Case report: Complex paraneoplastic syndromes in thymoma with nephrotic syndrome, cutaneous amyloidosis, myasthenia gravis, and Morvan's syndrome.

Background: Apart from myasthenia gravis (MG), thymoma is associated with a wide spectrum of autoimmune paraneoplastic syndromes (PNSs). Here, we report on a rare case presenting with four different PNSs, namely, MG, membranous nephropathy, cutaneous amyloidosis, and Morvan's syndrome associated with thymoma. Case presentation: A middle-aged man was frequently hospitalized because of nephrotic syndrome (stage I membranous nephropathy), cutaneous amyloidosis, and MG with acetylcholine receptor (AChR) antibody and titin antibody positivity. Chest CT showed a thymic mass in the left anterior mediastinum, and he received intravenous immunoglobulin (IVIG), methylprednisolone pulse therapy, thoracoscopic thymoma resection, and radiotherapy. Postoperative pathological examination revealed a type B2 thymoma. During the perioperative stage, his electrocardiogram (ECG) showed myocardial infarction-like ECG changes; however, his levels of cardiac enzymes and troponin were normal, and he had no symptoms of precardiac discomfort. Six months after thymectomy, his nephrotic syndrome and MG symptoms were relieved; however, he presented with typical manifestations of Morvan's syndrome, including neuromyotonia, severe insomnia, abnormal ECG activity, and antibodies against leucine-rich glioma-inactivated 1 (LGI1) and γ-amino-butyric acid-B receptor (GABABR). His symptoms did not improve after repeated IVIG and steroid therapies. Finally, he received low-dose rituximab, and his symptoms gradually resolved. Conclusion: This case serves to remind us that apart from MG, thymoma is also associated with other autoimmune PNSs such as membranous nephropathy, cutaneous amyloidosis, and Morvan's syndrome. Autoimmune PNSs can present concurrently with or after surgical or medical therapy for thymoma. For Morvan's syndrome post-thymectomy with LGI1 antibody positivity, B-cell depletion therapy such as intravenous rituximab is an effective treatment.

UPLC-MS/MS Measurement of the Effect of Isavuconazole, Itraconazole and Fluconazole on the Pharmacokinetics of Selinexor in Rats.

OBJECTIVE: An ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of selinexor was established to investigate the effects of isavuconazole, itraconazole and fluconazole on the pharmacokinetics of selinexor in rats, respectively. METHODS: Twenty-four healthy male rats were randomly divided into four groups: group A, normal saline; group B, isavuconazole (20 mg/kg); group C, itraconazole (20 mg/kg); and group D, fluconazole (20 mg/kg). After 30 min of oral administration of normal saline, isavuconazole, itraconazole, and fluconazole, all the rats were given selinexor (8 mg/kg). The plasma concentration of selinexor was estimated by UPLC-MS/MS, and the pharmacokinetic parameters of selinexor were calculated by Drug and Statistics (DAS) 2.0 software. RESULTS: Under these experimental conditions, the method showed good linearity and stability. Intraday and interday accuracy and sample recovery were acceptable. Compared with group A, the Cmax, AUC(0-t) and AUC(0-∞) of selinexor in group B increased by 59.05%, 31.69%, and 31.45%; the Cmax, AUC(0-t) and AUC(0-∞) of selinexor in group C increased by 56.14%, 25.34%, and 25.08%; the Cmax, AUC(0-t) and AUC(0-∞) of selinexor in group D increased by 43.44%, 29.16%, and 31.96%, respectively. The Tmax of the experimental groups were extended, and CLz/F was also significantly reduced. CONCLUSION: These results indicated that isavuconazole, itraconazole, and fluconazole have significant inhibitory effects on selinexor pharmacokinetics and increased selinexor plasma exposure in rats. Therefore, when these drugs were used in combination, clinicians should pay attention to the changes in treatment effects and the occurrence of adverse reactions caused by the drug-drug interactions.

[Heavy Metal Contamination of Soils and Crops near a Zinc Smelter].

