[Prognostic value of skeletal muscle measured by CT at the T4 level in advanced EGFR-positive non-small cell lung cancer patients treated with ecotinib].

Objective: To investigate the prognostic value of skeletal muscle measured by CT at the level of the fourth thoracic vertebra (T4) in advanced epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) patients treated with ecotinib. Methods: The study retrospectively reviewed clinical and pathological characteristics of 176 patients with advanced EGFR-positive NSCLC who received ecotinib and underwent chest CT scans at Wuhan Union Hospital between January 2017 and October 2020. Among them, 70 were male and 106 were female, with ages ranging from 27 to 80 (58.6±10.6) years. As of August 21, 2021, the median follow-up duration was 19.2 months (95%CI: 15.3 to 23.7 months). The optimal cut-off value of skeletal muscle density (T4-SMD) on CT images at the T4 level were determined using X-tile software. Kaplan-Meier analysis and log-rank test were used to plot progression-free survival curves. Cox proportional hazards regression models were employed to analyze factors influencing 1-year progression-free survival (PFS), and a nomogram prognostic model was constructed accordingly. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were utilized to evaluate the predictive value of the nomogram. Results: The T4-SMD [M (Q1,Q3)] of 176 patients was 42.56 (37.05, 45.93) HU. Patients were divided into low T4-SMD group (n=122) and high T4-SMD group (n=54) based on the cut-off value (The values for males and females were 49.44 and 41.41 HU, respectively) of T4-SMD. The median PFS time and 1-year PFS rate in the low T4-SMD group were significantly lower than those in the high T4-SMD group [10.4 (95%CI: 9.3-11.8) vs 13.7 (95%CI: 11.1-18.5) months, 36.1% vs 59.3%, respectively, P=0.034]. Eastern Cooperative Oncology Group performance status (HR=3.308, 95%CI: 1.183-9.247, P=0.023), lactate dehydrogenase level (HR=1.852, 95%CI: 1.037-3.307, P=0.037), systemic immune-inflammation index (HR=1.772, 95%CI: 1.019-3.080, P=0.043), and T4-SMD (HR=0.563, 95%CI: 0.325-0.974, P=0.040) were prognostic factors for 1-year PFS in advanced EGFR-positive NSCLC patients treated with ecotinib. A nomogram for predicting 1-year PFS of advanced EGFR-positive NSCLC patients treated with ecotinib was constructed based on the four indicators selected by multivariate Cox regression analysis. The area under the ROC curve of the nomogram was 0.775 (95%CI: 0.676-0.874). The calibration curve showed good consistency between the predicted and actual 1-year PFS. DCA demonstrated good clinical prediction effectiveness of the nomogram. Conclusion: Low T4-SMD is a prognostic risk factor for patients with advanced EGFR-positive NSCLC receiving icotinib therapy.

[Comparison of the efficacy of PCSK9 inhibitors and statins on dyslipidemia in patients with type 2 diabetes].

Objective: To compare the efficacy of preprotein convertase subtilisin lysozyme 9 (PCSK9) inhibitors with statins in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 140 patients with T2DM (80 males and 60 females) in the People's Hospital Affiliated to Shandong First Medical University from January 2018 to January 2021 were selected, with a mean age of (55±5) years (41-72 years). The patients were divided into observation group (n=68) and control group (n=72) by the random number table method. Both groups were given conventional treatments such as hypoglycemic drugs, the control group was given statins to regulate lipids, and the observation group was given PCSK9 inhibitors to lower lipids. The differences of low-density lipoprotein cholesterol (LDL-C), interleukin (IL)-1, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) expression levels and standard-reaching rate of LDL-C between the two groups were compared. The correlation between serum PCSK9 level and fasting plasma glucose (FPG), hemoglobin A1c (HbA1c) and other indicators in T2DM patients was analyzed by Pearson correlation analysis. Results: After treatment, the LDL-C of the observation group was (2.3±0.7) mmol/L, which was lower than that of the control group [(2.7±0.7) mmol/L] (P=0.024); the standard-reaching rate of LDL-C of the observation group was 89.7% (61/68), which was higher than that of the control group [68.1% (49/72)] (P=0.002); the levels of IL-1, IL-6, TNF-, CRP, IL-10 and IL-8 in the observation group after treatment were (27.6±6.6) ng/L, (36.7±6.9) ng/L, (40.1±8.9) ng/L, (7.8±1.8) ng/L, (19.2±3.3) ng/L, (13.7±3.3) ng/L, respectively, which were lower than those in the control group [(30.6±7.9) ng/L, (40.1±7.3) ng/L, (43.4±9.2) ng/L, (10.4±2.5) ng/L, (30.7±3.7) ng/L, (26.8±3.4) ng/L, respectively] (all P<0.05). After treatment, the PCSK9 level in the observation group was (74±13) µg/L, which was lower than that in the control group [(97±14) µg/L] (P<0.001). The level of PCSK9 in T2DM patients was positively correlated with LDL-C, IL-1, IL-6 and TNF-α (r=0.390, 0.433, 0.398 and 0.562, all P<0.05). Conclusion: PCSK9 inhibitors have better lipid-regulating effects in patients with T2DM and can improve the level of inflammation at the same time.

