The P38MAPK/ATF2 signaling pathway is involved in PND in mice.

Accumulating evidence indicates that microglia-mediated neuroinflammation in the hippocampus contributes to the development of perioperative neurocognitive disorder (PND). P38MAPK, a point of convergence for different signaling processes involved in inflammation, can be activated by various stresses. This study aims to investigate the role of the P38MAPK/ATF2 signaling pathway in the development of PND in mice. Aged C57BL/6 mice were subjected to tibial fracture surgery under isoflurane anesthesia to establish a PND animal model. The open field test was used to evaluate the locomotor activity of the mice. Neurocognitive function was assessed with the Morris water maze (MWM) and fear conditioning test (FCT) on postoperative days 1, 3 and 7. The mice exhibited cognitive impairment accompanied by increased expression of proinflammatory factors (IL-1ß, TNF-α), proapoptotic molecules (caspase-3, bax) and microglial activation in the hippocampus 1, 3 and 7 days after surgery. Treatment with SB239063 (a P38MAPK inhibitor) decreased the expression of proinflammatory factors, proapoptotic molecules and Iba-1 in the CA1 region of the hippocampus. The number of surviving neurons was significantly increased. Inhibition of the P38MAPK/ATF2 signaling pathway attenuates hippocampal neuroinflammation and neuronal apoptosis in aged mice with PND, thus improving the perioperative cognitive function of the mice.

Metabolic engineering of commensal bacteria for gut butyrate delivery and dissection of host-microbe interaction.

An overwhelming number of studies have reported the correlation of decreased abundance of butyrate-producing commensals with a wide range of diseases. However, the molecular-level mechanisms whereby gut butyrate causally affects the host mucosal immunity and pathogenesis were poorly understood, hindered by the lack of efficient tools to control intestinal butyrate. Here we engineered a facultative anaerobic commensal bacterium to delivery butyrate at the intestinal mucosal surface, and implemented it to dissect the causal role of gut butyrate in regulating host intestinal homeostasis in a model of murine chronic colitis. Mechanistically, we show that gut butyrate protected against colitis and preserved intestinal mucosal homeostasis through its inhibiting effect on the key pyroptosis executioner gasdermin D (GSDMD) of colonic epithelium, via functioning as an HDAC3 inhibitor. Overall, our work presents a new avenue to build synthetic living delivery bacteria to decode causal molecules at the host-microbe interface with molecular-level insights.

SNRPD1 conveys prognostic value on breast cancer survival and is required for anthracycline sensitivity.

BACKGROUND: Cancers harboring spliceosome mutations are highly sensitive to additional perturbations on the spliceosome that leads to the development of onco-therapeutics targeting the spliceosome and opens novel opportunities for managing aggressive tumors lacking effective treatment options such as triple negative breast cancers. Being the core spliceosome associated proteins, SNRPD1 and SNRPE have been both proposed as therapeutic targets for breast cancer management. Yet, their differences regarding their prognostic and therapeutic use as well as roles during carcinogenesis are largely unreported. METHODS: We conducted in silico analysis at gene expression and genetic levels to differentiate the clinical relevance of SNRPD1 and SNRPE, and explored their differential functionalities and molecular mechanistic associations with cancer in vitro. RESULTS: We showed that high SNRPD1 gene expression was prognostic of poor breast cancer survival whereas SNRPE was not. The SNRPD1 expression quantitative trait loci, rs6733100, was found independently prognostic of breast cancer survival using TCGA data. Silencing either SNRPD1 or SNRPE independently suppressed the growth of breast cancer cells, but decreased migration was only observed in SNRPD1-silenced cells. Knocking down SNRPD1 but not SNRPE triggers doxorubicin resistance in triple negative breast cancer cells. Gene enrichment and network analyses revealed the dynamic regulatory role of SNRPD1 on cell cycle and genome stability, and the preventive role of SNRPE against cancer stemness that may neutralize its promotive role on cancer cell proliferation. CONCLUSION: Our results differentiated the functionalities of SNRPD1 and SNRPE at both prognostic and therapeutic levels, and preliminarily explained the driving mechanism that requires additional explorations and validations.

Hsa_circRNA_0040462: a sensor of cells' response to CAP treatment with double-edged roles on breast cancer malignancy.

