The influencing factors of hearing protection device usage among noise-exposed workers in Guangdong Province: a structural equation modeling-based survey.

BACKGROUND: There are numerous complex barriers and facilitators to continuously wearing hearing protection devices (HPDs) for noise-exposed workers. Therefore, the present study aimed to investigate the relationship between HPD wearing behavior and hearing protection knowledge and attitude, HPD wearing comfort, and work-related factors. METHOD: A cross-sectional study was conducted with 524 noise-exposed workers in manufacturing enterprises in Guangdong Province, China. Data were collected on hearing protection knowledge and attitudes, HPD wearing comfort and behavior, and work-related factors through a questionnaire. Using structural equation modeling (SEM), we tested the association among the study variables. RESULTS: Among the total workers, 69.47% wore HPD continuously, and the attitudes of hearing protection (26.17 ± 2.958) and total HPD wearing comfort (60.13 ± 8.924) were satisfactory, while hearing protection knowledge (3.54 ± 1.552) was not enough. SEM revealed that hearing protection knowledge had direct effects on attitudes (ß = 0.333, p < 0.01) and HPD wearing behavior (ß = 0.239, p < 0.01), and the direct effect of total HPD wearing comfort on behavior was ß = 0.157 (p < 0.01). The direct effect also existed between work shifts and behavior (ß=-0.107, p < 0.05). Indirect relationships mainly existed between other work-related factors, hearing protection attitudes, and HPD wearing behavior through knowledge. Meanwhile, work operation had a direct and negative effect on attitudes (ß=-0.146, p < 0.05), and it can also indirectly and positively affect attitudes through knowledge (ß = 0.08, p < 0.05). CONCLUSION: The behavior of wearing HPD was influenced by hearing protection knowledge, comfort in wearing HPD, and work-related factors. The results showed that to improve the compliance of noise-exposed workers wearing HPD continuously when exposed to noise, the HPD wearing comfort and work-related factors must be taken into consideration. In addition, we evaluated HPD wearing comfort in physical and functional dimensions, and this study initially verified the availability of the questionnaire scale of HPD wearing comfort.

Prevalence of low back pain in professional drivers: a meta-analysis.

OBJECTIVE: This meta-review aimed to investigate the prevalence of low back pain (LBP) in professional drivers. STUDY DESIGN: This study is a meta-analysis. METHODS: PubMed, Scopus, Embase, and Web of Science were searched for cross-sectional studies on the prevalence of LBP in professional drivers up to August 2023. The Agency for Healthcare Research and Quality was utilized for cross-sectional analytical studies. Statistical analysis of the included outcome indicators was conducted using Stata 16.0. The prevalence of LBP among professional drivers was measured using the random effects model, and heterogeneity was evaluated utilizing subgroup analysis. This meta-analysis review was registered with PROSPERO on April 28, 2023, under the registration number CRD42023422205. RESULTS: In total, 1, 558 results met the inclusion and exclusion criteria, and 53 studies were included. The meta-analysis results indicated that professional drivers had a LBP prevalence of 35.0%, 95%CI (0.266, 0.433) for one week, 33.80%, 95%CI (0.233, 0.443) for one month, and 55.30%, 95%CI (0.503,0.603) for one year. In the global population of professional drivers, the prevalence of LBP was 56.0%, 95%CI (0.472, 0.648) and 54.5%, 95%CI (0.488, 0.602) without and with a history and high risk of LBP, respectively. CONCLUSIONS: LBP remains prevalent among international drivers and has multiple contributing factors, highlighting the urgent need for increased awareness and prevention strategies.

Vinculin Identified as a Potential Biomarker in Hand-Arm Vibration Syndrome Based on iTRAQ and LC-MS/MS-Based Proteomic Analysis.

Local vibration can induce vascular injuries, one example is the hand-arm vibration syndrome (HAVS) caused by hand-transmitted vibration (HTV). Little is known about the molecular mechanism of HAVS-induced vascular injuries. Herein, the iTRAQ (isobaric tags for relative and absolute quantitation) followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics approach was applied to conduct the quantitative proteomic analysis of plasma from specimens with HTV exposure or HAVS diagnosis. Overall, 726 proteins were identified in iTRAQ. 37 proteins upregulated and 43 downregulated in HAVS. Moreover, 37 upregulated and 40 downregulated when comparing severe HAVS and mild HAVS. Among them, Vinculin (VCL) was found to be downregulated in the whole process of HAVS. The concentration of vinculin was further verified by ELISA, and the results suggested that the proteomics data was reliable. Bioinformative analyses were used, and those proteins mainly engaged in specific biological processes like binding, focal adhesion, and integrins. The potential of vinculin application in HAVS diagnosis was validated by the receiver operating characteristic curve.