To evaluate the influence of mining activities on heavy metal contamination and health risks in a zinc-smelting area in Guizhou Province, Pb, Cd, Zn, and Cu in agriculture soils and dominant crops were monitored and analyzed. A single factor pollution index and a comprehensive pollution index were calculated to assess the quality of soils and crops. Furthermore, the potential ecological risks of the four heavy metals in soils and crops were evaluated using the potential ecological risk index (RI). The potential health risks to adults and children induced by the intake of these heavy metals through consumption of crops were evaluated using the hazard quotient (HQ). The results showed that:①The farmlands in the zinc-smelting area were contaminated by heavy metals; the most polluted farm land was corn fields followed by paddy fields and wheat fields. The order of the heavy metal concentrations was Cd > Cu > Zn > Pb. The Nemero index of corn fields was higher than the threshold value of heavy pollution and was higher than that of the paddy and wheat fields. Cd contributed most to the integrated pollution index. ②The very high ecological risk was posed by Cd followed by Pb, Cu, and Zn. The results of the potential ecological risk assessment showed that 1.41% of the sites were classified as low risk, 21.1% classified as medium risk, 35.2% as high risk, and 42.3% as extremely high risk. ③The average concentrations of Pb, Cd, Zn, and Cu in rice were 0.145, 0.017, 16.97, and 2.704 mg·kg-1, respectively. The average concentrations of Pb, Cd, Zn, and Cu in corn were 0.094, 0.055, 26.81, and 4.464 mg·kg-1, respectively. The average concentrations of Pb, Cd, Zn, and Cu in wheat were 0.048, 0.085, 35.37, and 5.426 mg·kg-1, respectively.④Rice, corn, and wheat from the study area were subjected to pollution at different degrees. Among the three crops studied, wheat was polluted most heavily, followed by rice and corn. Contamination levels of rice and corn were safe, whereas the contamination of wheat reached alarming levels. ⑤The daily intake of individual heavy metals from food was below the standard exposure dose set by the United States Environmental Protection Agency. In addition, the assessment results for the comprehensive health risk index for the three crops indicate that the contamination of heavy metals poses health risks to adults and children by food ingestion. ⑥ Positive correlations were not observed between farmlands and crops.

Potentially toxic trace element contamination, sources, and pollution assessment in farmlands, Bijie City, southwestern China.

Artisanal zinc smelting activities, which had been widely applied in Bijie City, Guizhou Province, southwestern of China, can pollute surrounding farmlands. In the present study, 177 farmland topsoil samples of Bijie City were collected and 11 potentially toxic trace elements (PTEs), namely Pb, Zn, Cu, Ni, Co, Mn, Cr, V, Hg, As, and Cd were tested to characterize the concentrations, sources, and ecological risks. Mean concentrations of these PTEs in soils were (mg/kg) as follows: Pb (127), Zn (379), Cu (93.1), Ni (54.6), Co (26.2), Mn (1095), Cr (133), V (206), Hg (0.15), As (16.2), and Cd (3.08). Pb, Zn, and Cd had coefficients of variation greater than 100% and showed a high uneven distribution and spatial variability in the study area. Correlation coefficient analysis and principal component analysis (PCA) were used to quantify potential pollution sources. Results showed that Cu, Ni, Co, Mn, and V came from natural sources, whereas Pb, Zn, Hg, As, and Cd came from anthropogenic pollution sources. Geoaccumulation index and potential ecological risk indices were employed to study the pollution degree of PTEs, which revealed that Pb and Cd shared the greatest contamination and would pose serious ecological risks to the surrounding environment. The results of this study could help the local government managers to establish pollution control strategies and to secure food safety.

The recovery of Zn and Pb and the manufacture of lightweight bricks from zinc smelting slag and clay.

Novel lightweight bricks have been produced by sintering mixes of zinc smelting slag and clay. A two-stage sintered process has been proposed to recovery of Zn and Pb and reutilization of the zinc smelting slag. In the first stage of the process, called reduction and volatilization procedure, zinc and lead were reduced by the carbon contained in the zinc smelting slag and volatilized into the dust, and the dust can be used as a secondary zinc resource. In the second stage of the process, called oxidation sintering procedure, a lightweight brick was produced. Samples containing up to 60 wt.% zinc smelting slag and 40 wt.% kaolin clay were reduced at 1050°C for 6h, and then sintered at 1050°C for 4h. The recoveries of Zn and Pb from the brick are 94.5 ± 0.6% and 97.6 ± 0.2%, respectively. Low bulk density (1.42 g cm(-3)) and relatively high compressive strength (2 2MPa) sintered bricks were produced, and the leaching toxicity of the sintered bricks was below the regulatory thresholds of Chinese National Standards.

