Neoadjuvant Immunotherapy With Ipilimumab Plus Nivolumab in Mismatch Repair Deficient/Microsatellite Instability-High Colorectal Cancer: A Preliminary Report of Case Series.

BACKGROUND: Although ipilimumab plus nivolumab have significantly improved the survival of metastatic colorectal cancer (CRC) with mismatch repair deficient (dMMR) /microsatellite instability-high (MSI-H), the data on neoadjuvant setting is limited. PATIENTS AND METHODS: We enrolled 11 patients with advanced dMMR/MSI-H CRC. 10 patients were locally advanced and 1 was metastatic. Ten patients were treated with 1 dose of ipilimumab (1 mg/kg) and 2 doses of nivolumab (3 mg/kg), and 1 patient was treated with 1 dose of ipilimumab (1 mg/kg) and 2 doses of nivolumab (3 mg/kg) with 2 cycles. All the patients underwent surgery after immunotherapy. The aim of the study was to evaluate the safety and short-term efficacy of this strategy. RESULTS: Pathologic responses were observed in 11/11 (100%) dMMR/MSI-H tumors, with 9/11 (81.8%) achieving complete responses. Among these 9 cases with complete responses, 1 achieved a radiological noncomplete response after treatment with 1 dose of ipilimumab (1 mg/kg) and 2 doses of nivolumab (3 mg/kg), so another cycle of treatment with 1 dose of ipilimumab (1 mg/kg) and 2 doses of nivolumab (3 mg/kg) was administered, followed by surgery. The postoperative pathological evaluation was a complete response. Seven patients (63.6%) developed grade I/II adverse events. No patients developed grade III/IV adverse events or postoperative complications. CONCLUSION: Neoadjuvant immunotherapy with ipilimumab plus nivolumab induced tumor regression with a major clinical and pathological response in advanced dMMR/MSI-H CRC. Notably, patients do not achieve a complete response to neoadjuvant immunotherapy, additional neoadjuvant immunotherapy may offer benefits. Further research is needed to assess the long-term efficacy of this strategy.

Spatial and seasonal variations of the air pollution index and a driving factors analysis in china.

In this study, the daily air pollution index (API) of 110 cities based on ground monitoring was conducted on the 2011 data set from the Ministry of Environmental Protection of China. The pollutant concentrations, seasonal variations, and spatial autocorrelations were evaluated. The results show that the major principal pollutants in China are inhalable particles. In addition, the total number of clean days (API ≤ 50) is apparently smaller in the northern cities than in the southern cities as a result of fuel utilization and large-scale organized central heating. Seasonally, air pollution is most severe in winter and is caused by low-frequency rainfall, strong northwest winds, dry climate, and high energy consumption; this is followed by spring, which is a season of frequent sandstorms. According to spatial autocorrelation analysis, clusters with high API value agglomeration (High-High clusters) are mainly concentrated in the middle and northern parts of China, whereas clusters with low API agglomeration (Low-Low clusters) are principally concentrated in the southern parts of China due to a favorable climate and abundant rainfall. Meteorological data, including wind speed and temperature, have great impacts on API. The air quality effects of industrial structure, energy use, urban greening, and traffic congestion were also analyzed. With the ecological function of purifying the air, industries that use natural resources and urban greening could help to reduce API, whereas secondary industry and gas use, which have a positive coefficient, increase the API value. The risk of exposure to poor air quality is largest in the winter, smallest in the summer, and remains relatively unchanged in the spring and autumn.

Bioaccessibility and risk assessment of cadmium from uncooked rice using an in vitro digestion model.

Cadmium (Cd)-contaminated rice is one of the most important sources of cadmium exposure in the general population from some Asian countries. This study was conducted to assess cadmium exposure from uncooked rice in rural mining areas based on the bioaccessible fraction of cadmium using an in vitro digestion model. The biotoxic effects of cadmium in uncooked rice from mining areas were much higher than those in the control area, based not only on their higher total concentration (52.49 vs. 7.93 µg kg(-1)), but also on their higher bioaccessibility (16.94% vs. 2.38%). In the mining areas, the bioaccessible fraction of cadmium in uncooked rice has a significant positive correlation with the total concentration of cadmium in rice and there was quarterly unsafe rice to the public in the mining areas. The results indicated that the in vitro digestion model could be a useful and economical tool for providing the solubilization or bioaccessibility of uncooked rice in the mining area. The results could be helpful in conducting future experiments of cooked rice in the vitro model.