Prevalence of work-related musculoskeletal disorders among workers in the automobile manufacturing industry in China: a systematic review and meta-analysis.

OBJECTIVES: Work-related musculoskeletal disorders (WMSDs) have become one of the major occupational health problems. Lots of auto workers in China are exposed to WMSDs. However, there are few systematic review and meta-analysis about WMSDs in this field. This study aimed to evaluate the prevalence of WMSDs among these workers. METHODS: This study was carried out using the Systematic Reviews and Meta-analyses method under the most up to date PRISMA guidelines. A literature search was conducted for studies on the epidemiology of WMSDs among auto workers in China from inception to August 2022, using English and Chinese databases (China National Knowledge Infrastructure, Wanfang Data, China Biology Medicine Disc, China Science and Technology Journal Database, PubMed, and Web of Science). All statistical analyses were performed using STATA V.16.0. RESULTS: Out of the 849 references identified, 26 articles were were eligible for inclusion, of which 12 reported the overall 12-month prevalence of WMSDs, while 14 stated the 12-month prevalence of WMSDs on body regions. The overall 12-month prevalence rate of WMSDs among workers was 53.1% [95% Confidence Interval (CI) = 46.3% to 59.9%]. The lower back/waist was the body region affected most (36.5%, 95%CI = 28.5% to 44.5%). The definition on WMSDs of "Chinese version" resulted in a high prevalence of WMSDs. Obesity, high educational level, long job tenure, female, logistic workers, and foundry workers are factors that led to a high prevalence rate of WMSDs in the lower back/waist. CONCLUSIONS: This study showed a high prevalence rate of WMSDs among auto workers in China. Thus, it is necessary to pay particular stress to them. Several effective measures should be taken to prevent these workers from WMSDs. TRIAL REGISTRATION: This review was registered on PROSPERO (registration number CRD42023467152).

Local vibration induced vascular pathological structural changes and abnormal levels of vascular damage indicators.

BACKGROUND: The vascular component of the hand-arm-vibration syndrome (HAVS) is often characterized by vibration-induced white fingers (VWF). Active substances secreted by the vascular endothelial cells (VEC) maintain a dynamic balance but damage to the blood vessels may occur when the equilibrium is altered, thus forming an important pathological basis for VWF. This study was aimed at investigating vascular damage indicators as a basis for an early detection of disorders caused by vibration, using the rat tail model. METHODS AND RESULTS: Experiments were conducted using a control group of rats not exposed to vibration while two exposed groups having different exposure durations of 7 and 14 days were randomly formed. Following exposure, the structural changes of tail tissue samples in anesthetized rats were observed. Enzyme-linked immunosorbent assay (ELISA) was used for analyzing four vascular damage indicators myosin regulatory light chain (MLC2), endothelin-1 (ET-1), vinculin (VCL) and 5-hydroxytryptamine (5-HT) in tail blood samples. We found that both vascular smooth muscle and endothelial cells displayed changes in morphology characterized by vacuolization and swelling in the vibration-exposed group. The levels of vascular damage indicators were altered under the vibration. CONCLUSION: The degree of vascular pathology increased with the longer duration exposure. Furthermore, the levels of MLC2, ET-1 and 5-HT in rat plasma were associated with vascular injury caused by local vibration.

The hand-arm vibration syndrome associated with the grinding of handheld workpieces in a subtropical environment.

