Investigation of critical factors influencing the underestimation of hearing loss predicted by the ISO 1999 predicting model.

OBJECTIVE: To analyze factors influencing the underestimation of noise-induced permanent threshold shift (NIPTS) among manufacturing workers, providing baseline data for revising noise exposure standard. DESIGN: A cross-sectional study was designed with 2702 noise-exposed workers from 35 enterprises from 10 industries. Personal noise exposure level(LAeq,8h) and noise kurtosis level were determined by a noise dosimeter. Questionnaires and hearing loss tests were performed for each subject. The predicted NIPTS was calculated using the ISO 1999:2013 model for each participant, and the actual measured NIPTS was corrected for age and sex. The factors influencing the underestimation of NIPTS were investigated. RESULTS: The predicted NIPTS at each test frequency (0.5, 1, 2, 3, 4, or 6kHz) and mean NIPTS at 2, 3, 4, and 6kHz (NIPTS2346) using the ISO 1999:2013 model were significantly lower than their corresponding measured NIPTS, respectively (P < 0.001). The ISO model significantly underestimated the NIPTS2346 by 12.36 dB HL. The multiple linear regression analysis showed that noise exposure level, exposure duration, age, and kurtosis could affect the degree of underestimation of NIPTS2346. The generalized additive model (GAM) with (penalized) spline components showed nonlinear relationships between critical factors (age, exposure duration, noise level, and kurtosis) and the underestimated NIPTS2346.The underestimated NIPTS2346 decreased with an increase in exposure duration (especially over ten years). There was no apparent trend in the underestimated NIPTS2346 with age. The underestimated NIPTS2346 decreased with the increased noise level [especially > 90 dB(A)]. The underestimated NIPTS2346 increased with an increase in noise kurtosis after adjusting for the noise exposure level and exposure duration and ultimately exhibiting a linear regression relationship. CONCLUSIONS: The ISO 1999 predicting model significantly underestimated the noise-induced hearing loss among manufacturing workers. The degree of underestimation became more significant at the noise exposure condition of fewer than ten years, less than 90 dB(A), and higher kurtosis levels. It is necessary to apply kurtosis to adjust the underestimation of hearing loss and consider the applying condition of noise energy metrics when using the ISO predicting model.

Attenuating glucose metabolism by Fbxw7 promotes Taxol sensitivity of colon cancer cells through downregulating NADPH oxidase 1 (Nox1).

BACKGROUND: Colorectal cancer (CRC), one of the most common malignancies worldwide, is associated with poor survival and has a high mortality rate. Taxol is a chemotherapeutic agent that has been clinically applied as a first-line drug against diverse cancers. Yet, development of drug resistance has become the major challenge for anti-cancer treatments. F-box and WD40 domain protein 7 (Fbxw7) is a known tumor suppressor which is frequently downregulated in cancers. However, the biological roles and mechanisms of Fbxw7 in Taxol resistance are still under investigation. METHODS: We report that Fbxw7 is significantly inactivated in CRC tumors and cell lines compared with normal tissues and colon cells. Expressions of Fbxw7 and Nox1 were detected from human colon tumors and cells by qRT-PCR and Western blot. Glycolysis rate was assessed by glucose uptake and lactate product assay. Interactions between Fbxw7 and Nox1 were determined by co-immunoprecipitation (Co-IP). Chemosensitivity and resistance of colon cancer cells were determined by MTT assay and Annexin V-FITC assay. RESULTS: Overexpression of Fbxw7 sensitized colon cancer cells to Taxol. Moreover, we observed a negative correlation between Fbxw7 and glucose metabolism. From the established Taxol-resistant (TR) cell line from HCT-116, Fbxw7 was found to be markedly downregulated in HCT-116 TR cells. We detected that NADPH oxidase 1 (Nox1), a superoxide-generating NADPH oxidase, is negatively regulated by Fbxw7. The Co-IP assay showed that Fbxw7 interacted with Nox1, which was observed to be significantly upregulated in CRC tissues. Nox1 therefore promotes the Taxol resistance and glucose metabolism of colon cancer cells. Finally, rescue experiments demonstrated that the Fbxw7-promoted Taxol sensitivity was partially through the Nox1-glycolysis axis. Restoration of Nox1 in Fbxw7-overexpressed TR colon cancer cells significantly recovered the Taxol resistance, which could be further overridden by glycolysis inhibition. CONCLUSIONS: Collectively, this study uncovered that targeting the Fbxw7-Nox1-glucose metabolism axis could be an effective strategy against chemoresistant colon cancer.