Cold atmospheric plasma (CAP) represents a novel onco-therapeutic approach that has demonstrated its efficacy in many types of tumors. The efficacy of CAP is dose-dependent that determines the panel of tumors feasible for receiving CAP treatment under a certain parameter configuration. Identifying markers for easy and fast prognosis of tumors' sensitivity in response to CAP exposure is of critical value towards optimized therapeutic outcome, the lack of which has largely limited the translation of CAP into clinics. Circular RNAs represent a novel type of biomarkers for disease diagnosis that is featured by easy detection and stability. Through whole transcriptome sequencing, followed by in vitro validations, computational predictions and preliminary functional studies, we identified hsa_circRNA_0040462 as a sensor of breast cancer cells' response to CAP treatment. Yet we warrant the use of hsa_circRNA_0040462 as an onco-therapeutic target given its double-edged roles on breast cancer progression, i.e., suppressive on the growth and promotive on the migrative ability of triple negative breast cancer cells. Our study for the first time focused on markers prognostic of CAP's efficacy and tumors' sensitivity to CAP treatment under a certain parameter configuration, and reported hsa_circRNA_0040462 as a sensor of cells' response to CAP treatment. Also, the uncovered dual roles of hsa_circRNA_0040462 further advanced our knowledge on the complex yet critical regulatory functionalities of circular RNAs in cancer progression.

Cancer stem cell transcriptome landscape reveals biomarkers driving breast carcinoma heterogeneity.

BACKGROUND: Breast carcinomas are heterogeneous diseases with distinct clinical outcomes and cancer stem cell (CSC) percentages. Exploring breast carcinoma stem cell landscape could help understand the heterogeneity of such cancers with profound clinical relevance. METHODS: We conducted transcriptional profiling of CSCs and non-stem cancer cells isolated from three triple-negative breast carcinoma cell lines, analyzed the CSC transcriptome landscape that drives breast carcinoma heterogeneity through differentially expressed gene identification, gene ontology (GO) and pathway enrichment analyses as well as network construction, and experimentally validated the network hub gene. RESULTS: We identified a CSC feature panel consisting of 122 and 381 over-represented and under-expressed genes capable of differentiating breast carcinoma subtypes. We also underpinned the prominent roles of the PI3K-AKT pathway in empowering carcinoma cells with uncontrolled proliferative and migrative abilities that ultimately foster cancer stemness, and revealed the potential promotive roles of ATP6V1B1 on breast carcinoma stemness through functional in vitro studies. CONCLUSIONS: Our study contributes in identifying a CSC feature panel for breast carcinomas that drives breast carcinoma heterogeneity at the transcriptional level, which provides a reservoir for diagnostic marker and/or therapeutic target identification once experimentally validated as demonstrated by ATP6V1B1.

Minimally invasive surgery for paravertebral or psoas abscess with spinal tuberculosis - a long-term retrospective study of 106 cases.

BACKGROUND: Minimally invasive surgery (MIS) is a common treatment option for paravertebral or psoas abscesses (PAs) in patients with spinal tuberculosis (ST). However, its efficacy remains controversial. The aim of the study was to evaluate the efficacy of MIS for PA with ST combined with anti-tuberculous chemotherapy. METHODS: A total of 106 consecutive patients who underwent MIS for ST with PA from January 2002 to Oct 2012 were reviewed. The MIS involved computed tomography (CT)-guided percutaneous catheter drainage and percutaneous catheter infusion chemotherapy. Clinical outcomes were evaluated based on the changes observed on preoperative and postoperative physical examination, inflammatory marker testing, and magnetic resonance imaging (MRI). RESULTS: The mean follow-up period was 7.21 ± 3.15 years. All surgeries were successfully completed under CT-guidance without intraoperative complications and all patients experienced immediate relief of their symptoms, which included fever and back pain. The preoperatively elevated erythrocyte sedimentation rate and C-reactive protein values returned to normal at a mean period of 3 months postoperatively. Solid bony union was observed in 106 patients and no abscesses were found on MRI examination. CONCLUSION: MIS carries advantages in terms of less invasiveness, precise drainage, and enhanced local drug concentration. While the technique has not been fully characterized and clinically prove, its use in addition to conservative chemotherapy and open debridement and instrumental fixation may be recommended for patients with ST and PA.

Long noncoding RNA PXN-AS1-L promotes non-small cell lung cancer progression via regulating PXN.

