The Combined Effect of Elevated Blood Pressure and Occupational Noise Exposure on Bilateral High-Frequency Hearing Loss: Evidence From a Large Sample Cross-sectional Study.

BACKGROUND: Combined effect of elevated blood pressure and occupational noise exposure on hearing loss have rarely been evaluated among Chinese population. METHODS: This cross-sectional study was conducted in 242,811 participants. Logistic regression model was performed to estimate the independent and combined associations. RESULTS: Compared with participants without occupational noise exposure, the risk of bilateral high-frequency hearing loss (BHFHL) was significantly higher for noise exposure 10 years or more (odds ratio [OR] = 1.29, 95% confidence interval [95% CI] = 1.23-1.35). Compared with no hypertension, participants with grade 1 hypertension had higher risk of BHFHL in all age groups (OR, 1.14; 95% CI, 1.09-1.20). As to the combined effect, the highest BHFHL risk was found in males (OR, 1.51; 95% CI, 1.37-1.67), especially among participants with grade 1 hypertension older than 50 years (OR, 1.65; 95% CI, 1.46-1.88). CONCLUSIONS: Elevated blood pressure may synergistically influence hearing loss combined with occupational noise exposure.

Analysis of influencing factors of quality of life of patients with pneumoconiosis in Chongqing based on a structural equation model / 中国职业医学

@#Objective To analyze the influencing factors of quality of life of patients with occupational pneumoconiosis in Methods Chongqing using a structural equation model. A total of 1 181 pneumoconiosis patients in Chongqing were selected - as the research subjects using convenient sampling method. The Chinese version of the SF 36 Scale was used to investigate the quality of life of the patients. Amos 24.0 software was used to construct a structural equation model reflecting the quality of life of Results ， （ ），（ ） （ ）， patients. The scores of physical health mental health and quality of life were 61.7±18.5 68.7±20.5 and 64.7±16.8 respectively. The scores of the eight dimensions of the quality of life of the research subjects were lower than that of the （ P ） Chongqing City municipal and national norms all <0.01 . Multiple linear regression results showed that personal monthly ， ， ， income pneumoconiosis stage complications employment status and smoking were the influencing factors of the quality of life （ P ） ， of pneumoconiosis patients all <0.05 . The results of the structural equation model showed that the stage of pneumoconiosis ， ， complications personal monthly income and pulmonary rehabilitation treatment could directly affect the physical and mental （ P ） ， health of the research subjects all <0.05 . In addition the stage of pneumoconiosis and complications indirectly affected the （ P ）Conclusion physical and mental health of patients by affecting pulmonary rehabilitation treatment all <0.05 . The structural equation model can be used to verify the influencing factors of the quality of life of patients with occupational pneumoconiosis. ， Complications personal monthly income and pneumoconiosis stage are the main factors affecting the quality of life of patients with occupational pneumoconiosis.

Knockdown of lncRNA MALAT1 Alleviates LPS-Induced Acute Lung Injury via Inhibiting Apoptosis Through the miR-194-5p/FOXP2 Axis.

