Substantial decline of organ preservation fluid contamination following adoption of ischemia-free liver transplantation: a post-hoc analysis.

INTRODUCTION: Preservation fluid (PF) contaminations are common in conventional liver transplantation (CLT) and presumably originate from organ or PF exposures to the external environment in a non-strict sterile manner. Such exposures and PF contamination may be avoided in ischaemia-free liver transplantation (IFLT) because of the strict sterile surgical procedures. In this study, the authors evaluated the impact of IFLT on organ PF contamination. METHODS: A post-hoc analysis using data from the first randomized controlled trial of IFLT was performed to compare the incidence, pathogenic spectrum of PF contamination, and incidence of early recipient infection between IFLT and CLT. Multivariable logistic regression was used to explore risk factors for PF contamination. RESULTS: Of the 68 cases recruited in the trial, 64 were included in this post-hoc analysis. The incidence of culture-positive PF was 9.4% (3/32) in the IFLT group versus 78.1% (25/32) in the CLT group ( P <0.001). Three microorganisms were isolated from PF in the IFLT group, while 43 were isolated in the CLT group. The recipient infection rate within postoperative day 14 was 3.1% (1/32) in the IFLT group vs 15.6% (5/32) in the CLT group, although this difference did not reach statistical significance ( P =0.196). Multivariate analysis revealed that adopting IFLT is an independent protective factor for culture-positive PF. CONCLUSION: PF contamination is substantially decreased in IFLT, and IFLT application is an independent protective factor for PF contamination. Using rigorous sterile measures and effective antibiotic therapy during IFLT may decrease PF contamination.

Compact multi-channel radio frequency pulse-sequence generator with fast-switching capability for cold-atom interferometers.

Cold-atom interferometers have matured into a powerful tool for fundamental physics research, and they are currently moving from realizations in the laboratory to applications in the field. A radio frequency (RF) generator is an indispensable component of these devices for controlling lasers and manipulating atoms. In this work, we developed a compact RF generator for fast switching and sweeping the frequencies and amplitudes of atomic-interference pulse sequences. In this generator, multi-channel RF signals are generated using a field-programmable gate array (FPGA) to control eight direct digital synthesizers (DDSs). We further propose and demonstrate a method for pre-loading the parameters of all the RF pulse sequences to the DDS registers before their execution, which eliminates the need for data transfer between the FPGA and DDSs to change RF signals. This sharply decreases the frequency-switching time when the pulse sequences are running. Performance characterization showed that the generated RF signals achieve a 100 ns frequency-switching time and a 40 dB harmonic-rejection ratio. The generated RF pulse sequences were applied to a cold-atom-interferometer gyroscope, and the contrast of atomic interference fringes was found to reach 38%. This compact multi-channel generator with fast frequency/amplitude switching and/or sweeping capability will be beneficial for applications in field-portable atom interferometers.

Endoscopic Screening for Missed Lesions of Synchronous Multiple Early Gastric Cancer during Endoscopic Submucosal Dissection.

Aims: To evaluate the value of endoscopic screening during endoscopic submucosal dissection (ESD) in the detection of synchronous multiple early gastric cancer (SMEGC) and the risk factors for missed diagnosis of SMEGC. Methods: We conducted gastric endoscopic screening during ESD operation in 271 patients with early gastric cancer (EGC) referred for ESD, and endoscopic follow-up within 1 year after the operation. The detection and characteristics of SMEGC were analyzed in three stages: before ESD, during ESD operation, and within 1 year after ESD. Results: SMEGC was detected in 37 of 271 patients (13.6%). Among them, 21 patients with SMEGC (56.8%) were diagnosed before ESD, 9 (24.3%) were diagnosed with SMEGC by endoscopic screening during ESD operation, and 7 (18.9%) were found to have EGC lesions in the stomach during postoperative endoscopic follow-up within 1 year. The preoperative missed detection rate of SMEGC was 43.2%, and the rate of missed detection could be reduced by 24.3% (9/37) with endoscopic screening during ESD operation. Missed SMEGC lesions were more common in flat or depressed type and smaller in size than the lesions found before ESD. The presence of severe atrophic gastritis and age ≥60 years were significantly correlated with SMEGC (P < 0.05), while multivariate analysis showed that age ≥60 years was an independent risk factor (OR = 2.63, P < 0.05) for SMEGC. Conclusions: SMEGC lesions are apt to be missed endoscopically. Special attention should be paid to small, depressed, or flat lesions in detecting SMEGC, especially in elderly patients or (and) patients with severe atrophic gastritis. Endoscopic screening during ESD operation can effectively reduce the missed diagnosis rate of SMEGC.