BACKGROUND: Increasingly evidences suggest that long noncoding RNAs (lncRNAs) play important roles in various cancers. LncRNA PXN-AS1-L is recently revealed to act as on oncogene in liver cancer. However, the expression, functions, and mechanisms of action of PXN-AS-L in non-small cell lung cancer (NSCLC) remain unclear. METHODS: The expression of PXN-AS1-L in primary NSCLC tissues, NSCLC bone metastasis tissues, and cell lines was measured by quantitative real-time PCR. The correlations between PXN-AS1-L expression and clinicopathological characteristics of NSCLC patients were analyzed by Pearson Chi square test and log-rank test. The roles of PXN-AS1-L in cell viability, proliferation, apoptosis, and migration of NSCLC cells, and in vivo NSCLC tumor growth were investigated by a series of gain-of-function and loss-of-function assays. The regulatory roles of PXN-AS1-L on PXN were determined by quantitative real-time PCR and western blot. RESULTS: PXN-AS1-L was up-regulated in NSCLC tissues compared with noncancerous lung tissues, and PXN-AS1-L was further up-regulated in NSCLC bone metastasis tissues. Increased expression of PXN-AS1-L was positively associated with advanced TNM stages and poor prognosis. Gain-of-function and loss-of-function assays showed that PXN-AS1-L increased cell viability, promoted cell proliferation, inhibited cell apoptosis, and promoted cell migration of NSCLC cells. Xenograft assays showed that PXN-AS1-L also promoted NSCLC tumor growth in vivo. Mechanistically, we found that PXN-AS1-L, as an antisense transcript of PXN, up-regulated the expression of PXN. PXN was also up-regulated in NSCLC tissues. The expression of PXN and PXN-AS1-L was positively correlated in NSCLC tissues. Furthermore, PXN knockdown attenuated the roles of PXN-AS1-L in increasing cell viability, promoting cell proliferation, inhibiting cell apoptosis, and promoting cell migration of NSCLC cells. CONCLUSIONS: Our data revealed that PXN-AS1-L is up-regulated and acts as an oncogene in NSCLC via up-regulating PXN. Our data suggested that PXN-AS1-L might serve as a potential prognostic biomarker and therapeutic target for NSCLC.

Some Physical Properties of Protein Moiety of Alkali-Extracted Tea Polysaccharide Conjugates Were Shielded by Its Polysaccharide.

Polysaccharide conjugates were alkali-extracted from green tea (TPC-A). Although it contained 11.80% covalently binding proteins, TPC-A could not bind to the Coomassie Brilliant Blue dyes G250 and R250. TPC-A had no expected characteristic absorption peak of protein in the UV-vis spectrum scanning in the range of 200-700 nm. The UV-vis wavelength of 280 nm was not suitable to detect the presence of the protein portion of TPC-A. The zeta potential of TPC-A merely presented the negative charge properties of polysaccharides instead of the acid-base property of its protein section across the entire pH range. Furthermore, TPC-A was more stable when the pH of solution exceeded 4.0. In addition, no precipitation or haze was generated in the TPC-A/(-)-epigallocatechin gallate (EGCG) mixtures during 12 h storage. TPC-A has emulsifying activity, which indicated that its protein moiety formed hydrophobic groups. Thus, it was proposed that some physical properties of TPC-A protein were shielded by its olysaccharide, since the protein moiety was wrapped by its polysaccharide chains.

Treatment of Andersson lesion-complicating ankylosing spondylitis via transpedicular subtraction and disc resection osteotomy, a retrospective study.

BACKGROUND: Andersson lesion (AL) can occur in patients with ankylosing spondylitis (AS). Surgical instrumentation and fusion is considered the principle management in symptomatic AL that fails to resolve from a conservative treatment. However, there is significant controversy over the ideal management. The purpose of this study is to introduce our experience and explore the efficacy and feasibility of transpedicular subtraction and disc resection osteotomy technique for patients with AL-complicating AS. METHODS: From January 2009 to January 2013, 17 consecutive patients with Andersson lesion-complicating ankylosing spondylitis treated with transpedicular subtraction and disc resection osteotomy technique were retrospectively reviewed. All patients completed a follow-up of at least 2 years. RESULTS: The average surgical time was 219 min with a mean intraoperative blood loss of 876 ml. The average preoperative regional angle was 29.1°, 4.9° postoperatively, and 5.9° at the final follow-up. The global angle changed from 59.1° preoperatively to 24.7° after surgery with the sagittal vertical axis (SVA) changed from 153.7 to 41.1 mm. The mean VAS back pain scores decreased from 6.4 preoperatively to 1.1 postoperatively and the ODI score improved from 50.9 preoperatively to 16.9 at the final follow-up. Solid fusion was obtained in all patients. CONCLUSION: The transpedicular subtraction and disc resection osteotomy achieve satisfactory kyphosis correction, good fusion and favorable clinical outcomes with less blood loss and complications than other approaches, implying an alternative method in patients with Andersson lesion-complicating ankylosing spondylitis.