[Relationship between longevity and soil environment in Xiayi County, Henan Province, China].

Based on field investigation and laboratory analysis, exploration was done of distribution of macro and micro elements in the soils and distribution of longevity population in Xiayi County, Henan Province, China, and relationship between the spatial variation of the distribution of soil elements and the distribution of the longevity population. It was found that longevity population was distributed in a belt running across Xiayi county from northeast to southwest. In the northeast part, the longevity rate (over 95 years old) reached 187 per million and while in the northwest part, it was only 83. The concentrations of heavy metals such as Cd, Cr, Cu, Ni, Pb, Zn in Xiayi soils were (0.177 +/- 0.057), (63.9 +/- 7.48), (23.6 +/- 5.63), (29.5 +/- 3.80), (21.8 +/- 3.37) and (64.80 +/- 8.81) mg x kg(-1), respectively, all up to the criteria for grade II soils in the National Standard for Soil Environment Quality of China; Moreover, the soils in longevous areas were rich in Cr, Zn, K and Mg. K and Mg in Xiayi soils were 1.30 and 1.79 as times as high as the background value of Henan Province and 1.21 and 2.62 times that of the country, respectively. In Liji, Huodian and Zhongfeng where the centenarian rate was relatively low, the soils were low in Cu, Se and Zn, but high in Na. The findings clearly indicate that the soil rich in Cr, Zn, K and Mg and free of any heavy metal pollution is a major contributor to the longevity in the area, while uneven distribution of Se, Zn, Cu and Na in the soil is the key factor affecting the distribution of longevity population in Xiayi County.

[Determination of five trace elements (Pb, Cd, Se, As and Hg) in human whole blood by temperature-controllable wet digestion and ICP-MS technique].

A method for the determination of five trace elements, including Pb, Cd, Se, As and Hg concentrations in human whole blood by HNO3-H2O2 digestion under temperature-controllable condition and ICP-MS was described. Under the optimum experimental conditions and instrumental operation parameters, the limit of detection for the five elements were 2-40 ng x L(-1). The system had a good stability with RSDs of the determination of value repeated 3 times less than 3%. The accuracy of the method was evaluated by the results of determination of the Chinese national standard references GBW(E)09034-09036 and GBW09101b, and the analytical results well agreed with the certified values. Using this method, the concentration of the five elements in whole blood of 34 habitants from mercury mining area in western Human province was studied. The result showed that the blood Se and blood As level was at security scope, however, blood Pb, Cd and Hg level was too high and beyond the safety thresholds which should be concerned about. The analytical method mentioned above can be used for determination of trace elements in human blood to achieve a convenient and rapid operation and accurate result.

[Determination of life elements in hair and urine with brick-tea fluorosis in Inner Mongolia by ICP-OES].

In brick-tea fluorosis affected areas XiLinHot city in Inner Mongolia, herdsmen who like drinking a large amount of brick tea in everyday life and Han habitants rarely drinking brick tea as control group were enrolled, and their hair and urine were sampled. The concentrations of Ca, Mg, K, Al, P, Cu, Zn and Fe in hair and urine were detected using ICP-OES. The RSDs of the method were between 2.32% and 8.03%, and the analytical results of the hair reference samples were consistent with the certified values. The results showed that the contents of Al, Mg and K in hair, and contents of Al and Ca in urine of herdsmen who were accustomed to drinking brick tea were obviously higher than those in control group (P<0.05), while the contents of K in urine of herdsmen who were accustomed to drinking brick tea was lower than those in control group (P<0.05), and other elements did not have statistic significance (P>0.05). Chronically drinking brick tea probably brings metabolic disorder of Ca and Al in human body, and the interaction mechanism of life elements in brick-tea fluorosis should be further studied.