PURPOSE: We aimed to identify and verify the key genes and lncRNAs associated with acute lung injury (ALI) and explore the pathogenesis of ALI. Research showed that lower expression of the lncRNA metastasis-associated lung carcinoma transcript 1 (MALAT1) alleviates lung injury induced by lipopolysaccharide (LPS). Nevertheless, the mechanisms of MALAT1 on cellular apoptosis remain unclear in LPS-stimulated ALI. We investigated the mechanism of MALAT1 in modulating the apoptosis of LPS-induced human pulmonary alveolar epithelial cells (HPAEpiC). METHODS: Differentially expressed lncRNAs between the ALI samples and normal controls were identified using gene expression profiles. ALI-related genes were determined by the overlap of differentially expressed genes (DEGs), genes correlated with lung, genes correlated with key lncRNAs, and genes sharing significantly high proportions of microRNA targets with MALAT1. Quantitative real-time PCR (qPCR) was applied to detect the expression of MALAT1, microRNA (miR)-194-5p, and forkhead box P2 (FOXP2) mRNA in 1 µg/ml LPS-treated HPAEpiC. MALAT1 knockdown vectors, miR-194-5p inhibitors, and ov-FOXP2 were constructed and used to transfect HPAEpiC. The influence of MALAT1 knockdown on LPS-induced HPAEpiC proliferation and apoptosis via the miR-194-5p/FOXP2 axis was determined using Cell counting kit-8 (CCK-8) assay, flow cytometry, and Western blotting analysis, respectively. The interactions between MALAT1, miR-194-5p, and FOXP2 were verified using dual-luciferase reporter gene assay. RESULTS: We identified a key lncRNA (MALAT1) and three key genes (EYA1, WNT5A, and FOXP2) that are closely correlated with the pathogenesis of ALI. LPS stimulation promoted MALAT1 expression and apoptosis and also inhibited HPAEpiC viability. MALAT1 knockdown significantly improved viability and suppressed the apoptosis of LPS-stimulated HPAEpiC. Moreover, MALAT1 directly targeted miR-194-5p, a downregulated miRNA in LPS-stimulated HPAEpiC, when FOXP2 was overexpressed. MALAT1 knockdown led to the overexpression of miR-194-5p and restrained FOXP2 expression. Furthermore, inhibition of miR-194-5p exerted a rescue effect on MALAT1 knockdown of FOXP2, whereas the overexpression of FOXP2 reversed the effect of MALAT1 knockdown on viability and apoptosis of LPS-stimulated HPAEpiC. CONCLUSION: Our results demonstrated that MALAT1 knockdown alleviated HPAEpiC apoptosis by competitively binding to miR-194-5p and then elevating the inhibitory effect on its target FOXP2. These data provide a novel insight into the role of MALAT1 in the progression of ALI and potential diagnostic and therapeutic strategies for ALI patients.

Accuracy study of a binocular-stereo-vision-based navigation robot for minimally invasive interventional procedures.

BACKGROUND: Medical robot is a promising surgical tool, but no specific one has been designed for interventional treatment of chronic pain. We developed a computed tomography-image based navigation robot using a new registration method with binocular vision. This kind of robot is appropriate for minimal invasive interventional procedures and easy to operate. The feasibility, accuracy and stability of this new robot need to be tested. AIM: To assess quantitatively the feasibility, accuracy and stability of the binocular-stereo-vision-based navigation robot for minimally invasive interventional procedures. METHODS: A box model was designed for assessing the accuracy for targets at different distances. Nine (three sets) lead spheres were embedded in the model as puncture goals. The entry-to-target distances were set 50 mm (short-distance), 100 mm (medium-distance) and 150 mm (long-distance). Puncture procedure was repeated three times for each goal. The Euclidian error of each puncture was calculated and statistically analyzed. Three head phantoms were used to explore the clinical feasibility and stability. Three independent operators conducted foramen ovale placement on head phantoms (both sides) by freehand or under the guidance of robot (18 punctures with each method). The operation time, adjustment time and one-time success rate were recorded, and the two guidance methods were compared. RESULTS: On the box model, the mean puncture errors of navigation robot were 1.7 ± 0.9 mm for the short-distance target, 2.4 ± 1.0 mm for the moderate target and 4.4 ± 1.4 mm for the long-distance target. On the head phantom, no obvious differences in operation time and adjustment time were found among the three performers (P > 0.05). The median adjustment time was significantly less under the guidance of the robot than under free hand. The one-time success rate was significantly higher with the robot (P < 0.05). There was no obvious difference in operation time between the two methods (P > 0.05). CONCLUSION: In the laboratory environment, accuracy of binocular-stereo-vision-based navigation robot is acceptable for target at 100 mm depth or less. Compared with freehand, foramen ovale placement accuracy can be improved with robot guidance.

Attenuation of hyperoxic acute lung injury by Lycium barbarum polysaccharide via inhibiting NLRP3 inflammasome.