Correlations of pathomorphological parameters between lesions at the invasive front and lymph node metastases in colorectal cancer: a retrospective clinical study.

BACKGROUND: Lymph node (LN) metastasis is one of the most important indicators to evaluate stage, choose treatment strategy, and predict outcome of colorectal cancer (CRC). The morphological correlation between primary tumors and LN metastases can help predict the incidence of LN metastasis in CRC more accurately and assist with more individualized risk-stratification management decisions. METHODS: A retrospective study was devised with paired tissue specimens from the invasive front of primary tumors and LN metastases in 426 patients after a radial surgery for CRC. According to the presence (N +) or absence (N-) of regional LN metastasis and the number of LN metastases (pN1a/1b/1c/2a/2b), comparisons were performed regarding tumor budding (TB) and poorly-differentiated clusters (PDC). In addition, their correlation with the incidence of LN metastasis and the extent were explored. RESULTS: The TB and PDC in the invasive front of primary tumors presented significant correlations with the incidence of LN metastasis and the number of LN metastases in CRC (P < 0.001). TB2/3 led to a risk of LN metastasis 6.68-fold higher than TB1, while PDC2/3 resulted in a risk of LN metastasis 8.46-fold higher than PDC1. Additionally, the risk of developing 4 or more LN metastases was 3.08-fold and 2.86-fold higher upon TB2/3 and PDC2/3 than that with TB1 and PDC1, respectively. Moderate positive correlations were found between the invasive front of primary tumors and LN metastases in terms of TB and PDC, respectively. CONCLUSIONS: TB and PDC, at the invasive tumor front are important morphological markers to evaluate LN metastasis in CRC, and they can be employed as reference indicators to assess or predict the potential of LN metastasis in CRC in clinical practice.

Efficacy and safety of patient-controlled intravenous analgesia after APS team standardized postoperative pain management: A 6-year experience of an acute pain service in 107802 Chinese patients.

There are few studies on the impact of postoperative pain management (such as Acute Pain Service, APS) on the prognosis of patients, especially the research on large samples, even less data on Chinese patients. It is reported that only 25.12 % of hospitals in China have established APS or similar teams, and less than 10 % of them are responsible for the whole process of postoperative analgesia services. Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology has established a professional APS team led by anesthesiologists (TJ-APS), and has a standardized workflow and management system. Based on the TJ-APS standardized postoperative pain management, the incidence and adverse effects of postoperative pain in different types of surgical patients were analyzed. In total, 107,802 patients receiving intravenous PCA from the Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology were selected between January 2016 and December 2021, which were under TJ-APS standardized postoperative analgesia process, postoperative analgesia strategy based on the principle of "low opioid, multimodal, specialization and individualization", as well as regular ward rounds and 24-h on call on-duty system. We assessed the incidence and adverse effects of postoperative pain in different types of surgical patients. Based on the TJ-APS standardized postoperative pain management, the incidence of poor postoperative analgesia in patients with intravenous PCA is significantly lower than that reported in the current literature (20 %), and mainly occurs in biliary-pancreatic surgery, extrahepatic surgery and gastrointestinal surgery. The overall incidence of adverse effects was 5.52 %, of which nausea and vomiting was the highest, especially among gynecological tumors and gynecological patients, which were 10.75 % and 8.68 % respectively, but both were lower than the level reported in the current literature (20 %). This APS multimodal management and analgesia process can provide reference and guidance for PCA management of postoperative acute pain.

Piezoelectrically-activated antibacterial catheter for prevention of urinary tract infections in an on-demand manner.

