Role of siderophore in Pseudomonas fluorescens biofilm formation and spoilage potential function.

We investigated the function of pyoverdine in the biofilm formation, motility, and spoilage potential of Pseudomonas fluorescens. We targeted and identified two major genes (pvdA and pvdE) that are involved in the biosynthesis of siderophores. We next constructed ΔpvdA and ΔpvdE mutants of P. fluorescens PF08 and found that the deletion of pyoverdine led to a biofilm-to-motivity transition as both ΔpvdA and ΔpvdE mutants displayed enhanced motility, reduced level of exopolysaccharides (EPSs), and attenuated biofilm formation. In addition, the lack of synthesis of pyoverdine promoted the spoilage of fish fillets stored at 4 °C. Based on the effect of pyoverdine deletion on the phenotype; we report that pyoverdine regulates the transcription levels of htpX, phoA, flip, flgA, and RpoS, suggesting that pyoverdine-mediated iron absorption may affect the regulation of flagellum and stress resistance. This study emphasizes the important role of pyoverdine in the formation of biofilm, motility, and spoilage of P. fluorescens PF08.

Pexmetinib suppresses osteoclast formation and breast cancer induced osteolysis via P38/STAT3 signal pathway.

Breast cancer metastases to the bone can lead to a series of bone-related events that seriously affect the quality of life. Pexmetinib, a novel p38 mitogen-activated protein kinase (p38) inhibitor that has been evaluated in phase I clinical trials for myelodysplastic syndrome, but the effects of Pexmetinib on breast cancer induced osteolysis haven't been explored. Here, we found that Pexmetinib inhibited receptor activator of nuclear factor-κB ligand-induced osteoclast formation and bone resorption in vitro. Pexmetinib suppressed p38-mediated signal transducer and activator of transcription 3 (STAT3), which direct regulated transcription of the nuclear factor of activated T cells 1 (NFATc1), leading to reduced osteoclast formation. Moreover, Pexmetinib exerted anti-tumor effects in breast cancer cells in vitro via suppressing p38-mediated STAT3 activation and matrix metalloproteinases (MMPs) expression. Furthermore, Pexmetinib suppressed breast cancer-associated osteolysis in vivo. These results suggest that Pexmetinib may be a promising drug for the treatment of breast cancer-induced osteolysis.

Development of a time-temperature indicator based on Maillard reaction for visually monitoring the freshness of mackerel.

Due to the highly cost-effective and maneuverable property, Maillard reaction-based time-temperature indicators (TTIs) are considered ideal devices for temperature track and quality indication. The objective of this study was to develop a cold-sensitive TTI based on the Maillard reaction reflecting the freshness of chilled seafood. Firstly, the color evolution trends of a series of Maillard reaction-based TTIs were investigated and the xylose-lysine group represented obvious color change. Fourier transform infrared (FTIR) spectroscopy revealed the color change was associated with the formation of CN bond in melanoidin. Simultaneously, the relationships of the color change of TTI with time and temperature were established. The activation energy value (Ea) of TTI was close to that of mackerel. There existed a good relevance (R2 = 0.98) between the color change of TTI and the total volatile basic nitrogen content of mackerel, suggesting this novel TTI might have the potential to monitor the freshness of mackerel.

Persistent effects of adverse childhood experiences on the course of pubertal development / 中国学校卫生