OBJECTIVES: To study the characteristics and the factors influencing the occurrence of the Hand-Arm Vibration Syndrome (HAVS) for a population grinding handheld workpieces in a subtropical environment. METHODS: A total of 803 workers grinding handheld workpieces formed the exposure group and 464 workers not exposed to hand-transmitted vibration (HTV) were recruited as the non-exposed group within the same factory in a subtropical climate area. The basic personal information and clinical symptoms reported were collected by trained physicians using a questionnaire and representative measurements were made of the HTV exposure levels and dose. RESULTS: The average HTV exposure dose A(8) was measured as 5.3 ± 2.0 m/s2. The proportion of grinders reporting finger blanching was 15.4% while it was 27.5% for finger numbness. Among the non-exposed group, that proportion was 0% and 6.3% respectively. There was a positive association between the vibration exposure duration and the occurrence of finger blanching, finger numbness and finger coldness. Riding a motorcycle to work was also identified as a factor that could contribute to a higher prevalence of finger blanching among the exposed workers, the OR value was found to be 1.75 (1.12, 2.75). CONCLUSIONS: Workers exposed to vibration in a subtropical area can also present evidence of finger blanching in addition to neurological symptoms. The reported rate of HAVS was positively associated with the exposure duration. And the levels of the duration of exposure relative to symptoms of vibration white finger in a subtropical temperate environment exposed to a high-frequency vibration might be deemphasized by the current ISO weighting. Motorcycle transportation to work was identified as a factor that could influence the development of the HAVS among the exposed population of grinders.

Cold water immersion test (10 °C, 10 min) for diagnosing vibration-induced white finger among a group of polishers in a subtropical environment.

OBJECTIVE: This study aimed to investigate whether the finger skin temperature (FST) after cold provocation (10 °C, 10 min) is as a useful indicator for assisting in the diagnosis of vibration-induced white finger (VWF) in a group of polishers in a subtropical environment. METHOD: Ninety male vibration-exposed metal polishers (30 patients and 60 controls) from the Guangdong Province in Southern China were recruited. The FSTs at 30, 20, 10, and 0 min before cold water immersion (FSTpre-30, FSTpre-20, FSTpre-10, and FSTbaseline) and 0, 5, 10, 15, 20, 25, and 30 min after immersion (FST0, FST5, FST10, FST15, FST20, FST25, and FST30) were measured on the index, middle, and ring fingers of both hands. RESULTS: During the first 20-min adaptation period, there was a significant increase in FST in three fingers on both hands in the two groups. In contrast, there were no significant differences between FSTpre-10 and FSTbaseline. Furthermore, FSTpre-30, FSTpre-20, FSTpre-10, and FSTbaseline of the three fingers in both hands did not differ significantly. During recovery, the indicators FST5-0, FST10-0, R5, and R10 for the index finger of the left hand in patients were lower than for the controls. Among the various indicators, the absolute recovery rate, FST5-0, at 5 min after immersion was identified as the best diagnosis indicator with a sensitivity of 76.7% and specificity of 70.0% when applied to the index finger of the left hand. CONCLUSION: The cold water immersion test as applied in a subtropical environment can have a fair discriminating ability for diagnosing VWF.

Overexpression of lncRNA IGFBP4-1 reprograms energy metabolism to promote lung cancer progression.

BACKGROUND: Reprogrammed energy metabolism as an emerging hallmark of cancer has recently drawn special attention since it facilitate cell growth and proliferation. Recently, long noncoding RNAs (lncRNAs) have been served as key regulators implicated in tumor development and progression by promoting proliferation, invasion and metastasis. However, the associations of lncRNAs with cellular energy metabolism in lung cancer (LC) need to be clarified. METHODS: Here, we conducted bioinformatics analysis and found insulin-like growth factor binding protein 4-1 (IGFBP4-1) as a new candidate lncRNA located in the upstream region of IGFBP4 gene. The expression levels of lnc-IGFBP4-1, mRNA levels of IGFBP4 in 159 paired lung cancer samples and adjacent, histological normal tissues by qRT-PCR. Over-expression and RNA interference (RNAi) approaches were adopted to investigate the biological functions of lnc-IGFBP4-1. The intracellular ATP level was measured using the Cell Titer-Glo Luminescent Cell Viability Assay kit, and changes in metabolic enzymes were examined in cancer cells and normal pulmonary epithelial cells with qRT-PCR. RESULTS: Our results showed that lnc-IGFBP4-1 was significantly up-regulated in LC tissues compared with corresponding non-tumor tissues (P < 0.01), and its expression level was significantly correlated with TNM stage (P < 0.01) and lymph node metastasis (P < 0.05). Further investigation showed that overexpression of lnc-IGFBP4-1 significantly promoted LC cell proliferation in vitro and in vivo, while downregulation of endogenous lnc-IGFBP4-1 could inhibited cell proliferation and induce apoptosis. Moreover, we found lnc-IGFBP4-1 could influences ATP production levels and expression of enzymes including HK2, PDK1 and LDHA, in addition, decline in both ATP production and these enzymes in response to 2-DG and 2-DG-combined Rho123, respectively, was observed in lnc-IGFBP4-1-overespressing LC cells, indicative of an enhanced aerobic glycolysis rate. Finally, lnc-IGFBP4-1 was observed to negatively correlate with gene IGFBP4, and lower expression level of IGFPB4 was found after lnc-IGFBP4-1-overexpression was transfected into PC9 cells, higher expression level of IGFPB4 was also found after lnc-IGFBP4-1-downregulation was transfected into GLC-82 cells, which indicates that IGFBP4 may exert its targeting function regulated by lnc-IGFBP4-1. CONCLUSIONS: Taken together, these findings provide the first evidence that lnc-IGFBP4-1 is significantly up-regulated in LC tissues and plays a positive role in cell proliferation and metastasis through possible mechanism of reprogramming tumor cell energy metabolism, which suggests that lnc-IGFBP4-1 may be a promising biomarker in LC development and progression and as a potential therapeutic target for LC intervention.