Catheter-associated urinary tract infection (CAUTI) is a common clinical problem, especially during long-term catheterization, causing additional pain to patients. The development of novel antimicrobial coatings is needed to prolong the service life of catheters and reduce the incidence of CAUTIs. Herein, we designed an antimicrobial catheter coated with a piezoelectric zinc oxide nanoparticles (ZnO NPs)-incorporated polyvinylidene difluoride-hexafluoropropylene (ZnO-PVDF-HFP) membrane. ZnO-PVDF-HFP could be stably coated onto silicone catheters simply by a one-step solution film-forming method, very convenient for industrial production. In vitro, it was demonstrated that ZnO-PVDF-HFP coating could significantly inhibit bacterial growth and the formation of bacterial biofilm under ultrasound-mediated mechanical stimulation even after 4 weeks. Importantly, the on and off of antimicrobial activity as well as the strenth of antibacterial property could be controlled in an adaptive manner via ultrasound. In a rabbit model, the ZnO-PVDF-HFP-coated catheter significantly reduced the incidence CAUTIs compared with clinically-commonly used catheters under assistance of ultrasonication, and no side effect was detected. Collectively, the study provided a novel antibacterial catheter to prevent the occurrence of CAUTIs, whose antibacterial activity could be controlled in on-demand manner, adaptive to infection situation and promising in clinical application.

Cold atmospheric plasmas target breast cancer stemness via modulating AQP3-19Y mediated AQP3-5K and FOXO1 K48-ubiquitination.

Cold atmospheric plasma (CAP) is selective against many cancers with little side effect, yet its molecular mechanism remains unclear. Through whole transcriptome sequencing followed by assays in vitro, in vivo and using clinical samples, we propose CAP as a promising onco-therapy targeting cancer stemness via the AQP3/FOXO1 axis. CAP-generated reactive species penetrated cells via AQP3 and suppressed RPS6KA3, a shared kinase of AQP3 and FOXO1. Reduced AQP3-19Y phosphorylation suppressed SCAF11-mediated AQP3-5K K48-ubiquitination that led to sabotaged FOXO1 stability. Inhibited FOXO1 phosphorylation retarded its regulatory activities in maintaining cancer stemness including ALDH1 and IL6. Enhanced anti-cancer efficacy was observed through combining CAP with Atorvastatin in vitro and in vivo. We propose CAP as a 'selective' onco-therapeutic against cancer stemness, with the AQP3/FOXO1 axis being one molecular mechanism. We report SCAF11 as an E3 ubiquitin ligase of both AQP3 and FOXO1, identify AQP3-5K as an AQP3 K48-ubiquitination site, and emphasize the essential role of AQP3-19Y in this process. We reposition Atorvastatin into the onco-therapeutic portfolio by synergizing it with CAP towards enhanced efficacy. We anticipate the efficacy of CAP in targeting malignancies of high stemness alone or as an adjuvant therapy towards the hope of ultimate cancer cure.

Cold atmospheric plasma for preventing infection of viruses that use ACE2 for entry.

Rational: The mutating SARS-CoV-2 potentially impairs the efficacy of current vaccines or antibody-based treatments. Broad-spectrum and rapid anti-virus methods feasible for regular epidemic prevention against COVID-19 or alike are urgently called for. Methods: Using SARS-CoV-2 virus and bioengineered pseudoviruses carrying ACE2-binding spike protein domains, we examined the efficacy of cold atmospheric plasma (CAP) on virus entry prevention. Results: We found that CAP could effectively inhibit the entry of virus into cells. Direct CAP or CAP-activated medium (PAM) triggered rapid internalization and nuclear translocation of the virus receptor, ACE2, which began to return after 5 hours and was fully recovered by 12 hours. This was seen in vitro with both VERO-E6 cells and human mammary epithelial MCF10A cells, and in vivo. Hydroxyl radical (·OH) and species derived from its interactions with other species were found to be the most effective CAP components for triggering ACE2 nucleus translocation. The ERα/STAT3(Tyr705) and EGFR(Tyr1068/1086)/STAT3(Tyr705) axes were found to interact and collectively mediate the effects on ACE2 localization and expression. Conclusions: Our data support the use of PAM in helping control SARS-CoV-2 if developed into products for nose/mouth spray; an approach extendable to other viruses utilizing ACE2 for host entry.

Side population cells in human gallbladder cancer cell line GBC-SD regulated by TGF-ß-induced epithelial-mesenchymal transition.

