Pancreas-specific immune-related adverse events in patients with lung cancer: a case series study.

Immune-related adverse events (irAEs) are one of the key concerns in cancer patients treated with immune checkpoint inhibitors (ICIs). Among the various irAEs, pancreas-specific irAE is a rare but special one with a variety of manifestations, such as pancreatic enzymes elevation, pancreatitis as well as diabetes. The current study reported 22 pancreas-specific irAEs in 21 patients with lung cancer, including pancreatic injury in 13 patients, pancreatitis in four patients and diabetes mellitus in five patients.

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Quantitative phosphoproteomic analysis of chicken DF-1 cells infected with Eimeria tenella, using tandem mass tag (TMT) and parallel reaction monitoring (PRM) mass spectrometry.

Eimeria tenella is an obligate intracellular parasite which causes great harm to the poultry breeding industry. Protein phosphorylation plays a vital role in host cell-E. tenella interactions. However, no comprehensive phosphoproteomic analyses of host cells at various phases of E. tenella infection have been published. In this study, quantitative phosphoproteomic analysis of chicken embryo DF-1 fibroblasts that were uninfected (UI) or infected with E. tenella for 6 h (PI6, the early invasion phase) or 36 h (PI36, the trophozoite development phase) was conducted. A total of 10,122 phosphopeptides matched to 3,398 host cell phosphoproteins were identified and 13,437 phosphorylation sites were identified. Of these, 491, 1,253, and 275 differentially expressed phosphorylated proteins were identified in the PI6/UI, PI36/UI, and PI36/PI6 comparisons, respectively. KEGG pathway enrichment analysis showed that E. tenella modulated host cell processes through phosphorylation, including focal adhesion, regulation of the actin cytoskeleton, and FoxO signaling to support its early invasion phase, and modulating adherens junctions and the ErbB signaling pathway to favor its trophozoite development. These results enrich the data on the interaction between E. tenella and host cells and facilitate a better understanding of the molecular mechanisms underlying host-parasite relationships.

Title: Analyse phosphoprotéomique quantitative de cellules DF-1 de poulet infectées par Eimeria tenella, par spectrométrie de masse avec marqueur de masse en tandem (TMT) et surveillance des réactions parallèles (PRM). Abstract: Eimeria tenella est un parasite intracellulaire obligatoire qui cause de graves dommages à l'industrie de l'élevage de volailles. La phosphorylation des protéines joue un rôle essentiel dans les interactions entre la cellule hôte et E. tenella. Cependant, aucune analyse phosphoprotéomique complète des cellules hôtes à différentes phases de l'infection par E. tenella n'a été publiée. Dans cette étude, une analyse phosphoprotéomique quantitative de fibroblastes DF-1 d'embryon de poulet non infectés (NI) ou infectés par E. tenella pendant 6 h (PI6, la phase d'invasion précoce) ou 36 h (PI36, la phase de développement des trophozoïtes) a été réalisée. Un total de 10 122 phosphopeptides correspondant à 3 398 phosphoprotéines de cellules hôtes ont été identifiés et 13 437 sites de phosphorylation ont été identifiés. Parmi celles-ci, 491, 1 253 et 275 protéines différentiellement phosphorylées exprimées ont été identifiées respectivement dans les comparaisons PI6/NI, PI36/NI et PI36/PI6. L'analyse d'enrichissement de la voie KEGG a montré qu'E. tenella modulait les processus de la cellule hôte par phosphorylation, y compris l'adhésion focale, la régulation du cytosquelette d'actine et la signalisation FoxO, pour aider sa phase d'invasion précoce, et la modulation des jonctions adhérentes et de la voie de signalisation ErbB pour favoriser le développement de son trophozoïte. Ces résultats enrichissent les données sur l'interaction entre E. tenella et les cellules hôtes et facilitent une meilleure compréhension des mécanismes moléculaires sous-jacents aux relations hôtes­parasites.