PLAGL2 promotes Snail expression and gastric cancer progression via UCA1/miR-145-5p/YTHDF1 axis.

OBJECTIVES: Although great progress has made in gastric cancer (GC) in the past years, the overall 5-year survival rate remains to be low for advanced GC patients. A recent study showed that PLAGL2 was increased in GC and enhanced the proliferation and metastasis of GC. Nevertheless, the underlying mechanism still needs to be investigated. METHODS: Gene and protein expressions were assessed using RT-qPCR and western blot. The migration, proliferation and invasion of GC cells were examined using scratch assay, CCK-8 assay and Transwell assay, respectively. ChIP-PCR, dual-luciferase assay, RIP-qPCR and CoiP were utilized to confirm the interaction among PLAGL2, UCA1, miR-145-5p and YTHDF1 as well as METTL3, YTHDF1 and eEF-2. A mouse xenograft model was used utilized to further confirm the regulatory network. RESULTS: PLAGL2 bound to the upstream promoter of UCA1, which regulated YTHDF1 by sponging miR-145-5p. METTL3 can mediate the m6A modification level of Snail. YTHDF1 recognized m6A-modified Snail by interacting with eEF-2 and thus promoted Snail expression, which eventually induced epithelial-mesenchymal transition (EMT) in GC cells and metastasis of GC. CONCLUSIONS: Overall, our study demonstrates that PLAGL2 enhances Snail expression and GC progression via the UCA1/miR-145-5p/YTHDF1 axis, suggesting that PLAGL2 may become a therapeutic target for GC treatment.

A randomized, double-blind, parallel control study to evaluate the biosimilarity of QL1209 with Perjeta® in healthy male subjects.

Purpose: This is the first study to compare the pharmacokinetics, safety and, immunogenicity of QL1209, a biosimilar of Perjeta®. Methods: This study was a randomized, double-blind, parallel-controlled clinical trial evaluating the biosimilarity between QL1209 (specification: 420 mg:14 ml, single use via, manufacturer: Qilu Pharmaceutical Co., Ltd., batch number: 201808001KJL) and Perjeta® (specification: 420 mg: 14 ml, single use via, manufacturer: Roche Pharma AG, batch number: H0309H02). The trial period was 99 days (blood samples for PK were collected 99 days after infusion). Serum concentrations were determined using a validated assay. PK parameters were calculated using a non-compartmental model and analyzed statistically. Anti-drug antibody (ADA)-positive samples were further tested for the presence of neutralization antibody detection (NAb). Results: A total of 137 healthy subjects were administrated. The subjects were randomized 1:1 to receive QL1209 or Perjeta® 420 mg intravenously. The geometric mean ratio (GMRs) for QL1209 versus Perjeta® are 104.14%, 104.09%, and 110.59% for Cmax, AUC0-t, and AUC0-∞, respectively, and their 90% confidence interval (CIs) all fell within the predefined bioequivalence margin 80.00-125%. The incidence of drug-related adverse events was 95.6% and 95.5% in the QL1209 and Perjeta® groups, respectively, also comparable between the two groups. Conclusion: The results of this comparative clinical pharmacology study demonstrated the PK similarity of QL1209 (420 mg: 14 ml) and Perjeta® (420 mg: 14 ml) and there was no significant difference in safety and immunogenicity between QL1209 and Perjeta® manufactured by Roche Pharma AG.

Chromobox 4 (CBX4) promotes tumor progression and stemness via activating CDC20 in gastric cancer.