Mounting evidence has shown that side population (SP) cells are enriched for cancer stem cells (CSCs) responsible for cancer malignancy. In this study, SP technology was used to isolate a small subpopulation of SP cells in human gallbladder cancer cell line GBC-SD, and SP cells which had superior potential for proliferation in vitro and tumorigenesis in vivo were identified. Importantly, the abundance of GBC-SD SP cells was increased by a transforming growth factor-ß (TGF-ß)-induced epithelial-mesenchymal transition (EMT), and this effect was accompanied with a strong up-regulation of ABCG2 mRNA expression, and a decreased sensitivity to mitoxantrone. SP cells were restored upon the removal of TGF-ß and the reversion of the cells to an epithelial phenotype, and smad3-specific siRNA reduced SP abundance in response to TGF-ß. In conclusion, TGF-ß-induced EMT by smad-dependent signaling pathway promotes cancer development and anti-cancer drug resistant phenotype by augmenting the abundance of GBC-SD SP cells, and a better understanding of mechanisms involved in TGF-ß-induced EMT may provide a novel strategy for preventing cancer progression.

Butyrate Suppresses Glucose Metabolism of Colorectal Cancer Cells via GPR109a-AKT Signaling Pathway and Enhances Chemotherapy.

Glycolysis inhibitors are promising therapeutic drugs for tumor treatment, which target the uniquely elevated glucose metabolism of cancer cells. Butyrate is a critical product of beneficial microbes in the colon, which exerts extraordinary anti-cancer activities. In particular, butyrate shows biased inhibitory effects on the cell growth of cancerous colonocytes, whereas it is the major energy source for normal colonocytes. Besides its roles as the histone deacetylases (HDACs) inhibitor and the ligand for G-protein coupled receptor (GPR) 109a, the influence of butyrate on the glucose metabolism of cancerous colonocytes and the underlying molecular mechanism are not fully understood. Here, we show that butyrate markedly inhibited glucose transport and glycolysis of colorectal cancer cells, through reducing the abundance of membrane GLUT1 and cytoplasmic G6PD, which was regulated by the GPR109a-AKT signaling pathway. Moreover, butyrate significantly promoted the chemotherapeutical efficacy of 5-fluorouracil (5-FU) on cancerous colonocytes, with exacerbated impairment of DNA synthesis efficiency. Our findings provide useful information to better understand the molecular basis for the impact of butyrate on the glucose metabolism of colorectal cancer cells, which would promote the development of beneficial metabolites of gut microbiota as therapeutical or adjuvant anti-cancer drugs.

Clinicopathological and prognostic significance of LINC00673 in human malignancy: a review and meta-analysis.

BACKGROUND: We conducted this research to investigate the relationship between long intergenic non-protein coding RNA 673 (linc00673) expression and prognosis and clinicopathological parameters in human malignancies. METHODS: The PubMed, Embase, WOS, and CNKI databases were used to collect eligible research data before 4 January 2021. Meta-analysis was performed using Stata 12.0 software. Pooled odds ratios (ORs) or hazard ratios (HRs) and their 95% confidence interval (CIs) were calculated to evaluate the association of linc00673 expression with survival outcomes and clinical parameters. RESULTS: We finally included 17 articles and a total of 1539 cases for the meta-analysis. The results indicated that linc00673 was significantly correlated with T stage (P=0.006), tumor stage (P<0.001), lymph node metastasis (P<0.001), and distant metastasis (P<0.001). In addition, the results suggested that elevated linc00673 expression predicted a poor overall survival (OS) time (P=0.013) and acted as an independent prognostic factor (P<0.001) for OS in patients with malignancy. Although potential evidence of publication bias was found in the studies on OS in relation to tumor stage in the multivariate analysis, the trim-and-fill analysis confirmed that the results remained stable. CONCLUSIONS: Overexpression of linc00673 was significantly correlated with shorter OS time in patients with malignant tumors. Moreover, the increased expression level of linc00673 was significantly correlated with T stage, tumor stage, lymph node metastasis, and distant metastasis. The results presented in this article revealed that linc00673 might be involved in the progression and invasion of malignancy and serve as a novel prognostic biomarker and potential therapeutic target for malignancy.

Cold atmospheric plasma selectively induces G0/G1 cell cycle arrest and apoptosis in AR-independent prostate cancer cells.