Physical discomforts, feeling of the high work intensity and the related risk factors of the frontline medical staff during COVID-19 epidemic: an early-outbreak, national survey in China.

Background: Facing the unknown virus, COVID-19 medical staff kept wearing thick personal protective equipment during their work in the early stage of the outbreak. The survey was designed to investigate the physical discomforts, the feeling of the work intensity and the related risk factors of the frontline medical staff during COVID-19 epidemic in the early outbreak. Methods: An national survey was carried out in China from March 17th 2020 to March 20th 2020 by applying a standardized WeChat questionnaire survey. The doctors or nurses working in the wards for the confirmed COVID-19 patients on front-line were eligible to participate in the survey. Descriptive analysis and multivariate logistic regression analysis were used. Results: A total number of 515 COVID-19 medical staff, including 190 physicians and 325 nurses participated in this survey. 375 medical staff (72.8%) experienced physical discomforts at work, mostly consist of dyspnea (45.8%), pain (41.0%), chest distress (24.1%), dizziness (18.8%), and weakness (17.5%), while wearing thick isolation clothes at work. The mean onset time and peak time of these symptoms were 2.4 h and 3.5 h after working, respectively. 337 medical staff (65.4%) suffered from sleep disorders. 51 medical staff (10%) were highly worried about being infected by COVID-19 even during their work breaks. 246 medical staffs (47.8%) felt high work intensity and the independent influential factors were the effective daily sleep time and anxiety levels at break time (p = 0.04). Conclusion: The frontline medical staff during COVID-19 epidemic felt different physical discomforts when they wear thick isolation clothes at work in the early outbreak and they felt high work intensity. These precious data will help optimize the work management strategy to ensure the physical and mental health of medical staff in the face of similar outbreaks in future.

Effectiveness and safety of Angong Niuhuang pill in treatment of acute stroke: a systematic review and Meta-analysis.

OBJECTIVE: To systematically evaluate the efficacy and safety of Angong Niuhuang pill (, ANP) in the treatment of acute stroke. This can provide ideas and basis for the treatment of this disease with integrated Traditional Chinese and Western Medicine. METHODS: Randomized controlled trials (RCTs) of China National Knowledge Infrastructure Database, Wanfang Database, Chinese BioMedical Literature Database, PubMed, Embase, and the Cochrane Library were searched from the establishment to March 2022. Two researchers screened the literature and extracted the data according to inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.3 software. RESULTS: A total of 28 RCTs were included, including 2745 patients in the acute stage of stroke (1375 in the experimental group and 1370 in the control group). Meta-analysis showed that compared with conventional treatment, combined treatment with ANP could improve the effective rate of acute stroke patients [relative risk () = 1.26, 95% confidence interval () (1.21, 1.31)], Glasgow Coma Scale scores [mean difference () = 2.01, 95% (1.04, 2.98)], Mini-mental State Examination scores [ = 4.79, 95% (2.22, 7.37)], Activities of Daily Living scores [ = 15.70, 95% (14.05, 17.36)] and the Barthel index scores [ = 13.89, 95% (12.12, 15.65)], reduce National Institute of Health stroke scale scores [ = -3.90, 95% (-4.96, -2.84)] and serum brain natriuretic peptide [ = -38.50, 95% (-46.85, -30.15)]. In terms of safety, the incidence of adverse reactions showed no statistical differences between the two groups [ = 0.71, 95% (0.43, 1.15), = 0.16], and no serious adverse reactions/events were observed, indicating a good safety. CONCLUSIONS: Existing clinical research evidence shows that ANP has good efficacy and safety in the treatment of acute stroke, which can provide a basis for the treatment of integrated Traditional Chinese and Western Medicine. However, the quality of included research methodology needs to be improved, and the above conclusions need to be verified by more high-quality studies.

Association Between Night Shift and Hypertension: A Cross-Sectional Study in Chinese Adults.

