ABSTRACT
Objective To conduct a survey on the status of noise hazards in Tianjin in 2020, to analyze the main distribution characteristics of noise hazards, and to put forward corresponding preventive and control measures. Methods A unified questionnaire was used to investigate the city-wide enterprises with more than 5 employees, normal production and operation, and noise hazards. The χ2 test was used to analyze the survey results. Results There were 8 560 enterprises with noise hazards, which were concentrated in the five outer suburban districts, the four districts around the city and the Binhai New Area, mainly small and medium-sized enterprises. Totally, 223 800 people were exposed to noise. The rates of noise hazard detection and physical examination of workers were 25.88% and 17.66%, and the rate of over standard detection and the rate of abnormal physical examination were 13.09% and 1.62%, respectively. The differences in noise detection rate, over standard detection rate and physical examination rate were significant in different administrative regions, enterprise scales and industries. The detection rate and physical examination rate of enterprises in the five outer suburban districts, micro-scale enterprises, and paper products industries were the lowest, while the rate of exceeding standards was the highest in the railway, shipping, aerospace and other transportation equipment manufacturing industries. Conclusion Noise is a common occupational hazard in enterprises in Tianjin. There are a large number of people who are exposed to noise. The detection rate and physical examination rate of noise are at a low level. Individual industries have a high rate of exceeding the standard. The current situation of noise hazard prevention and control is not optimistic. It is recommended to pay attention to it and take effective intervention measures.
ABSTRACT
Hypoxia, as an important hallmark of the tumor microenvironment, is a major cause of oxidative stress and plays a central role in various malignant tumors, including glioblastoma. Elevated reactive oxygen species (ROS) in a hypoxic microenvironment promote glioblastoma progression; however, the underlying mechanism has not been clarified. Herein, we found that hypoxia promoted ROS production, and the proliferation, migration, and invasion of glioblastoma cells, while this promotion was restrained by ROS scavengers N-acetyl-L-cysteine (NAC) and diphenyleneiodonium chloride (DPI). Hypoxia-induced ROS activated hypoxia-inducible factor-1α (HIF-1α) signaling, which enhanced cell migration and invasion by epithelial-mesenchymal transition (EMT). Furthermore, the induction of serine protease inhibitor family E member 1 (SERPINE1) was ROS-dependent under hypoxia, and HIF-1α mediated SERPINE1 increase induced by ROS via binding to the SERPINE1 promoter region, thereby facilitating glioblastoma migration and invasion. Taken together, our data revealed that hypoxia-induced ROS reinforce the hypoxic adaptation of glioblastoma by driving the HIF-1α-SERPINE1 signaling pathway, and that targeting ROS may be a promising therapeutic strategy for glioblastoma.
Subject(s)
Humans , Cell Hypoxia , Cell Line, Tumor , Glioblastoma/pathology , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Plasminogen Activator Inhibitor 1/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction , Tumor Microenvironment , Brain Neoplasms/pathologyABSTRACT
Objective:To observe the changes of optic disc structure in patients with high myopia and the correlation with the morphological markers of the fundus.Methods:A retrospective study. From July 2018 to January 2020, 90 patients (155 eyes) diagnosed as high myopia in Department of Ophthalmology of Beijing Friendship Hospital affiliated to Capital Medical University were included in the study. Among them, there were 31 males (52 eyes) and 59 females (103 eyes), with age of 57.1±14.2 years old and axial length (AL) of 28.5±2.6 mm. According to the classification of myopic macular degeneration, patients were divided into 4 groups based on forms and degree of lesions, including non-pathological myopia group, mild traction lesions group, severe traction lesions group and neovascular lesions group, 35, 58, 41, 21 eyes, respectively. The digitized fundus photographs and an Image J system were used to measure the horizontal, vertical, maximal, and minimal diameter of the optic disc, the horizontal and vertical diameter of the parapapillary δ zone and γ zone, ovality index, distance between the most superior point of the temporal