Effect of combined VEGF165/ SDF-1 gene therapy on vascular remodeling and blood perfusion in cerebral ischemia.

OBJECTIVE Therapeutic neovascularization is a promising strategy for treating patients after an ischemic stroke; however, single-factor therapy has limitations. Stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) proteins synergistically promote angiogenesis. In this study, the authors assessed the effect of combined gene therapy with VEGF165 and SDF-1 in a rat model of cerebral infarction. METHODS An adenoviral vector expressing VEGF165 and SDF-1 connected via an internal ribosome entry site was constructed (Ad- VEGF165-SDF-1). A rat model of middle cerebral artery occlusion (MCAO) was established; either Ad- VEGF165-SDF-1 or control adenovirus Ad- LacZ was stereotactically microinjected into the lateral ventricle of 80 rats 24 hours after MCAO. Coexpression and distribution of VEGF165 and SDF-1 were examined by reverse-transcription polymerase chain reaction, Western blotting, and immunofluorescence. The neurological severity score of each rat was measured on Days 3, 7, 14, 21, and 28 after MCAO. Angiogenesis and vascular remodeling were evaluated via bromodeoxyuridine and CD34 immunofluorescence labeling. Relative cerebral infarction volumes were determined by T2-weighted MRI and triphenyltetrazolium chloride staining. Cerebral blood flow, relative cerebral blood volume, and relative mean transmit time were assessed using perfusion-weighted MRI. RESULTS The Ad- VEGF165-SDF-1 vector mediated coexpression of VEGF165 and SDF-1 in multiple sites around the ischemic core, including the cortex, corpus striatum, and hippocampal granular layer. Coexpression of VEGF165 and SDF-1 improved neural function, reduced cerebral infarction volume, increased microvascular density and promoted angiogenesis in the ischemic penumbra, and improved cerebral blood flow and perfusion. CONCLUSIONS Combined VEGF165 and SDF-1 gene therapy represents a potential strategy for improving vascular remodeling and recovery of neural function after cerebral infarction.

The Use of the Kurtosis-Adjusted Cumulative Noise Exposure Metric in Evaluating the Hearing Loss Risk for Complex Noise.

OBJECTIVE: To test a kurtosis-adjusted cumulative noise exposure (CNE) metric for use in evaluating the risk of hearing loss among workers exposed to industrial noises. Specifically, to evaluate whether the kurtosis-adjusted CNE (1) provides a better association with observed industrial noise-induced hearing loss, and (2) provides a single metric applicable to both complex (non-Gaussian [non-G]) and continuous or steady state (Gaussian [G]) noise exposures for predicting noise-induced hearing loss (dose-response curves). DESIGN: Audiometric and noise exposure data were acquired on a population of screened workers (N = 341) from two steel manufacturing plants located in Zhejiang province and a textile manufacturing plant located in Henan province, China. All the subjects from the two steel manufacturing plants (N = 178) were exposed to complex noise, whereas the subjects from textile manufacturing plant (N = 163) were exposed to a G continuous noise. Each subject was given an otologic examination to determine their pure-tone HTL and had their personal 8-hr equivalent A-weighted noise exposure (LAeq) and full-shift noise kurtosis statistic (which is sensitive to the peaks and temporal characteristics of noise exposures) measured. For each subject, an unadjusted and kurtosis-adjusted CNE index for the years worked was created. Multiple linear regression analysis controlling for age was used to determine the relationship between CNE (unadjusted and kurtosis adjusted) and the mean HTL at 3, 4, and 6 kHz (HTL346) among the complex noise-exposed group. In addition, each subject's HTLs from 0.5 to 8.0 kHz were age and sex adjusted using Annex A (ISO-1999) to determine whether they had adjusted high-frequency noise-induced hearing loss (AHFNIHL), defined as an adjusted HTL shift of 30 dB or greater at 3.0, 4.0, or 6.0 kHz in either ear. Dose-response curves for AHFNIHL were developed separately for workers exposed to G and non-G noise using both unadjusted and adjusted CNE as the exposure matric. RESULTS: Multiple linear regression analysis among complex exposed workers demonstrated that the correlation between HTL3,4,6 and CNE controlling for age was improved when using the kurtosis-adjusted CNE compared with the unadjusted CNE (R = 0.386 versus 0.350) and that noise accounted for a greater proportion of hearing loss. In addition, although dose-response curves for AHFNIHL were distinctly different when using unadjusted CNE, they overlapped when using the kurtosis-adjusted CNE. CONCLUSIONS: For the same exposure level, the prevalence of NIHL is greater in workers exposed to complex noise environments than in workers exposed to a continuous noise. Kurtosis adjustment of CNE improved the correlation with NIHL and provided a single metric for dose-response effects across different types of noise. The kurtosis-adjusted CNE may be a reasonable candidate for use in NIHL risk assessment across a wide variety of noise environments.