OBJECTIVE: The purpose of this study was to explore the effect of night-shift work on the risk of hypertension for improving workers' health. METHODS: A total of 10,038 Chinese participants were constituted in the cross-sectional study. Logistic regression and restricted cubic spline were used to estimate the effect of night shift on hypertension. RESULTS: There were higher odds of having hypertension in any night-shift workers (odds ratio [OR], 1.16 [95% confidence interval, 1.03-1.30]) when compared with day workers. Having 5 to 10 night shifts per month were significantly more likely to be hypertensive (OR, 1.19 [95% confidence interval, 1.03-1.38]). The OR for hypertension increased as the number of night shifts increased as the result of the restricted cubic spline. CONCLUSIONS: Our results support the hypothesis that night shift is associated with an elevated risk of hypertension.

Associations of exposure to multiple metals with the risk of age-related cataract in Anhui, China: a case-control study.

It's well-known that multiple metal elements can lead to the change of oxidative stress response levels in vivo. However, their relationship with age-related cataract (ARC) had not been well studied. We designed a case-control study including 210 individuals with ARC and 210 matched control group. The metal levels in their urine specimens were measured using graphite furnace atomic absorption spectrometry (GFAAS) and inductively coupled plasma optical emission spectrometry (ICP-OES). Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to select representative metals into the multi-element model and reduce dimension. Multivariate logic analysis and Bayesian kernel machine regression (BKMR) were subsequently used to explore the association of ARC risk with multiple metal elements. We found that magnesium (Mg), chromium (Cr), arsenic (As), manganese (Mn), and selenium (Se) were positively associated with ARC in the single-element model. The multiple exposure model indicated a positive association between Mg and As, in which the OR in their highest quartile were 3.32 (95% CI: 1.24-8.89) and 7.09 (95% CI: 2.56-19.63). The BKMR model also showed the effect of As increased monotonically with its increasing concentration, and high levels of Mg and As had a significant positive effect on ARC risk. In conclusion, we found that exposure to multiple metals was associated with increased ARC risk. Further research is needed to verify these findings in the future.

Exposure to multiple trace elements and thyroid cancer risk in Chinese adults: A case-control study.

The incidence of thyroid cancer (TC) has increased rapidly in last decades. Multiple trace elements in the external environment have important effects with thyroid function. However, the evidence for these on TC risk were rarely reported. A total of 585 newly diagnosed TC patients and 585 healthy controls were included in this study, and 14 urinary elements were measured to explain the fixed-exposure effect on TC risk. Conditional logistic regressions were used to reflect the multi-element associations, and Bayesian kernel machine regression (BKMR) was applied to show the tendency of mixed effects. Furthermore, the interaction effects were examined by Generalized linear model (GLM). The levels of lithium (Li), cobalt (Co), strontium (Sr), zinc (Zn) and copper (Cu) had negative effects with TC risk, nevertheless lead (Pb), arsenic (As) and chromide (Cr) showed positive effects. The BKMR and GLM models reflected the effect fluctuations of different elements, and there was a slight interaction effects between Li and Cr, Co, Zn and Pb. Further study is required to confirm these results in the future.

Predictors of Maternal Death Among Women With Pulmonary Hypertension in China From 2012 to 2020: A Retrospective Single-Center Study.