Purpose: Androgen receptor-independent prostate cancers do not respond to androgen blockage therapies and suffer from high recurrence rate. We aim to contribute to the establishment of novel therapeutic approaches against such malignancies. Materials and Methods: We examined whether and how cold atmospheric plasma delivers selectivity against AR-independent prostate cancers via cell viability, transwell assay, wound healing, cell apoptosis assay, flow cytometry, intracellular hydrogen peroxide determination assay, RONS scavenger assay and western blot using human normal epithelial prostatic cells PNT1A and AR-negative DU145 prostate cancer cells. Results: We show that cold atmospheric plasma could selectively halt cell proliferation and migration in androgen receptor-independent cells as a result of induced cell apoptosis and G0/G1 stage cell cycle arrest, and such outcomes were achieved through modulations on the MAPK and NF-kB pathways in response to physical plasma induced intracellular redox level. Conclusion: Our study reports cold atmospheric plasma induced reduction on the proliferation and migration of androgen receptor-independent prostate cancer cells that offers novel therapeutic insights on the treatment of such cancers, and provides the first evidence on physical plasma induced cell cycle G0/G1 stage arrest that warrants the exploration on the synergistic use of cold atmospheric plasma and drugs such as chemotherapies in eradicating such cancer cells.

Isobavachalcone prevents osteoporosis by suppressing activation of ERK and NF-κB pathways and M1 polarization of macrophages.

Estrogen receptors alpha (ERα), a member of the nuclear receptor protein family, was found to play an important role in maintaining bone mass. Its downstream signaling proteins such as ERK and NF-κB were reported to be involved in development of osteoporosis, which meant that targeting ERα might be an effective strategy for searching for new drugs to prevent bone loss. In this study, we demonstrate that isobavachalcone (ISO), as one of bioactive compounds isolated from Psoralea corylifoliaLinn, has high affinity with ERα. The effects of ISO are investigated on receptor activator of NF-κB ligand (RANKL)-induced osteocalstogenesis. It is reported that ISO inhibits the RANKL-mediated increase of osteoclast-related genes MMP9, cathepsink and TRAR in RAW264.7 cells. Moreover, in vitro experiment shows that ISO exhibits an inhibitory effect on ERK and NF-κB signaling pathway, and suppresses RANKL-induced expression of osteoclast-related transcription factors NFATc1 and c-Fos. However, the impact of ISO in these molecules is eliminated by the application of ERα antagonist AZD9496.We further verified pharmacological effects of ISO in ovariectomized osteoporotic mice, and ISO significantly prevented bone loss and decreased M1 polarization of macrophages from marrow and spleen. Collectively, our data suggest that ISO prevents osteoporosis via suppressing activation of ERK and NF-κB signaling pathways as well as M1 polarization of macrophages.

Improvement of Sleep Quality in Patients With Ankylosing Spondylitis Kyphosis After Corrective Surgery.

STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of this study is to investigate the changes in sleep quality in patients surgically treated for kyphosis due to ankylosing spondylitis (AS) and the correlation between these changes and spinal sagittal realignment. SUMMARY OF BACKGROUND DATA: Sleep problems are prevalent in AS patients. However, little attention has been paid to the sleep quality in patients with AS kyphosis and the effect of surgical intervention on sleep quality. METHODS: We have retrospectively reviewed 62 patients with AS-induced thoracolumbar kyphosis who underwent surgically treatment from October 2012 to November 2016. Sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Preoperative and postoperative radiological characteristics and supine function were documented. We compared the above-mentioned parameters pre- and 24 months postoperatively and analyzed the correlation of the changes in the PSQI with the changes in radiological characteristics. RESULTS: Fifity-one patients (82%) classified as poor sleepers preoperatively. In addition to use of sleeping medication, each domain of the PSQI and the total PSQI were increased postoperatively. Improved sleep quality was correlated with changes in spinal sagittal characteristics, among which the lumbar lordosis (LL) and the chin-brow vertical angle (CBVA) were the independent correlation factors. The number of patients with supine dysfunction decreased from 89% to 15% after surgery. Significant differences were identified in the PSQI scores between the patients with and without supine dysfunction either pre- or postoperatively. CONCLUSION: Surgical correction of spinal deformity may improve sleep quality and supine function in patients with AS. Spinal sagittal realignment may be correlated with the improvement of sleep quality. LEVEL OF EVIDENCE: 4.