A Bioinspired Gradient Design Strategy for Cellulose-Based Electromagnetic Wave Absorbing Structural Materials.

Cellulose nanofiber (CNF) possesses excellent intrinsic properties, and many CNF-based high-performance structural and functional materials have been developed recently. However, the coordination of the mechanical properties and functionality is still a considerable challenge. Here, a CNF-based structural material is developed by a bioinspired gradient structure design using hollow magnetite nanoparticles and the phosphorylation-modified CNF as building blocks, which simultaneously achieves a superior mechanical performance and electromagnetic wave absorption (EMA) ability. Benefiting from the gradient design, the flexural strength of the structural material reached ∼205 MPa. Meanwhile, gradient design improves impedance matching, contributing to the high EMA ability (-59.5 dB) and wide effective absorption width (5.20 GHz). Besides, a low coefficient of thermal expansion and stable storage modulus was demonstrated as the temperature changes. The excellent mechanical, thermal, and EMA performance exhibited great potential for application in stealth equipment and electromagnetic interference protecting electronic packaging materials.

[Improvement of solubility of epimedium flavonoid secondary glycoside components by traditional Chinese medicine polysaccharides and its mechanism].

The poor solubility of insoluble components of traditional Chinese medicine(TCM) is an important factor restricting the development of its preparations. Natural polysaccharides of TCM can be used as functional components to increase the solubility of insoluble components. Epimedium flavonoid secondary glycoside components(EFSGC) have been shown to have positive effects on the prevention and treatment of osteoporosis, but they exhibit poor solubility. Therefore, the strategy of solubilizing EFSGC with TCM polysaccharides was adopted, and its effect on the permeability and stability of EFSGC was evaluated in this study. Based on the equilibrium solubility experiment of EFSGC, it was found that Panax notoginseng crude polysaccharide(PNCP) had the best solubilization effect on EFSGC among the ten kinds of TCM polysaccharides, which increased the solubility of EFSGC from 0.8 mg·mL~(-1) to 13.3 mg·mL~(-1). It should be noted that after the solubilization of EFSGC by preparation technology, the effects on permeability and stability should be considered. Therefore, this study also investigated these two properties. The results showed that PNCP increased the effective transmittance of EFSGC from 50.5% to 71.1%, which could increase the permeability of EFSGC significantly. At the same time, it could improve the stability of EFSGC in the simulated gastric juice environment. In order to explain the solubilization mechanism of PNCP on EGSGC, critical micelle concentration, particle size, potential, differential scanning calorimetry, and infrared spectroscopy were analyzed. It was preliminarily inferred that the mechanism was as follows: PNCP and EFSGC could self-assemble into aggregates for solubilization by intermolecular hydrogen bonding interaction in water. In summary, PNCP can not only improve the solubility of EFSGC but also improve its permeability and stability. This study lays the foundation for the application of TCM polysaccharides as a functional component to solubilize insoluble components.

Icaritin ameliorates RANKL-mediated osteoclastogenesis and ovariectomy-induced osteoporosis.

A rapidly aging society and longer life expectancy are causing osteoporosis to become a global epidemic. Over the last five decades, a number of drugs aimed at reducing bone resorption or restoring bone mass have been developed, but their efficacy and safety are limited. Icaritin (ICT) is a natural compound extracted from anti-osteoporosis herb Epimedium spp. and has been shown to inhibit osteoclast differentiation. However, the molecular mechanism by which ICT weaken RANKL-induced osteoclast differentiation has not been completely investigated. Here, we evaluated the anti-osteoclastogenic effect of ICT in vitro and the potential drug candidate for treating osteoporosis in vivo. In vitro study, ICT was found to inhibit osteoclast formation and bone resorption function via downregulating transcription factors activated T cell cytoplasm 1 (NFATc1) and c-fos, which further downregulate osteoclastogenesis-specific gene. In addition, the enhanced mitochondrial mass and function required for osteoclast differentiation was mitigated by ICT. The histomorphological results from an in vivo study showed that ICT attenuated the bone loss associated with ovariectomy (OVX). Based on these results, we propose ICT as a promising new drug strategy for osteoporosis that inhibits osteoclast differentiation.

The Combination of Chrysin and Cisplatin Induces Apoptosis in HepG2 through Down-regulation of cFLIP and Activity of Caspase.