Vibration characteristics of golf club heads in their handheld grinding process and potential approaches for reducing the vibration exposure.

To control vibration-induced white finger among workers performing the fine grinding of golf club heads, the aims of this study are to clarify the major vibration sources in the grinding process, to identify and understand the basic characteristics of the club head vibration, and to propose potential approaches for reducing the vibration exposure. The vibrations on two typical club heads and two belt grinding machines were measured at a workplace. A simulated test station was also constructed and used to help examine some influencing factors of the club head vibration. This study found that the club head vibration was the combination of the vibration transmitted from the grinding machines and that generated in the grinding process. As a result, any factor that affects the machine vibration, the grinding vibration, and/or the dynamic response of the club head can influence the vibration exposure of the fingers or hands holding the club head in the grinding process. The significant influencing factors identified in the study include testing subject, grinding machine, machine operation speed, drive wheel condition, club head model, mechanical constraints imposed on the club head during the grinding, and machine foot pad. These findings suggest that the vibration exposure can be controlled by reducing the grinding machine vibration, changing the workpiece dynamic properties, and mitigating the vibration transmission in its pathway. Many potential methods for the control are proposed and discussed. RELEVANCE TO INDUSTRY: Vibrations on handheld workpieces can be effectively transmitted to the hands, especially the fingers. As a result, a major component of the hand-arm vibration syndrome - vibration-induced white finger - has been observed among some workers performing the grinding and/or polishing tasks of the handheld workpieces such as golf club heads. The results of this study can be used to develop more effective methods and technologies to control the vibration exposure of these workers. This may help effectively control this occupational disease.

The role of Pten/Akt signaling pathway involved in BPA-induced apoptosis of rat Sertoli cells.

Bisphenol-A (BPA), one of endocrine-disrupting chemicals, is a male reproductive toxicant. Previous studies have revealed the direct cytotoxicity of BPA in many cultured cells, such as mitotic aneuploidy in embryonic cells and somatic cells, and apoptosis in neurons and testicular Sertoli cells. To understand the action of BPA and assess its risk, the Pten/Akt pathway was investigated in cultured Sertoli cells to elucidate the mechanism of the reproductive effects of BPA. The results showed that over 50 µM BPA treatment could decrease the viability of Sertoli cells and cause more apoptosis. In addition, BPA could induce the increase in mRNA levels of Pten and Akt. The protein level of Pten was increased; however, the protein levels of phospho-Akt and procaspase-3 were decreased after BPA exposure. Taken together, observed results suggested that the Pten/Akt pathway might be involved in the apoptotic effects of BPA on Sertoli cells.

Dietary calcium intake and mortality risk from cardiovascular disease and all causes: a meta-analysis of prospective cohort studies.