Background: Previous studies have suggested that pregnant women with pulmonary hypertension (PH) have high maternal mortality. However, indexes or factors that can predict maternal death are lacking. Methods: We retrospectively reviewed pregnant women with PH admitted for delivery from 2012 to 2020 and followed them for over 6 months. The patients were divided into two groups according to 10-day survival status after delivery. Predictive models and predictors for maternal death were identified using four machine learning algorithms: naïve Bayes, random forest, gradient boosting decision tree (GBDT), and support vector machine. Results: A total of 299 patients were included. The most frequent PH classifications were Group 1 PH (73.9%) and Group 2 PH (23.7%). The mortality within 10 days after delivery was 9.4% and higher in Group 1 PH than in the other PH groups (11.7 vs. 2.6%, P = 0.016). We identified 17 predictors, each with a P-value < 0.05 by univariable analysis, that were associated with an increased risk of death, and the most notable were pulmonary artery systolic pressure (PASP), platelet count, red cell distribution width, N-terminal brain natriuretic peptide (NT-proBNP), and albumin (all P < 0.01). Four prediction models were established using the candidate variables, and the GBDT model showed the best performance (F1-score = 66.7%, area under the curve = 0.93). Feature importance showed that the three most important predictors were NT-proBNP, PASP, and albumin. Conclusion: Mortality remained high, particularly in Group 1 PH. Our study shows that NT-proBNP, PASP, and albumin are the most important predictors of maternal death in the GBDT model. These findings may help clinicians provide better advice regarding fertility for women with PH.

Associations between environmental exposure to polybrominated diphenyl ethers and nodular goiter risk: A case-control study.

Polybrominated diphenyl ethers (PBDEs) are widespread and persistent environmental contaminants, but their association with nodular goiter (NG) remains unknown. The present case-control study of 179 NG cases and 358 matched normal controls aimed to investigate the association between PBDEs and risk of NG. The plasma concentrations of 8 PBDEs congeners (BDE-28, -47, -99, -100, -153, -154, -183, and -209) were determined by gas chromatograph-mass spectrometer. Conditional logistic regression model was used to evaluate the odds ratio (OR) and 95% confidence interval (CI) for the association between each PBDEs congener and NG. Bayesian kernel machine regression (BKMR) was used to evaluate the association between overall levels of 8 PBDEs mixture and NG. The results of logistic model suggested that increased risk of NG was associated with elevated concentrations of all PBDEs congeners, except for BDE-209. In BKMR model, the risk of NG increased with the increase in overall exposure level of 8 PBDEs mixture. Compared to when all PBDEs mixture were at their median value, the risk of exposure-response function for NG increased by 0.34 units when all PBDEs were at their 75th percentile. In women, the results showed similar trends after additional adjustment for age at menarche and menopausal status. These findings provide novel epidemiological evidence for the prevention of NG. However, larger prospective studies are required to address the associations between PBDEs exposure and NG risk.

The incidence, clinical characteristics, and outcome of polytrauma patients with the combination of pulmonary contusion, flail chest and upper thoracic spinal injury.

BACKGROUND: Chest trauma was the third most common cause of death in polytrauma patients, accounting for 25% of all deaths from traumatic injury. Chest trauma involves in injury to the bony thorax, intrathoracic organs and thoracic medulla. This study aimed to investigate the incidence, clinical characteristics, and outcome of polytrauma patients with pulmonary contusion, flail chest and upper thoracic spinal injury. METHODS: Patients who met inclusion criteria were divided into groups: Pulmonary contusion group (PC); Pulmonary contusion and flail chest group (PC + FC); Pulmonary contusion and upper thoracic spinal cord injury group (PC + UTSCI); Thoracic trauma triad group (TTT): included patients with flail chest, pulmonary contusion and the upper thoracic spinal cord injury coexisted. Outcomes were determined, including 30-day mortality and 6-month mortality. RESULTS: A total 84 patients (2.0%) with TTT out of 4176 polytrauma patients presented to Tongji trauma center. There was no difference in mean ISS among PC + FC group, PC + UTSCI group and TTT group. Patients with TTT had a longer ICU stay (21.4 days vs. 7.5 and 6.2; p<0.01), relatively higher 30-day mortality (40.5% vs. 6.0% and 4.3%; p<0.01), and especially higher 6-month mortality (71.4% vs. 6.5%, 13.0%; p<0.01), compared to patients with PC + FC or with PC + UTSCI. The leading causes of death for patients with TTT were ARDS (44.1%) and pulmonary infection (26.5%) during first 30 days after admission. For those patients who died later than 30 days during the 6 months, the predominant underlying cause of death was MOF (53.8%). CONCLUSIONS: Lethal triad of thoracic trauma (LTTT) were described in this study, which consisting of pulmonary contusion,flail chest and the upper thoracic spine cord injury. Like the classic "lethal triad", there was a synergy between the factors when they coexist, resulting in especially high mortality rates. Polytrauma patients with LTTT were presented relatively high 30-day mortality and 6 months mortality. We should pay much more attention to the patients with LTTT for further minimizing complications and mortality.