[Spatial distribution and ecological significance of heavy metals in soils from Chatian mercury mining deposit, western Hunan province].

Ores, waste tailings and slag, together with three typical soil profiles (natural soil profiles far from mine entrance and near mine entrance, soil profile under slag) in Chatian mercury mining deposit (CMD), western Hunan province were sampled and their concentrations of mercury (Hg), arsenic (As), lead (Pb), cadmium (Cd), zinc (Zn) were determined by HG-ICP-AES and ICP-MS. Enrichment factor and correlation analysis were taken to investigate the origins, distribution and migration of Hg, as well as other heavy metals in the CMD. The results show that Hg is enriched in the bottom of the soil profile far from mine entrance but accumulated in the surface of soil profiles near mine entrance and under slag. The soil profiles near mine entrance and under slag are both contaminated by Hg, while the latter is contaminated more heavily. In the soil profile under slag, Hg concentration in the surface soil, Hg average concentration in the total profile, and the leaching depth of soil Hg are 640 microg x g(-1), (76.74 +/- 171.71) microg x g(-1), and more than 100 cm, respectively; while 6.5 microg x g(-1), (2.74 +/- 1.90) microg x g(-1), and 40 cm, respectively, are found in the soil profile near mine entrance. Soil in the mercury mine area is also polluted by Cd, As, Pb, Zn besides metallogenic element Hg, among which Cd pollution is relatively heavier than others. The mobility of the studied heavy metals in soil follows the order as Hg > Cd > As > Zn approximately equal to Pb. The leaching depth of the heavy metals is influenced by total concentration in the surface soil and soil physico-chemical parameters. The origins, distribution and migration of heavy metals in soil profile in the mining area are related to primary geological environment, and strongly influenced by human mining activities.

Fluoride in drinking water, brick tea infusion and human urine in two counties in Inner Mongolia, China.

The objective of this study was to detect the fluoride level in the drinking water and the urine of habitants aged 16-55 years living in Inner Mongolia China. Furthermore, fluoride concentration of the brick tea infusion samples which were drunk by Mongolia herdsmen in everyday life living in SumuErga village of Ejin Horo Banner, Inner Mongolia China was also determined. A total of 117 participants (61 female and 56 male) were recruited from two counties for a cross-sectional study on health effects of chronic fluoride exposure from drinking water and drinking brick tea infusion. The fluoride concentration in drinking water, urine and brick tea infusion samples were determined using fluoride ion selective electrode method obtained from the Ministry of Health of the People's Republic of China. The average fluoride concentration in drinking water samples was 0.32+/-0.01 mg/L at AretengXire town of Ejin Horo Banner, 0.70+/-0.19 mg/L at SumuErga village of Ejin Horo Banner, and 2.68+/-1.15 mg/L at ZhalaiNuoer district of Manzhouli city. The average fluoride concentration in brick tea infusion samples which collected from Mongolia herdsmen at SumuErga village of Ejin Horo Banner was 1.81+/-1.09 mg/L. The average urinary fluoride concentration at AretengXire town of Ejin Horo Banner was 0.59+/-0.48 mg/L, at SumuErga village of Ejin Horo Banner was 1.45+/-0.93 mg/L and at ZhalaiNuoer district of Manzhouli city was 3.06+/-1.53 mg/L. The higher fluoride levels in the urine of participants may be associated to higher fluoride in drinking water at ZhalaiNuoer of Manzhouli city. However, drinking brick tea infusions with higher fluoride may be the cause of the higher fluoride contents in the Mongolia herdsmen's urine.

[Lead uptake by plant in soil-plant system at lead-zinc deposit area of western Hunan province].

Contents of lead in several crops as well as its uptake and distribution by paddy in typical lead-zinc deposit area of western Hunan province were studied based on field systematic sampling and laboratory analysis. The average concentration of lead in rice, maize and soy bean in the deposit was 2.4, 1.2 and 3.3 times higher than that in control area, respectively, suggesting that crops in the deposit were heavily contaminated by the element. Significant difference of the lead concentrations in crops was found among different crop species and different organs of the same crops. The average concentration of lead followed the trend: soy bean > rice > maize (among crop species), and root > haulm > seed (among organs). Paddy root exhibited strong binding and tolerant capacity to lead. Correlation analysis indicated that soil lead was main retention in paddy root, whereas the gaseous lead might be the main source for lead in the aerial part of crop. Heavy metals such as Hg, Cd as well as Pb co-enriched in crops, therefore the mechanism and health risk of the combined pollution of heavy metals in the deposit crops should be paid attention to.