superior arterial arcade and most inferior point of the temporal inferior arterial arcade (VDA), angle between the temporal arterial arcade and optic disc (angle kappa), distance between the optic disc center and the fovea (DFD), angle between the horizontal disc axis and the disc-fovea line (DFA). The correlation between the diameter of the optic disc and other parameters was analyzed. Univariate and multivariate analysis were used to compare differences between groups.Results:The horizontal diameter of the optic disc was positively correlated with the horizontal diameter of the δ zone ( r=0.300, P<0.001), Kappa angle ( r=0.260, P=0.003), and elliptic index ( r=0.650, P<0.001); it was negatively correlated with DFD ( r=-0.190, P=0.030). Optic disc vertical diameter and optic disc horizontal diameter ( r=0.280), δ-zone horizontal diameter ( r=0.330) and vertical diameter ( r=0.460), γ-zone horizontal diameter ( r=0.430) and vertical diameter ( r=0.390), DFD ( r=0.390) was positively correlated ( P<0.001); it was negatively correlated with DFA ( r=-0.210, P=0.001) and Kappa angle ( r=-0.210, P=0.004). Compared with the non-pathological myopia group, there were statistically significant differences in the horizontal and vertical diameters of the optic disc in the severe traction disease group ( P<0.05). Among them, the horizontal diameter difference did not depend on the eye axis and age difference; the vertical diameter difference was caused by the eye axis difference. Compared with the non-pathological myopia group, the difference in the horizontal diameter of the optic disc in the neovascular disease group was statistically significant ( P<0.05), and did not depend on the difference in the axis and age; the difference in the vertical diameter of the optic disc was not statistically significant ( P>0.05). Conclusion:The morphology of optic disc was related to several fundus morphological markers, which was differentiated according to the age, AL and the degree of disease in patients with high myopia.
ABSTRACT
Objective:To analyze and screen microRNA (miRNA) related to the prognosis of gastric cancer(GC) by bioinformatics analysis, and to construct and validate a risk score model.Methods:The human genome miRNA sequencing data and corresponding clinicopathological data of the 491 samples (446 GC tissue samples and 45 normal gastric tissue samples) were downloaded from the cancer genome atlas (TCGA) database. The differentially expressed microRNA (DEM) was analyzed with edgeR package of R 4.0.2 software and the obtained DEM’s profile was randomly divided into training set and test set according to the ratio of 1∶1. The miRNA related to prognosis were analyzed and screened with univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression analysis was further performed to analyze the screened prognostic-related miRNA and then the prognostic risk score model was constructed. Kaplan-Meier curve, receiver operating characteristic curve (ROC), and dynamic area under the ROC were drawn to evaluate the predictive power of the model.Results:A total of 175 DEM in GC tissues were screened out based on the cut-off criteria of |log2 Fold Change|>1.5 and P<0.01. Six DEMs related to the overall survival rate of patients with GC were screened out by univariate Cox regression and LASSO regression analysis, and then a five-miRNA risk score model was successfully constructed by multivariate Cox regression. The risk score=0.183×hsa-miRNA-184+ 0.086×hsa-miRNA-675-0.231×hsa-miRNA-2115+ 0.548×hsa-miRNA-3943-1.455×hsa-miRNA-1246. In the training set, test set and overall data set, the cumulative survival rates of the patients with higher risk score were lower than those of the patients with lower risk score, respectively, and the differences were statistically significant ( χ2=18.90, 9.50 and 26.70, all P<0.05). The prediction power of the model was better than that of TNM stage. And the results of stratified analysis showed the predictive ability of the model in patients with early GC. The results of univariate Cox regression and multivariate Cox regression demonstrated that the risk score of the model, gae and M stage were independent risk factors for poor prognosis in patients with GC (hazard ratio(95% confidence interval)1.19(1.07 to 1.32), 1.20(1.06 to 1.40), 1.50(1.01 to 2.23), 1.90(1.28 to 2.90), 1.34(1.15 to 1.57), 2.10(1.05 to 4.40); all P<0.05). Conclusion:The 5-miRNA risk score model based on 5 miRNAs which was an independent prognostic factor had high accuracy in predicting the prognosis of patients with GC.