[Clinical characteristics of patients with acute pulmonary embolism in high altitude area of Yunnan province in China].

Objective: To analyze the clinical features of patients with acute pulmonary embolism (APE) living in high altitude area of Yunnan province. Methods: This was a cross-sectional retrospective study. APE patients, hospitalized in our hospital between January 2017 and December 2019, were included. The selected patients were divided into low-risk group, medium-risk group and high-risk group according to risk stratification. The clinical data of patients, including demographic data, the main symptoms, risk factors of APE, heart rate and systolic blood pressure and laboratory testing results (D-dimer, cardiac troponin I (cTNI), N terminal B-type natriuretic peptide (NT-proBNP)) and echocardiography and electrocardiogram examination results, were obtained through the electronic medical record system. The clinical characteristics of selected patients were analyzed. Results: A total of 392 patients, aged (63.5±15.7) years, 224 males (57.14%), were included in this study and there were 59 low-risk, 304 medium-risk and 29 high-risk patients in this cohort. The main clinical manifestations were chest pain (157(40.05%)), dyspnea (107(27.30%)), hemoptysis (55(14.03%)), syncope as the first symptom (20(5.10%)), and only 6 cases (1.53%) presented with the typical "Virchow's triad". Most of the patients were accompanied by atypical chest tightness (223(56.89%)) and cough (208(53.06%)). The main risk factors were venous thrombosis of lower limbs (179(45.66%)), hypertension (138(35.20%)), surgery (63(16.07%)), and chronic obstructive pulmonary disease (COPD) (62(15.82%)). There were 57 cases (14.54%) of coronary heart disease, 57 cases (14.54%) of diabetes, 51 cases (13.01%) of cerebral infarction, 47 cases (12.00%) of advanced age, 15 cases (3.83%) of tumor, 7 cases (1.79%) of activity restriction, 6 cases (1.53%) of pregnancy and 4 cases (1.02%) of hormone use in this cohort. The proportion of lower extremity venous thrombosis was significantly higher in low-risk group than in medium-risk group (P<0.01), COPD was more common in high-risk and medium-risk groups than in low-risk group (P<0.01), hypertension was more common in high-risk group than in medium-and low-risk groups (P<0.01). The proportion of advanced age was significantly higher in medium-risk group than in low-risk group (P<0.01). There were no significant differences in RBC and hemoglobin level between low-, medium-and high-risk groups (P>0.05). The level of D-dimer was significantly higher in high-risk group than in medium-and low-risk groups (P<0.05). Levels of NT-proBNP and cTNI were significantly higher in high-risk group than in medium- and low-risk groups (P<0.05). Increased proportion of cTNI and NT-proBNP was significantly higher in high-risk group than in medium- and low-risk groups (P<0.05). There were 105 (26.79%) patients with pulmonary hypertension (PAH). The incidence of PAH was significantly higher in high-risk group than in low-risk group (P<0.01). There were 104 patients (26.53%) with right ventricular enlargement, and the incidence of right ventricular enlargement was significantly higher in high-risk group than in medium-and low-risk groups (P<0.01). Characteristic changes of electrocardiogram in patient with APE were T-wave inversion of limb leads (98(25.00%)), followed by SⅠQⅢTⅢ (83(21.17%)). Conclusions: The main clinical manifestations of APE in Yunnan high altitude area are chest pain and dyspnea, and syncope is the first symptom in some patients, but the typical "Virchow's triad" is rare. The most common risk factors are lower extremity venous thrombosis, hypertension, and COPD. Clinical symptoms, risk factors and laboratory examination results differ among patients with different risk stratification.

[The impact of occupational aluminum exposure on workers' overall cognitive function and various cognitive fields].

