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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.

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.

Systematic review and meta-analysis.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).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.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.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.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.

Photovoltaic (PV) systems operating in the outdoor environment are vulnerable to various factors, especially dust impact. Abnormal operations lead to massive power losses, and severe faults as short circuit may cause safety problems and fire hazards. Therefore, monitoring the operation status of PV systems for timely troubleshooting potential failure and effective cleaning scheme are the focus of current research works. In this study, I–V characteristics of PV strings under various fault states are analyzed, especially soiling condition. Because labeled data for PV systems with specific faults are challenging to record, especially in the large-scale ones, a novel algorithm combining artificial bee colony algorithm and semi-supervised extreme learning machine is proposed to handle this problem. The proposed algorithm can diagnose PV faults using a small amount of simulated labeled data and historical unlabeled data, which greatly reduces labor cost and time-consuming. Moreover, the monitoring of dust accumulation can warn power plant owners to clean PV modules in time and increase the power generation benefits. PV systems of 3.51 and 3.9 kWp are used to verify the proposed diagnosis method. Both numerical simulations and experimental results show the accuracy and reliability of the proposed PV diagnostic technology.

Jun-ming Huang, Chen-zhong Wang, Shun-yi Lu, Zhe Wang, Zuo-qin Yan Department of Orthopaedics, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of ChinaCorrespondence: Zuo-qin Yan 180 Feng Lin Road, Xuhui District, Shanghai, 200032, People’s Republic of ChinaEmail yan.zuoqin@zs-hospital.sh.cnBackground: 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.Keywords: osteoclast, Oroxin B, MAPK, NF-κB, RANKL, osteoporosis

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.This study was performed to evaluate the efficacy and safety of parecoxib for early postoperative cognitive dysfunction (POCD) in elderly patients.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.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 S100β levels remained inconsistent.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.

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.

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

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.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.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).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.

Fault diagnosis of photovoltaic (PV) arrays is an essential task for improving the reliability and safety of a photovoltaic system (PVS). The PVS faults at the DC side are difficult to detect by traditional protective devices, which may reduce power conversion efficiency and even lead to safety matters and fire disaster. This study investigates a newly-designed fault diagnostic method for a PVS according to the following three steps. First, optimal fault features are extracted by analyzing I-V curves from different faults, including hybrid faults of the PVS under the standard test condition (STC). Moreover, the trust-region-reflective (TRR) deterministic algorithm combined with the particle-swarm-optimization (PSO) metaheuristic algorithm is proposed to standardize fault features into the ones under the STC. In addition, a multi-class adaptive boosting (AdaBoost) algorithm, which is the stage-wise additive modeling using multi-class exponential (SAMME) loss function based on the classification and regression tree (CART) as the weak classifier, is utilized to establish the fault diagnostic model. The effectiveness of the fault diagnostic model could long-term maintain by periodically updating the feature standardization equations to standardize the fault features into the ones under the STC. Various types of the PV modules are used to validate the generalization of the fault diagnostic method. Both the numerical simulations and experimental results show the accuracy and reliability of the proposed fault diagnostic method.

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 IKKβ, 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.

In this paper, BP neural network (BPNN) is studied to model and predict NOX emission of direct injection diesel engine. The model selects four parameters as input, namely rotation speed, load, exhaust temperature and fuel-air ratio. Through testing, it is concluded that the prediction performance of BPNN model will be greatly affected by the initial weight and threshold, so that the prediction accuracy of the model is not high. In order to reduce the influence of initial weight and threshold on the prediction performance of BPNN model, this paper adopts Particle Swarm Optimization (PSO) algorithm to optimize the initial weight and threshold of BPNN, and establishes the corresponding prediction model of NOX emission of diesel engine. The results show that the prediction model of BPNN optimized by PSO algorithm can effectively reduce the influence of initial weight and threshold on BPNN and make the prediction results of the model more reliable. In particular, when PSO adopts non-linear dynamic weight strategy and synchronous learning factor strategy, the prediction performance of BPNN model is more provided with reliability.

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.