BACKGROUND: Considerable controversy exists regarding the association between dietary calcium intake and risk of mortality from cardiovascular disease and all causes. Therefore, we performed a meta-analysis of prospective cohort studies to examine the controversy. METHODS: We identified relevant studies by searching MEDLINE, Embase, and the Cochrane Library databases between 1 September 2013 and 30 December 2013. Reference lists of relevant articles were also reviewed. Observational prospective studies that reported relative risks and 95% confidence intervals for the association of calcium intake with cardiovascular and all-cause mortality were eligible. Study-specific relative risks were pooled using a random-effects model. RESULTS: In this meta-analysis, 11 prospective studies with 12 independent cohorts, involving 757,304 participants, were eligible. There was evidence of a non-linear association between dietary calcium intake and risk of mortality from cardiovascular disease (P for non-linearity <0.01) and all causes (P for non-linearity <0.01). A dose-response analysis showed a U-shaped relationship between dietary calcium intake and cardiovascular mortality. Intakes that were lower and higher than around 800 mg/day were gradually associated with a higher risk of cardiovascular mortality. For all-cause mortality, we also observed a threshold effect at intakes around 900 mg/day. The risk of all-cause mortality did not decrease further at intakes above 900 mg/day. CONCLUSIONS: This meta-analysis of prospective cohort studies suggests that dietary calcium intake is associated with cardiovascular mortality in a U-shaped manner and that high dietary calcium intake (>900 mg/day) is not associated with a decreased risk of all-cause mortality.

Microvascular abnormalities induced by hand-transmitted vibration reflects in finger systolic blood pressure: a cross-sectional study in China.

OBJECTIVE: Local vibration can cause microcirculatory abnormalities such as blood stasis and symmetrical intermittent digital artery vasospasm. Finger SBP (FSBP) measurement is a potential way of assessing vascular components. This study aims to comprehensively investigate the relationship between the occurrence of the vibration-induced white finger (VWF) and changes in FSBP and then set the application value of FSBP measurements in the early diagnosis of VWF. METHODS: All samples were judgmental sampling from one factory. Totally 50 patients with VWF were the case group, while 50 without occupational hand-transmitted vibration exposure were the control group. FSBP measurements and epidemiological feature investigations were taken. RESULTS: There were significant reductions in FSBP level and %FSBP index at both 10 °C and 30 °C in fingers reported VWF ( P  < 0.05). The %FSBP abnormal rate of the index, ring and little finger in the VWF group was higher than the control (44.00% vs. 18.00%, 78.00% vs. 26.00%, 64.00% vs. 8.00%). The %FSBP of the ring and little finger had a relatively high application value (area under curve = 0.902, 0.737), while their standard regression coefficients were -0.23 and -0.412. The diagnostic cutoff value of the ring finger was 77.60%, while the sensitivity and specificity were 86.67%. CONCLUSION: FSBP measurements were proven helpful in monitoring and diagnosing VWF prospectively and proved to have great application value in our study. %FSBP of the ring finger was the appropriate diagnostic index in FSBP measurements, while its abnormal value could be set as 80.00%.

A new diagnostic scoring system to differentiate Hirschsprung's disease from Hirschsprung's disease-allied disorders in patients with suspected intestinal dysganglionosis.

PURPOSE: To create a simple diagnostic scoring system to differentiate Hirschsprung's disease (HD) from Hirschsprung's disease-allied disorders (HAD) in patients with suspected intestinal dysganglionosis (IDs). METHODS: Between 1998 and 2008, 967 patients with suspected intestinal dysganglionosis underwent surgical treatment at the pediatric surgery department of Tongji Hospital. The diagnosis of HD or HAD was confirmed by postoperative pathological examination. All patients underwent preoperative work-up including barium enema, anorectal manometry, and histochemical acetylcholinesterase staining of rectal mucosa. Known risk factors for IDs were recorded. The predicting score was calculated by summing the scores of the risk factors and three preoperative tests. The sensitivity, specificity, accuracy, positive predictive values, negative predictive values, positive likelihood ratios, and negative likelihood ratios of the predicting score were calculated. The cutoff score for predicting HD was determined using receiver operating characteristic (ROC) analysis. The accuracy of the predicting score was measured by the area under the ROC curve. RESULTS: Failed or delayed passage of meconium, age <3 years and male gender were risk factors associated with HD. The area under the ROC curve of the predicting score was 0.927 (95 % confidence interval, 0.910-0.944). A predicting score of more than 5 was used as a cutoff for predicting HD. The scoring system achieved 83.1 % sensitivity, 89.5 % specificity, and 85.9 % accuracy in predicting HD. CONCLUSION: Patients with a predicting score of more than 5 are more likely to be diagnosed with HD, whereas a score less than 5 are mostly indicative of HAD.

Impact of Previous Local Treatment for Brain Metastases on Response to Molecular Targeted Therapy in BRAF-Mutant Melanoma Brain Metastasis: A Systematic Review and Meta-Analysis.