Thoracic Spine Fractures with Blunt Aortic Injury: Incidence, Risk Factors, and Characteristics.

BACKGROUND: The coexistence of thoracic fractures and blunt aortic injury (BAI) is potentially catastrophic and easy to be missed in acute trauma settings. Data regarding patients with thoracic fractures complicated with BAI are limited. METHODS: The authors conducted a prospective, observational, single-center study including patients with thoracic burst fractures. A multivariate logistic regression model was developed to determine the risk factors of aortic injury. RESULTS: In total, 124 patients with burst fractures of the thoracic spine were included. The incidence of BAI was 11.3% (14/124) in patients with thoracic burst fractures. Among these patients, 11 patients with BAI were missed diagnoses. The main risk factors of BAI were as follows: Injury severity score (OR 1.184; 95% CI, 1.072-1.308; p = 0.001), mechanism of injury, such as crush (OR 10.474; 95% CI, 1.905-57.579; p = 0.007), flail chest (OR = 4.917; 95% CI, 1.122-21.545; p = 0.035), and neurological deficit (OR = 8.299; 95% CI, 0.999-68.933; p = 0.05). CONCLUSIONS: BAI (incidence 11.3%) is common in patients with burst fractures of the thoracic spine and is an easily missed diagnosis. We must maintain a high suspicion of injury for BAI when patients with thoracic burst fractures present with these high-risk factors.

Body mass index and weight gain after middle adulthood are associated with risk of papillary thyroid cancer: A case-control study.

BACKGROUND: It is unclear whether weight change after middle adulthood influences the risk of thyroid cancer. The aim of this study was to investigate associations between the risk of papillary thyroid cancer (PTC) and body mass index (BMI) and weight change after middle adulthood (age 35). METHODS: A matched case-control study based on three hospitals included 516 pairs of cases newly diagnosed with PTC and controls. Current height and weight after defecation in the morning were measured by trained nurses. During measurement, all subjects were requested to wear lightweight clothing and no shoes. Weight at age 35 was self-reported. BMI and weight change were modeled as continuous and categorical variables. Conditional and unconditional logistic regression models were used to estimate the odds ratio (OR) and 95% confidence interval (95%CI) for the association between BMI and weight change after middle adulthood and PTC. RESULTS: After adjustment for covariates, measured BMI at the time of current diagnosis was positively associated with PTC (OR 1.16, 95%CI 1.10-1.21). According to WHO BMI guidelines for Asia-Pacific populations, the OR (95%CI) for PTC risk in obesity was 2.99 (1.92-4.67) compared to normal weight (p-trend <0.001). Moreover, PTC was positively associated with BMI at age 35; the OR (95%CI) for PTC risk per unit increase in BMI was 1.06 (1.02-1.11). Compared to stable weight (changed <0.5 kg/year), weight gain ≥1.0 kg/year after middle adulthood was positively associated with PTC (OR 2.57, 95%CI 1.39-4.76, p-trend <0.001). Compared to maintaining non-overweight status, the PTC risk was significantly increased in those individuals who gained weight and became overweight after middle adulthood (OR 3.82, 95%CI 2.50-5.85). CONCLUSION: This study showed that high BMI and obesity were positively associated with increased risk of PTC, and weight gain after middle adulthood also could elevate the PTC risk.