Microsurgical treatment for central gyrus region meningioma with epilepsy as primary symptom.

BACKGROUND: The objective of this article was to investigate the operation outcome, complications, and the patient's quality of life after surgical therapy for central gyrus region meningioma with epilepsy as the primary symptom. METHODS: All patients get at least 6 months of follow-up (range, 6-34 mo) after surgery. They underwent preoperative magnetic resonance imaging and video electroencephalography, and their clinical manifestations, imaging characteristics, microsurgical methods, and prognosis were retrospectively analyzed. RESULTS: The meningioma was located in the front and back of the central sulcus vein in 3 and 2 patients, respectively; in the compressed precentral gyrus and central sulcus vein in 3 patients; and in the precentral gyrus and postcentral gyrus each in 1 patient; beside the right sagittal sinus and invaded a thick draining vein on the brain surface in 1 patient and beside the right sagittal sinus and close to the precentral gyrus in 2 patients; invaded the superior sagittal sinus in 8 patients; crossed the cerebral falx and compressed cortex gyrus veins in 1 patient; invaded duramater and irritated skull hyperplasia in 3 patients; invaded duramater and its midline infiltrated into the superior sagittal sinus, was located behind the precentral gyrus, and enveloped the central sulcus vein. They were resected and classified by Simpson standards: 17 of the 26 patients had grade I, 6 patients had in grade II, and 3 patients had in grade III. CONCLUSIONS: Resection of central gyrus region meningioma by microsurgical technique avoids injury to the cerebral cortex, central sulcus vein, and other draining veins. Microsurgery improves the total resection rate, reduces recurrence rate, and lowers disability or death rate.

Evaluation of the combination of 1,3-dichloropropene and dazomet as an efficient alternative to methyl bromide for cucumber production in China.

BACKGROUND: The combination of 1,3-dichloropropene (1,3-D) and dazomet (DZ) offers a potential alternative to methyl bromide (MB) for soil disinfection. MB is scheduled to be withdrawn from routine use by 2015 in developing countries. Combination treatments of 1,3-D + DZ were evaluated in a laboratory study and in two commercial cucumber fields. RESULTS: Laboratory studies found that nearly all of the tested combinations of 1,3-D and DZ displayed positive synergistic activity on root-knot nematodes (Meloidogyne spp.), two major soilborne fungi (Fusarium spp. and Phytophthora spp.) and the seeds of two major weed species (Digitaria sanguinalis and Abutilon theophrasti). Field trials revealed that the combination of 1,3-D and DZ (at 10 + 25 g m(-2) ) successfully suppressed Meloidogyne spp. root galling, sharply reduced Fusarium spp. and Phytophthora spp. and maintained high cucumber yields. The combination treatment of 1,3-D + DZ was more effective than 1,3-D or DZ alone and provided results similar to methyl bromide with respect to pest control, plant mortality, plant height, yield and income. All of the treatments were significantly better than the non-treated control. CONCLUSION: The results indicate that the tested combination of 1,3-D and DZ offers an efficient alternative to methyl bromide for cucumber production.

[Analysis of new pneumoconiosis cases during 2006-2009 in Zhejiang province].

