Per- and polyfluoroalkyl substances (PFASs) are persistent organic pollutants (POPs). They are widely used in food packaging, tableware coating, stain resistant furniture, and other industrial production. Humans are exposed to PFASs on a daily basis through drinking water and intaking food, use of consumer products containing PFASs, and occupational exposure during the production of PFASs or related products. A growing body of toxicological studies has shown that PFASs exposure disrupts the thyroid hormone (TH) system and causes hypothyroidism, which is further supported by population epidemiological studies. PFASs can damage thyroid follicular cells and sodium/iodine transporters to impair iodine uptake by thyroid cells. They interfere with the synthesis of thyroglobulin, reduce the activity of thyroid peroxidase, and affect the synthesis and secretion of TH. They interfere with TH transportation and biological effects via TH competitive binding thyroid transporter or thyroid hormone receptor. They suppress TH signaling pathway and deiodinase activity, interfere negative feedback mechanism, and accelerate TH metabolism and excretion. The processes of TH synthesis, transport, degradation, and biological effects may all be affected by PFASs exposure. This paper described possible toxic mechanisms of PFASs on the thyroid from four aspects: TH biosynthesis, transport, action on target cells, and metabolic excretion stage, and summarized the thyroid toxicity associated with PFASs exposure.

This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRAS^G12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFR^L858R and EGFR^Δ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.01‍‒‍1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95% CI, 1.49‍‒‍2.63; P<0.0001), while classical activating mutations with EGFR^T790M showed no difference compared to classical activating mutations without EGFR^T790M in OS (adjusted HR, 0.96; 95% CI, 0.48‍‒‍1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95% CI, 0.39‍‒‍1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A(USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95% CI, 0.32‍‒‍0.82; P=0.0077), PFS (adjusted HR, 0.51; 95% CI, 0.38‍‒‍0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95% CI, 2.75‍‒‍8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95% CI, 1.88‍‒‍6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRAS^G12Cmutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFR^T790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Extracellular Matrix Proteins/genetics* ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins p21(ras)/genetics* ; Treatment Outcome

Objective To explore the safety and effectiveness of bridging therapy in elderly patients with acute stroke due to posterior circulation large vessel occlusion.Methods A total of 160 eld-erly patients with acute stroke caused by posterior circulation large vessel occlusion admitted to our department were prospectively recruited and randomly divided into bridging group(n=80)and control group(n=80).The bridging group received thrombolysis treatment and then mechan-ical thrombectomy.The control group received mechanical thrombectomy directly.Prognosis and adverse reactions were compared between the two groups.Results The NIHSS score and BATMAN score after treatment were significantly decreased in both groups(P＜0.01),and the two scores were obviously lower in the bridging group than the control group(6.54±1.23 vs 7.12± 0.98,2.12±0.34 vs 2.87±0.44,P＜0.01).There was no statistical difference in the conversion rate of bleeding after cerebral infarction between the two groups(5.00％vs 3.75％,P＞0.05).The number of intraoperative thrombus removal was significantly lower in the bridging group than the control group(2.43±0.33 vs 2.98±0.41,P＜0.01).Remarkable difference was observed in the mRS score between the two groups after treatment(P＜0.05),with the proportion of mRS score ranging from 0 to 1 larger in the bridging group than the control group(52.50％vs 27.50％,P＜0.05).Conclusion Bridging thrombolysis can significantly improve the neurological function in elderly patients with acute stroke due to posterior circulation occlusion.

This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRASG12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFRL858R and EGFRΔ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95％ confidence interval (CI), 1.01?1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95％ CI, 1.49?2.63; P<0.0001), while classical activating mutations with EGFRT790M showed no difference compared to classical activating mutations without EGFRT790M in OS (adjusted HR, 0.96; 95％ CI, 0.48?1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95％ CI, 0.39?1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A (USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95％ CI, 0.32?0.82; P=0.0077), PFS (adjusted HR, 0.51; 95％ CI, 0.38?0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95％ CI, 2.75?8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95％ CI, 1.88?6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRASG12C mutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFRT790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.

Abstract Bisphenols (BPs), which are mainly used in the production of polycarbonates and epoxy resins, are common endocrine disruptors (EDCs) in natural environments. Human mainly exposes to BPs via ingestion and skin. Previous studies have deteted BPs in human urine, serum, and milk samples, and children and pregnant women have a high level of exposure to to BPs. Based on international and national publications pertaining to BPs since 2009, this review describes the exposure to BPs in human urine, serum, and milk and summarizes neuroendocrine dysfunctions, oxidative stress injury and epigenetics changes caused by BPs, so as to provide insights into reducing the exposure to and health risk of BPs.

Phthalic acid esters (PAEs) are commonly used plasticizers and solvents. Human body is exposed and absorbed mainly through diet, skin and air inhalation. The biological samples such as urine, blood, saliva, semen and breast milk generally contain PAEs and their metabolites, but the concentrations of PAEs metabolites vary in different samples. In the general population, the levels of PAEs are higher in children than in adults, and higher in women than in men; the levels of PAEs are higher in the occupational population than in the general population. In this paper, the research of PAEs related human biomonitoring in the general population and occupational population at home and abroad is reviewed, so as to provide the basis for reducing the exposure of PAEs and related health risk.