[Distribution of arsenic species and its DNA damage in subchronic arsenite-exposed mice].

OBJECTIVE: To study the arsenic distribution, speciation, its effects on the balance of other elements and the DNA damage by subchronic arsenite exposure in mice. METHODS: The 8-week-old C57BL/6N mice were matched by weight and divided into control group and supplementation group, which were given 0 or 10 microg/ml of sodium arsenite in the drinking water, and continuous exposed for 6 months. RESULTS: Arsenic was found in various tissues and organs. The highest ones were in the kidney, lung and liver, reached (563.9 +/- 222.5), (458.6 +/- 191.0) and (279.8 +/- 81.2) ng/g, respectively while the lowest in the blood and brain, reached (82.2 +/- 26.7) ng/ml and (101.8 +/- 30.1) ng/g, respectively. Arsenic exists mainly in the form of dimethylarsinous acid (DMA). Compared to the control group, there was a significant difference (P < 0.05) between arsenic and chromium, copper, zinc, selenium, lead in some organs of arsenic exposed group, but not cadmium. Furthermore, the 8-hydroxydeoxyguanosine (8-OHdG) level of the exposed group was (149.1 +/- 1.0) ng/ml, which was significantly higher than the control group of (76.4 +/- 27.9) ng/ml. CONCLUSION: Arsenic accumulated in various tissues and organs mainly in the form of DMA, which affected the balance of chromium, copper, zinc, selenium and lead in the body, and led to DNA damage after subchronic exposure.

Organic selenium supplementation increases mercury excretion and decreases oxidative damage in long-term mercury-exposed residents from Wanshan, China.

Due to a long history of extensive mercury mining and smelting activities, local residents in Wanshan, China, are suffering from elevated mercury exposure. The objective of the present study was to study the effects of oral supplementation with selenium-enriched yeast in these long-term mercury-exposed populations. One hundred and three volunteers from Wanshan area were recruited and 53 of them were supplemented with 100 µg of organic selenium daily as selenium-enriched yeast while 50 of them were supplemented with the nonselenium-enriched yeast for 3 months. The effects of selenium supplementation on urinary mercury, selenium, and oxidative stress-related biomarkers including malondialdehyde and 8-hydroxy-2-deoxyguanosine were assessed. This 3-month selenium supplementation trial indicated that organic selenium supplementation could increase mercury excretion and decrease urinary malondialdehyde and 8-hydroxy-2-deoxyguanosine levels in local residents.

Mercury in human hair and blood samples from people living in Wanshan mercury mine area, Guizhou, China: an XAS study.

Human hair and blood samples from persons living in the town of Wanshan, a mercury mine area in Guizhou Province of China, were collected and the quantitative speciation and structural information of Hg and S in hair samples and of Hg in erythrocyte and serum samples were studied using X-ray absorption spectroscopy. Least-squares fitting of the X-ray absorption near-edge spectra found that inorganic mercury is the major mercury species in hair samples (91.74%), while inorganic and methyl mercury are both about 50% of total mercury in RBC and serum samples, which is in agreement with the data obtained by acidic extraction, fractionation of Hg(2+) and CH(3)Hg(+) and quantification by ICP-MS. Curve-fitting analysis revealed that the Hg-S bond length and coordination number in hair were 0.248+/-0.002 nm and 3.10, respectively, while the S-Hg bond length and coordination number in hair were 0.236+/-0.002 nm and 4.05. The Hg-S bond length and coordination number in RBC were 0.251+/-0.003 nm and 4.09, respectively, while they were 0.228+/-0.002 nm and 4.08 in serum, respectively. The techniques for speciation, structural and binding information described in this study will find the potential application in similar studies of other elements.