Background: Melanoma brain metastases (BMs) are associated with poor prognosis and are the main cause of mortality in melanoma patients. BRAF inhibitors have shown intracranial activity in both treatment-naïve and previously treated BM patients. We aimed to investigate if there was any difference in response of BRAF inhibitors in these two cohorts. Materials and Methods: Electronic database search included PubMed, Medline, and Cochrane library until March 2021 for studies with desired comparative outcomes. Outcomes of interest that were obtained for meta-analysis included intracranial response rate as the primary outcome and survival and safety outcomes as the secondary outcomes. Review Manager version 5.4 was used for data analysis. Results: Three studies comprising 410 BRAF-mutated melanoma patients with BMs were included according to eligibility criteria. The comparative cohort included patients with treatment-naïve BMs (TN cohort; n = 255) and those who had progressive disease after receiving local brain treatment for BMs (PT cohort; n = 155). Meta-analysis revealed that BRAF inhibitors (vemurafenib and dabrafenib) and BRAF/MEK inhibitor combination (dabrafenib and trametinib) induced significantly higher intracranial disease control (OR 0.58 [95% CI: 0.34, 0.97], p = 0.04) and a trend toward improved progression-free survival (PFS) (HR 1.22 [95% CI: 0.98, 1.52], p = 0.08) in the PT cohort as compared to the TN cohort. Overall survival was not significantly different between the cohorts (HR 1.16 [95% CI: 0.89, 1.51], p = 0.28). Subgroup analysis revealed that PFS was significantly improved (HR 1.67 [95% CI: 1.06, 2.62], p = 0.03), and a trend toward improved OS (HR 1.62 [95% CI: 0.95, 2.75], p = 0.08) was achieved in patients receiving BRAF/MEK inhibitor combination and patients with BRAFv600K mutation receiving dabrafenib alone. No increase in overall adverse events (AEs), grade 3/4 AEs, and severe adverse events (SAEs) was observed between the cohorts. Conclusions: BRAF inhibitors (plus MEK inhibitor) may achieve better intracranial disease stability in BRAF-mutant melanoma patients who have received previous local treatment for BMs. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/), identifier CRD42020185984.

Joint effects of polycyclic aromatic hydrocarbons, smoking, and XPC polymorphisms on damage in exon 2 of KRAS gene among young coke oven workers.

Genetic polymorphisms may contribute to individual susceptibility to DNA damage induced by environmental exposure. In this study, we evaluate the effects of co-exposure to PAHs, smoking and XPC polymorphisms, alone or combined, on damage in exons. A total of 288 healthy male coke oven workers were enrolled into this study, and urinary 1-hydroxypyrene (1-OH-Pyr) was detected. Base modification in exons of KRAS and BRAF gene, and polymorphisms of XPC were determined in plasma by real-time PCR. We observed 1-OH-Pyr was positively related to damage in exon 2 of KRAS (KRAS-2) and in exon 15 of BRAF (BRAF-15), respectively, and KRAS-2 and BRAF-15 were significantly associated with increased 1-OH-Pyr. A stratified analysis found 1-OH-Pyr was significantly associated with KRAS-2 in both smokers and non-smokers, while 1-OH-Pyr was significantly associated with BRAF-15 only in smokers. Additionally, individuals carrying both rs2228001 G-allele (GG+GT) and rs3731055 GG homozygote (GG) genotype appeared to have more significant effect on KRAS-2. The high levels of 1-OH-Pyr were associated with KRAS-2 only in rs2228001 GG+GT genotype carriers and the high levels of 1-OH-Pyr were associated with KRAS-2 only in rs3731055 GG genotype carriers and the most severe KRAS-2 was observed among subjects carrying all four of the above risk factors. Our findings indicated the co-exposure effect of PAHs and smoking could increase the risk of KRAS-2 by a mechanism partly involving XPC polymorphisms.

Bevacizumab Treatment of Radiation-Induced Brain Necrosis: A Systematic Review.