Objective@#To explore the influence of adverse childhood experiences (ACEs) on pubertal development of boys and girls and to provide a reference for the development of intervention measures.@*Methods@#A stratified cluster sampling method was used to select a total of 1 156 students in grades three and four in the boarding school system and public primary schools in Huangshan City and surrounding towns in September 2018, using the Childhood Trauma Questionnaire (CTQ) and the Pubertal Development Scale (PDS). For the baseline self-assessment survey, according to different dimensions, abuse children score no exposure groups. Children were divided into an exposure group and a high exposure level group, according to their childhood experiences. PDS self-report questionnaire was administered two years later, and an analysis of ACE type and severity of the continuous impact of youth development was conducted.@*Results@#In the baseline survey, there were 53 girls (11.32%) and 51 boys (7.41%) who developed earlier. The rate of early development in girls was higher than that of boys, and the difference was statistically significant(χ 2=5.21, P<0.05). Univariate analysis showed gender differences in the effects of type and severity of ACEs and abuse on adolescent development at both baseline and follow-up. There were gender differences in the rate of early development between boys and girls at baseline and at follow-up between the exposure groups. Regression analysis showed that the higher the degree of emotional abuse, emotional neglect, and sexual abuse in girls, the higher the PDS score(B=0.22, 0.15, 0.08, P<0.05). In boys, the more severe the emotional abuse experienced, the higher the PDS score, and the more severe the physical abuse experienced, the lower the PDS score(B=0.20, 0.04, P<0.05).@*Conclusion@#Attention should be paid to the influence of ACEs and gender differences during youth development among male and female students, and more longterm studies should also be carried out.

Arthroscopy-Assisted Reduction in the Management of Isolated Medial Malleolar Fracture.

PURPOSE: To evaluate the feasibility of arthroscopic reduction percutaneous fixation (ARPF) in the treatment of isolated medial malleolar fracture and compare the results with those of conventional open reduction internal fixation (ORIF). METHODS: This prospective study enrolled 77 patients with isolated medial malleolar fracture between November 2011 and February 2016. The patients were assigned to the ARPF (n = 34) and ORIF (n = 43) groups. The Olerud-Molander ankle score (OMAS), ankle range of motion (ROM), visual analog scale, and radiographic evaluation were determined at the scheduled follow-up. RESULTS: In the ARPF group, 11 of 34 patients (32.4%) had chondral lesions. Tears of the deltoid ligament and anterior inferior tibiofibular ligament were noted in 3 (8.8%) and 15 (44.1%) patients, respectively. The mean follow-up was 5 years. The mean OMAS was higher in the ARPF group than in the ORIF group. The differences were statistically significant at 6 months (mean ± standard deviation, 80.2 ± 4.0 for ARPF vs 77.2 ± 4.1 for ORIF, P = .005) and 1 year (92.9 ± 4.9 vs 88.1 ± 4.6, P < .001), but not at the latest follow-up (P = .081). Ankle ROM was markedly improved in the ARPF group, unlike in the ORIF group at 6 months (dorsiflexion, P = .025; plantarflexion, P < .001) and 1 year (dorsiflexion and plantarflexion, P < .001). The improvement remained at the latest follow-up in plantarflexion (P = .001) but not in dorsiflexion (P = .354). CONCLUSIONS: Arthroscopy-assisted reduction is a feasible alternative modality with superior short-term outcomes for treating isolated medial malleolar fracture, but its superiority may be attenuated in the intermediate term. LEVEL OF EVIDENCE: Level III, comparative study.

Mindfulness interventions for rheumatoid arthritis: A systematic review and meta-analysis.

OBJECTIVES: To explore the effect of mindfulness interventions in improving outcomes for patients with rheumatoid arthritis. METHODS: Following the collective strategy of Cochrane Collaborative Group, the Cochrane Library, PubMed, EMBASE, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, and Wanfang Database were searched from the establishment of databases to September 2019. Reference lists were searched for additional studies. Risk of bias was assessed using Revman 5.3. Disagreement was resolved by discussion. RESULTS: A total of 6 RCTs were included, including 337 patients. The results showed that the improvement of pain intensity in mindfulness group after intervention was better than that in the control group, and the difference was significant [WMD = 0.65, 95% CI (-1.11, - 0.18), P = 0.006]. There were significant differences in depression between the two groups [SMD = 0.47, 95% CI (- 0.86, - 0.07), P = 0.02]. The results showed that there were significant differences in DSA28 between the two groups [WMD = -0.29,95% CI (- 0.38, - 0.19), P ＜0.00001]. The results showed that there were no significant differences in anxiety and CPR between the two groups. CONCLUSION: mindfulness interventions can significantly improve pain intensity, depression, and symptoms in patients with rheumatoid arthritis compared with conventional therapy. But the result still needs to be confirmed by more high-quality, large-sample randomized controlled trials.