This meta-analysis was performed to clarify whether the two single nucleotide polymorphisms (ApaI and BsmI) in vitamin D receptor (VDR) gene conferred susceptibility to adolescent idiopathic scoliosis (AIS). A comprehensive literature search in five online databases (PubMed, EMBASE, ISI Web of Science, CNKI, and Wanfang) was performed to identify studies that analyzed the association between VDR gene polymorphisms and risk of AIS. Observational studies met the predetermined inclusion criteria were selected for meta-analysis. The most appropriate genetic model was identified using a genetic model-free approach. Meta-analysis was performed using RevMan 5.3 software. Five eligible studies were included in this meta-analysis, which involved a total of 717 cases and 554 controls. A statistically significant association was observed between BsmI polymorphism and AIS (OR 1.90, 95% CI 1.32, 2.62). In subgroup analysis by ethnicity, the association between BsmI polymorphism and AIS was significant in Asians (OR 2.06, 95% CI 1.56, 2.73) but not in Caucasians (OR 0.70, 95% CI 0.23, 2.19). However, the ApaI polymorphism was not associated with AIS. Moreover, no evidence of association between BMD and the two VDR gene polymorphisms was detected. Meta-analysis of existing data suggested that BsmI was associated with increased risk of AIS in Asian populations. Nevertheless, further studies with rigorous design and more ethnic groups are encouraged to validate our findings. These slides can be retrieved under Electronic Supplementary Material.

Skeletal stem cells (SSCs) are a population of progenitor cells which give rise to postnatal skeletal tissues including bone, cartilage and bone marrow stroma, however not to adipose, haematopoietic or muscle tissue. Growth plate chondrocytes exhibit the ability of continuous proliferation and differentiation, which contributes to the continuous physiological growth. The growth plate has been hypothesized to contain SSCs which exhibit a desirable differentiation capacity to generate bone and cartilage. Due to the heterogeneity of the growth plate chondrocytes, SSCs in the growth plate are not well studied. The present study used cluster of differentiation (CD)146 and CD105 as markers to isolate purified SSCs. CD105+ SSCs and CD146+ SSCs were isolated using a magnetic activated cell sorting method. To quantitatively investigate the proliferation and differentiation ability, the colony-forming efficiency (CFE) and multi‑lineage differentiation capacity of CD105+ SSCs and CD146+ SSCs were compared with unsorted cells and adipose-derived stem cells (ASCs). It was revealed that CD105+ and CD146+ subpopulations represented subsets of SSCs which generated chondrocytes and osteocytes, however not adipocytes. Compared with CD105+ subpopulations and ASCs, the CD146+ subpopulation exhibited a greater CFE and continuous high chondrogenic differentiation capacity in vitro. Therefore, the present study suggested that the CD146+ subpopulation represented a chondrolineage‑restricted subpopulation of SSCs and may therefore act as a valuable cell source for cartilage regeneration.

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.

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-1β (IL-1β)-induced chondrocytes. Results No marked UA cytotoxicity was noted, and UA protected cartilage from damage following IL-1β 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-1β significantly activated and upregulated the expression of p-ERK 1/2, p-JNK, p-P38, and p-P65, while UA protected chondrocytes against IL-1β-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-1β-induced cell injury in chondrocytes via its anti-inflammatory action. UA may be a promising therapeutic agent in the treatment of OA.

Magnesium and Mg-based alloys are promising biomaterials for orthopedic implants because of their degradability, osteogenic effects, and biocompatibility. However, the drawbacks of these materials include high hydrogen gas production, unexpected corrosion resistance, and insufficient mechanical strength duration. Surface modification can protect these biomaterials and induce osteogenesis. In this work, a SrHPO4 coating was developed for our patented biodegradable Mg-Nd-Zn-Zr alloy (abbr. JDBM) through a chemical deposition method. The coating was characterized by in vitro immersion, ion release, and cytotoxicity tests, which showed a slower corrosion behavior and excellent cell viability. RNA sequencing of MC3T3E1 cells treated with SrHPO4-coated JDBM ion release test extract showed increased Tlr4, followed by the activation of the downstream PI3K/Akt signaling pathway, causing proliferation and growth of pre-osteoblasts. An intramedullary nail (IMN) was implanted in a femoral fracture rat model. Mechanical test, radiological and histological analysis suggested that SrHPO4-coated JDBM has superior mechanical properties, induces more bone formation, and decreases the degradation rate compared with uncoated JDBM and the administration of TLR4 inhibitor attenuated the new bone formation for fracture healing. SrHPO4 is a promising coating for JDBM implants, particularly for long-bone fractures.