BACKGROUND: Radiation brain necrosis (RBN) is a serious complication in patients receiving radiotherapy for intracranial disease. Many studies have investigated the efficacy and safety of bevacizumab in patients with RBN. In the present study, we systematically reviewed the medical literature for studies reporting the efficacy and safety of bevacizumab, as well as for studies comparing bevacizumab with corticosteroids. MATERIALS AND METHODS: We searched PubMed, Cochrane library, EMBASE, and ClinicalTrials.gov from their inception through 1 March, 2020 for studies that evaluated the efficacy and safety of bevacizumab in patients with RBN. Two investigators independently performed the study selection, data extraction, and data synthesis. RESULTS: Overall, the present systematic review included 12 studies (eight retrospective, two prospective, and two randomized control trials [RCTs]) involving 236 patients with RBN treated who were treated with bevacizumab. The two RCTs also had control arms comprising patients with RBN who were treated with corticosteroids/placebo (n=57). Radiographic responses were recorded in 84.7% (200/236) of patients, and radiographic progression was observed in 15.3% (36/236). Clinical improvement was observed in 91% (n=127) of responding patients among seven studies (n=113). All 12 studies reported volume reduction on T1 gadolinium enhancement MRI (median: 50%, range: 26%-80%) and/or T2 FLAIR MRI images (median: 59%, range: 48%-74%). In total, 46 responding patients (34%) had recurrence. The two RCTs revealed significantly improved radiographic response in patients treated with bevacizumab (Levin et al.: p = 0.0013; Xu et al.: p < 0.001). Both also showed clinical improvement (Levin et al.: NA; Xu et al.: p = 0.039) and significant reduction in edema volume on both T1 gadolinium enhancement MRI (Levin et al.: p=0.0058; Xu et al.: p=0.027) and T2 FLAIR MRI (Levin et al.: p=0.0149; Xu et al.: p < 0.001). Neurocognitive improvement was significantly better after 2 months of treatment in patients receiving bevacizumab than in those given corticosteroids, as assessed by the MoCA scale (p = 0.028). The recurrence rate and side effects of the treatments showed no significant differences. CONCLUSIONS: Patients with RBN respond to bevacizumab, which can improve clinical outcomes and cognitive function. Bevacizumab appears to be more efficacious than corticosteroid-based treatment. The safety profile was comparable to that of the corticosteroids.

The interaction effects of FEN1 rs174538 polymorphism and polycyclic aromatic hydrocarbon exposure on damage in exon 19 and 21 of EGFR gene in coke oven workers.

Polycyclic aromatic hydrocarbon (PAH) exposure and genetic susceptibility were conductive to genotoxic effects including gene damage, which can increase mutational probability. We aimed to explore the dose-effect associations of PAH exposure with damage of exons of epidermal growth factor receptor (EGFR) and breast cancer susceptibility gene 1 (BRCA1), as well as their associations whether modified by Flap endonuclease 1 (FEN1) genotype. Two hundred eighty-eight coke oven male workers were recruited, and we detected the concentration of 1-hydroxypyrene (1-OH-pyr) as PAH exposure biomarker in urine and examined base modification in exons of EGFR and BRCA1 respectively, and genotyped FEN1 rs174538 polymorphism in plasma. We found that the damage indexes of exon 19 and 21 of EGFR (EGFR-19 and EGFR-21) were both significantly associated with increased urinary 1-OH-pyr (both Ptrend < 0.001). The levels of urinary 1-OH-pyr were both significantly associated with increased EGFR-19 and EGFR-21 in both smokers and nonsmokers (both P < 0.001). Additionally, we observed that the urinary 1-OH-pyr concentrations were linearly associated with both EGFR-19 and EGFR-21 only in rs174538 GA+AA genotype carriers (both P < 0.001). Moreover, FEN1rs rs174538 showed modifying effects on the associations of urinary 1-OH-pyr with EGFR-19 and EGFR-21 (both Pinteraction < 0.05). Our findings revealed the linear dose-effect association between exon damage of EGFR and PAH exposure and highlight differences in genetic contributions to exon damage and have the potential to identify at-risk subpopulations who are susceptible to adverse health effects induced by PAH exposure.

Efficacy and Safety of Actively Personalized Neoantigen Vaccination in the Management of Newly Diagnosed Glioblastoma: A Systematic Review.