Background: The Chromobox homolog 4 (CBX4) has been found to be overexpressed in multiple malignancies. However, the associations between CBX4 and gastric cancer (GC) have remained unclear. This study aimed to determine the biological roles of CBX4 in GC and identify effective therapeutic targets. Methods: The 3-(4,5-dimethylthiazol-2-yl) (MTT) assays were used to screen CBX family members. Differential analysis was utilized to evaluate the CBX4 levels. Kaplan-Meier analysis was used to perform prognostic analysis. Western blotting assay, quantitative polymerase chain reaction (qPCR) assay and immunohistochemistry (IHC) were used to assess CBX4 expressions. Colony formation assay, Cell Counting Kit-8 (CCK-8) assay, and Transwell assay were used to assess progression features of cells. The tail vein injection model was utilized to determine the metastatic efficacy of GC cells. Tumor sphere formation assay was used to assess tumor stemness maintenance ability. Chromatin immunoprecipitation (ChIP)-qPCR assay was used to evaluate the associations between CBX4 and CDC20. A subcutaneous tumor model was used to assess the in vivo growth ability of GC. Results: The MTT assay revealed that only CBX4 inhibition could lead to notable restriction of GC growth, as compared to others. Differential analysis suggested that CBX4 was upregulated in tumor samples relative to normal tissues. Less favorable overall survival (OS) outcomes were noticed in GC patients with high CBX4 in comparison to those with low CBX4. High CBX4 could notably enhance cell proliferation capacity, migration ability, and in vivo metastatic efficacy. Gene set enrichment analysis (GSEA) indicated the relationships between CBX4 and GC stemness, and CBX4 overexpression could remarkably elevate self-renewal ability of GC cells. In addition, CBX4 could mainly promote CDC20 messenger RNA (mRNA) levels, and targeting CBX4 suppressed the relative CDC20 levels. The ChIP-qPCR assay further demonstrated that CBX4 coordinated with H3K4me3 to bind at the CDC20 promoter region. Additionally, CBX4 depended on CDC20 to drive GC growth. Lastly, downregulated CBX4 could notably inhibit the growth of GC in vivo. Conclusions: This study highlights the oncogenic roles of CBX4 in GC. CBX4 activates CDC20 to maintain stemness features of GC, thereby creating therapeutic vulnerabilities in the treatment of GC.

Novel Role of Long Non-Coding RNA ASAP1-IT1 in Progression of Hepatocellular Carcinoma.

The long non-coding RNA (lncRNA) ASAP1-IT1 has been recently shown to aberrantly increase in ovarian and bladder cancer, while its role in other malignancies remains unexplored. This study was to characterize the expression and assess the potential role of ASAP1-IT1 in hepatocellular carcinoma (HCC). Fifty-four paired HCC and histologically normal tissues were obtained from HCC patients. Human HCC cell lines (HepG2, Huh7, SMMC-7721, and BEL-7402) and a normal liver cell line (LO2) were used for in vitro studies. ASAP1-IT1-specific siRNAs were used to silence ASAP1-IT1 expression, while the pcDNA-ASAP1-IT1 vector was constructed to up-regulate its expression. In situ hybridization and qRT-PCR were performed to characterize subcellular localization and expression of ASAP1-IT1. Cell proliferation and migration assays were conducted to examine the role of ASAP1-IT1 in the progression of HCC. In silico analysis was conducted to predict putative miRNA binding sites, which were validated by luciferase reporter assays. ASAP1-IT1 levels were significantly increased in HCC tissues and cells compared with controls. Notably, higher ASAP1-IT1 levels were significantly associated with poorer prognosis of HCC patients. In situ hybridization analysis revealed that ASAP1-IT1 was mainly localized in the nucleus of hepatoma cells and differentially expressed in trabecular, compact, and pseudoglandular forms of liver cancer. Furthermore, knockdown of ASAP1-IT1 significantly suppressed cell proliferation and migration, while its overexpression significantly promoted cell proliferation and migration of HCC cells. Mechanistically, ASAP1-IT1 might exert its role in HCC progression, at least in part, by directly interacting with miR-221-3p. In conclusion, ASAP1-IT1 is abnormally elevated in HCC, and higher levels are correlated with poorer prognosis. An underlying mechanism has been proposed for ASAP1-IT1-associated promotion of proliferation and migration in HCC cells. These findings have provided evidence supporting the oncogenic role of ASAP1-IT1 in HCC.

Transcriptional analysis of the expression, prognostic value and immune infiltration activities of the COMMD protein family in hepatocellular carcinoma.