Lycium barbarum polysaccharide (LBP), an active component from Goji berry which is a traditional Chinese medicine, has anti-inflammatory and antioxidant features. The aim of our study was to investigate whether LBP has any role in hyperoxia-induced acute lung injury (ALI). Using a murine model of hyperoxia-induced ALI, we investigate the effect of LBP on pulmonary pathological changes as well as Sirtuin 1 (SIRT1) and the nucleotide binding domain and leucine-rich repeat pyrin domain containing 3 (NLRP3) inflammasome. Exposure to 100% oxygen for 72 h in male C57BL/6 mice resulted in increased protein levels of tumor necrosis factor-α and interleukin-1ß in lung tissues, and aggravated lung histological alterations. These hyperoxia-induced changes and mortality were improved by LBP. LBP markedly suppressed the activation of NLRP3 inflammasome both in vivo and in vitro. Moreover, LBP upregulated SIRT1 expression compared with vehicle-treated group. Importantly, knockdown of SIRT1 reversed the inhibitory effect of LBP on NLRP3 inflammasome activation in vitro. LBP meliorated hyperoxia-induced ALI in mice by SIRT1-dependent inhibition of NLRP3 inflammasome activation.

Tripterygium wilfordii Hook F versus conventional synthetic disease-modifying anti-rheumatic drugs as monotherapy for rheumatoid arthritis: a systematic review and network meta-analysis.

BACKGROUND: Tripterygium wilfordii Hook F (TwHF), a medicinal plant that has been widely used in Chinese traditional medicine, is proven effective for treating rheumatoid arthritis (RA), but its clinical efficacy and safety remain largely undefined in comparison with conventional synthetic disease modifying anti-rheumatic drugs (DMARDs). METHODS: PubMed, Embase, Cochrane Library, CNKI, VIP, CBM, and WanFang Databases. Endpoints were ACR 20, 50, and 70, and the number of withdrawals due to adverse events. Initially, traditional pairwise meta-analysis was performed by using a random-effects model. Then, we performed network meta-analysis to compare different therapies by using frequentist approach. RESULTS: A total of 22 trials (5255 participants) were identified. By direct comparison, TwHF was superior to sulphasalazine according to ACR 20, 50 and 70. TwHF was superior to placebo according to ACR 20 and 50. By indirect comparisons, TwHF was superior to methotrexate, leflunomide, sulphasalazine, tacrolimus, minocycline and placebo according to ACR 20. Ranking by the Surface under the Cumulative Ranking curve (SUCRA) values showed that TwHF had the greatest probability for being the best treatment option according to ACR 20 (92.0 %) and ACR 50 (81.3 %), and the highest probability to be in the second (57.8 %) ranking position after leflunomide (69.6 %) according to ACR 70. By both direct and indirect comparisons, TwHF caused no more significant withdrawals than the placebo. The SUCRA values showed that TwHF had the highest probability to rank sixth (26.7 %) after the placebo (45.6 %) in causing withdrawals. CONCLUSIONS: Our data suggest that TwHF is effective and safe in the treatment of RA and has better clinical efficacy in terms of ACR 20 and 50 than existing conventional synthetic DMARDs. In the absence of head-to-head treatment comparison, the confidence in these estimates is low. Future comparative efficacy studies are warranted.

[Experimental research in vitro of TK/GCV system for osteosarcoma MG-63 cell damage].

OBJECTIVE: To study the killing effects of the liposome-mediated thymidine kinase (TK)/ganciclovir (GCV) system on MG-63 osteosarcoma (OS) cells and its bystander effects. METHODS: Liposome-mediated TK gene transfected into MG-63 OS cells, the efficiency of transfection was analyzed by flow cytometry and observed under inverted fluorescence microscope. Non-transfected osteosarcoma MG-63 cells were divided into three groups,in the experimental group 1 transfected TK/GCV cells cultured in solutiona liquid mixture by supernatant by 1/10,1/7,1/5,1/2 ratio to original broth; in the experimental group 2 transfected cells cultured in solutiona liquid mixture of supernatant filtered through 0.22 microm filter by 1/10,1/7, 1/5, 1/2 ratio to original broth, in control group the transfection cells cultured in original culture solution. Cell growth inhibition rate and osteosarcoma cell sensitivity to TK/GCV system were measured by MTT assay in each group. RESULTS: The TK gene was transfected into MG-63 OS cells successfully by liposome-mediated, flow cytometry instrument detection TK gene transfection cell transfection efficiency can reach 75.5%. Six days later the MTT assay showed that in the experimental group 1 inhibition rate of all concentration ratio of the mixed culture fluid were statistically significant as compared with the control group (P < 0.05), and in the experimental group 2 that of the 1/10 and 1/7 of concentration ratio of mixed culture medium was not statistically significant as compared with the control group (P > 0.05). TK gene transfected MG-63 cells increased with the the GCV concentration,the cell apoptosis rate increased. CONCLUSION: The experiment demonstrated that the MG-63 OS cells are sensitive to the liposome-mediated TK/GCV system and bystander effects are significant.