OBJECTIVE: To analyze the characteristics of pneumoconiosis cases in Zhejiang province and to provide the evidence for pneumoconiosis control and prevention measures in Zhejiang province. METHODS: The data of new pneumoconiosis cases were from national surveillance system of occupational disease in Zhejiang province during 2006-2009, and were analyzed for distribution, age, exposure duration, pneumoconiosis phases and enterprise types. RESULTS: During 2006-2009, 819 new pneumoconiosis cases (173, 157, 209 and 280 cases, respectively) were reported, 86.9% cases suffered from silicosis. Most of pneumoconiosis cases were distributed in Ningbo, Wenzhou areas and in building materials, machinery, coal, geological and mining, light industries and construction enterprise. The average ages of new pneumoconiosis cases were (47.8 +/- 10.0), (52.5 +/- 13.1), (55.5 +/- 11.2) and (55.9 +/- 12.2) years old, respectively and showed a significant increase trend (P<0.05). The average exposure duration of new pneumoconiosis cases were (12.4 +/- 8.6), (12.9 +/- 9.4), (12.4 +/- 8.6) and (15.7 +/- 10.0) years. The average exposure duration of phase I, phase II, phase III new pneumoconiosis cases were (14.3 +/- 9.87), (12.4 +/- 8.7) and (11.4 +/- 7.1) years, respectively and there were significant differences (P<0.05). CONCLUSION: New pneumoconiosis cases in Zhejiang province are increasing year by year, the main type of pneumoconiosis is silicosis, the distribution of pneumoconiosis cases is associated with the areas and enterprises, and the exposure duration of new pneumoconiosis cases is relatively shorter.

[Therapeutic effect of infliximab on moderate and severe active rheumatoid arthritis].

OBJECTIVE: To evaluate the clinical efficacy of infliximab in the treatment of moderate and severe active rheumatoid arthritis (RA). METHODS: This randomized double-blind II/III clinical trial involved 30 patients with moderate and severe active RA, who were randomly allocated into 3 groups (groups A, B, and C) at the ratio of 3:1:1. At weeks 0, 2, 6, and 14, the patients in groups A and C received infliximab or placebo, and those in group B had placebo at week 14 with a stable background dose of methotrexate. The indicators for efficacy evaluation included the proportions of ACR20/50/70 of the responders and DAS28. The sharp scores of the hand joints were recorded before and after the treatment. RESULTS: Twenty-nine patients completed the clinical trial (18 in group A, 5 in group B, and 6 in group C). At week 14, the proportions of ACR20/50/70 in the 3 groups reached 83.33%, 60%, and 33.33%, respectively (P<0.05), as compared to 100%, 100%, and 33.33% at week 18 (P<0.05). The other indicators for clinical efficacy evaluation also suggested similar clinical improvement of the patients (P=0.000). The proportions of the patients with DAS28<3.2 and DAS28<2.6 were significantly different. Compared to the baseline, the Sharp scores in group A showed no significant changes at week 18 (P>0.930), while those in group C exhibited significant radiographic progression (P<0.044). CONCLUSION: Infliximab produces good short-term therapeutic effect against moderate and severe active RA and may help arrest the radiographic progression of the diseases, which can be more obvious in patients with moderate severity.

[Knowledge and practice regarding tuberculosis among final-year medical students in Hunan, China].

OBJECTIVE: To ascertain the level of knowledge, skills and ability about tuberculosis among final-year medical students in Hunan province of China. METHODS: The final-year medical students from 3 medical schools were asked to complete a pre-tested questionnaire by random sampling. The questionnaire consisted of 12 and 6 multiple-choice questions assessing knowledge and practices about tuberculosis, respectively. RESULTS: Four hundred and thirty-nine questionnaires were returned with a response rate of 97.6%. The majority of the students knew well on signs/symptoms associated with tuberculosis, but only a few students knew the prevalence of smear-positive pulmonary tuberculosis in China in 2000, while 25.5% of them knew of the BCG vaccination. 33.5% of the participants understood the policy of convergence case-management of tuberculosis. Analysis showed that six of twelve items were slightly statistically different among the respondents. The study also demonstrated that 334 respondents had prescribed 80 different treatment regimens but only 16.8% were correct. 33.4% of the participants ordered sputum examination during tuberculosis treatment course. Only 4.5% had transferred the patients with tuberculosis to local tuberculosis dispensary after their discharge from hospital. CONCLUSIONS: Knowledge and practice competency regarding tuberculosis among the final-year medical students were generally inadequate. Many misunderstandings were found in the field of BCG vaccination, the status of tuberculosis and the performance of National Tuberculosis Project (NTP). These findings suggest that there is a lack of emphasis on proper health education about tuberculosis. Students in medical schools need more training and more practice.