Evaluation of the efficacy of polyethylene glycol in combination with different doses of linaclotide in a fractionated bowel preparation for colonoscopy: a prospective randomized controlled study.

BACKGROUND AND AIM: The ideal bowel cleansing program still needs to be explored. The aim was to compare the bowel cleansing effect and patient tolerance of low-dose polyethylene glycol (PEG) combined with different doses of linaclotide in fractionated bowel preparation. METHODS: The subjects were randomly assigned to the 3LPEG group, 2LPEG + 2L group, or 2LPEG + L group. The primary outcome was to use the Ottawa Bowel Preparation Scale (OBPS) to evaluate the efficacy of bowel cleansing, and the secondary outcomes were the detection rate of adenomas and polyps, adverse reactions, tolerance, and defecation dynamics; subsets of patients with chronic constipation and irritable bowel syndrome were also analyzed. RESULTS: A total of 753 patients were randomly assigned. In ITT analysis, the success of preparation of the 2LPEG + 2L group was better than that of the 2LPEG + L group or the 3LPEG group (92.0% vs. 82.3% vs. 82.1%; P = 0.002). Compared with the 3LPEG group, the 2LPEG + L group showed similar but non-inferior results (82.3% vs. 82.1%, P > 0.05). The 2LPEG + 2L group was similar to the 2LPEG + L group in terms of adverse reaction, tolerance, willingness to reuse, and sleep quality, but both were superior to the 3LPEG group. In a subgroup analysis of chronic constipation, the 2LPEG + 2L group had the best cleansing effect on the right colon and mid colon, while in the subgroup analysis of irritable bowel syndrome, the tolerance was better in the 2LPEG + 2L group and the 2LPEG + L group than the 3LPEG group. CONCLUSIONS: 2LPEG + 2L is a feasible bowel preparation regimen.

Graphene-Based Biosensors with High Sensitivity for Detection of Ovarian Cancer Cells.

Ovarian cancer has the highest mortality rate in the world. Therefore, it is urgent but still challenging to develop an efficient circulating tumor cell (CTC) detection method to sensitively detect ovarian cancer. To address such issues, herein, for the first time, we present a novel CTC detection method for ovarian cancer cells by designing sensitive and rapid graphene-based biosensors. This graphene-based sensor, consisting of a cell pool and two electrodes, can be prepared by a conventional chip fabrication process. It demonstrates high-sensitivity detection even for several ovarian cancer cells by comparing the electrical signal before and after adding cell solution. Moreover, the graphene-based biosensors can perform rapid detection with good repeatability. This suggests that this novel method is possible to use for the early detection of ovarian cancer with very low CTC cell concentration. This work provides a novel and quick strategy to detect ovarian cancer and further judge or predict the risk of the transfer of ovarian cancer.

Introduction of Mercaptoethyl at Sorafenib Pyridine-2-Amide Motif as a Potentially Effective Chain to Further get Sorafenib-PEG-DGL.

The crystal structure of the sorafenib and B-RAF complex indicates that the binding cavity occupied by the pyridine-2-carboxamide in sorafenib has a large variable space, making it a reasonable modification site. In order to identify novel compounds with anti-cancer activity, better safety and polar groups for further application, five sorafenib analogs with new pyridine-2-amide side chains were designed and synthesized. Preliminary pharmacologic studies showed that these compounds displayed much lower toxicities than that of sorafenib. Among them, compound 10b bearing mercaptoethyl group kept relevant antiproliferation potency compared to sorafenib in Huh7 and Hela cell lines with values of IC50 58.79 and 63.67 M, respectively. As a small molecule inhibitor targeting protein tyrosine kinases, thiol in compound 10b would be an active group to react with maleimide in a mild condition for forming nanoparticles Sorafenib-PEG-DGL, which could be developed as a delivery vehicle to improve the concentration of anti-tumor therapeutic agents in the target cancer tissue and reduce side effects in the next study.

Preoperative localisation of pulmonary ground-glass opacity using medical adhesive before thoracoscopic resection.

OBJECTIVES: To evaluate the safety and efficiency of computed tomography (CT)-guided medical adhesive, α-cyanoacrylate, for preoperative localisation of pulmonary ground-glass opacity (GGO) used for guiding the video-assisted thoracoscopic surgical (VATS) excision METHODS: The procedure was performed on 188 consecutive patients with solitary GGO (pure GGO = 90 cases; mixed GGO = 98 cases) prior to the thoracoscopic procedure. The complications and efficacy of this method were analysed. The resected GGO was analysed pathologically. RESULTS: The mean duration of the procedure was 16.3 ± 5.2 min. The preoperative localisation was 100% successful. All GGOs were successfully resected by VATS. Asymptomatic pneumothorax was developed in 16/188 patients (8.5%) and mild pulmonary haemorrhage occurred in 15 cases (7.9%) post-localisation. None of the patients required any further treatment for the complications. CONCLUSION: Preoperative localisation using CT-guided medical adhesive, α-cyanoacrylate, is a safe and short-duration procedure, with high accuracy and success rates with respect to VATS resection of GGO. KEY POINTS: • Preoperative localisation is crucial for successful resection of GGO by VATS. • Preoperative adhesive localisation provides an up to 100% successful localisation rate with few complications. • Preoperative adhesive localisation enabled VATS resection in 100% of the GGO. • Preoperative adhesive localisation is safe and effective for VATS resection of GGO.