Associations of exposure to multiple trace elements with the risk of goiter: A case-control study.

Goiter is one of common endocrine diseases, and its etiology has not been fully elucidated. The changes in trace elements' levels have an important impact on the thyroid. We designed a case-control study, which involved 383 goiter cases and 383 matched controls. We measured these elements in the urine of participants by inductively coupled plasma optical emission spectrometry (ICP-OES), graphite furnace atomic absorption spectrometry (GFAAS) and As3+-Ce4+ catalytic spectrophotometry. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to select the elements into multi-element models, conditional logistic regression models were applied to analyze the association between elements and goiter risk. Bayesian kernel machine regression (BKMR) model was used to depict elements' mixtures and evaluate their joint effects. Finally, 7 elements were included in the multi-element model. We found that the concentrations of lithium (Li), strontium (Sr) and barium (Ba) had a negative effect with goiter risk, and lead (Pb) and iodine (I) showed an extreme positive effect. Additionally, compared with the lowest levels, patients with highest quartiles of I and Pb were 6.49 and 1.94 times more likely to have goiter, respectively. On the contrary, in its second and third quartiles, arsenic (As) showed a negative effect (both OR<1). BKMR model showed a certain interaction among Pb, As, Sr and Li on goiter risk. Further large sample studies are needed to confirm these findings in the future.

Thyroid hormones in relation to polybrominated diphenyl ether and metals exposure among rural adult residents along the Yangtze River, China.

Although several studies indicate that exposure to polybrominated diphenyl ethers (PBDEs) and metals may influence thyroid function, the evidence is limited and inconsistent in general population. The current study was conducted to determine the levels of plasma PBDEs and urinary metals and evaluate the associations of co-exposure to both with thyroid hormones (THs) among rural adult residents along the Yangtze River, China. A total of 329 subjects were included in current analyses, and 8 PBDEs congeners and 14 urinary metals were measured to reflect the levels of environmental exposure. Multiple linear regression models were used to evaluate the association between PBDEs, metals and THs levels. Bayesian Kernel Machine Regression (BKMR) was used to examine PBDEs and metals mixtures in relation to THs. The geometric mean (GM) and 95% confidence interval (CI) of total measured PBDEs was 65.10 (59.96, 70.68) ng/g lipid weights (lw). BDE-209 was the most abundant congener, with a GM (95% CI) of 47.91 (42.95, 53.26) ng/g lw, accounting for 73.6% of the total PBDEs. Free thyroxine (FT4) was significantly negatively associated with BDE-28, 47, 99, 100, 154, and 183, and urinary strontium [ß (95% CI): -0.04 (-0.07, -0.02)], but positively associated with selenium [ß (95% CI): 0.04 (0.02, 0.06)]. Free triiodothyronine (FT3) was negatively associated with BDE-28 [ß (95% CI): -0.03 (-0.05, -0.01)] and urinary arsenic [ß (95% CI): -0.01 (-0.02, -0.001)]. The current study did not observe a statistically significant association of thyroid-stimulating hormone (TSH) with PBDEs and urinary metals. BKMR analyses showed similar trends when these chemicals were taken into consideration simultaneously. We found no significant interaction in the association between individual chemical at the 25th versus 75th percentiles and THs estimates, comparing the results when other chemicals were set at their 10th, 50th, and 90th percentile levels. Further study is required to confirm these findings and determine potential mechanisms.

Reproductive and menstrual factors for papillary thyroid cancer risk: A case-control study in Chinese women.