Objective: To evaluate the effects of occupational aluminum exposure on workers' overall cognitive function and cognitive fields. Methods: From July to August 2019, using the method of cluster sampling, 101 and 117 workers were selected from the electrolytic aluminum workshop of an aluminum plant in a region and the maintenance workshop of a plant in the same region. The venous blood of the subjects was collected, the plasma was extracted, and the blood aluminum concentration was measured by ICP-MS. According to the blood aluminum concentration and type of work, 93 workers who were lower than the median blood aluminum concentration and in the maintenance workshop of a factory were divided into low aluminum exposure group, and 85 workers who were higher than the median blood aluminum concentration and in the electrolytic aluminum workshop of an aluminum factory were divided into high aluminum exposure group. The basic information of the respondents, was collected through the employee physical examination form. The overall cognitive function of workers was evaluated by Beijing Montreal Cognitive Assessment Scale (MoCA) . Multiple linear regression analysis and logistic regression analysis were used for multiple statistical analysis. Results: Compared with the low aluminum exposure group (25.42±1.808) , the total score of MoCA in the high aluminum exposure group (23.84±2.919) was significantly lower, and the scores of visual space, executive function, abstract and delayed recall were significantly lower (P<0.05) . Linear regression analysis showed that the total score of MoCA, visual space and executive function, naming and delayed recall were negatively correlated with blood aluminum concentration (ß=-0.018、-0.008、-0.003、-0.008, P<0.05) .MOCA total score, visual space and executive function, attention, language, abstraction, orientation were positively correlated with educational level (ß=0.853、0.310、0.216、0.171、0.412、0.122, P<0.05) . Logistic regression analysis showed that adjusting for age, smoking, drinking and education, blood aluminum was a risk factor for mild cognitive impairment (OR=1.017, P<0.05) ; Education level was the protective factor of mild cognitive impairment (OR=0.419, P<0.05) . Conclusion: Occupational aluminum exposure can affect the overall cognitive function of workers, and occupational aluminum exposure increases the risk of MCI.

[Effects of occupational exposure to aluminum on verbal function of workers].

Objective: To explore the effect of occupational aluminum (Al) exposure on workers' overall cognitive level and speech function. Methods: In July 2019, by using cluster sampling method, the group of 232 exposed to Al from an Al plant in Shanxi Province were selected as the exposed group, and the group of 228 not exposed to Al were selected as the control group. The blood Al concentration was determined by inductively coupled plasma mass spectrometry (ICP-MAS) . The exposed group was divided into high exposure group and low exposure group according to the median (M) concentration of Al in serum. The general cognitive function and speech function were evaluated with the Montreal Cognitive Assessment Scale (MoCA) , and the differences in the general cognitive function and speech function between the groups were compared, and non-conditional logistic regression was used to analyze the possible influencing factors of mild cognitive impairment (MCI) . Results: There were significant differences in age, working age, education and drinking status between Al exposed group and control group (P<0.05) . The total MoCA score, animal naming tese (ANT) score and category fluency repetition (CFT) score in Al exposure group were lower than control group and the differences were statistically significant (P<0.05) . The full rate of ANT was lower than that of CFT in Al exposure group (P<0.05) . The total MoCA score, ANT score and CFT score in the high exposure group were significantly lower than those in the control group (P<0.05) . The score of MoCA, ANT and CFT in high exposure group were lower than those in low exposure group between the level of serum aluminum>60 µg/L group and ≤60 µg/L group (P<0.05) . Logistic regression analysis showed that working age, serun Al concentration, ANT score, CFT score and SR score were the possible influencing factors of MCI in occupational Al exposure workers (P<0.05) . Conclusion: Occupational Al exposure can lead to impaired speech function of workers, the higher the ANT score, CFT score and SR score, the lower working age and serum Al concentration, the lower risk of MCI.

[Clinical characteristics analysis of children with reversible posterior leukoen-cephalopathy syndrome during the treatment of hematological tumor].