Cisplatin is a chemotherapy drug commonly used for the treatment of human cancers, however, drug resistance poses a major challenge to clinical application of cisplatin in cancer therapy. Recent studies have shown that chrysin, a natural flavonoid widely found in various plants and foods, demonstrated effective anti-cancer activity. In the present study, we found that the combination chrysin and cisplatin significantly enhanced the apoptosis of Hep G2 cancer cells. Combination of chrysin and cisplatin increased the phosphorylation and accumulation of p53 through activating ERK1/2 in Hep G2 cells, which led to the overexpression of the pro-apoptotic proteins Bax and DR5 and the inhibition of the anti-apoptotic protein Bcl-2. In addition, combination of chrysin and cisplatin promoted both extrinsic apoptosis by activating caspase-8 and intrinsic apoptosis by increasing the release of cytochrome c and activating caspase-9 in Hep G2 cells. Our results suggest that combination of chrysin and cisplatin is a promising strategy for chemotherapy of human cancers that are resistant to cisplatin.

LINC00152, a novel long noncoding RNA (lncRNA), was identified as an oncogene involved various cancers. This study was designed to explore the clinical significance and prognosis role of LINC00152.Eligible studies were recruited by a systematic search in PubMed, Web of Science, and Embase up to August 23, 2017. Odds ratios (ORs), hazard ratios (HRs) and 95% confidence interval (95% CI) were pooled using Review Manager 5.3 and STATA 12.0.A total of 10 studies with 913 patients were included to evaluate the association between LINC00152 expression and clinicopathological factors, overall survival (OS) and disease-free survivals (DFS). The results indicated that the expression level of LINC00152 was positively correlated with tumor size (OR = 5.19, 95% CI: 2.33-11.52, p .0001), TNM stage (OR = 3.12, 95% CI: 1.77-5.51, p .0001) and lymph node metastasis (OR = 3.41, 95% CI: 2.13-5.48, p .00001). Moreover, elevated LINC00152 could predict unfavorable OS with pooled HR of 1.66 (95% CI: 1.29-2.13, p .0001) and poor DFS (HR = 2.13, 95% CI: 1.39-3.25, p = .0005) in cancer patients.LINC00152 was correlated with advanced clinicopathological features and poor prognosis as a novel predictive biomarker in various cancers.

Epiphyseal growth plate is highly dynamic tissue which is controlled by a variety of endocrine, paracrine hormones, and by complex local signaling loops and mechanical loading. Mechano growth factor (MGF), the splice variant of the IGF-I gene, has been discovered to play important roles in tissue growth and repair. However, the effect of MGF on the growth plate remains unclear. In the present study, we found that MGF mRNA expression of growth plate chondrocytes was upregulated in response to mechanical stimuli. Treatment of MGF had no effect on growth plate chondrocytes proliferation and differentiation. But it could inhibit growth plate chondrocytes apoptosis and inflammation under mechanical overload. Moreover, both wound healing and transwell assay indicated that MGF could significantly enhance growth plate chondrocytes migration which was accompanied with YAP activation and nucleus translocation. Knockdown of YAP with YAP siRNA suppressed migration induced by MGF, indicating the essential role of YAP in MGF promoting growth plate chondrocytes migration. Furthermore, MGF promoted YAP activation through RhoA GTPase mediated cytoskeleton reorganization, RhoA inhibition using C3 toxin abrogated MGF induced YAP activation. Importantly, we found that MGF promoted focal adhesion(FA) formation and knockdown of YAP with YAP siRNA partially suppressed the activation of FA kinase, implying that YAP is associated with FA formation. In conclusion, MGF is an autocrine growth factor which is regulated by mechanical stimuli. MGF could not only protect growth plate chondrocytes against damage by mechanical overload, but also promote migration through activation of RhoA/YAP signaling axis. Most importantly, our findings indicate that MGF promote cell migration through YAP mediated FA formation to determine the FA-cytoskeleton remodeling.