AIM: The study aims to investigate the combined effects of chrysin and cisplatin on hepatoma(HepG2) cell lines in vivo and in vitro. OBJECTIVE: Studies have suggested that chrysin can enhance the sensitivity of tumor cells to apoptosis. Drug resistance in tumor cells reduced the effectiveness of chemotherapy drugs such as cisplatin. We investigated whether the combination of chrysin and cisplatin can induce more apoptosis than chrysin alone and cisplatin alone. METHODS: HepG2 cells were pretreated with chrysin for 2 h, followed by the addition of cisplatin for another 24 h. The morphologic changes were observed under inverted microscope and the cell viability was measured using the MTT test. The protein and cleavage of caspase-3,8,9, PARP, and cFLIP were determined by Western blotting. RESULTS: The cell viability of the HepG2 cell can be reduced by the combination of chrysin pretreatment for 2 h and cisplatin addition for 24 h; Caspase-3,8,9 and PARP were cleaved after 12 h treatment with chrysin and cisplatin; Pancaspase inhibitor, Z-VAD-fmk, could reverse the apoptosis induced by chrysin and cisplatin in HepG2 cells; cFLIP was down-regulated by the combination of chrysin and cisplatin, and could be reversed by Z-VAD-fmk; the xenografted HepG2 cells formed a tumor in one week; At the end of the experiment, there were significant differences in relative tumor volume (RTV) and relative tumor proliferation rate between the combined group and the control group, the chrysin group and the cisplatin group; Western blotting showed that the levels of PARP, cFLIP, and caspase-3 proteins in isolated tumor tissues also decreased under the combined action of chrysin and cisplatin. CONCLUSION: The combination of chrysin and cisplatin induces apoptosis of hepatic tumor in vivo and in vitro. It downregulates cFLIP and then activates caspase-8, which triggers caspase-mediated apoptosis of HepG2 cell.

Titanium-coated PEEK Versus Uncoated PEEK Cages in Lumbar Interbody Fusion: A Systematic Review and Meta-analysis of Randomized Controlled Trial.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: This study was performed to compare the fusion and subsidence rate of titanium-coated polyetheretherketone (Ti-PEEK) versus polyetheretherketone (PEEK) cages after lumbar fusion and to investigate the clinical effect on patient-reported outcomes (PROMs). SUMMARY OF BACKGROUND DATA: Ti-PEEK cages have been developed to combine the advantages of both titanium alloy and PEEK, but whether they are superior to uncoated PEEK cages in bone fusion is still inconclusive. METHODS: PubMed, EMBASE, ISI Web of Science, CENTRAL, and CNKI were searched to identify randomized controlled trials that compared the efficacy of Ti-PEEK and PEEK cages in lumbar fusion. Difference in fusion rate and subsidence rate was indicated by risk ratio and its associated 95% confidence interval (95% confidence interval). Mean difference was calculated for Oswestry Disability Index and visual analogue scale for low back pain. Subgroup analysis was performed by time course after the surgery. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to evaluate the certainty of evidence. RESULTS: Four randomized controlled trials involving 325 patients (160 patients in Ti-PEEK group and 165 patients in PEEK group) that underwent lumbar fusion were included by our current study. Low to moderate evidence suggested that Ti-PEEK and PEEK cages exhibited equivalent fusion rate and subsidence rate at any follow-up time. Low to moderate evidence suggested that there was no difference in PROMs except for visual analogue scale measured at 6 months (mean difference: -0.57, 95% confidence interval -0.94, -0.21; P =0.002) but the difference was not clinically relevant according to the minimal clinically important difference. CONCLUSION: Low to moderate evidence showed that Ti-PEEK and PEEK had equivalent effect in bone fusion and cages subsidence at any follow-up time after lumbar fusion surgeries. Low to moderate evidence showed no clinically important difference in PROMs.

Baohuoside I Inhibits Osteoclastogenesis and Protects Against Ovariectomy-Induced Bone Loss.