OBJECTIVE: To analyze the clinical characteristics of patients with hematological tumor or disease before and after reversible posterior leukoen-cephalopathy syndrome (RPLS). METHODS: Five patients were both from Peking University First Hospital Pediatric Hematology-oncology Department in the period from March 2012 to March 2017. The gender, age, BMI, underlying diseases, with or without renal damage, hypertension family history, clinical manifestations of convulsions, hemoglobin, and blood pressure, serum sodium levels before and after convulsion, and other data of the children with RPLS were retrospectively analyzed. In the meantime, we followed up the five patients for 6 months to 66 months, kept a watchful eye on their original condition and the recovery of symptoms and signs of the nervous system. The relevant literature was reviewed. RESULTS: All of the subjects were females in school-age or pre-school age. The underlying diseases were malignant tumor associated with renal involvement or on one side of nephrectomy in 4 of these subjects, while the other one was refractory autoimmune hemolytic anemia. All of the subjects suffered from mild or moderate anemia. The day before RPLS occurred they received chemotherapy made up with cyclophosphamide, vincristine, and actinomycin-D, or the therapy with cyclosporin A and glucocorticoid. The clinical manifestations were afebrile convulsion after getting up in the mooring or in the afternoon. We observed elevation of blood pressure and cutting down of serum sodium compared with themselves. All of the cases recovered soon after management with diazepam, furosemide and amlodipine besylate. Four of them had a good outcomes and did not remain any sequela, while only one girl became childish in emotion and behavior, and then returned gradually to normal two years later. However, by long-term follow-up, the elevation of blood pressure was mainly reviewed in literature. CONCLUSION: The patients attacked by RPLS, with hematology or oncology cases, could have the underlying disease of renal damage and anemia. Blood pressure elevation and serum sodium falling down at the same time may play an important role during the occurrence of RPLS. Remaining stable of blood pressure and electrolyte level together will possibly reduce or mitigate RPLS.

[The effect of aluminum trichloride on expression of phosphorylated tau and Aß in SH-SY5Y cells].

Objective: To investigate the expression of phosphorylated tau (p-tau) and Aß in SH-SY5Y cells induced by aluminum or/and ApoE ε4 allele, and study the interaction between aluminum and ApoE ε4 allele. Methods: SH-SY5Y cells were assigned to control group, 400 µmol/L AlCl(3) group, ApoEε4 transfected group and 400 µmol/L AlCl(3) with Apo Eε4 transfected group. The cell viability was measured by CCK-8 assay; the expressions of p-tau and Aß was determined with ELISA Kit after AlCl(3) exposure or or/and ApoE ε4 transfection. Results: The viability of cells exposed to 400 µmol/L AlCl(3) or/and ApoE ε4 transfected were significantly lower than that of controls (P<0.05) . The expressions of total tau, tau-181, tau-231, tau-396 and Aß in 400 µmol/L Al(3)+ or/and ApoE ε4 transfected exposed cells showed significantly higher than those of controls (P<0.05) . Based on the factorial design, a significant interaction exists, and there is a synergistic effect between AlCl(3) and ApoE ε4 (P<0.05) . Conclusion: Aluminum and ApoE ε4 allele could increase expression of p-tau and Aß deposition; there was a synergistic interaction between aluminum and ApoE ε4 allele on cell death, tau phosphorylation and Aß deposition of SH-SY5Y.

[Influence of occupational aluminum exposure on cognitive function and glutamate receptor protein expression in workers].