[Pollution characteristics analysis of Hg, Pb and As in soils of nonferrous metal mine area by the BCR and HG-ICP-AES technique].

A method for the determination of Hg, Pb and As concentrations in soil and sediment samples by the BCR and HG-ICP-AES technique was described. Under the optimum experimental conditions and instrumental operation parameters, the detection limits of Hg, Pb and As of the method were 0.6, 1.5 and 0.8 ng x mL(-1) , respectively. Meanwhile, the analytical results of Hg, Pb and As in the Chinese national standard sediment reference samples were in good agreement with the certified values with the RSDs below 8%. Using the BCR and HG-ICP-AES technique, the content of each chemical species of Hg, Pb and As in soils of nonferrous metal mine area in western Hunan province was studied. The result showed that the Hg, Pb and As contents in soils were dominated by residual form, followed by organic and Fe-Mn oxides form, whereas acid-exchangeable form was rather low. The concentrations of the four Hg species in mine soil were 1.2, 3.0, 47 and 272 times higher than those in the control soil. While the concentrations of Pb and As in the same samples were 1.2, 4.6, 8.1 and 4.5 times and 1.5, 2.9, 3.3 and 2.2 times higher than those in the control soil, respectively. The results indicated that the soil in mine area in western Hunan province was co-polluted polluted by Hg, Pb and As.

[Chemical speciation and pollution characteristics of soil mercury in mercury deposit area of Western Hunan-Eastern Guizhou province].

By the BCR extraction procedures and HG-ICP-AES technique, the chemical speciation and pollution characteristics of soil mercury in typical mercury deposit areas of Western Hunan-Eastern Guizhou province were studied. It was found that the concentrations of mercury in soils are dominated by residual form, followed by organic-sulfide form. Fe-Mn oxides and acid-exchangeable form are rather low. The percent of the four mercury species in soils are 85.77%, 12.44%, 0.93% and 0:86%, respectively. The total concentrations and each species of mercury in soils show positive relationship with the concentration of sands, and negative relationship with the concentration of clays in soils. They also increase with the soil pH value. Mercury concentration in soils has spatial changes. In general, the concentrations in the surface soil are higher than those of sub-surface soils. Furthermore, the concentrations rapidly decrease with the distance from the pollution source increased and vary among different soil samples from different location and land use type. The results indicated that exogenous mercury pollution caused by human activities provides significant influence on environmental toxicity and pollution characteristics of mercury in soils of mercury deposit area.

[Determination of trace mercury and arsenic in human hair of polymetallic mining area by HG-ICP-AES].

In the present paper, a method for the determination of trace elements such as Hg and As in biological samples by HG-ICP-AES was presented. Under the optimum experimental conditions and instrumental operation parameters, both the RSDs of Hg and As with the method were below 3%, and the detection limits were 0.6 ng Hg x mL(-1) and 0.8 ng As x mL(-1), respectively, satisfying the demand of detecting trace Hg and As concentration in biological samples. Meanwhile, the analytical results of Hg and As in the national standard reference samples such as human hair (GBW 09101), rice (GBW 08503) and tea leaf (GBW 08505) were in good agreement with the certified values, with RSDs around 5%. Using the HG-ICP-AES method, the concentrations of Hg and As in human hair samples of polymetallic mining area in western Hunan province were determined, and the result shows that human in the mining area was exposed to high levels of Hg and As. The concentrations of Hg and As in the mining area were 1.290 and 1.865 microg x g(-1) respectively, 3.59 and 2.44 times higher than those in the control area, respectively.

[Determination of trace elements in drinking water of Kashin-Beck disease (KBD) affected and non-affected areas in Tibet by ICP-AES].