Glabridin inhibits osteosarcoma migration and invasion via blocking the p38- and JNK-mediated CREB-AP1 complexes formation.

Osteosarcoma is the most common bone malignancy, and it seriously affects the quality of life of affected children and adolescents. Glabridin (GLA), a major component of licorice root extract, has been reported to exert antitumor effects against a variety of tumor types; however, its effects on osteosarcoma have not been elucidated. In the current study, we investigate the effects and potential antimetastatic mechanisms of GLA on osteosarcoma in vitro and in vivo. Flow cytometry showed that GLA induced G2/M cell cycle phase arrest and promoted cell apoptosis. Transwell and wound-healing assays showed that GLA significantly decreased the migration and invasion of osteosarcoma cells. Further western blotting and quantitative real-time polymerase chain reaction showed that the expression of matrix metalloproteinase (MMP)-2 and MMP-9 in MG63 and HOS cells were reduced after GLA treatment. Moreover, western blotting demonstrated that GLA downregulated the phosphorylation of p38 mitogen-activated protein kinases and c-Jun N-terminal kinase. A coimmunoprecipitation assay illustrated that formation of cAMP response element-binding protein (CREB)-activating protein 1 (AP1) complexes and the DNA binding activities of CREB and AP1 in MG63 and HOS cells were impaired following treatment with GLA. Finally, GLA inhibited tumor growth and suppressed osteosarcoma cell metastasis in vivo. Overall, our findings highlight the potential of GLA as a therapeutic agent for the prevention and treatment of tumor metastasis.

A Novel Diterpenoid Suppresses Osteoclastogenesis and Promotes Osteogenesis by Inhibiting Ifrd1-Mediated and IκBα-Mediated p65 Nuclear Translocation.

Osteoporosis develops because of impaired bone formation and/or excessive bone resorption. Although the pharmacological treatment of osteoporosis has been extensively developed, alternative treatments are still needed. Here, we showed that oridonin (ORI), a diterpenoid isolated from Rabdosia rubescens, can suppress osteoclastogenesis and enhance osteogenesis. ORI inhibited the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast formation and bone resorption through the inhibition of p65 nuclear translocation. ORI-induced inhibition of this translocation led to an increase in osteoblast differentiation and mineralization through the promotion of Smad1/Smad5 phosphorylation. Further analyses demonstrated that the inhibition of p65 nuclear translocation is due to the suppression of IκBα phosphorylation and the induced proteasomal degradation of interferon-related development regulator 1 (Ifrd1), a transcriptional corepressor that is involved in the suppression of NF-κB nuclear translocation. Moreover, mice treated with ORI at catabolic and anabolic windows showed a considerable attenuation of ovariectomy (OVX)-induced osteoporosis. Taken together, our findings reveal that ORI protects against OVX-induced bone loss via inhibiting osteoclastic bone resorption but enhancing osteoblastic bone formation through abolishing both Ifrd1-mediating and IκBα-mediated p65 nuclear translocation. These results show the potential of ORI for treatment of osteoporosis and highlight Ifrd1 as a another novel promising target for anti-osteoporotic drugs. © 2017 American Society for Bone and Mineral Research.

The Peripheral Blood Mononuclear Cell Count Is Associated With Bone Health in Elderly Men: A Cross-Sectional Population-Based Study.

The peripheral blood mononuclear cell (PBMC) count is a routinely used and meaningful index for infection and blood diseases. PBMCs may be closely related to osteoclasts and include osteoclast precursors; we examined the association between the PBMC count and bone health. This research included 2806 community men aged ≥50 years who underwent full health examinations from October 2007 through December 2011 in four medical centers. The PBMC count was significantly high among subjects with "at least osteopenia" compared with controls. In analysis of covariance adjusted for potential confounders, the bone mineral density (BMD) value and T-score had a significant decreasing trend across the quartiles of PBMC count. In univariate analysis, the PBMC count had a strong association with "at least osteopenia" (odds ratio [OR] = 2.520, 95% confidence interval [CI]: 1.397-4.547). After adjustment for confounding factors (multivariate analysis) from Model 1 to 4, PBMC count remained as an independent risk factor for "at least osteopenia" (OR = 2.481, 95% CI: 1.176-5.236). Moreover, after adjusting for all confounding variables, participants had a significantly high OR in the body mass index (BMI) <25 group (OR = 2.798, CI: 1.122-6.973; P = 0.027) and systolic blood pressure (SBP) <140 group (OR = 2.519, CI: 1.059-5.993; P = 0.037). In conclusion, the PBMC count is significantly associated with bone loss in elderly men and the exact mechanism requires further clarification.