Pregnane X receptor (PXR) which belongs to the nuclear hormone receptor superfamily plays vital roles in several biological functions, especially in the inflammatory procedure. Besides that, PXR is revealed by recent studies to have essential effects on bone tissue. As an agonist of PXR, meclizine is a piperazine-derived histamine H1 antagonist, and has been frequently used for prevention and treatment of vomiting and nausea. Because osteoclastogenesis is characterized by the activation of inflammation-related signaling pathways, we speculated that meclizine may affect formation and function of osteoclast. In the present study, we explored the effect of meclizine on RANKL-induced osteoclastogenesis both in vivo and in vitro. In primary bone marrow-derived macrophages (BMMs), meclizine reduced osteoclast formation and bone resorption in a dose-dependent manner, while knockdown of PXR with siRNA partially abrogated the osteoclastogenesis inhibition of meclizine. On the one hand, at the molecular level, meclizine attenuated RANKL-induced activation of c-Fos, NFATc1, nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPKs), including ERK and p38, but not JNK. Meanwhile, meclizine reduced the expression of osteoclast-specific genes, including TRAP, MMP9, Cathepsin K and NFATc1. On the other hand, meclizine decreased OVX-induced bone loss by repressing osteoclast activity. In conclusion, our results indicated that meclizine inhibits osteoclastogenesis via regulation of several RANKL signaling pathways and PXR was involved in the processes. Therefore, meclizine may be considered as a novel therapeutic candidate for osteoclast-related diseases.

Objective This study aims to evaluate the efficacy and safety of parecoxib injection in pain relief after laparoscopic surgeries. Methods A comprehensive literature search based on 4 online databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) 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 Collaboration's tool was applied to evaluate the methodological quality of included studies. A standardized data collection sheet was designed to extract data from included studies. RevMan version 5.3 (The Cochrane Collaboration, Copenhagen, Denmark) was selected to perform meta-analysis. Results A total of 1,060 participants who were scheduled for gynecological laparoscopic surgery or laparoscopic cholecystectomy (LC) were enrolled in 12 selected RCTs. The methodological qualities of the studies were evaluated as moderate to high. The combined data showed that perioperative parecoxib injection could significantly reduce the proportion of patients who required adjuvant pain relieve after laparoscopic surgeries. Significantly lower pain scores in the parecoxib groups were observed, which proved that preoperative or intraoperative injection of 40 mg parecoxib was more effective than placebo for immediate pain relief after LC. But preoperative injection of 40 mg parecoxib showed no improvement compared with placebo in the management of immediate pain following gynecological laparoscopic surgery. The occurrence of adverse events showed no differences between perioperative parecoxib administration and placebo control. Conclusion Perioperative parecoxib administration was effective in reducing the proportion of patients who required adjuvant pain relief after laparoscopic surgeries without significant adverse events compared with placebo. The effect of parecoxib injection on immediate pain relief remains in question. Future RCTs with larger sample sizes are encouraged.

Iguratimod is known for its anti‑inflammatory activities and therapeutic effects in patients with rheumatoid arthritis. It has previously been demonstrated that iguratimod attenuates bone destruction and osteoclast formation in the Walker 256 rat mammary gland carcinoma cell‑induced bone cancer pain model. Therefore, it was hypothesized that iguratimod may additionally exhibit therapeutic effects on benign osteoclast‑associated diseases including postmenopausal osteoporosis. In the present study, ovariectomized mice were used to investigate the effects of iguratimod in vivo. Bone marrow mononuclear cells were cultured to detect the effects of iguratimod on receptor activator of nuclear factor‑κB ligand (RANKL)‑induced osteoclastogenesis in vitro and the molecular mechanisms involved. It was demonstrated that iguratimod may prevent ovariectomy‑induced bone loss by suppressing osteoclast activity in vivo. Consistently, iguratimod may inhibit RANKL‑induced osteoclastogenesis and bone resorption in primary bone marrow mononuclear cells. At the molecular level, peroxisome proliferator‑activated receptor‑γ (PPAR‑γ)/c‑Fos pathway, which is essential in RANKL‑induced osteoclast differentiation, was suppressed by iguratimod. Subsequently, iguratimod decreased the expression of nuclear factor of activated T cells c1 and downstream osteoclast marker genes. The results of the present study demonstrated that iguratimod may inhibit ovariectomy‑induced bone loss and osteoclastogenesis by modulating RANKL signaling. Therefore, iguratimod may act as a novel therapeutic to prevent postmenopausal osteoporosis.