[Construction of lentivirus vector containing human LIM mineralization protein-1 (LMP-1) and its expression in rat bone mesenchymal stem cells].

OBJECTIVE: To construct a recombiant lentivirus vector of human LMP-1 and detect the expression of LMP-1 in infected rat bone mesenchymal stem cells. METHODS: LMP-1 gene from the cDNA library were extracted by Polymerase Chain Reaction (PCR). The LMP-1 genes were connected into lentiviral vectors pGC-FU-EGFP which was linearized by Age I enzyme to produce recombiant lentivirus vector called as pGC-FU-LMP-1-EGFP,then packaged by 293T cells. The virus supernant congtaining LV-LMP-1-EGFP was harvested, concentrated and titrated. The rat BMSCs were transfected with recombiant lentivirus LV-LMP-1-EGFP at the most appropriate MOI. The mRNA and protein expression of LMP-1 were detected by RT-PCR and Western blot. RESULTS: 1LV-LMP-1I-EGFP was recombined successfully and the titer reached 2x108TU/ml. 2The efficiency of infection was 93.5% ,which was get after LV-LMP-1-EGFP infected rat BMSCs at the most appropriate MOI=100. The expression of LMP-1 gene was confirmed by RT-PCR and Western blot. CONCLUSION: Lentivirus vector containing human LMP-1 gene is constructed successfully,which can transfected efficiently into rat BMSCs,and the infected rat BMSCs can effectively express LMP-1.

[Clinical effect analysis of ankylosing spondylitis treated by Chinese medical syndrome differentiation].

OBJECTIVE: To evaluate the curative effect and safety of Bushen Qiangji Decoction (BQD) and Qingre Qiangji Decoction (QQD) in treating ankylosing spondylitis (AS) patients, and to verify the clinical utility of AS syndrome differentiation and treatment scheme [Shen-deficiency induced stasis obstruction syndrome (SDISOS) and dampness-heat obstruction syndrome (DHOS) being two basic syndrome types, Shen invigorating blood activating method (SIBAM) and heat clearing dampness resolving method (HCDRM) being two basic treatment methods]. METHODS: Totally 354 AS patients of SDISOS and DHOS were randomly assigned to the treatment group and the control group using a multi-center randomized, positive drug parallel-controlled clinical trail. Patients in treatment group were treated by BQD or QQD according to syndrome typing, while those in the control group took Sulfasalazine enteric-coated tablet (SECT), 24 weeks as one therapeutic course. After treatment, the clinical efficacy was evaluated by using ASAS20 standard (set by Asessment in Ankylosing Spondylitis working group), Chinese medical efficacy evaluation standards, and BASDAI, BASFI, BASMI, night-pain index, spinal pain index, PGA, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). RESULTS: After 24 weeks of treatment by BQD or QQD, ASAS20 standard rate was 86.75% in the treatment group, and the total effective rate of Chinese medical syndrome was 85.47%. They could significantly reduce patients' integrals of Chinese medical syndrome, BASDAI, BASFI, BASMI, night-pain index, spinal pain index, and PGA (all P < 0.01). CONCLUSIONS: QQD and BQD got confirmable clinical effects in treating AS, providing strong evidence of evidence-based medicine for syndrome differentiation and treatment of AS.