Reliability and variability in the interpretation of lumbar high intensity zone.

OBJECTIVE: The aim of this study was to evaluate the reliability of high intensity zone (HIZ) and to assess discrepancy in the interpretation, as well as investigate the effects of parameters of HIZ on interobserver variation. METHODS: Four spine surgeons made independent observations on lumbar magnetic resonance imaging (MRI) from 207 consecutive patients from 3 institutions. The κ statistic was used to characterize inter- and intraobserver reliability for visual assessments of HIZ. The corresponding MRI was provided to 2 additional spine surgeons for quantitative measurements. The parameters of HIZ, including signal intensity (SI) and area ratio (HIZ%), were used to assess the interobserver variation of HIZ. RESULTS: The overall interobserver agreement for visual assessments was substantial (κ=0.62 at L4-5 and 0.61 at L5-S1), and intraobserver agreement was excellent (κ=0.84 at L4-5 and 0.86 at L5-S1). Of 93 observed HIZ, 17 instances (18.3%) were agreed upon by all visual observers. The SI with full agreement was significantly brighter than all the others (p<0.01). The HIZ% with 2 agreements was significantly smaller than those with 4 agreements (p=0.04) and 3 agreements (p=0.03). Although fewer observers with consensus were associated with smaller HIZ%, the difference was not significant (p>0.05). CONCLUSION: The reliability in the interpretation of HIZ was sufficient for spine surgeons with differing levels of experience. This study highlighted that signal intensity was the primary cause of variability in visual observation.

Association between serum uric acid and bone health in general population: a large and multicentre study.

Previous studies proposed that serum uric acid (UA), an endogenous antioxidant, could be a protective factor against bone loss. However, recently, a study with a population of US adults did not note the protective effects of serum UA. Therefore, the exact association between serum UA and bone health remains unclear. We performed a retrospective consecutive cohort study in a Chinese population to examine the association between serum UA and bone health. This cross-sectional study included 17,735 individuals who underwent lumbar spine bone mineral density (BMD) measurements as part of a health examination. In covariance analyses (multivariable-adjusted), a high serum UA level was associated with a high BMD, T-score, and Z-score. In binary logistic regression analyses (multivariable-adjusted), a high serum UA level was associated with low odds ratios (ORs) for at least osteopenia and osteoporosis in male (age ≥50 years) (OR = 0.72-0.60 and OR = 0.49-0.39, respectively) and postmenopausal female participants (OR = 0.61-0.51 and OR = 0.66-0.49, respectively). In conclusion, serum UA is associated with BMD, the T-score, and the Z-score, and has a strong protective effect against at least osteopenia and osteoporosis.

[Genetic characteristics of enterovirus 71 VP1 and epidemiology of hand-foot-mouth disease in Xinxiang in 2011].