Fat infiltration within the bone marrow is easily observed in some postmenopausal women. Those fats are mainly derived from bone marrow mesenchymal stem cells (BMMSCs). The increment of adipocytes derived from BMMSCs leads to decreased osteoblasts derived from BMMSCs, so the bidirectional differentiation of BMMSCs significantly contributes to osteoporosis. Icariin is the main extractive of Herba Epimedii which is widely used in traditional Chinese medicine. In this experiment, we investigated the effect of icariin on the bidirectional differentiation of BMMSCs through quantitative real-time PCR, immunofluorescence, western blot, and tissue sections in vitro and in vivo. We found that icariin obviously promotes osteogenesis and inhibits adipogenesis through detecting staining and gene expression. Micro-CT analysis showed that icariin treatment alleviated the loss of cancellous bone of the distal femur in ovariectomized (OVX) mice. H&E staining analysis showed that icariin-treated OVX mice obtained higher bone mass and fewer bone marrow lipid droplets than OVX mice. Western blot and immunofluorescence showed that icariin regulates the bidirectional differentiation of BMMSCs via canonical Wnt signaling. This study demonstrates that icariin exerts its antiosteoporotic effect by regulating the bidirectional differentiation of BMMSCs through the canonical Wnt signaling pathway.

Chondrosarcoma is a bone tumor characterized by the secretion of a cartilage-like extracellular matrix. It has been proved to lack extracellular sensor primary cilia. This study aimed to illustrate a feasible therapeutic method for chondrosarcoma by regulating primary cilia assembly through inhibiting histone deacetylases 6 (HDAC6) activation. In order to detect the interaction between primary cilia and HDAC6 in human chondrosarcoma, Tubastatin A and small interfering RNA (siRNA) were used to inhibit the endogenous expression of HDAC6. Cell viability test and Transwell assay were applied to evaluate the effects of malignant biological properties. Primary cilia staining and related proteins were detected. The abnormal expression of HDAC6 and cilia intraflagellar transport protein 88 (IFT88) was found in chondrosarcoma tissues. The inhibition of HDAC6 could downregulate the proliferation of chondrosarcoma cells in a concentration- and time-dependent manner and suppress the invasion capacity of tumor cells. Besides, the downregulation of HDAC6 exhibited a negative effect on the proliferation of relevant proteins but a positive effect on the primary cilia-related expression of IFT88 and acetylated α-tubulin. Primary cilia restoration could be observed after HDAC6 siRNA transfection. The Aurora A-HDAC6 cascade was involved in regulating primary cilia resorption by affecting α-tubulin deacetylation and Tubastatin A could inhibit chondrosarcoma cell growth in vivo. These results indicate that restricting HDAC6 can restore primary cilia assembly accompanied with suppressed chondrosarcoma cell proliferation and invasion capacities. Thus, promoting primary cilia restoration by targeting HDAC6 may be a feasible potential therapeutic method for chondro-sarcoma treatment.