BACKGROUND: The copper metabolism MURR1 domain (COMMD) protein family involved in tumor development and progression in several types of human cancer, but little is known about the function of COMMD proteins in hepatocellular carcinoma (HCC). METHODS: The ONCOMINE and the UALCAN databases were used to evaluate the expression of COMMD1-10 in HCC and the association of this family with individual cancer stage and tumor grade. Kaplan-Meier (K-M) Plotter and Cox analysis hint the prognostic value of COMMDs. A network comprising 50 most similar genes and COMMD1-10 was constructed with the STRING database. Gene set enrichment analysis (GSEA) was performed using LinkedOmics database. The correlations between COMMD expression and the presence of immune infiltrating cells were also analyzed by the tumor immune estimation resource (TIMER) database. GSE14520 dataset and 80 HCC patients were used to validated the expression and survival value of COMMD3. Human HCC cell lines were also used for validating the function of COMMD3. RESULTS: The expression of all COMMD family members showed higher expression in HCC tissues than that in normal tissues, and is associated with clinical cancer stage and pathological tumor grade. In HCC patients, the transcriptional levels of COMMD1/4 are positively correlated with overall survival (OS), while those of COMMD2/3/7/8/9 are negatively correlated with OS. Multivariate analysis indicated that a high level of COMMD3 mRNA is an independent prognostic factor for shorter OS in HCC patients. However, the subset of patients with grade 3 HCC, K-M survival curves revealed that high COMMD3/5/7/8/9 expression and low COMMD4/10 expression were associated with shorter OS. In addition, the expression of COMMD2/3/10 was associated with tumor-induced immune response activation and immune infiltration in HCC. The expression of COMMD3 from GSE14520 dataset and 80 patients are both higher in tumor than that in normal tissue, and a higher level of COMMD3 mRNA is associated with shorter OS. Knockdown of COMMD3 inhibits human HCC cell lines proliferation in vitro. CONCLUSIONS: Our study indicates that COMMD3 is an independent prognostic biomarker for the survival of HCC patients. COMMD3 supports the proliferation of HCC cells and contributes to the poor OS in HCC patients.

Type II Collagen Sponges Facilitate Tendon Stem/Progenitor Cells to Adopt More Chondrogenic Phenotypes and Promote the Regeneration of Fibrocartilage-Like Tissues in a Rabbit Partial Patellectomy Model.

OBJECTIVE: Fibrocartilage transition zone (FC) is difficult to regenerate after surgical re-attachment of tendon to bone. Here, we investigated whether type II collagen-sponges (CII-sponges) facilitated tendon stem/progenitor cells (TSPCs) to adopt chondrogenic phenotypes and further observed if this material could increase the FC areas in bone-tendon junction (BTJ) injury model. METHODS: CII-sponges were made as we previously described. The appearance and pore structure of CII-sponges were photographed by camera and microscopies. The viability, proliferation, and differentiation of TSPCs were examined by LIVE/DEAD assay, alamarBlue, and PKH67 in vitro tracking. Subsequently, TSPCs were seeded in CII-sponges, Matrigel or monolayer, and induced under chondrogenic medium for 7 or 14 days before being harvested for qPCR or being transplanted into nude mice to examine the chondrogenesis of TSPCs. Lastly, partial patellectomy (PP) was applied to establish the BTJ injury model. CII-sponges were interposed between the patellar fragment and tendon, and histological examination was used to assess the FC regeneration at BTJ after surgery at 8 weeks. RESULTS: CII-sponges were like sponges with interconnected pores. TSPCs could adhere, proliferate, and differentiate in this CII-sponge up to 14 days at least. Both qPCR and immunostaining data showed that compared with TSPCs cultured in monolayer or Matrigel, cells in CII-sponges group adopted more chondrogenic phenotypes with an overall increase of chondrocyte-related genes and proteins. Furthermore, in PP injured model, much more new formed cartilage-like tissues could be observed in CII-sponges group, evidenced by a large amount of positive proteoglycan expression and typical oval or round chondrocytes in this area. CONCLUSION: Our study showed that CII-sponges facilitated the TSPCs to differentiate toward chondrocytes and increased the area of FCs, which suggests that CII-sponges are meaningful for the reconstruction of FC at bone tendon junction. However, the link between the two phenomena requires further research and validation.

Increased risk markers in women with polycystic ovary syndrome and gestational diabetes mellitus during mid-pregnancy.