Platelet-derived growth factor BB enhances osteoclast formation and osteoclast precursor cell chemotaxis.

Enhanced osteoclast formation increases bone resorption, which triggers bone remodeling. Platelet-derived growth factor BB (PDGF-BB) enhances precursor cell homing, angiogenesis, and bone healing, and thereby could also treat osteoporosis. However, the effect of PDGF-BB on osteoclast formation is not fully understood. We investigated whether exogenous recombinant PDGF-BB directly affects osteoclast formation and osteoclast precursor cell chemotaxis. The murine monocyte-macrophage cell line RAW264.7 and bone-marrow-derived macrophages were cultured with recombinant mouse PDGF-BB with or without a platelet-derived growth factor receptor ß inhibitor (AG-1295) or a Janus kinase 2 inhibitor (AG-490) to analyze the effect on osteoclastogenesis in vitro. PDGF-BB with or without AG-490 or AG-1295 was locally administrated in the mandibular fracture of 16-week-old Sprague Dawley rats (n = 18) for 1-2 weeks to analyze the effect on osteoclastogenesis in vivo. The effect of the treatments on osteoclast formation, osteoclast precursor cell migration, and expression of osteoclastogenic signaling molecules was analyzed. PDGF-BB enhanced osteoclast formation both in vitro and in vivo, but AG-490 and AG-1295 inhibited this effect. PDGF-BB enhanced phosphorylation of extracellular-signal-regulated kinase 1/2 (ERK1/2), Akt, and signal transducer and activator of transcription 3 (STAT3) in RAW264.7 cells. AG-490 inhibited PDGF-BB-induced STAT3 phosphorylation. PDGF-BB enhanced RAW264.7 cell migration and gene expression of osteoclastogenic signaling molecules (i.e., nuclear factor of activated T cells 1, dendrocyte-expressed seven transmembrane protein, and B-cell lymphoma 2), and treatment with AG-1295, AG-490, or S3I-201 (a STAT3 inhibitor) reduced this effect. PDGF-BB enhanced osteoclast formation, osteoclast precursor cell chemotaxis, and phosphorylation of STAT3, Akt, and ERK1/2. but AG-1295 and AG-490 reduced this effect. These findings reflect the complexity of PDGF-BB in bone biology.

Use of Computer-Assisted Navigation in the Retrieval of Accidentally Displaced Third Molars.

PURPOSE: The purpose of this study was to describe the application of computer-assisted navigation for the retrieval of accidentally displaced mandibular third molars. PATIENTS AND METHODS: All patients identified as having an accidentally displaced mandibular third molar or root fragment and presented to the authors' department from April 2013 through June 2015 were included in this prospective study. Retrieval of the displaced molar was performed in these patients under the guidance of computer-assisted navigation, in which a registered forceps was used to clamp and retrieve the molar. Postoperative complications were assessed for all patients. RESULTS: Twelve patients were included in this case series. Using computer-assisted navigation, the operation proceeded successfully in all patients. These patients displayed uneventful healing without postoperative complications. CONCLUSION: Computer-assisted navigation is a safe, straightforward, and minimally invasive treatment method that can be applied for the retrieval of accidentally displaced third molars. It is recommended as an intraoperative tool for the retrieval of teeth or tooth fragments displaced into areas that are difficult to access.

P. gingivalis in oral-prostate axis exacerbates benign prostatic hyperplasia via IL-6/IL-6R pathway.

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH. METHODS: The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration. RESULTS: P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH. CONCLUSION: P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.

Manipulating electrostatic field to control the distribution of bioactive proteins or polymeric microparticles on planar surfaces for guiding cell migration.