Bone-resorbing osteoclasts are essential for skeletal remodelling, and the hyperactive formation and function of osteoclasts are common in bone metabolic diseases, especially postmenopausal osteoporosis. Therefore, regulating the osteoclast differentiation is a major therapeutic target in osteoporosis treatment. Icariin has shown potential osteoprotective effects. However, existing studies have reported limited bioavailability of icariin, and the material basis of icariin for anti-osteoporosis is attributed to its metabolites in the body. Here, we compared the effects of icariin and its metabolites (icariside I, baohuoside I, and icaritin) on osteoclastogenesis by high-content screening followed by TRAP staining and identified baohuoside I (BS) with an optimal effect. Then, we evaluated the effects of BS on osteoclast differentiation and bone resorptive activity in both in vivo and in vitro experiments. In an in vitro study, BS inhibited osteoclast formation and bone resorption function in a dose-dependent manner, and the elevated osteoclastic-related genes induced by RANKL, such as NFATc1, cathepsin K, RANK, and TRAP, were also attenuated following BS treatment. In an in vivo study, OVX-induced bone loss could be prevented by BS through interrupting the osteoclast formation and activity in mice. Furthermore, mechanistic investigation demonstrated that BS inhibited osteoclast differentiation by ameliorating the activation of the MAPK and NF-kB pathways and reducing the expression of uPAR. Our study demonstrated that baohuoside I could inhibit osteoclast differentiation and protect bone loss following ovariectomy.

The efficacy of platelet rich plasma on anterior cruciate ligament reconstruction: a systematic review and meta-analysis.

Anterior cruciate ligament (ACL) rupture is a common musculoskeletal injury, most frequently affecting young and physically active patients. Platelet-rich plasma (PRP) has been widely used in ACL reconstruction to augment the graft healing. However, high-level studies addressing its clinical efficacy could not reach a consensus. In this study, we assess the efficacy of PRP on pain relief, functional improvement along with radiological changes in patients who underwent ACL reconstruction. We performed comprehensive literature search and included 17 RCTs containing 970 participants who underwent ACL reconstruction. The combined data showed significant difference between PRP and control with regard to VAS score (MD: -1.12, 95% CI -1.92, -0.31; P = .007), subjective IKDC score (MD: 6.08, 95% CI 4.39, 7.77; P < .00001) and Lysholm score (MD: 8.49, 95% CI 1.63, 15.36; P = .02) by postoperative 6 months, but only pain reduction was deemed clinically important. At the end of one year's follow-up, no clinically meaningful improvement in VAS (MD: -0.47, P = .04), subjective IKDC score (MD: 3.99, P = .03), Lysholm score (MD: 2.30, P = .32), objective IKDC score (RR: 1.03, P = .09) and knee joint laxity (MD: 0.17, P = .28) was seen. In terms of radiological findings, about one-third of the studies favored PRP to facilitate the graft healing, improve the harvest site morbidity and prevent tunnel widening. In summary, moderate quality of evidence suggested that PRP could provide short-term but not long-term clinically important pain reduction.

Oroxin B Attenuates Ovariectomy-Induced Bone Loss by Suppressing Osteoclast Formation and Activity.

BACKGROUND: Osteoclasts are the major players in bone resorption and have always been studied in the prevention and treatment of osteoporosis. Previous studies have confirmed that a variety of flavonoids inhibit osteoporosis and improve bone health mainly through inhibiting osteoclastogenesis. Oroxin B (OB) is a flavonoid compound extracted from traditional Chinese herbal medicine Oroxylum indicum (L.) Vent, exerts potent antitumor and anti-inflammation effect, but its effect on osteoclastogensis remains unknown. METHODS: We comprehensively evaluated the effect of OB on the formation and function of osteoclasts and the underling mechanism by bone marrow-derived macrophage in vitro. In vivo, we used mice ovariectomized model to verify the protective effect of OB. RESULTS: OB was found to inhibit osteoclast formation and bone resorption function in vitro, in a dose-dependent manner and the increased osteoclastic-related genes induced by RANKL (NFATc1, c-fos, cathepsin K, RANK, MMP9 and TRAP) were also attenuated following OB treatment. Mechanistical investigation showed OB abrogated the increased phosphorylation level of MAPK and NF-κB pathway, and diminished the expression of the vital transcription factors for osteoclastogenesis. OB also prevented ovariectomy (OVX)-induced bone loss by inhibiting osteoclast formation and activity in mice. CONCLUSION: Our study demonstrated that OB may act as an anti-osteoporosis agent by inhibiting osteoclast maturation and attenuating bone resorption.