OBJECTIVE: This study aimed to investigate application of the urine albumin-to-creatinine ratio (ACR), serum beta 2-microglobulin (ß2-MG), and cystatin C as risk markers in a cohort of women with polycystic ovary syndrome (PCOS) for the incidence of gestational diabetes mellitus (GDM). METHODS: In this cross-sectional study, we analyzed 312 pregnant women with PCOS and classified them as those with and without GDM. For all participants, elbow venous blood and clean middle urine were collected in the morning after 8 hours of an empty stomach. RESULTS: Logistic regression analysis showed that the ACR, urine ß2-MG levels, and serum cystatin C levels were important markers for women with PCOS concomitant with GDM. Receiver operating characteristic curve analysis showed that the area under the curve of CysC was 0.81 with the threshold based on >0.93 and that of ß2-MG was 0.72 with the threshold based on >1.25. CONCLUSIONS: Increased levels of ß2-MG and cystatin C and a high ACR might be risk factors for Chinese women with PCOS and GDM during mid-pregnancy.

Upregulated RACK1 attenuates gastric cancer cell growth and epithelial-mesenchymal transition via suppressing Wnt/ß-catenin signaling.

Purpose: As there have been few studies on the effects of the receptor for activated C kinase 1 (RACK1) on gastric cancer (GC), we aimed to explore such effects and the mechanism that may be involved. Patients and methods: Normal gastric epithelial cells and six GC cell lines were used to detect the mRNA expression of RACK1. Overexpressing RACK1 was transfected in HGC27 and MGC803 cells. The effects of overexpressing RACK1 on cell viability, migration, and invasion were determined by cell counting kit-8, wound scratch, and Transwell assay, respectively. The expressions of epithelial-mesenchymal transition (EMT) and Wnt/ß-catenin signaling related genes were detected using quantitative real-time PCR or Western blot. Wnt pathway agonist LiCl was added into RACK1 overexpressing GC cells, and then cell viability, migration, and invasion were also detected. Results: RACK1 was downregulated in GC cell lines. Under the circumstance that overexpressing RACK1 was successfully transfected in the two lowest RACK1-expressing GC cells, significant inhibition of cell viability, migration, and invasion, promotion to the mRNA and protein expression of E-cadherin, as well as a decrease in the N-cadherin and Snail expressions could be observed. Overexpressing RACK1 also enhanced the protein level of phosphorylation-ß-catenin/ß-catenin and attenuated c-Jun protein expression. Additionally, LiCl could partially reverse the inhibitory effects of cell viability, migration and invasion by overexpressing RACK. Conclusion: We found RACK1 possibly inhibited epithelial-mesenchymal transition of GC cells through limitation of the Wnt/ß-catenin pathway, thereby suppressing cell migration and invasion; RACK1 could also suppress cell growth.

Development and validation of a prediction rule for estimating gastric cancer risk in the Chinese high-risk population: a nationwide multicentre study.

OBJECTIVE: To develop a gastric cancer (GC) risk prediction rule as an initial prescreening tool to identify individuals with a high risk prior to gastroscopy. DESIGN: This was a nationwide multicentre cross-sectional study. Individuals aged 40-80 years who went to hospitals for a GC screening gastroscopy were recruited. Serum pepsinogen (PG) I, PG II, gastrin-17 (G-17) and anti-Helicobacter pylori IgG antibody concentrations were tested prior to endoscopy. Eligible participants (n=14 929) were randomly assigned into the derivation and validation cohorts, with a ratio of 2:1. Risk factors for GC were identified by univariate and multivariate analyses and an optimal prediction rule was then settled. RESULTS: The novel GC risk prediction rule comprised seven variables (age, sex, PG I/II ratio, G-17 level, H. pylori infection, pickled food and fried food), with scores ranging from 0 to 25. The observed prevalence rates of GC in the derivation cohort at low-risk (≤11), medium-risk (12-16) or high-risk (17-25) group were 1.2%, 4.4% and 12.3%, respectively (p<0.001).When gastroscopy was used for individuals with medium risk and high risk, 70.8% of total GC cases and 70.3% of early GC cases were detected. While endoscopy requirements could be reduced by 66.7% according to the low-risk proportion. The prediction rule owns a good discrimination, with an area under curve of 0.76, or calibration (p<0.001). CONCLUSIONS: The developed and validated prediction rule showed good performance on identifying individuals at a higher risk in a Chinese high-risk population. Future studies are needed to validate its efficacy in a larger population.