The study was performed to examine the enterovirus 71(EV71) VP1 genetic feature and the epidemiology of hand-foot-mouth disease (HFMD) in Xinxiang in 2011. Real-time RT-PCR was used for the detection of Pan-enterovirus, Coxsackievirus A 16(CA16) and EV71 from stool specimens of HFMD. The VP1 region was amplified from 10 EV71 positive samples and the products were sequenced. EV71 genotypes were characterized by homology and phylogenetic tree analyses. Additionally, epidemic data of Xinxiang HFMD in 2011 was analyzed. The results revealed that 73% of the specimens from severe cases were determined as EV71 positive, which was significantly higher than CA16-positive ones (19%) (P < 0.01). Ten EV71 strains isolated in Xinxiang belonged to C4a cluster of sub-genotype C4, with 2.8% nucleotide and 0.9% amino acid sequences divergence among them. At position 170 in VP1 gene, an alanine(A) was predominant in 9 isolates, while a valine(V) residue was observed in one isolate. Compared to the representative C4a strains which were closely related to Xinxiang isolates, the amino acid variations of the pre-dominant Xinxiang strains generally occurred at position 292, threonine --> alanine (T --> A). A total of 1118 HFMD cases were reported in Xinxiang in 2011, and 92% of them were younger than 3 years old; the incidence rate peaked in April and December, suggesting that it is very necessary to strengthen HFMD prevention and control even in cold weather.

Local injection/induction of osteoclasts for the treatment of calcified tendinitis.

Calcified tendinitis is characterized by calcification in the rotary cuff tendon of the shoulder. The rationale of therapeutic methods is mainly removal of the calcification. Osteoclasts are the principle cells capable of resorbing bone and calcified tissues. Therefore, we hypothesized local injection of cultured human osteoclasts or induction of osteoclasts by recombinant RANKL in vivo may be effective for the treatment of calcified tendonitis. Human osteoclasts cultured in vitro is technically feasible and the osteoclasts are capable of active bone resorption. Thus, injection of osteoclasts may help remove the calcified tendonitis. In addition, human RANKL is commercially available. Therefore, local RANKL injection can recruit peripheral monocytes and macrophages. In the presence of RANKL, these monocytes and macrophages can subsequently differentiate into osteoclasts that can directly resorb calcification via their bone resorbing machinery. Different from the other treatments, the advantage of this therapeutic method includes: (1) less invasive because only local injection/induction of osteoclasts into the calcified lesion is conducted; (2) more efficient by direct osteoclasts injection or using RANKL to recruit osteoclasts to efficiently resorb calcification. Therefore, we proposed local injection/induction of osteoclasts as a potential biological method for clinical treatment of calcified tendinitis.

Expression changes of transforming growth factor-beta1 and thrombospondin-1 in cavernous tissues of diabetic rats.

OBJECTIVE: To assess transforming growth factor-beta1 (TGF-beta1) and thrombospondin-1 (TSP-1) expression in the cavernous tissue of rats with streptozotocin (STZ)-induced diabetes. MATERIALS AND METHODS: Twenty male Sprague-Dawley rats were randomly divided into 2 groups: diabetics and controls. We injected STZ intraperitoneally to induce diabetes, and studied the alterations in TGF-beta1 and TSP-1 expression in the cavernous tissue of the 2 groups by immunohistochemistry and real-time quantitative reverse transcription polymerase chain reaction. HE staining was also applied to determine morphological changes. Weight, blood sugar and urine sugar were measured before and after model induction in both groups. RESULTS: Expression of TGF-beta1 and TSP-1 increased significantly in the cavernous tissue of the diabetic rats compared to the control group. CONCLUSIONS: TGF-beta1 and TSP-1 expression changes in cavernous tissues may play an important role in diabetic erectile dysfunction.

Comparison of paraspinal muscle injury in one-level lumbar posterior inter-body fusion: modified minimally invasive and traditional open approaches.

OBJECTIVE: To determine differences in paraspinal muscle injury between a modified minimally invasive approach (MMIA) and a traditional operative approach (TOPA) for one-level instrumented posterior lumbar inter-body fusion (PLIF). METHODS: From March 2006 to May 2008, a consecutive series of 91 patients who underwent a one-level instrumented PLIF procedure using one of two different approaches (MMIA in 41 patients and TOPA in 50), and who were operated on by one group of surgeons at a single institution, was studied. The following data were compared between the two groups: surgical time, blood loss, and changes in postoperative serum concentration of creatinine kinase (CK). More than 1 year post operation, low back pain was evaluated by a visual analog scale (VAS) and the Oswestry disability index (ODI). Some patients were also evaluated by MRI to allow comparison of the preoperative and postoperative cross sectional area (CSA) and fat degeneration grades at the operative level. RESULTS: There was no statistically significant difference in surgical time, but blood loss, serum concentration of CK, and scores of the VAS and ODI were markedly less in the MMIA group compared with the TOPA group. In the TOPA group, the postoperative CSA of the multifidus muscles was significantly smaller than it was pre-operatively. In contrast, there was no significant difference between the pre- and post-operative CSA of the multifidus muscles in the MMIA group. There was more fatty infiltration postoperatively than preoperatively in both the TOPA and MMIA groups, the increase in fatty infiltration being greater in the TOPA than in the MMIA group. CONCLUSION: Compared with TOPA, MMIA can significantly lessen paraspinal muscle injury, and reduce the incidence of low back pain.