Triclosan, widely used in various personal care products, is one of the most common environmental endocrine disruptors in our life. It can be detected from water, soil and dust, and its environmental exposure level increased with consumption. Human body are exposed to triclosan through food and water, but the evidence that triclosan exposure leads to adverse health effects is not sufficient. This paper summarizes the progress of studies related to environmental concentration, population exposure and health risks of triclosan in recent years.

Objective : To understand the status of rural environmental sanitation and summer diarrhea among rural residents in Zhejiang Province,and to provide evidence for improvement of rural environmental sanitation and prevention and control of summer diarrhea. Methods : The stratified random sampling method was used. Five or six counties each were selected from the east,middle and west of Zhejiang Province;five townships（excluded Chengguan Town）were selected from each selected county;four villages were selected as field survey points from each township;five households were selected from each survey point;one family member（householder or housewife）was selected from each selected household. The information about the environmental sanitation status and prevalence of summer diarrhea were obtained by literature review,interviews,questionnaire suvey,field investigation and laboratory tests. Logistic regression model was used to analyze the influencing factors for occurrence of summer diarrhea among rural residents. Results : There were 2 000 households surveyed. In the past two weeks,108 households had families with diarrhea and the prevalence of diarrhea was 5.40%. A total of 1 828 households disposed the household waste in the garbage bins or pools,accounting for 91.40%. There were 1 926 households with organized sewage discharge,accounting for 96.30%. There were 768 households with nymphs found in the kitchen,accounting for 38.40%;404 households with live egg sheaths found,accounting for 20.20%;592 households with cockroach traces found,accounting for 29.60%;564 households with rat traces found,accounting for 28.20%;and 1 206 households with flies found,accounted for 60.30%. There were 1 314 households with disease vectors around the house,accounting for 65.70%. There were 1 944 household with sanitary toilets,accounting for 97.20%. A total of 1 915 households had habits of drinking boiled water,accounting for 96.57%. The results of multivariate logistic regression analysis showed that rat traces found in the kitchen（OR=2.026,95%CI: 1.362-3.013）were a risk factor for summer diarrhea in rural residents,while drinking boiled water（OR=0.272,95%CI: 0.091-0.811）was a protective factor. Conclusion The sanitary environment and family health habits of rural residents were related to the prevalence of diarrhea in summer. Paying attention to kitchen hygiene and drinking boiled water could prevent summer diarrhea.

Objective: To learn the disinfection effect and its influencing factors of drinking water in rural areas of Zhejiang Province,so as to provide scientific basis for the control of microbial pollution in drinking water and prevention of waterborne diseases. Methods: A total of 5 299 samples from 879 rural water plants Zhejiang Province were collected by stratified sampling method in 2017. The disinfection effect of water samples was assessed quality according to GB 5749-2006 Hygienic Standards for Drinking Water. Logistic regression models were used to analyze the influencing factors for disinfection effect of rural drinking water. Results: There were 540 rural water plants in Zhejiang Province adopting routine process for water purification,accounting for 61.43%;771 ones using surface water,accounting for 87.72%. About 4 458 samples（84.13%）were disinfected and the qualified rate was 86.05%,22.32% of which were disinfected by chlorine dioxide and the qualified rate was 100.00%. The results of multivariate logistic regression analysis showed that scale of water plant,disinfectant residue,use frequency of disinfection equipment,disinfection,season and source water turbidity were the influencing factors for the disinfection effect of rural drinking water（P<0.05）;disinfection,disinfectant residue,use frequency of disinfection equipment and source water turbidity were the influencing factors for the disinfection effect of finished water（P<0.05）;disinfection,disinfectant residue,use frequency of disinfection equipment,source water turbidity and scale of water plant were the influencing factors for the disinfection effect of tap water（P<0.05）;disinfectant residue,use frequency of disinfection equipment,source water turbidity and scale of water plant were the influencing factors forthe disinfection effect of surface water（P<0.05）;disinfectant residue,use frequency of disinfection equipment,source water turbidity and pH were the influencing factors for the disinfection effect of groundwater（P<0.05）. Conclusion The disinfection effect of drinking water in rural areas of Zhejiang Province is associated with source water quality,scale of plants,water purification technique and so on. The disinfection process should be improved,the management of water plants should be strengthened to reduce the risk of microbial contamination.

Objective To study the clinical value of amplitude integrated EEG(aEEG),EEG reactivity,EEG patterns,and Glasgow Coma Scale(GCS) scores of predicting the prognosis in comatose patients with severe traumatic brain injury.Methods Sixty-four hospitalized comatose patients with severe traumatic brain injury were evaluated by aEEG,EEG reactivity,EEG patterns and GCS and followed up for one year to observe the prognosis of the patients.Results Accuracy of aEEG,EEG reactivity,EEG patterns and GCS in predicting outcomes of comatose patients with severe traumatic brain injury correctly classified as 73.4％,68.8％,73.4％,64.1％ respectively.The accuracy of GCS in evaluating the prognosis of comatose patients with severe traumatic brain injury was lower than that of the other three methods (P＜0.05).There were positive correlations among aEEG,EEG reactivity,EEG patterns,and GCS (r=0.574-0.843,P＜ 0.05).There were positive correlations between aEEG,EEG reactivity,EEG patterns,GCS and the patients' prognosis(r=0.647,0.609,0.621,0.532,P＜ 0.05).Conclusion As a new electroencephalographic technique,aEEG combined with EEG reactivity,EEG patterns,and GCS can be effectively used to evaluate the prognosis of STBI coma patients,which has a certain clinical value.