Natural Germacrane Sesquiterpenes Inhibit Osteoclast Formation, Bone Resorption, RANKL-Induced NF-κB Activation, and IκBα Degradation.

Osteolytic bone diseases are commonly presented with enhanced osteoclast formation and bone resorption. Sesquiterpene lactone natural compounds have been found to possess anti-inflammatory and immune-modulation effects. Here, we identified three germacrane sesquiterpenes using computer-based virtual screening for the structural similarity with sesquiterpene lactone, parthenolide. We showed that natural germacrane sesquiterpene compounds A, B, and C inhibit osteoclast formation and bone resorption in a dose-dependent manner, with relative potency compound A > compound C > compound B based on their equimolar concentrations. Mechanistic studies by Luciferase reporter gene assay and Western blot analysis showed that germacrane sesquiterpene compound A inhibits RANKL-induced activation of NF-κB and IκBα degradation. This study reveals that natural germacrane sesquiterpene compounds are inhibitors for osteoclast formation and bone resorption, and provides evidence that naturally-occurring compounds might be beneficial as alternative medicine for the prevention and treatment of osteolysis.

[ISOLATION OF RAT PATELLAR TENDON STEM CELLS AND EFFECT OF MECHANICAL STRETCHING ON Sox-9 EXPRESSION].

OBJECTIVE: To isolate the tendon stem cells (TSCs) from rat patellar tendon and to investigate the effect of mechanical stretching on the expression of Sox-9. METHODS: TSCs were isolated from Sprague Dawley rat (12 weeks old) patellar tendon by collagenase digestion and low density culture. The cell colony morphology and number were observed by crystal violet staining; the cell morphology was observed by inverted phase contrast microscope, and the immunophenotypes of mesenchymal stem cells (MSCs) were determined by flow cytometry. The TSCs at passage 3 was given the mechanical stretching at 4%, 0.17 Hz for 4 hours and 24 hours in the experimental group, and cells without stretching was used as control. The Sox-9 gene and protein expressions were detected by real-time fluorescence quantitative PCR and Western blot. RESULTS: Primary cells showed clonal growth and star shape; after subculture, cells at passage 1 showed fibroblast-like shape. The cells formed cell colonies after 7 days; the expressions were positive for CD29, CD44, and CD90 and negative for CD45. The result of real-time fluorescence quantitative PCR showed that Sox-9 gene was down-regulated at 4 hours after mechanical stretching compared with control (P < 0.05), and up-regulated at 24 hours after mechanical stretching when compared with control group (P < 0.05). The result of Western blot showed that Sox-9 protein expression was lower at 4 hours after stretching, but higher at 24 hours after mechanical stretching than that in control group (P < 0.05). CONCLUSION: The rat patellar TSCs can be isolated successfully, and mechanical stretching inhibits the Sox-9 expression, but the inhibited effect might stimulate the Sox-9 expression after the mechanical stretching effect disappears.

Comparative and quantitative proteomic analysis of normal and degenerated human annulus fibrosus cells.

Degeneration of the intervertebral disc (IVD) is a major chronic medical condition associated with back pain. To better understand the pathogenesis of IVD degeneration, we performed comparative and quantitative proteomic analyses of normal and degenerated human annulus fibrosus (AF) cells and identified proteins that are differentially expressed between them. Annulus fibrosus cells were isolated and cultured from patients with lumbar disc herniation (the experimental group, degenerated AF cells) and scoliosis patients who underwent orthopaedic surgery (the control group, normal AF cells). Comparative proteomic analyses of normal and degenerated cultured AF cells were carried out using 2-D electrophoresis, mass spectrometric analyses, and database searching. Quantitative analyses of silver-stained 2-D electrophoresis gels of normal and degenerated cultured AF cells identified 10 protein spots that showed the most altered differential expression levels between the two groups. Among these, three proteins were decreased, including heat shock cognate 71-kDa protein, glucose-6-phosphate 1-dehydrogenase, and protocadherin-23, whereas seven proteins were increased, including guanine nucleotide-binding protein G(i) subunit α-2, superoxide dismutase, transmembrane protein 51, adenosine receptor A3, 26S protease regulatory subunit 8, lipid phosphate phosphatase-related protein, and fatty acyl-crotonic acid reductase 1. These differentially expressed proteins might be involved in the pathophysiological process of IVD degeneration and have potential values as biomarkers of the degeneration of IVD.