Objective: To investigate the influence of occupational aluminum exposure on cognitive function and glutamate receptor protein expression in peripheral blood lymphocytes in workers and the possibility of glutamate receptor being used as a biomarker for cognitive impairment in aluminum workers. Methods: From October to December, 2014, cluster sampling was performed to select 121 workers in aluminum electrolysis workshop as exposure group and 231 workers in thermoelectric workshop and logistics department as control group. Mini-Mental State Examination, clock drawing test, digit span test (DST) , verbal fluency test (VFT) , and Fuld Object-Memory (FOM) Evaluation were used to analyze cognitive function. Graphite furnace atomic absorption spectrophotometry was used to measure plasma aluminum level as an exposure indicator. Enzyme-linked immunosorbent assay was used to measure the content of glutamate receptor proteins in peripheral blood lymphocytes, including the subunits of N-methyl-D-aspartate receptor NR1, NR2A, and NR2B and metabotropic glutamate receptor 1 (mGluR1) . The correlation between cognitive function indices and the content of glutamate receptor proteins was analyzed. Results: There was no significant difference in plasma aluminum level between the control group and the exposure group (132.52±80.40 µg/L vs 182.88±72.32 µg/L, P>0.05) . According to the plasma aluminum level, the study subjects were divided into control group and low-, medium-, and high-level plasma aluminum groups, and there were significant differences in plasma aluminum level between these groups (all P<0.01) . The high-level plasma aluminum group had a significantly lower memory ability score than the control group and the low- and medium-level plasma aluminum groups (all P<0.05) . The high-level plasma aluminum group had lower DST and digital span forward (DSF) scores than the control group and the low-and medium-level plasma aluminum groups. The low-, medium-, and high-level plasma aluminum groups had lower digital span backward (DSB) scores than the control group. The medium-and high-level plasma aluminum groups had lower VFT scores than the control group and the low-level plasma aluminum group. The high-level plasma aluminum group had significantly lower expression of NR1 and NR2A proteins than the control group and the low-and medium-level plasma aluminum groups, and the medium- and high-level plasma aluminum groups had significantly higher expression of mGluR1 protein than the control group and the low-level plasma aluminum group (all P<0.05) . The expression of NR1 and NR2A proteins was negatively correlated with plasma aluminum level (r=-0.475 and -0.692, both P<0.05) , andthe expression of mGluR1 protein was positively correlated with plasma aluminum level (r=0.756, P<0.05) . The expression of NR1 protein was positively correlated with DSF, DSB, DST, and VFT scores (r(s)=0.213, 0.249, 0.271, and 0.228, all P<0.05) , and the expression of NR2A protein was positively correlated with VFT score (r(s)=0.206, P<0.05) . Conclusion: Occupational aluminum exposure may affect workers' memory function, and the expression of NR1 and NR2A in peripheral blood lymphocytes is correlated with cognitive function indices and can be used as biomarkers for cognitive impairment in aluminum workers.

[Autoimmune disorder secondary to DiGeorge syndrome: a long-term follow-up case report and literature review].

DiGeorge syndrome is the most common chromosome microdeletion disease. The classical complications include congenital heart disease, hypothyroidism, immunodeficiency, facial abnormalities, and hypocalcemia. According to whether there is an absence or hypoplasia of the thymus, DiGeorge syndrome can be divided into two types, complete DiGeorge syndrome and partial DiGeorge syndrome. The patient was a female born with congenital heart disease, facial abnormalities and cleft palate. When the patient went to school, she had learning difficulty and had problems in communication and personal social behavior. Breath-holding occurred when she was 6 years old. She got infections about 2-3 times a year, which was easy to be cured each time. Chromosome microdeletion test of peripheral blood showed the classical 22q11.2 microdeletion, and no evidence showed that she has thymus absence, thus her disease was diagnosed as partial DiGeorge syndrome. When the patient was 6 years old, the blood routine test showed slight thrombocytopenia, and reexaminations after that indicated the similar result. When 9 years old, she was found with anemia and severe thrombocytopenia. At the age of 10, the patient was admitted to our hospital, complaining of petechia in the body and mucous of mouth. According to the various examinations results, doctors eventually considered the situation as an autoimmune disorder phenomenon. After being treated by pulse-dose methylprednisolone for three days, the bleeding ceased. Then the patient orally took prednisone acetate and pulse-dose cyclophosphamide, however the thrombocyte and hemoglobin levels had not been back to a normal range. But when the dose of prednisone acetate was reduced, the blood platelet count declined again while the hemoglobin kept normal. The long-term follow-up of this case lasted for more than 20 years. Until now, the patient is taking orally prednisone acetate as a maintainance treatment, and the anemia has been improved since, but thrombocytopenia still exists. The mechanism of DiGeorge syndrome in combination with immunodeficiency is still unclear. The most likely reason is that this phenomenon has some relationship with the dysfunction of the thymus and finally had an effect on the function of T cells. The clinical manifestation is always stubborn and need treatment and follow-up visit for a long time.

[Association between H3K4me3/BDNF and the cognitive function of workers occupationally exposed to aluminum].

