and Iva, aiming to treat CF and lung infection simultaneously. In order to improve solubility and dissolution for the water-insoluble Iva, Iva was encapsulated into bovine serum albumin (BSA) nanoparticles (Iva-BSA-NPs). Inhalable composite microparticles of Iva-BSA-NPs were produced by spray-freeze-drying using water-soluble Col as the matrix material and l-leucine as an aerosol enhancer. The optimal formulation showed an irregularly shaped morphology with fine particle fraction (FPF) values of 73.8 ± 5.2% for Col and 80.9 ± 4.1% for Iva. Correlations between "D×ρtapped" and FPF were established for both Iva and Col. The amorphous solubility of Iva is 66 times higher than the crystalline solubility in the buffer. Iva-BSA-NPs were amorphous and remained in the amorphous state after spray-freeze-drying, as examined by powder X-ray diffraction. In vitro dissolution profiles of the selected DPI formulation indicated that Col and Iva were almost completely released within 3 h, which was substantially faster regarding Iva release than the jet-milled physical mixture of the two drugs. In summary, this study developed a novel inhalable nanocomposite microparticle using a synergistic water-soluble drug as the matrix material, which achieved reduced use of excipients for high-dose medications, improved dissolution rate for the water-insoluble drug, and superior aerosol performance.