Accumulation of LDL/ox-LDL in the necrotic region participates in osteonecrosis of the femoral head: a pathological and in vitro study.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a common but intractable disease that appears to involve lipid metabolic disorders. Although numerous studies have demonstrated that high blood levels of low-density lipoprotein (LDL) are closely associated with ONFH, there is limited evidence to explain the pathological role of LDL. Pathological and in vitro studies were performed to investigate the role of disordered metabolism of LDL and oxidized LDL (ox-LDL) in the femoral head in the pathology of ONFH. METHODS: Nineteen femoral head specimens from patients with ONFH were obtained for immunohistochemistry analysis. Murine long-bone osteocyte Y4 cells were used to study the effects of LDL/ox-LDL on cell viability, apoptosis, and metabolism process of LDL/ox-LDL in osteocytes in normoxic and hypoxic environments. RESULTS: In the pathological specimens, marked accumulation of LDL/ox-LDL was observed in osteocytes/lacunae of necrotic regions compared with healthy regions. In vitro studies showed that ox-LDL, rather than LDL, reduced the viability and enhanced apoptosis of osteocytes. Pathological sections indicated that the accumulation of ox-LDL was significantly associated with impaired blood supply. Exposure to a hypoxic environment appeared to be a key factor leading to LDL/ox-LDL accumulation by enhancing internalisation and oxidation of LDL in osteocytes. CONCLUSIONS: The accumulation of LDL/ox-LDL in the necrotic region may contribute to the pathology of ONFH. These findings could provide new insights into the prevention and treatment of ONFH.

COL12A1 rs970547 Polymorphism Does Not Alter Susceptibility to Anterior Cruciate Ligament Rupture: A Meta-Analysis.

Objective: Currently available evidence regarding the association between collagen type XII α1 (COL12A1) polymorphism and risk of anterior cruciate ligament rupture (ACLR) remains elusive. The aim of our present study was to assess the association between COL12A1 rs970547 polymorphism and ACLR risk. Methods: Five online databases, namely, PubMed, EMBASE, ISI Web of Science, CENTRAL, and CNKI, were searched from their inception data up to December 2020 to identify relative observational studies. The methodological quality of each individual study was evaluated using the Newcastle-Ottawa Scale (NOS). The "model-free approach" was employed to estimate the magnitude of effect of COL12A1 rs970547 polymorphism on ACLR, and the association was expressed using odds ratio (OR) and its associated 95% confidence interval (95% CI). Subgroup analysis was performed by ethnicity and sex of included subjects. Results: Eight studies involving 1,477 subjects with ACLR and 100,439 healthy controls were finally included in our study. The methodological quality of included studies was deemed moderate to high based on NOS scores. The "model-free" approach suggested no genotype differences between ACLR and healthy control for the rs970547 polymorphism, but we still used the allele model to present the combined data. Under the random-effect model, there was no significant difference in the frequency of effecting allele between ACLR and control (OR: 0.91, 95% CI 0.77, 1.08; p = 0.28). Stratified analysis by sex and ethnicity also showed no difference in allele frequency. Conclusion: The findings of this current meta-analysis suggested that rs970547 was not associated with ACLR risk in male, female, and the overall population among Asians or Caucasians.

Modified pedicle screw-rod versus anterior subcutaneous internal pelvic fixation for unstable anterior pelvic ring fracture: a retrospective study and finite element analysis.

OBJECTIVES: This study compared the stability and clinical outcomes of modified pedicle screw-rod fixation (MPSRF) and anterior subcutaneous internal pelvic fixation (INFIX) for the treatment of anterior pelvic ring fractures using the Tornetta and Matta grading system and finite element analyses (FEA). METHODS: In a retrospective review of a consecutive patient series, 63 patients with Orthopaedic Trauma Association (OTA)/Arbeitsgemeinschaft für Osteosynthesefragen (AO) type B or C pelvic ring fractures were treated by MPRSF (n = 30) or INFIX (n = 33). The main outcome measures were the Majeed score, incidence of complications, and adverse outcomes, and fixation stability as evaluated by finite element analysis. RESULTS: Sixty-three patients were included in the study, with an average age of 34.4 and 36.2 in modified group and conventional group, respectively. Two groups did not differ in terms of the injury severity score, OTA classification, cause of injury, and time to pelvic surgery. However, the MPSRF group had a rate of higher satisfactory results according to the Tornetta and Matta grading system than the conventional group (73.33% vs 63.63%) as well as a higher Majeed score (81.5 ± 10.4 vs 76.3 ± 11.2), and these differences were statistically significant at 6 months post-surgery. FEA showed that MPSRF was stiffer and more stable than INFIX and had a lower risk of implant failure. CONCLUSIONS: Both MPSRF and INFIX provide acceptable biomechanical stability for the treatment of unstable anterior pelvic ring fractures. However, MPSRF provides better fixation stability and a lower risk of implant failure, and can thus lead to better clinical outcomes. Therefore, MPSRF should be more widely applied to anterior pelvic ring fractures.