PURPOSE: Glioblastoma (GBM) shows frequent relapse and is highly resistant to treatment; therefore, it is considered fatal. Various vaccination protocols that have been tested in patients with GBM, which is the most common and aggressive primary brain tumor, have indicated safety and efficacy, to some extent, when used alone or in combination with standard of care. Recently, neoantigen-based personalized vaccines have shown tremendous immunogenicity and safety in GBM. We aimed to systematically review the medical literature for clinical trials to evaluate the efficacy and safety of neoantigen-based personalized vaccines for newly diagnosed GBM. METHODS: We conducted a literature search for clinical trials on PubMed, Cochrane Library, China National Knowledge Infrastructure, and ClinicalTrials.gov until March 20, 2021. The primary outcomes of interest were immunogenicity and safety of the therapy. Efficacy outcomes, such as progression-free survival and overall survival, were secondary outcomes of interest. RESULTS: Two clinical trials involving 24 patients were included in this review. High immunogenicity was observed in both studies. The GAPVAC-101 trial reported 50% APVAC1-induced and 84.7% APVAC2-induced immunogenicity with CD8+ and CD4+ T cell responses in 92% (12/13) and 80% (8/10) immune responders, respectively. Two out of five patients showed CD4+ and CD8+ T cell responses in the study by Keskin et al. Dexamethasone use had limited immunogenicity in a trial by Keskin et al (6/8). No serious treatment-related adverse events were reported. CONCLUSION: Actively personalized vaccines aimed at unmutated peptides and neoantigens for patients with GBM are safe and highly immunogenic, particularly when administered in combination. Larger studies are warranted to investigate the role.

Radiation Plus Anti-PD-1 Therapy for NSCLC Brain Metastases: A Retrospective Study.

BACKGROUND: Radiation therapy (RT) is the mainstay of brain metastases (BMs), and anti-PD-1 blockade has led to intracranial responses in non-small cell lung carcinoma (NSCLC) patients with BMs. OBJECTIVE: This study aimed to evaluate the efficacy and safety of adding anti-PD-1 blockade to RT in the management of NSCLC patients with BM in terms of survival outcome. MATERIALS AND METHODS: We retrospectively reviewed 70 NSCLC patients with BMs who were treated with whole brain radiation therapy (WBRT) between January 2016 and January 2021. Of the 70 patients, 29 additionally received anti-PD-1 therapy within 30 days of WBRT initiation. Baseline characteristics of the patients and efficacy outcomes such as progression-free survival (PFS) and overall survival (OS) were statistically compared using SPSS v26. Results were obtained using the Chi-square test/Fisher exact test, t-test, Kaplan-Meier, and Cox regression survival analyses. RESULTS: The median survival for the entire cohort was 24 months (95% CI, 19.5-28.5). The median survival times for WBRT alone and WBRT plus anti-PD-1 therapy cohorts were 20 months (95% CI, 11.6-28.3) and 27 months (95% CI, 19.5-28.5), respectively (p=0.035). There was no statistical difference in PFS for the treatment cohorts (median PFS for WBRT alone: 7 months vs. 12 months for WBRT plus anti-PD-1, p=0.247). In EGFR wild-type subgroup (n=31), both PFS (p=0.037) and OS (p=0.012) were significantly improved. Only the treatment group (WBRT plus anti-PD-1) was a significant predictor of OS on univariate and multivariate analyses (p=0.040). There were no significant differences in adverse events among the treatment groups. CONCLUSIONS: NSCLC patients with BM receiving additional anti-PD-1 therapy may derive better OS than WBRT alone without any increase in adverse events. Prospective well-designed studies are warranted to validate and elucidate the additive effects of the two modalities in this group of patients.

Evaluation of work-related musculoskeletal disorders among sonographers in general hospitals in Guangdong province, China.

Introduction. Research on the prevalence of and potential risk factors associated with work-related musculoskeletal disorders (WMSDs) among sonographers in China is scarce. More evidence is required to mitigate WMSDs among sonographers in Guangdong province, China. Objective. The present study aimed to determine the prevalence of and potential associated factors for WMSDs among sonographers in general hospitals in Guangdong province, China. Methods. A self-reported questionnaire was distributed to sonographers from 14 general hospitals selected by convenience sampling in Guangdong province. Multivariate logistic regression was used to analyze associations between potential factors and WMSDs in the most affected body areas. Results. In this study, 249 sonographers completed the questionnaire, yielding a response rate of 75.5%. The 12-month period prevalence of WMSDs was 95.2%, and the four most affected regions were the right shoulder (81.1%) followed by the neck (74.7%), right wrist/hand (59.4%) and lower back (57.0%). Among symptomatic sonographers, 31.2% were absent from work. Gender, years of experience, number of patients per day, shift type and lumbar support were associated with WMSDs in the most affected regions. Conclusion. Lower workload, more regular rest breaks and good ergonomics of working conditions are encouraged to alleviate WMSDs among sonographers in Guangdong province.