Background.Ulinastatin, identified as a urinary trypsin inhibitor, has been widely used in patients with inflammatory disorders. However, little is known about its effect on postoperative cognitive dysfunction (POCD). The aim of our current work is to review the current body of literature.Methods.A systematic literature search in PubMed and EMBASE was performed to identify randomized controlled trials. Incidence of POCD, MMSE score, and laboratory indicators (IL-6, TNF-α, CRP, and S100β) were selected as outcomes.Results.Five RCTs involving 461 elderly patients that underwent surgical operations were identified. The meta-analysis suggested no statistical difference of incidence of POCD between ulinastatin and control groups on postoperative day 1; but ulinastatin could significantly decrease the incidence of POCD on postoperative day 3 and day 7 when compared with control treatment. Ulinastatin was effective in improving the MMSE score on day 1, day 3, and day 7 after operation. IL-6 and S100βconcentrations were lower up to postoperative day 2. The incidences of postoperative complications in ulinastatin groups were lower than control.Conclusion.Ulinastatin administration was effective in treating early POCD (postoperative day 3 and day 7) and reducing IL-6 and S100βconcentrations within two days after operations. Studies with larger-scale and rigorous design are urgently needed.

Purpose.This study aims to determine the clinical efficacy of acupuncture therapy in the treatment of obstructive sleep apnea.Methods.A systematic literature search was conducted in five databases including PubMed, EMBASE, CENTRAL, Wanfang, and CNKI to identify randomized controlled trials (RCTs) on the effect of acupuncture therapy for obstructive sleep apnea. Meta-analysis was conducted using the RevMan version 5.3 software.Results.Six RCTs involving 362 subjects were included in our study. Compared with control groups, manual acupuncture (MA) was more effective in the improvement of apnea/hypopnea index (AHI), apnea index, hypopnea index, and mean SaO2. Electroacupuncture (EA) was better in improving the AHI and apnea index when compared with control treatment, but no statistically significant differences in hypopnea index and mean SaO2were found. In the comparison of MA and nasal continuous positive airway pressure, the results favored MA in the improvement of AHI; there was no statistical difference in the improvement in mean SaO2. No adverse events associated with acupuncture therapy were documented.Conclusion.Compared to control groups, both MA and EA were more effective in improving AHI and mean SaO2. In addition, MA could further improve apnea index and hypopnea index compared to control.

To explore the toxicity of joint exposure to diazinon, propoxur and bisphenol A on phagocytosis.Flow cytometer was employed to detect the influence of diazinon and bisphenol A, propoxur and bisphenol A in mixture (mixed according to ratio of IC(50)) on mouse macrophage RAW264.7 cells' function to phagocyte fluorescent microspheres, adopting the percentage of phagocytic cells (PP) and the phagocytic index (PI) as measurement indicators. The final concentrations of mixture of diazinon and bisphenol A were (0.4 + 0.1), (3.6 + 0.7), (36.2 + 7.2), (43.4 + 8.7), (52.1 + 10.4), (62.5 + 12.5), (75.0 + 15.0) µg/ml; while those of mixture of propoxur and bisphenol A were (0.2 + 2.0 × 10(-2)), (2.4 + 0.2), (23.7 + 2.0), (35.6 + 3.0), (53.3 + 4.4), (80.0 + 6.7), (120.0 + 10.0) µg/ml. Then based on the dose-response relationship, a 2 × 2 factorial design was then carried out among different doses of mixture with statistical significance to statistically evaluate the interaction between diazinon and bisphenol A, propoxur and bisphenol A.After the joint exposure, compared to the control group (PP = (23.6 ± 2.2)%; PI = 0.36 ± 0.03), any dose of the mixture of diazinon and bisphenol A ((52.1 + 10.4), (62.5 + 12.5), (75.0 + 15.0) µg/ml) could significantly increase the levels of PP ((29.0 ± 1.4)%, t = 3.89, P0.05; (30.2 ± 2.3)%, t = 4.74, P0.05; (35.0 ± 3.4)%, t = 8.21, P0.05) and PI (0.43 ± 0.03, t = 3.86, P0.05; 0.41 ± 0.02, t = 2.95, P0.05; 0.46 ± 0.03, t = 5.34, P0.05); while that of propoxur and bisphenol A ((35.6 + 3.0), (53.3 + 4.4), (80.0 + 6.7), (120.0 + 10.0) µg/ml) reduced the levels of PP ((20.6 ± 1.1)%, t = -3.00, P0.05; (20.2 ± 1.0)%, t = -3.42, P0.05; (19.4 ± 1.3)%, t = -4.23, P0.05; (18.8 ± 2.1)%, t = -4.81, P0.05) and PI (0.31 ± 0.01, t = -4.75, P0.05; 0.31 ± 0.01, t = -4.58, P0.05; 0.30 ± 0.01, t = -4.92, P0.05; 0.27 ± 0.02, t = -7.80, P0.05) on the contrary. The 2 × 2 factorial design was carried out between the mixture of diazinon (60.0 µg/ml; PP = (28.5 ± 3.4)%; PI = 0.49 ± 0.07) and bisphenol A (12.0 µg/ml; PP = (35.7 ± 2.7)%; PI = 0.67 ± 0.07), and the mixture of propoxur (48.0 µg/ml ; PP = (28.1 ± 2.2)%; PI = 0.48 ± 0.04) and bisphenol A (4.0 µg/ml; PP = (34.4 ± 2.7)%; PI = 0.59 ± 0.07). The mixture of diazinon and bisphenol A (PP = (30.4 ± 1.4)%, F(interaction) = 6.22, P0.05; PI = 0.53 ± 0.03, F(interaction) = 7.35, P0.05) and the mixture of propoxur and bisphenol A (PP = (27.5 ± 4.1)%, F(interaction) = 4.56, P0.05; PI = 0.46 ± 0.08, F(interaction) = 11.13, P0.05) both showed a significant antagonistic interaction on phagocytosis of RAW264.7 cell.It is suggested that the interactions between diazinonbisphenol A and propoxurbisphenol A both played the antagonistic role on phagocytic function of macrophages in vitro.