Objective: To investigate the influence of occupational aluminum exposure on cognitive function and its relationship with tri-methyl histone H3 lysine residues 4 points (H3K4me3) and brain-derived neurotrophic factor (BDNF) levels. Methods: By cluster random sampling method, a total of 235 cases of male workers selected from a Shanxi aluminum factory were recruited in the study in September 2015. Used the occupational epidemiological investigation questionnaire, which included Mini-Mental State Examination (MMSE) , Clock Drawing Test (CDT) , Digit Span Test (DST, including forward test DSFT and backward test DSBT) , Fuild Object Memory Evaluation (FOME) and Verbal Fluency Test (VFT) , to collect workers' basic information and assess their cognitive function score. Detected the concentration of aluminum in plasma by graphite furnace atomic absorption spectrometry. Workers were divided into three groups by the 25 percentile and 75 percentile of the aluminum content, such as low, middle and high aluminum concentration groups. The concentrations of H3K4me3 in lymphocyte and BDNF in plasma were determined by enzyme-linked immunosorbent assay. Results: The levels of aluminum in plasma was 134.36 (100.14, 178.96) µg/L. The scores of MMSE, DSFT, DSBT, DST of high aluminum concentration group were lower than low aluminum group (27.98±1.25 vs 28.83±1.54, 9.19±2.00 vs 10.64±2.87, 6.08±1.63 vs 7.19±3.07, 15.27±3.11 vs 17.81±4.72, all P<0.05) , the scores of CDT, FOME, VFT among three groups had no statistical significance (all P>0.05) . The expression levels of H3K4me3 and BDNF of high aluminum concentration group were lower than the low group [ (18.45±9.81) ng/µg Pro vs (23.76±9.89) ng/µg Pro, (26.07±10.18) ng/ml vs (31.66±9.24) ng/ml, all P<0.05]. Multiple correlation analysis showed that aluminum concentration were negatively correlated toH3K4me3, BDNF, MMSE, DSFT, DST, respectively (r(s)=-0.307、-0.214、-0.252、-0.197, -0.181, all P<0.01) . Conclusion: Exposure to occupational aluminum for a long time may change cognitive function, which go along with the decreasing of H3K4me3 level in lymphocyte and BDNF protein expression in plasma.

Genetic diversity analysis of okra (Abelmoschus esculentus L.) by inter-simple sequence repeat (ISSR) markers.

Okra (Abelmoschus esculentus L.) is not only a nutrient-rich vegetable but also an important medicinal herb. Inter-simple sequence repeat (ISSR) markers were employed to investigate the genetic diversity and differentiation of 24 okra genotypes. In this study, the PCR products were separated by electrophoresis on 8% nondenaturing polyacrylamide gel and visualized by silver staining. The 22 ISSR primers produced 289 amplified DNA fragments, and 145 (50%) fragments were polymorphic. The 289 markers were used to construct the dendrogram based on the unweighted pair-group method with arithmetic average (UPGMA) cluster analysis. The dendrogram indicated that 24 okras were clustered into 4 geographically distinct groups. The average polymorphism information content (PIC) was 0.531929, which showed that the majority of primers were informative. The high values of allele frequency, genetic diversity, and heterozygosity showed that primer-sample combinations produced measurable fragments. The mean distances ranged from 0.045455 to 0.454545. The dendrogram indicated that the ISSR markers succeeded in distinguishing most of the 24 varieties in relation to their genetic backgrounds and geographical origins.

Assessment of future anthropogenic change and associated benthic risk in coastal environments using sedimentary metal indicators.

Indicators of estuarine health are frequently compromised by large, natural temporal and spatial variance, which often mask long-term environmental trends and confound remedial actions. Ecosystem indicators seldom provide information on the pristine condition or the history of anthropogenic change of a water body. The current investigation used sedimentary metals and novel field and analytical techniques to determine the pristine condition and assess the magnitude and history of human-induced temporal and spatial change of an estuarine system. Two vintages of normalised metal concentrations in surficial sediment (1992 and 2007) indicate Cu and Zn concentrations have increased over the period, while Pb concentrations have declined - a change verified by strategically located sedimentary cores. Assuming no change in metals supply and dispersion, Cu and Zn are predicted to increase in concentration and areal extent, whereas Pb concentrations and areal cover will decrease. High concentrations of sedimentary Cu may be having an adverse affect on the health of benthic animals over extensive areas, which are predicted to expand if no remedial strategy is implemented.

Statins improve asthma symptoms by suppressing inflammation: a meta-analysis based on RCTs.