Association of ITGAV polymorphisms and risk of rheumatoid arthritis: evidence from a meta-analysis.

OBJECTIVE: Currently published papers regarding the relationship between integrin alpha V (ITGAV) gene polymorphisms and rheumatoid arthritis (RA) are contradictory. The aim of this meta-analysis was to evaluate the associations between the ITGAV gene polymorphisms and RA risk. METHODS: Comprehensive literature search based on four electronic databases was applied to retrieve all related data. Two independent reviewers screened each article for eligibility according to the predetermined inclusion criteria. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to assess associations between ITGAV gene polymorphisms and RA. RESULTS: Six articles involving 5794 RA patients and 5297 healthy controls were included in this meta-analysis. The combined data indicated that rs3911238, rs3738919, rs3768777, and rs10174098 in ITGAV gene were not associated with RA risk in the overall population. However, stratification analysis by ethnicity suggested that rs3768777 was related with risk of RA among Caucasian population (OR 3.51, 95%CI 2.06, 5.97; P < 0.0001), but not among Asian population (OR 1.06, 95%CI 0.67, 1.69; P = 0.81). CONCLUSIONS: Our meta-analysis confirmed that the ITGAV gene rs3768777 polymorphisms might be a risk factor among Caucasians. However, larger-scale studies in Caucasian population are still warranted to confirm the findings of our study.

Pinocembrin alleviates glucocorticoid-induced apoptosis by activating autophagy via suppressing the PI3K/Akt/mTOR pathway in osteocytes.

Glucocorticoids are widely used in clinical practice, but are associated with potentially severe side effects like glucocorticoid-induced osteoporosis (GIOP) and glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH). Glucocorticoid-induced osteocyte apoptosis plays critical roles in the pathological processes of both GIOP and GA-ONFH. Pinocembrin is a natural flavonoid that may exert protective effects on osteocytes. The present study investigated the effects of pinocembrin on glucocorticoid-induced apoptosis of murine long bone osteocyte Y4 (MLO-Y4) cells and sought to elucidate the underlying molecular mechanism. We found that pinocembrin attenuated glucocorticoid-induced cell viability injury and apoptosis of MLO-Y4 cells. Moreover, pinocembrin increased Beclin-1 and LC3B-II level, but decreased p62 expression, suggesting that pinocembrin activates autophagy in glucocorticoid-treated MLO-Y4 cells. The protective effects of pinocembrin on glucocorticoid-induced apoptosis of MLO-Y4 cells were mimicked by a known stimulator of autophagy but prevented by a known inhibitor of autophagy. Pinocembrin also suppressed the PI3K/Akt/mTOR signaling pathway, which regulates cell autophagy, in glucocorticoid-treated MLO-Y4 cells. In conclusion, the results indicate that pinocembrin alleviates glucocorticoid-induced osteocyte apoptosis by activating autophagy via suppressing the PI3K/Akt/mTOR pathway. Pinocembrin may represent a potential natural agent for preventing and treating GIOP and GA-ONFH.

Urolithin a attenuates IL-1ß-induced inflammatory responses and cartilage degradation via inhibiting the MAPK/NF-κB signaling pathways in rat articular chondrocytes.

BACKGROUND: Osteoarthritis (OA) is characterized by inflammation and extracellular matrix (ECM) degradation and is one of the most common chronic degenerative joint diseases that causes pain and disability in adults. Urolithin A (UA) has been widely reported for its anti-inflammatory properties in several chronic diseases. However, the effects of UA on OA remain unclear. The aim of the current study was to investigate the anti-inflammatory effects and mechanism of UA in interleukin-1ß (IL-1ß)-induced chondrocytes. RESULTS: No marked UA cytotoxicity was noted, and UA protected cartilage from damage following IL-1ß stimulation in micromasses. Moreover, UA promoted the expression of anabolic factors including Sox-9, Collagen II, and Aggrecan while inhibiting the expression of catabolic factors such as matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) in rat chondrocytes. Protective effects of UA were also observed in ex vivo organ culture of articular cartilage. Mechanistically, IL-1ß significantly activated and upregulated the expression of p-ERK 1/2, p-JNK, p-P38, and p-P65, while UA protected chondrocytes against IL-1ß-induced injury by activating the mitogen-activated kinase (MAPK)/nuclear factor-κB (NF-κB) signaling pathways. CONCLUSION: Our results provide the evidence that UA could attenuate IL-1ß-induced cell injury in chondrocytes via its anti-inflammatory action. UA may be a promising therapeutic agent in the treatment of OA.