ABSTRACT
Objective To understand the occupational hazards of dust related enterprises in Tianjin, and to provide a scientific basis for formulating regulatory policies and effectively curbing the high incidence of pneumoconiosis. Methods The basic situation of the enterprise, the occupational health management status, and the occupational health status of the workers were described and analyzed. Results Most of the enterprises exposed to dust in Tianjin were small and micro enterprises, manufacturing enterprises and private enterprises. The reporting rate of occupational hazard items was uneven (P < 0.01). As the scale of the enterprise decreased, the comprehensive training rate of occupational health, the training rate of enterprise leaders, the training rate of occupational health management personnel, the comprehensive implementation rate of occupational hazard detection and the detection rate decreased accordingly (P < 0.01). Conclusion Tianjin should focus on the supervision of small and micro enterprises, strengthen the occupational health training of small and micro enterprises, and implement hierarchical and effective supervision for enterprises of different sizes in different regions. Meanwhile, enterprises should bear the main responsibility of occupational health, so as to ensure the continuity of occupational health management measures such as occupational hazard detection and occupational health inspection.
ABSTRACT
A 57-year-old man was admitted to hospital with diarrhea for 10 months and dizziness for 4 months. The patient had 1-2 liters watery stool per day, without pyogenic blood or abnormality in gastroenteroscopy examination. The level of hemoglobin and albumin was generally normal, and fasting test was positive. At the same time, he was accompanied with hyperalgesia of lower limbs and orthostatic hypotension. After the discussion of multiple disciplinary teams, the patient was diagnosed with amyloidosis by sural nerve biopsy, myocardial MRI, and the assays of urine immunoelectrophoresis and serum free light chain. Light chain amyloidosis was confirmed after excluded the diagnosis of familial amyloidosis. The patient was improved after courses of chemotherapy with melphalan and dexamethasone.
ABSTRACT
BACKGROUND@#Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE).@*METHODS@#This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE.@*RESULTS@#This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively.@*CONCLUSIONS@#Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.
ABSTRACT
Objective@#Analyzes of the monitoring results of silicosis in key occupational disease monitoring in Tianjin in 2017, providing reference for continuous monitoring, and prevention and control work of silicosis.@*Methods@#Monitor and analyze the current state of silica dust hazard enterprises, the health status of silica dust workers, and the characteristics of newly developed silicosis cases in accordance with the national 2017 work plan for key occupational disease monitoring and occupational health risk assessment.@*Results@#In 2017, 210 enterprises have silica dust hazard in Tianjin, silica dust workplaces exceed the standard rate is 34.73%, 5 695 workers' health examination who contact with silica dust were collected. 2 were detected occupational contraindication, the abnormal detection rate of chest examination is 3.60%, the abnormal index of lung function mainly is FVC, the abnormal rate is 15.8%. The abnormal rate increases with working years. In 2017, 193 new cases of silicosis were reported most cases were developed after years of decontamination. Most enterprises with cases had already out of market, only 7 were still producing.@*Conclusion@#The key prevention and control in Tianjin was enterprises with silica dust excess of standard, as well as older and longer working years workers, adopting effective measures to reduce the concentration of silica dust in workplace is a fundamental measure to reduce the risk of silicosis.
ABSTRACT
Objective To investigate the effects of radical prostatectomy on the overall survival (OS)and tumor-specific survival in prostate cancer(PCa)patients aged 75 years and older.Methods Clinical data of patients aged 75 and older with localized PCa from Surveillance,Epidemiology,and End Results(SEER)Database from 2004 to 2016 were retrospectively analyzed.There were 17 899 cases of PCa undergoing radical prostatectomy and 3 648 cases of PCa without surgery in this study.The OS and prostate cancer-specific survival(PSS)were compared between the surgery group and the nonsurgery group.Results For 75-79-year-old patients with high-risk localized PCa,the OS and PSS in the surgery group were better than in the non-surgery group (OR =1.49,95 ％ CI:1.22 ～ 1.82,P ＜ 0.01;OR=1.43,95％CI:1.09～2.04,P＜0.05).For patients aged 75-79 years with low-risk PCa and patients aged 80 years and older with low-,middle-,or high-risk PCa,the OS was worse in the surgery group than in the non-surgery group(OR =0.54,95％CI:0.38～0.76,P＜0.01;OR =0.47,95％CI:0.34～0.66,P＜0.01;OR =0.58,95％CI:0.44～0.78,P＜0.01;OR =0.59,95％CI:0.51 ～0.68,P＜0.01).For patients aged 75-79 years with low-or medium-risk PCa and patients aged 80 years and older with medium-risk PCa,there was no statistical difference in PSS between the surgery and non-surgery groups(P＞0.05).Conclusions Age limits for prostatectomy should be extended as a result of increasing average life expectancy.Patients aged 75-79 years with high-risk PCa can be considered for surgical treatment,while it should not be recommended for patients aged 75-79 years with low-or medium-risk localized PCa or aged more than 80 years.Many factors should be considered in making treatment decisions for prostate cancer.