OBJECTIVE: Asthma is a chronic airway inflammatory disease caused by high infiltration of multiple inflammatory cells and factors in airway tissues. Statins may inhibit inflammation, hence improve asthma symptoms. This meta-analysis aimed to assess the efficacy of statins in the treatment of asthma patients. MATERIALS AND METHODS: We searched in PubMed, OVID, Cochrane Library, and Web of Science databases using the following key words: "statin", "atorvastatin", "simvastatin", "pravastatin", "rosuvastatin", "pitavastatin", "fluvastatin", and "asthma". The effects of statins on function, serum biomarkers, sputum mediators, and serum biochemical markers were analyzed from the identified studies. RESULTS: Twelve articles (613 participants) were included in the meta-analysis. Results showed that statins significantly improved asthma symptoms (ACQ score: MD: -0.43, 95% CI: -0.47 - -0.38, p<0.01; ACT score: MD: 1.96, 95% CI: 1.26-2.67, p<0.01). Furthermore, statins significantly reduced serum hsCRP (MD: -0.50, p=0.02) and cholesterol (MD: -32.76, p<0.01) levels and the proportion of sputum eosinophils (MD: -1.25, p<0.01) and IL6 levels (MD: -64.56, p=0.04) in sputum. However, lung function was not significantly different between the statin and placebo treatment groups. CONCLUSIONS: Although statins did not change the lung function in patients with asthma, they improved asthma symptoms and reduced the serum hsCRP, sputum eosinophil ratio, and IL6 levels.

Author Correction: Nitrosative stress induces downregulation of ribosomal protein genes via MYCT1 in vascular smooth muscle cells.

Correction to: European Review for Medical and Pharmacological Sciences 2021; 25 (18): 5653-5663-DOI: 10.26355/eurrev_202109_26784-PMID: 34604957, published online on 30 September, 2021. After publication, the authors applied to add another corresponding author. Therefore, both Dr. Xiaosun Guo and Dr. Fan Jiang are the corresponding authors of this article. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/26784.

Nitrosative stress induces downregulation of ribosomal protein genes via MYCT1 in vascular smooth muscle cells.

OBJECTIVE: In our previous genomic studies in human intracranial aneurysms, we observed downregulations in the expression of a number of ribosomal protein genes and the c-Myc-related gene MYC target 1 (MYCT1). So far there is no information about the roles of MYCT1 in vascular cells. Our study aims to investigate the functional roles of MYCT1 in vascular smooth muscle cells (SMCs). MATERIALS AND METHODS: Primary SMCs were isolated from rat thoracic aorta and cultured in vitro. The mRNA and protein expressions were determined by real-time PCR and western blot respectively. Apoptosis was detected by measuring caspase 3/7 activity. Collagen production was determined with ELISA. RESULTS: Using PCR, we validated our previous genomic data showing that the expressions of MYCT1 and ribosomal protein genes were decreased in human aneurysm tissues. In vascular SMCs, we showed that nitrosative stress downregulated the expression of both MYCT1 and ribosomal proteins. Knockdown of MYCT1 mimicked the effects of nitrosative stress on ribosomal protein expressions, whereas overexpression of MYCT1 blunted the effects of nitrosative stress. MYCT1-dependent downregulation of ribosomal proteins compromised the protein translational capacity of the cells for collagen production. Moreover, the endogenously expressed MYCT1 in vascular SMCs was involved in maintaining normal cellular functions including survival, proliferation and migration. CONCLUSIONS: MYCT1-dependent gene regulation may, at least partly, explain the downregulated expressions of ribosomal proteins observed in human intracranial aneurysms. It is suggested that MYCT1 may represent a novel molecular target for counteracting the decreased activity of aneurysmal SMCs for tissue repairmen/regeneration.

Organic trace minerals improve eggshell quality by improving the eggshell ultrastructure of laying hens during the late laying period.

The objective of this study was to investigate the effects of low inclusion levels of organic trace minerals (iron, copper, manganese, and zinc) on performance, eggshell quality, serum hormone levels, and enzyme activities of laying hens during the late laying period. A total of 405 healthy hens (HY-Line White, 50-week-old) were randomly divided into 3 treatments, with 9 replications per treatment and 15 birds per replication. The dietary treatments included a basal diet supplemented with inorganic trace minerals at commercial levels (CON), a basal diet supplemented with inorganic trace minerals at 1/3 commercial levels (ITM), and a basal diet supplemented with proteinated trace minerals at 1/3 commercial levels (TRT). The trial lasted 56 D (8 wk). Compared with the CON group, the ITM group showed decrease in (P < 0.05) egg production, eggshell strength, eggshell palisade layer, palisade layer ratio, serum estrogen, luteinizing hormone, glycosaminoglycan concentration, and carbonic anhydrase activity and increase in (P < 0.05) egg loss and mammillary layer ratio. However, the TRT group almost kept all the indices close to the CON group (P > 0.05). Furthermore, hens fed with low inclusion levels of organic trace minerals had smaller mammillary knobs (P < 0.05) than those in the CON and ITM groups. In conclusion, hens fed with low inclusion levels of proteinated trace minerals had better performance and eggshell strength than those fed with identical levels of inorganic compounds; organic trace minerals improved eggshell quality by improving the eggshell ultrastructure of laying hens during the late laying period.