Intravenous parecoxib for early postoperative cognitive dysfunction in elderly patients: evidence from a meta-analysis.

BACKGROUND: Inflammation plays a key role in the etiology and pathology of postoperative cognitive dysfunction (POCD). Cyclooxygenase (COX)-2 inhibitor parecoxib is used for the treatment of acute pain due to its potent anti-inflammatory and analgesic effects. Herein, we evaluated the efficacy and safety of parecoxib on early POCD in geriatric patients. OBJECTIVE: This study was performed to evaluate the efficacy and safety of parecoxib for early postoperative cognitive dysfunction (POCD) in elderly patients. METHODS: Comprehensive literature search based on six electronic databases was applied to retrieve all related randomized controlled trials (RCTs). Two independent reviewers screened each article for eligibility according to the predetermined inclusion criteria. The Cochrane's Tool was applied to evaluate the methodological quality of included studies. RevMan 5.3 was used to conduct meta-analysis. RESULTS: Eight RCTs comprising a total of 1106 subjects prepared for orthopedic surgical operation were selected. All the identified RCTs were conducted in China. The methodological qualities of included studies were judged to be medium to high. The integrated data showed that perioperative intravenous parecoxib could remarkably reduce the incidence of POCD with improved Mini-Mental State Examination (MMSE) score. Parecoxib could significantly reduce the concentrations of interleukin-6, but results regarding the changes in tumor necrosis factor-alpha, C-reactive protein, and S100ß levels remained inconsistent. CONCLUSION: Perioperative parecoxib administration is effective in reducing the incidence of POCD and improving the MMSE score compared with control. However, the beneficial effect of parecoxib has been tested only in the Chinese population. Future RCTs in western countries with larger-scale and more comprehensive neurological tests are needed.

Impact of national Human Development Index on liver cancer outcomes: Transition from 2008 to 2018.

BACKGROUND: Liver cancer is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide. Socioeconomic development, indicated by the Human Development Index (HDI), is closely interconnected with public health. But the manner in which social development and medical advances influenced liver cancer patients in the past decade is still unknown. AIM: To investigate the influence of HDI on clinical outcomes for patients with existing liver cancer from 2008 to 2018. METHODS: The HDI values were obtained from the United Nations Development Programme, the age-standardized incidence and mortality rates of liver cancer were obtained from the GLOBOCAN database to calculate the mortality-to-incidence ratio, and the estimated 5-year net survival of patients with liver cancer was provided by the CONCORD-3 program. We then explored the association of mortality-to-incidence ratio and survival with HDI, with a focus on geographic variability across countries as well as temporal heterogeneity over the past decade. RESULTS: From 2008 to 2018, the epidemiology of liver cancer had changed across countries. Liver cancer mortality-to-incidence ratios were negatively correlated and showed good fit with a modified "dose-to-inhibition response" pattern with HDI (r = -0.548, P < 0.0001 for 2018; r = -0.617, P < 0.0001 for 2008). Cancer survival was positively associated with HDI (r = 0.408, P < 0.01) and negatively associated with mortality-to-incidence ratio (r = -0.346, P < 0.05), solidly confirming the interrelation among liver cancer outcome indicators and socioeconomic factors. Notably, in the past decade, the HDI values in most countries have increased alongside a decreasing tendency of liver cancer mortality-to-incidence ratios (P < 0.0001), and survival outcomes have simultaneously improved (P < 0.001), with significant disparities across countries. CONCLUSION: Socioeconomic factors have a significant influence on cancer outcomes. HDI values have increased along with improved cancer outcomes, with significant disparities among countries.

Combination of quercetin and cisplatin enhances apoptosis in OSCC cells by downregulating xIAP through the NF-κB pathway.