Down-regulation of some miRNAs by degrading their precursors contributes to anti-cancer effect of mistletoe lectin-I.

BACKGROUND AND PURPOSE: Mistletoe lectin-I (ML-I), the main anti-cancer component of mistletoe extracts, was originally thought to act exclusively on 28S rRNA. Here, we investigate the down-regulating effect and mechanism of CM-1, an ML-I isolated from Chinese mistletoe, on some miRNAs. EXPERIMENTAL APPROACH: The anti-cancer effects of CM-1 were assessed in vitro and in vivo in colorectal cancer cells. The miRNAs down-regulated by CM-1 were identified by miRNA microarray assay and validated by qRT-PCR analysis. The suppression of host gene transcription or by degradation of precursors was determined by qRT-PCR and enzyme activity assays respectively. The qRT-PCR, Western blot and immunohistochemistry were used to examine the expression of their target gene and related downstream effector. Cell proliferation was assayed in stably transfected HEK-293 cells with different levels of these miRNAs. KEY RESULTS: CM-1 showed prominent anti-neoplastic activity towards CLY and HT-29 cells both in vitro and in vivo. The miR-135a&b were the miRNAs most down-regulated by CM-1. Their host gene transcription was largely up-regulated, while their precursors were degraded directly by CM-1. The expression of their target gene adenomatous polyposis coli and the phosphorylation of related effector ß-catenin were both significantly up-regulated. The IC(50) values of CM-1 on derivative HEK-293 cells with high miR-135a&b levels were 2-4 times lower than that of control cells. CONCLUSIONS AND IMPLICATIONS: CM-1 down-regulated some miRNAs by degrading their precursors, which contributes to its prominent anti-cancer activity.

Allelic diversity and haplotype structure of HLA loci in the Chinese Han population living in the Guanzhong region of the Shaanxi province.

The allele and haplotype frequencies of HLA-A, -B and -DRB1 loci in 10,000 healthy unrelated Han individuals living in the Guanzhong region of the Shaanxi Province were analyzed with the methods of SSO, SSP and SBT. Subsequently, these data were compared with results obtained in Han populations living in other regions as well as to other ethnic groups, using genetic distance measurements, neighbor-joining dendrograms and principal component analysis. In total 18 alleles were detected at the HLA-A locus, 46 alleles at the HLA-B locus and 14 alleles at the HLA-DRB1 locus. HLA-A*02 was the most common HLA-A allele (29.70%), followed by A*11 (18.70%), and A*24 (15.75%); whereas at the HLA-B locus, the allele with the highest frequency was HLA-B*13 (10.76 %), followed by B*46 (7.93%), B*51 (7.68%). At the HLA-DRB1 locus, the most common alleles were HLA-DRB1*15 (15.54%), DRB1*09 (13.18%) and DRB1*04 (11.21%). Three-loci haplotype analysis revealed that HLA A*30- B*13- DRB1*07 (4.11%), A*02 -B*46 -DRB1*09 (2.57%) and A*33 -B*58 -DRB1*17 (1.32%) were the most common haplotypes in this population. Four two-loci haplotypes, including HLA-A*30-B*43, A*30-B*53, B*43-DRB1*07 and B*73-DRB1*04 had significant linkage disequilibrium (relative linkage disequilibrium parameter equals to 1). Compared with other populations, our results indicated that the Han populations in different regions had a similar allelic diversity of HLA -A, -B, and -DRB1 loci. The Han population in the Guanzhong region of the Shaanxi Province had a close genetic relationship with the Northern and Southern Han populations. In summary, the similarities and differences of the HLA allelic diversity and haplotype structure between the Han population in the Guanzhong region and related populations, regarding HLA genotype distribution, provide basic information for further studies of the HLA heterogeneity and anthropological studies.

Differential sensitivity of colorectal cancer cell lines to artesunate is associated with expression of beta-catenin and E-cadherin.