Effects of mercury released from gold extraction by amalgamation on renal function and environment in Shanxi, China.

We investigated the distribution of mercury and its impacts on the renal function of the residents living in mercury-contaminated area due to gold extraction by amalgamation in some area of Shanxi, China. The results showed that mercury concentrations in contaminated air in four seasons were 79-240 ng/m(3). The mercury concentration in the river across contaminated area was also high. The mercury contents in the grain were higher than those in the non-mercury contaminated area. The urinary mercury and urinary beta(2)-microglobulin for the residents living in the contaminated area were 1.24 +/- 3.80 microg/L and 228.98 +/- 4.34 microg/g Cr, higher than those in the non-mercury contaminated area.

Expression of CD27, CD28 and IL-17A in peripheral blood from patients with colorectal carcinoma.

OBJECTIVE: To compare the different expressions of CD27, CD28, IL-17A, IFN-γ and TNF-α in the peripheral blood sampled from patients with colorectal carcinoma and healthy volunteers. PATIENTS AND METHODS: Vδ2 T cells were isolated from the peripheral blood mononuclear cells (PBMCs) of patients with the colorectal carcinoma (CRC, n = 30) and healthy controls (HC, n = 21). The proportion of CD27, CD28, IL-17A, IFN-γ and TNF-α of Vδ2 T cells was detected by the flow cytometry. RESULTS: We found that the proportion of IL-17A of Vδ2 T cells in PBMCs was higher in the CRC vs. the HC group (p < 0.05). A significant positive correlation was observed between the expression of IFN-γ and TNF-α of Vδ2 T cells. In the CRC patients, the proportions of IL-17A of CD27- Vδ2 T cells and CD28+ Vδ2 T cells were higher than those of CD27+ Vδ2 T cells and CD28- Vδ2 T cells, whereas the expression of IFN-γ and TNF-α of CD27-Vδ2 T cells was lower than that of CD27+ Vδ2 T cells. CONCLUSIONS: Vδ2 T cells from PBMCs had higher expression of IL-17A in CRC patients than that in the HC group. The expression of IFN-γ and TNF-α of Vδ2 T cells from PBMCs was positively correlated. The cytokine profiles of peripheral Vδ2 T cells were likely determined by a CD27 and CD28 involving mechanism.

Expression, purification, and activity of recombinant MHV-A59 3CLpro.

The 3C-like proteinase (3CLpro) of MHV-A59 is predicted to mediate the majority of proteolytic processing events within the gene 1 polyprotein. We have overexpressed 3CLpro in E. coli as a fusion protein with maltose binding protein (MBP). The MBP-3CLpro fusion protein was purified from contaminating E. coli proteins by amylose column chromatography, and r3CLpro was cleaved from the fusion protein by factor Xa. Recombinant 3CLpro (r3CLpro) was able to cleave a polypeptide substrate containing mutated inactive 3CLpro and portions of the flanking domains. R3CLpro cleaved substrate completely within 5 minutes and the activity of r3CLpro was sensitive to inhibition by serine and cysteine proteinase inhibitors; however, it was not inhibited by EDTA, suggesting that metal ions were not critical for 3CLpro activity.

Processing of the MHV-A59 gene 1 polyprotein by the 3C-like proteinase.

The 3C-like proteinase of mouse hepatitis virus (MHV-3CLpro) is predicted to cleave at least 10 sites in the gene 1 polyprotein, resulting in processing of proteinase, polymerase and helicase proteins from the polyprotein. We have used E. coli expressed recombinant 3CLpro (r3CLpro) to define cleavage sites in carboxy-terminal region of the ORF 1a polyprotein. Polypeptides containing one or more putative 3CLpro cleavage site were translated in vitro from subcloned regions of gene 1, and the polypeptides were incubated with r3CLpro. Analysis of the cleavage products confirmed several putative cleavage sites, as well as identifying cleavage sites not previously predicted by analysis of the MHV sequence. Antibodies directed against a portion of the ORF 1a polyprotein were used to probe virus infected cells, and detected proteins that correspond to the cleavage sites used by 3CLpro in vitro. These results suggest that MHV 3CLpro cleaves at least 7 sites in the ORF 1a polyprotein, and that the specificity of 3CLpro for cleavage site dipeptides may be broader than previously predicted.