Could local delivery of bisphosphonates be a new therapeutic choice for hemangiomas?

Hemangiomas are endothelial neoplasms that affected about 8-12% of one-year-old children. Their life cycle is characterized by a rapid endothelial proliferation phase, followed by a slow involution phase. About 10% of the hemangiomas will cause functional complications or psychological concern requiring active treatments. Current therapy methods, such as intra-lesional or systemic administration of corticosteroids, systemic interferon treatment, or surgery, are diverse but uncertainty. To date, the etiology of hemangiomas is still controversial. However, general consensus on the importance of the endothelial cells leads hemangioma pathogenesis to angiogenesis. Thus, local delivery of anti-angiogenic agents may be of great interest for the treatment of hemangiomas. Bisphosphonates are potent in inhibiting osteoclast activity and promoting apoptosis, which are widely used for the treatment of osteoporosis and osteolysis diseases with minor adverse side effects. In addition to its anti-osteolytic effect, bisphosphonates are currently shown to be capable of anti-angiogenesis and induction of apoptosis in tumor cells. Experimental evidences demonstrated that bisphosphonates can inhibit capillary tube formation and vessel sprouting by impairing endothelial proliferation and migration, as well as reducing the serum fibroblast growth factor-2 and vascular endothelial growth factor. Moreover, it is not impossible to deliver bisphosphonates to local lesion by a new local drug delivery system (DDS), which employed the biocompatible calcium phosphate as the drug carriers for clinical use. This local drug delivery system is a suitable carrier for loading and releasing of bioactive bisphosphonates. Therefore, we hypothesis that local deliver of bisphosphonates by fine calcium phosphate particles may be a potential treatment of hemangiomas. By employing proper calcium phosphate particles, bioactive bisphosphonates will be gradually released and exert their anti-angiogenesis effect, destructing rapid proliferation of epithelial cells and promoting the involution of hemangiomas without systematic adverse side effects.

Design and fabrication of a photonic crystal channel drop filter based on an asymmetric silicon-on-insulator slab.

We report on the design and fabrication of a photonic crystal (PC) channel drop filter based on an asymmetric silicon-on-insulator (SOI) slab. The filter is composed of two symmetric stick-shape micro-cavities between two single-line-defect (W1) waveguides in a triangular lattice, and the phase matching condition for the filter to improve the drop efficiency is satisfied by modifying the positions and radii of the air holes around the micro-cavities. A sample is then fabricated by using electron beam lithography (EBL) and inductively coupled plasma (ICP) etching processes. The measured Q factor of the filter is about 1140, and the drop efficiency is estimated to be 73% +/- 5% by fitting the transmission spectrum.

[Repair of soft-tissue defects of feet and ankles by using an expanded reverse island flap with a saphenous neuro-vascular pedicle].

OBJECTIVE: To evaluate a expanded reverse island flap with a saphenous neuro-vascular pedicle for repairing the defects of the feet and ankles. METHODS: An expanded reverse island skin flap, with the Six saphenous neuro-vascular pedicle, was designed to repair the skin defects on the feet and ankles. RESULTS: patients with the defects of the feet and ankles were treated with the expanded saphenous island flap and all of the The expanded reversed island skin flaps were survived. The largest flap size was 12 cm x 10 cm. CONCLUSIONS: flap could be a good option for repairing the defects of the feet and ankles.