BACKGROUND: Thyroid cancer (TC) is threefold more common in women than men. Reproductive and menstrual factors may be related to the onset of papillary thyroid cancer (PTC). This study aims to determine the association of reproductive and menstrual factors with PTC in Chinese females. METHODS: A total of 335 histologically confirmed cases of PTC were recruited in this case-control study. The controls were matched for age with a deviation of ± 2 years, which conducted from September 2016 to February 2019. Logistic regression models were applied to identify the association of reproductive and menstrual factors with PTC. RESULTS: After adjustment by some variables, early menarche age (OR ≤ 13 years vs. > 13years = 2.40, 95 % CI 1.12-5.13) and shorter lifetime breastfeeding (OR <6 months vs. ≥ 6 months = 1.99, 95 % CI 1.11-3.55) significantly increased the risk of PTC, whereas younger age at first pregnancy had a protective effect against PTC (OR ≤ 24years vs. > 24 years = 0.66, 95 % CI 0.44-0.98). There was a positive correlation between premenopausal and PTC in the lower age group (OR premenopausal vs. Menopause by natural =2.34, 95 %CI 1.03-5.28). CONCLUSIONS: Early menarche age, abortion, shorter breastfeeding duration and premenopausal may be related to the occurrence of PTC. Early age at first pregnancy and larger number of full-time pregnancies were possible to decrease the risk of PTC.

Exposure to 2,4-dichlorophenol, 2,4,6-trichlorophenol, pentachlorophenol and risk of thyroid cancer: a case-control study in China.

Thyroid cancer (TC) has inflicted huge threats to the health of mankind. Chlorophenols (CPs) were persistent organic pollutant and can lead to adverse effects in human health, especially in thyroid. However, epidemiological studies have revealed a rare and inconsistent relationship between internal exposure to CPs and TC risk. The purpose of this study was to investigate the correlation between urinary CPs and TC risk in Chinese population. From June 2017 to September 2019, a total of 297 histologically confirmed TC cases were recruited. Age- and gender-matched controls were enrolled at the same time. Gas chromatography-mass spectrometry (GC-MS) was used to determine the levels of three CPs in urine. Conditional logistic regression models were adopted to assess the potential association. Restricted cubic spline function was used to explore the non-liner association. After adjusting for confounding factors, multivariate analysis showed that, compared with the first quartile, the fourth quartile concentrations of 2,4-dichlorophenol (2,4-DCP), 2,4,6-trichlorophenol (2,4,6-TCP), and pentachlorophenol (PCP) were associated with TC risk (odds ratio (OR)2,4-DCP =2.28, 95% confidence interval (CI): 1.24-4.18; OR2,4,6-TCP =3.09, 95% CI: 1.66-5.77; ORPCP =3.30, 95% CI: 1.71-6.36, respectively), when CPs were included in the multivariate model and restricted cubic spline function as continuous variables, presenting significant dose-response relationships. Meanwhile, whether in the TC group with tumor diameter > 1 cm or metastatic TC, the changes of 2,4,6 TCP and PCP concentrations were positively correlated with the risk of TC. Our study suggests that higher concentrations of urinary CPs are associated with increased TC risks. Moreover, 2,4,6-TCP and PCP have certain effects on the invasiveness of thyroid cancer. Targeted public health policies should be formulated to reduce the CP pollution. These findings need further in-depth studies to confirm and relevant mechanism also needed to be clarified.

Narciclasine attenuates sepsis-induced myocardial injury by modulating autophagy.

Acute myocardial injury (AMI) is often secondary to sepsis, which is a life-threatening disease associated with severe cardiac inflammation. Narciclasine, a plant alkaloid isolated from different members of the Amaryllidaceae family, has been extensively characterized as an antitumor and anti-inflammatory compound. In addition, autophagy is critical for sepsis-induced myocardial injury. However, the role and mechanism of autophagy by which narciclasine confers cardioprotection are still unclear. The present study aimed to investigate the underlying mechanism by which narciclasine affects the pathogenesis of sepsis-induced myocardial injury. Narciclasine effectively attenuated LPS-induced myocardial inflammation in vitro and in vivo. In addition, narciclasine protected cardiac function and suppressed the expression of inflammatory cytokines in LPS-induced heart tissue. Furthermore, narciclasine upregulated LPS-induced autophagic activity, and the autophagy inhibitor 3-MA abrogated narciclasine-mediated protection against LPS-induced AMI. Importantly, narciclasine exerted an inhibitory effect on the JNK signaling pathway, and JNK activity was tightly associated with narciclasine-induced autophagy and the consequent protective effects during AMI. Taken together, our findings indicate that narciclasine protects against LPS-induced AMI by inducing JNK-dependent autophagic flux; hence, narciclasine may be an effective and novel agent for the clinical treatment of sepsis-induced myocardial injury.