ABSTRACT
The application of immunological checkpoint inhibitors (ICIs) has modified many treatment strategies of malignant tumors, which has become a milestone in cancer therapy. The principle of action can be explained as "brake theory". After releasing the brakes by ICIs, unprecedented systemic toxicities, even some refractory and fatal immune-related adverse effects (irAEs) may develop. In this article, we summarized the recommended treatments of grade 3-4 severe irAEs in the latest European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network (NCCN)/American Society of Clinical Oncology (ASCO), Society for Immunotherapy of Cancer (SITC) and Chinese Society of Clinical Oncology (CSCO) guidelines and consensus. We also performed a systemic review of case reports and reviews of irAEs up to May 20, 2019 in PubMed and Chinese journals. Successful applications of specific immunosuppressive drugs and stimulating factors beyond the above guidelines and consensus were supplemented and highlighted, including agents blocking interleukin 6 (IL-6), rituximab, anti-tumor necrosis factor-α (TNFα) monoclonal antibody (mAb), anti-integrin 4 mAb, Janus kinase inhibitors, thrombopoietin receptor agonists and antithymocyte globulin (ATG) etc. We put some concerns of using high-dose steroids for long-term, and emphasize the secondary infections, tumor progression, and unavailability of ICI re-challenge during steroid treatment. We propose the "De-escalation Therapy" principle for severe and refractory irAEs, and suggest that immunosuppressive drugs specifically targeting cytokines should be used as early as possible. Many irAEs in the era of immunotherapy are unprecedented compared with traditional chemotherapy and small-molecule targeted therapy, which is a big challenge to oncologists. Therefore, the establishment of multidisciplinary system is very important for the management of cancer patients.
ABSTRACT
Immunocheckpoint inhibitors (ICIs) activated the patients' tumor immunity to kill the tumor cell, and brought new hope to patients with tumor. However, a series of immunocheckpoint inhibitors related adverse effects (irAEs) may also occur based on immune injury. Glucocorticoids are the basis for the treatment of such irAEs. However, the usage, dosage and course of treatment of glucocorticoid in irAEs are different from those in classic autoimmune diseases. Meanwhile, long-term use of large doses of glucocorticoids may cause serious adverse effects too. In this paper, the mechanism, dosage forms, adverse effects and management of glucocorticoids are described in detail, providing references and suggestions for oncologists to apply glucocorticoids in clinical practice.
ABSTRACT
The increasing use of immunocheckpoint inhibitors in tumors has brought new hope of survival to patients with advanced tumors. However, the immune system activated by immunocheckpoint inhibitors, mainly activated T-cell immunity, may attack normal tissues and organs of the human body and lead to a variety of adverse effects. In the lung, they could induce checkpoint inhibitor associated pneumonitis (CIP). CIP is different from known pulmonary interstitial pneumonitis, and had a potentially fatal risk if it was not being properly treated. We will summarize the characteristics of CIP and give our advice on how to manage immunocheckpoint inhibitor associated pneumonitis.
ABSTRACT
Immunotherapy of malignant tumors has become a hot spot in the field of cancer research and treatment, bringing new hope to patients with advanced cancer. Activation of molecular programmer death protein-1 and T lymphocyte-associated antigen 4-related signaling pathways at the immunological checkpoint can inhibit T lymphocyte activation and thereby block the inflammatory response. Tumor cells achieve immune escape by activating the molecular pathways associated with immune checkpoints. The immune checkpoint inhibitor can wake up T lymphocytes and enhance the body's clearance of tumor cells. However, the role of immune checkpoint inhibitors is not specific to tumor cells, and it can cause side effects of multiple systems including the cardiovascular system while killing tumor cells. We will summarize the relevant cardiac side effects and give advice on how to manage it.