While cisplatin is a first-line chemotherapeutic drug commonly used to treat patients with oral squamous cell carcinoma (OSCC), the cisplatin-resistance poses a major challenge for its clinical application. Recent studies have shown that quercetin, a natural flavonoid found in various plants and foods possesses an anti-cancer effect. The following study examined the combined effect of quercetin and cisplatin on OSCC apoptosis in vitro and in vivo (using a mice tumor model). We found that quercetin promotes cisplatin-induced apoptosis in human OSCC (cell lines Tca-8113 and SCC-15) by down-regulating NF-κB. Pretreatment of cancer cells with quercetin inhibited the phosphorylation Akt and IKKß, and led to the suppression of NF-κB and anti-apoptotic protein xIAP. In addition, we observed that the pretreatment of cancer cells with quercetin improves extrinsic and intrinsic apoptosis by activating caspase-8 and caspase-9, respectively. Our in vivo data also indicated that the combination of quercetin and cisplatin may inhibit the xenograft growth in mice. To sum up, our results provide a new evidence for the application of quercetin and cisplatin in OSCC therapy.

Corrigendum: Ulinastatin Inhibits Osteoclastogenesis and Suppresses Ovariectomy-Induced Bone Loss by Downregulating uPAR.

[This corrects the article DOI: 10.3389/fphar.2018.01016.].

Ulinastatin Inhibits Osteoclastogenesis and Suppresses Ovariectomy-Induced Bone Loss by Downregulating uPAR.

Recent studies indicate that uPAR acts a crucial part in cell migration and the modulation of bone homeostasis. As a natural serine protease inhibitor, ulinastatin owns the capacity to reduce proinflammatory factors, downregulate the activation of NF-κB and mitogen-activated protein kinases (MAPKs) signaling pathways. Osteoclastogenesis has been demonstrated to be related with low-grade inflammation which involves cell migration, thus we speculate that ulinastatin may have a certain kind of impact on uPAR so as to be a potential inhibiting agent of osteoclastogenesis. In this research, we investigated the role which ulinastatin plays in RANKL-induced osteoclastogenesis both in vivo and in vitro. Ulinastatin inhibited osteoclast formation and bone resorption in a dose-dependent manner in primary bone marrow-derived macrophages (BMMs), and knockdown of uPAR could completely repress the formation of osteoclasts. At the molecular level, ulinastatin suppressed RANKL-induced activation of cathepsin K, TRAP, nuclear factor-κB (NF-κB) and MAPKs, and decreased the expression of uPAR. At the meantime, ulinastatin also decreased the expression of osteoclast marker genes, including cathepsin K, TRAP, RANK, and NFATc1. Besides, ulinastatin prevented bone loss in ovariectomized C57 mice by inhibiting the formation of osteoclasts. To sum up, this research confirmed that ulinastatin has the ability to inhibit osteoclastogenesis and prevent bone loss, and uPAR plays a crucial role in that process. Therefore, ulinastatin could be chosen as an effective alternative therapeutics for osteoclast-related diseases.

Diagnostic Value of Contrast-Enhanced Spectral Mammography for Screening Breast Cancer: Systematic Review and Meta-analysis.

BACKGROUND: Contrast-enhanced spectral mammography (CESM) is a new image examination technology that has developed over the past few years. As CESM technology keeps improving, a current meta-analysis review is needed to systematically evaluate the potential diagnostic value of CESM. METHODS: A total of 18 studies were included in the review. Sensitivity, specificity, and other important parameters of CESM accuracy for breast cancer diagnosis were pooled and analyzed using random-effects models. Summary receiver operating characteristic curves were calculated for overall accuracy estimation. RESULTS: The summary estimates for CESM in the diagnosis of breast cancer were as follows: the pooled sensitivity and specificity were 0.89 (95% confidence interval [CI], 0.88-0.91) and 0.84 (95% CI, 0.82-0.85), respectively. Positive likelihood ratio was 3.73 (95% CI, 2.68-5.20), negative likelihood ratio was 0.10 (95% CI, 0.06-0.15), and diagnostic odds ratio was 71.36 (95% CI, 36.28-140.39). The area under the curve was 0.96 (standard error = 0.011). CONCLUSION: CESM has a high diagnostic accuracy for evaluating breast cancer and can be considered as a useful test for initial assessment of breast lesions.