We report a general strategy to generate linear and circular gradients of active proteins or polymeric microparticles on planar surfaces by controlling the distribution of electrostatic field during electrohydrodynamic jet printing or electrospray process. Taking fibronectin as an example, we generated a circular gradient of fibronectin and investigated its effect on accelerating the migration of fibroblasts to suit for use in wound closure. In another demonstration, we created linear gradients of laminin in unidirectional and bidirectional patterns, respectively. We showed that such gradations significantly promoted the migration of human neuroblastoma cells with the increase of laminin content. When we changed fibronectin/laminin to electrosprayed poly(lactic-co-glycolic acid) (PLGA) microparticles, we found similar results in terms of guiding cell migration, except that the guidance cues varied from biological signal to topographic structure. Taken together, this method for generating linear/circular gradients of fibronectin/laminin and PLGA microparticles can be readily extended to different types of bioactive proteins and polymeric microparticles to suit wound closure, nerve repair, and related applications involving cell migration.

Exogenous melatonin positively regulates lignin biosynthesis in Camellia sinensis.

Melatonin (MT) is a bioactive molecule that can regulate various developmental processes. Changes in lignin content play important roles in plant growth and development. Herein, quantitative analysis and histochemical staining showed that lignin content significantly increased over time, and melatonin treatment triggered the lignification at 8 and 16 d in tea leaves. The POD activity participated in lignin formation had also been significantly improved. The effect of melatonin on the increase of lignin content was attenuation over time. Sequencing results based on transcriptome at 8 and 16 d showed that 5273 and 3019 differentially expressed genes (DEGs) were identified in CK1 vs. MT1 and CK2 vs. MT2, respectively. A total of 67 DEGs were annotated to lignin biosynthesis, and 38 and 9 genes were significantly up-regulated under melatonin treatment, respectively. Some transcription factor genes such as MYB were also identified among the two pairwise comparisons, which might relate to lignin metabolism. Melatonin increased the degree of lignification in tea leaves by modifying the enzyme genes expression involved in lignin synthesis pathway. These results provide a reference for further study on the molecular mechanism of the dynamic changes of lignin content induced by melatonin treatment in tea plants.

Minimally invasive maxillary sinus augmentation with simultaneous implantation on an elderly patient: A case report.

BACKGROUND: In this case study, a minimally invasive transalveolar approach using platelet-rich fibrin and bone substitute with simultaneous implantation was carried out in an elderly patient. We analyzed the cone-beam computed tomography (CBCT) findings to evaluate bone regeneration. CASE SUMMARY: A 65-year-old female with no contraindications for dental implants and loss of maxillary bilateral molars is described. Examination by CBCT showed the available vertical bone height in the bilateral posterior maxilla was 0.5-6.8 mm in the left and 2.8-6.5 mm in the right. The patient underwent a transalveolar approach using platelet-rich fibrin and bone substitute with simulataneous placement of an implant 10 mm in length. Six months post-surgery, the implant showed excellent osseointegration with the bone graft. Thereafter, full-ceramic crowns were fitted. Follow-up at 2 years demonstrated satisfactory prognosis. CONCLUSION: Platelet-rich fibrin and bone substitute can be used to augment the maxillary sinus with a vertical bone height less than 4 mm.

[Ethanol-induced influence on the structure and arsenate adsorption of resin-based nano-hydrated ferric oxide].

Here the role of ethanol in the synthesis of a new nanocomposite (D201-HFO) was evaluated in terms of its structure variation and arsenate adsorption. Results indicated that the ethanol-induced procedure improved the dispersion of HFO inside the polymer host D201 and increased the HFO sorption capacities towards arsenate by 20%. Also, the ethanol-induced procedure resulted in the increase of pore size, pore volume, and specific surface area of D201-HFO by 52%, 65% and 28%, respectively. Nevertheless, ethanol rinsing did not affect the mechanical strength of D201-HFO and the crystal type of the immobilized HFO. Little effects of the ethanol process was observed on the pH and co-anion dependent adsorption of arsenate. Furthermore, the ethanol step posed insignificant influence on the fix-bed adsorption and the repeated use of the adsorbent. The results showed that the ethanol procedure exerted little influence on the sorption properties of D201-HFO from the viewpoint of practical application and thus, it could not be included.

An improved screw-free method for electrode implantation and intracranial electroencephalographic recordings in mice.

We recently developed a glue-based method for the implantation of intracranial electrodes in mice. Our approach is to secure a preconstructed electrode array using a cyanoacrylate-based glue (similar to Krazy Glue). This method is applicable to both young and aging mice and is suitable for long-term electroencephalographic recordings. In the present experiment, we explored whether the glue-based method is capable of securing individual electrodes in addition to securing the electrode array. C57 black mice aged 25-35 days or 13-19 months were operated on under isoflurane anesthesia. Monopolar or bipolar electrodes were inserted independently in the ipsilateral hippocampal CA3 and entorhinal cortical areas, and they were fixed onto the skull using the glue together with dental acrylic, but without anchoring screws. We found that the implanted electrodes were stable and allowed repeat intracranial recordings and electrical stimulation in freely moving mice.