Chrysin exists widely in plants, honey and propolis. The anti-cancer property of chrysin has been demonstrated though the molecular mechanism is not clear. In this study, we found that pre-treatment with chrysin could promote the cell death induced by TRAIL according to the morphological changes and appearance of sub-G1 peak in four human cancer cell lines. In HCT-116 cells, the results of flow cytometry analysis showed that the percentage of sub-G1 reached (38.89 ± 3.78) % when pre-treatment of chrysin was used at 40 μM, but that was only (2.53 ± 0.10) % in the untreated group and (13.22 ± 0.20) % in TRAIL alone group. The differences between the combination and the untreated or TRAIL alone group were all significant (P

To establish the 3T3 mouse fibroblast neutral red uptake (NRU-PT) phototoxicity test method, and evaluate the practicality of the method in detecting potential phototoxicity of the cosmetic products.Fifteen phototoxic and 9 non-phototoxic chemicals were tested in our laboratories, the phototoxic potential of the test chemicals was evaluated in a prediction model in which either the photo irritation factor (PIF) or the mean photo effect (MPE) was compared with the coherence and sensitivity of the method. 20 kinds of functional cosmetics were detected and the results were analyzed by the 3T3 NRU-PT in vitro and Guinea pig skin phototoxicity test (in vivo).Both PIF and MPE of the chemicals were highly reproduced, and the correlation between in vitro and in vivo data was almost perfect. All the non-phototoxic provided a negative result, while 14 of the 15 phototoxic tested chemicals gave clear positive results. For cosmetics, the correlation between in vitro and in vivo data was consistent.The 3T3 NRU PT test was established successfully, it should be used as a good alternative method for assessing the phototoxic potential of the chemicals and cosmetics in China.

To explore a flow cytometry (FCM)-based method for discriminating aneugen- or clastogen-induced micronuclei.Cells were stained with anti-CD71-FITC and PI, and the PI fluorescent signal intensity of micronucleated reticulocyte (MN-RET) in the peripheral blood of NIH mouse treated with COL or CP was detected by flow cytometry.The ratio of the median of the intensity of MN-RET fluorescent signals to that of nucleated cell was low in the cyclophosphamide treated mouse, while the median was high in the colchicine treated mouse.The flow cytometry-based micronucleus assay can be used to discriminate primarily smaller MN induced by the clastogen exposure from the larger MN induced by an aneugen.