Semaphorin3A increases M1-like microglia and retinal ganglion cell apoptosis after optic nerve injury.

BACKGROUND: The mechanisms leading to retinal ganglion cell (RGC) death after optic nerve injury have not been fully elucidated. Current evidence indicates that microglial activation and M1- and M2-like dynamics may be an important factor in RGC apoptosis after optic nerve crush (ONC). Semaphorin3A (Sema3A) is a classic axonal guidance protein,which has been found to have a role in neuroinflammation processes. In this study, we investigated the contribution of microglial-derived Sema3A to progressive RGC apoptosis through regulating paradigm of M1- and M2-like microglia after ONC. METHOD: A mouse ONC model and a primary microglial-RGC co-culture system were used in the present study. The expression of M1- and M2-like microglial activation markers were assessed by real-time polymerase chain reaction (RT-qPCR). Histological and Western blot (WB) analyses were used to investigate the polarization patterns of microglia transitions and the levels of Sema3A. RGC apoptosis was investigated by TUNEL staining and caspase-3 detection. RESULTS: Levels of Sema3A in the mouse retina increased after ONC. Treatment of mice with the stimulating factor 1 receptor antagonist PLX3397 resulted in a decrease of retinal microglia. The levels of CD16/32 (M1) were up-regulated at days 3 and 7 post-ONC. However, CD206 (M2) declined on day 7 after ONC. Exposure to anti-Sema3A antibodies (anti-Sema3A) resulted in a decrease in the number of M1-like microglia, an increase in the number of M2-like microglia, and the amelioration of RGC apoptosis. CONCLUSIONS: An increase in microglia-derived Sema3A in the retina after ONC partially leads to a continuous increase of M1-like microglia and plays an important role in RGC apoptosis. Inhibition of Sema3A activity may be a novel approach to the prevention of RGC apoptosis after optic nerve injury.

Multiple metal exposure and obesity: A prospective cohort study of adults living along the Yangtze River, China.

Association between long-term exposure to multiple metals and obesity remains inconclusive, and prospective evidence on the region along the Yangtze River was limited. Thus, our study aimed to examine the association of multiple metal exposure and obesity. We measured baseline urine levels of 22 metals of 982 adults living along the Yangtze River, incidence of obesity was calculated from body mass index (BMI) and waist circumference (WC) measured at follow-up survey. Cox proportional hazards models were used to examine the hazard ratios (HR) and 95% confidence interval (CI) for the association between urinary metals and obesity, and the mixing effect of metals on obesity was estimated by using quantile g-computation. In multiple-metal models, arsenic was significantly associated with BMI/obesity, with the HR in the highest quartiles of 0.33 (95% CI: 0.16, 0.69; p-trend = 0.004). The HRs for WC/obesity of arsenic and molybdenum were 0.49 (95% CI: 0.32, 0.75 for the fourth vs. first quartile; p-trend = 0.002) and 1.83 (95% CI: 1.25, 2.70; p-trend = 0.001), respectively. Quantile g-computation mixtures approach showed a significantly negative joint effect of multiple metals on WC/obesity, with the HR of 0.26 (95% CI: 0.14, 0.47; p < 0.001) when increasing all seventeen metals by one quartile. Our study suggests that all seventeen metal mixed exposure may be negatively associated with obesity. Further cohort studies are needed to confirm these findings and clarify the underlying biological mechanisms.