Artesunate, a remarkable antimalarial agent, also reveals profound cytotoxic activity. In the present investigation, we compared the anticancer effects of artesunate on three colorectal cancer cell lines and analyzed the relationship between drug sensitivity and malignant phenotype of the tumor cells. The findings are as follows: poorly-differentiated was colorectal cancer cell line CLY showing nuclear beta-catenin accumulation and loss of E-cadherin; moderately-differentiated were Lovo cells with cytoplasmic distribution of the two proteins; and well-differentiated were HT-29 cells with membranous localization of them. Also, both in vitro and in vivo, poorly- or moderately-differentiated CLY and Lovo were more susceptible to artesunate treatment than well-differentiated HT-29. Furthermore, the sensitive response of CLY and Lovo to artesunate was associated with membranous translocation of beta-catenin and increased expression of E-cadherin, which indicated the inhibition of hyperactive Wnt signaling pathway and the reversion of the epithelial to mesenchymal transition, respectively. Due to the vital roles of Wnt pathway and the epithelial to mesenchymal transition in tumor differentiation, we thought artesunate could promote the re-differentiation and apoptosis of colorectal cancer cells by inhibition of hyperactive Wnt pathway and reversion of the epithelial to mesenchymal transition.

Artesunate attenuates the growth of human colorectal carcinoma and inhibits hyperactive Wnt/beta-catenin pathway.

Artesunate (ART), a remarkable antimalarial agent, also inhibited the growth of human colorectal carcinoma. As determined by MTT assay, flow cytometry analysis on apoptosis and indirect immunofluorescence analysis on the proliferation-associated marker Ki67, ART suppressed the proliferation and promoted the apoptosis of colorectal cancer cells in a dose-dependent manner. Furthermore, immunofluorescence analysis on beta-catenin and RT-PCR analysis on Wnt/beta-catenin target genes demonstrated ART translocated beta-catenin from nucleus to adherent junctions of membrane and reduced transcription mediated by beta-catenin. These results suggested the anticancer activity of ART correlated with the inhibition of hyperactive Wnt/beta-catenin signaling pathway. In vivo, ART significantly slowed the growth of colorectal tumor xenografts. Bioluminescent imaging also revealed that ART decreased the physiological activity of tumor xenografts and delayed spontaneous liver metastasis. These antitumor effects were related to the membranous translocation of beta-catenin and the inhibition of the unrestricted activation of Wnt/beta-catenin pathway, which was confirmed by the immunohistochemical staining of tumor tissues. These results and the known low toxicity are clues that ART might be a promising candidate drug for the treatment of colorectal carcinoma.

Establishment and characterization of a novel human colorectal cancer cell line (CLY) metastasizing spontaneously to the liver in nude mice.

Colorectal cancer (CRC) with liver metastasis is a fatal disease with rapid progression and poor patient outcome. However, the molecular mechanism involved in liver metastasis of CRC remains essentially unknown, largely because of the presence of few available CRC cell lines with liver metastasis origin and spontaneous metastatic potentials in nude mice. In this study, we established a novel metastatic CRC cell line, CLY, derived from liver metastasis of a 64-year-old Chinese CRC patient. The cell line was characterized by morphology, growth kinetics, tumorigenicity, spontaneous liver metastatic potential, and cytogenetics. Immunofluorescence analysis of beta-catenin and E-cadherin and methylation-specific PCR (MSP) of the E-cadherin gene (CDH1) promoter were also used to compare CLY with conventional CRC cell lines (HT-29 and Lovo). CLY exhibited compact and polygonal-shaped epithelial cells in vitro and its population doubling time was 29.5 h. Subcutaneous transplantation of CLY into nude mice resulted in subcutaneous tumor formation and spontaneous liver metastasis in all of 10 nude mice. Cytogenetic analysis identified aneuploidy karyotypes with a modal chromosome number of 60. In immunofluorescence analysis, CLY exhibited a low expression but high restricted nuclear localization of beta-catenin and a silenced expression of E-cadherin, which may be induced by hypermethylation of the E-cadherin gene (CDH1) promoter and differed from conventional CRC cell lines. Therefore, CLY is an ideal cell model for further exploring the metastatic mechanisms of CRC and testing new therapeutic reagents for CRC with liver metastasis.