ABSTRACT
Immune checkpoint inhibitors (ICIs) represent a major breakthrough in cancer therapy. Immune-related adverse events (irAEs) may occur during treatment due to their unique mechanism of action. Dermatologic toxicities appear to be one of the most prevalent irAEs. The most common symptoms are maculopapular rash and pruritus. Serious dermatologic AEs, including Stevens-Johnson syndrome and toxic epidermal necrolysis, are rare. In this review, we summarized guidelines of management of immunotherapy-related toxicities and case reports, and proposed treatment recommendation.
ABSTRACT
As a new type of anti-cancer drugs, immune checkpoint inhibitors (ICIs) have shown remarkable therapeutic effects in many malignant tumors. By virtue of their targets and mechanisms of action, ICIs can cause autoimmune and inflammatory effects, termed immune-related adverse events (irAEs). Unlike traditional therapies, irAEs are latent and unstable. Severe adverse reactions will force patients to discontinue treatment and even affect their survival. Therefore, with the wide application of ICIs in clinical practice, clinicians need to fully understand the possible adverse reactions of such drugs and appropriate treatment strategies, in order to improve the survival rate and treatment effect of patients receiving ICIs. In this article, we review the incidence, clinical features, diagnosis and treatment of immune-related endocrine events that may occur with administration of ICIs.
ABSTRACT
The increasing use of target therapy and immunocheckpoint inhibitors in cancers has brought new hope of survival to patients with advanced tumors. However, more and more adverse side-effects and toxicities of these medications had been reported, affect almost all human organs including the eye. These adverse effects may affect the entire ocular tissues, like eyelid, eye lashes, conjunctiva, cornea, uvea, retina, optic nerve and so on, which are always been ignored by patients and doctors. In this paper we will summarize the characteristics of the related ocular diseases and give our advice on how to diagnose and manage these diseases.
ABSTRACT
Immunotherapy for malignant tumors is a hot spot in current research and treatment of cancer. The activation of programmed cell death receptor-1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA)-4 relevant signaling pathway can inhibit the activation of T lymphocytes. Tumor cells can achieve immune escape by activating this signaling pathway. By inhibiting this signaling pathway, immune-checkpoint inhibitors (ICIs) activate T lymphocytes to clear the tumor cells. Therefore, the adverse effects of ICIs are mainly immune-related adverse events (irAEs). The digestive system, including gastrointestinal tract and liver are vital organs of digestion and absorption, metabolism and detoxification, as well as important immune related organs, which are the commonly affected system of irAEs. This review separately explains the incidence, clinical features, diagnosis and treatment of liver and gastrointestinal adverse events in ICIs.
ABSTRACT
Immune checkpoint inhibitors (ICIs) have been widely used in management of malignant tumor. Programmed death ligand 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors have been introduced to treat non-small cell lung cancer (NSCLC) in recent years. Currently, PD-1/PD-L1 inhibitors are considered to have minor side effects and do not independently increase the risk of infection. However, they may cause immune-related adverse events (irAEs) that can require immunosuppressive therapy with corticosteroids and/or immunosuppressants, leading to opportunistic infections. Furthermore, there were reports about reactivation of chronic/latent infections without irAEs. Thus, immune checkpoint inhibitor related infections have drawn more and more attention in the world. In this paper, we described the potential mechanism, available clinical data and recommendation of diagnosis and management for PD-1/PD-L1 inhibitor related infections.
ABSTRACT
Immune checkpoint inhibitors (ICIs) have made remarkable breakthroughs in cancer treatment. However, the widely use of ICIs is associated with a spectrum of immune-related adverse events (irAEs). These adverse events can affect any organ system. In this article, we have made a systemic review about the clinical characteristics of rheumatic irAEs, and also summarized irAEs in patients with pre-exsiting rheumatic disease. We also focus on the management of rheumatic irAEs.
ABSTRACT
Immune checkpoint inhibitors are able to reactivate the immune system therefore enhance the anti-tumor effects. However, over-activated T cells may induce immune related adverse events (irAEs). Hematological irAEs are rarely reported, which mainly represent as mono-lineage cytopenia or pancytopenia, including autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), neutropenia and aplastic anemia, sometimes even lethal, such as hemophagocytic lymphohistiocytosis. The clinical manifestations of hematological irAEs will be summarized and recommendations of diagnosis and treatment are proposed.