Epidermal stem cells cultured on collagen-modified chitin membrane induce in situ tissue regeneration of full-thickness skin defects in mice.

A Large scale of full-thickness skin defects is lack of auto-grafts and which requires the engineered skin substitutes for repair and regeneration. One major obstacle in skin tissue engineering is to expand epidermal stem cells (ESCs) and develop functional substitutes. The other one is the scaffold of the ESCs. Here, we applied type I collagen-modified chitin membrane to form collagen-chitin biomimetic membrane (C-CBM), which has been proved to have a great biocompatibility and degraded totally when it was subcutaneously transplanted into rat skin. ESCs were cultured, and the resulting biofilm was used to cover full-thickness skin defects in nude mice. The transplantation of ESCs- collagen- chitn biomimetic membrane (ESCs-C-CBM) has achieved in situ skin regeneration. In nude mice, compared to controls with collagen-chitin biomimetic membrane (C-CBM) only, the ESCs-C-CBM group had significantly more dermatoglyphs on the skin wound 10 w after surgery, and the new skin was relatively thick, red and elastic. In vivo experiments showed obvious hair follicle cell proliferation in the full-thickness skin defect. Stem cell markers examination showed active ESCs in repair and regeneration of skin. The results indicate that the collagen-modified chitin membrane carry with ESCs has successfully regenerated the whole skin with all the skin appendages and function.

Prevalence and correlates of cigarette smoking among Chinese schizophrenia inpatients receiving antipsychotic mono-therapy.

OBJECTIVE: To investigate the prevalence rate of cigarette smoking and its socio-demographic and clinical correlates in Chinese schizophrenia inpatients receiving antipsychotic mono-therapy. METHODS: This study was a cross-sectional, two-site, hospital-based survey. Four hundred and twenty-nine schizophrenia patients (male/female: 66.9% vs. 33.1%) were consecutively recruited from psychosis inpatient wards of two large specialty psychiatric hospitals in mainland China. Patients were assessed using a cigarette smoking questionnaire, the Positive and Negative Symptom Scale, the Simpson Angus Scale, the Barnes Akathisia Rating Scale, and the Abnormal Involuntary Movement Scale. Socio-demographic and other clinical data were also collected. We calculated the prevalence of current smoking in our sample as well as its indirectly standardized prevalence ratio (ISPR) using data from the 2010 Global Adult Tobacco Survey in China. RESULTS: The prevalence rate of current smoking was 40.6% in our sample, and 57.5% in males and 6.3% in females. The ISPRs of all patients, men and women were 1.11(95%CI: 0.95 ∼ 1.29), 1.07(95%CI = 0.91 ∼ 1.24) and 4.64(95% CI = 2.12 ∼ 8.82), respectively. The overall and male-specific prevalence of current smoking did not differ significantly between patients and the general population. In multiple logistic regression analysis, male sex, older age, poor marital status, alcohol use, use of first-generation antipsychotics, longer duration of illness, more frequent hospitalizations, and more severe negative symptoms were independently associated with current smoking. CONCLUSION: Male Chinese inpatients with schizophrenia who received a mono-therapy of antipsychotics were not more likely to smoke than the general population. Cigarette smoking is more common in schizophrenia patients with more severe illness.

Naringin abrogates osteoclastogenesis and bone resorption via the inhibition of RANKL-induced NF-κB and ERK activation.

Osteolytic bone diseases including osteoporosis are commonly accompanied with enhanced osteoclast formation and bone resorption. Naringin, a natural occurring flavonoid has been found to protect against retinoic acid-induced osteoporosis and improve bone quality in rats. Here, we showed that naringin perturbs osteoclast formation and bone resorption by inhibiting RANK-mediated NF-κB and ERK signaling. Naringin suppressed gene expression of key osteoclast marker genes. Naringin was found to inhibit RANKL-induced activation of NF-κB by suppressing RANKL-mediated IκB-α degradation. In addition, naringin inhibited RANKL-induced phosphorylation of ERK. This study identifies naringin as an inhibitor for osteoclast formation and bone resorption, and provides evidence that natural compounds such as naringin might be beneficial as an alternative medicine for the prevention and treatment of osteolysis.