Trace elements (Cu, Zn, Fe, Ca, Mg, Mn, Al, K, Ba, P, Sr, Cd, V, Cr, Ni, Pb and Co) concentrations in the drinking water of KBD-affected and non-affected areas were measured using ICP-AES. The RSD of this method was between 0.80% and 2.83%, and the analytical results of the reference samples were consistent with the certified values. The method was simple and accurate. The results indicated that there is an obvious difference in trace elements concentrations between KBD-affected areas and non-afffected areas. The results provided a scientific theoretical basis to improve the conditions of drinking water in KBD-affected areas in Tibet.

Arsenic accumulation by ferns: a field survey in southern China.

The objective of this study reported here was to characterize arsenic (As) accumulation by Pteris ferns by comparing 3 of the ferns of this genus with each other as well as with four non-Pteris ferns growing on seven sites in southern China with different As levels. A total of 112 samples, including 78 Pteris vittata, 13 P. cretica, 3 P. multifida and 18 ferns from other non-Pteris genera, with the soils in which they grew were collected for As and other elemental analyses. P. vittata was found to be the most dominant species and the most efficient As-accumulator, whereas P. multifida was the lowest As-accumulator among the Pteris ferns, with 4.54-3599, 28.7-757 and 11.2-341 mg kg(-1) As recorded in the fronds of P. vittata, P. cretica and P. multifida, respectively. Arsenic concentrations in non-Pteris ferns were generally much lower than those in Pteris ferns, with 0.81-1.32, 3.59, 10.7, 6.17-24.3 mg kg(-1) in the fronds of Blechumum orientale, Dicranopteris dichotoma, Pteridium aquilinum and Cyclosorus acuminatus, respectively. For P. vittata, the As bioaccumulation factor (ratio of As in fronds to that in soils) changed, whereas the As translocation factor (ratio of As in fronds to that in roots) remained unchanged among the different sites. The concentrations of Fe were very high in all of the collected fern sample, with the exception of B. orientale, with 207-6865, 637-3369, 375-1856, 1876, 493-6865 and 492 mg kg(-1) in the fronds of P. vittata, P. cretica, P. multifida, C. acuminatus, P. aquilinum and D. dichotoma, respectively. The association between Fe accumulation and As accumulation and tolerance in these ferns indicates the unique role of Fe in As-hyperaccumulation.

[Study advance on haloacetic acids in drinking water].

Haloacetic acids (HAAs) in drinking water have attracted more and more attention of researchers due to their higher potential combination of chlorine, their carcinogenic and mutagenic effects and higher carcinogenic. The formation mechanism, analytical methods, the effects of many factors on HAAs formation such as precursor types, chlorine doses, pH, temperature, bromide, reaction time and seasonal change, toxicological character and the minimizing technology of HAAs in resent studies about HAAs are discussed in details in this paper. Further researches are still needed to clarify the formation mechanism of HAAs and find a feasible minimizing technology. New concerns including toxicological characters that correlate with human and other HAAs exposure routes besides oral ingestion (i.e., inhalation and dermal adsorption) should be put forward.

[Determination of nine life elements in brick tea by ICP-AES].

ICP-AES was used for the direct determination of nine life elements (Ca, Mg, K, Al, P, Cu, Zn, Fe and Mn) in brick tea. The RSDs of the method were between 2.11% and 8.68%, and the analytical results of the tea reference samples were consistent with the certified values. The method was simple and accuracy. The analytical results of brick tea were compared with those of the ordinary leaf tea (green tea, scent tea and oolong tea). The Al, Fe, Mn, Ca and Mg contents of brick tea were about 5.78, 3.26, 2.19, 2.11 and 1.64 times higher than those of the ordinary leaf tea respectively. The P, K, Zn and Cu contents of brick tea were 48.70%, 85.68%, 78.19% and 98.78% times lower than those of the ordinary leaf tea respectively.

[Environmental quality of soil polluted by mercury and lead in polymetallic deposit areas of western Hunan Province].

The environmental quality of soil polluted by mercury and lead in typical polymetallic deposit areas of western Hunan province and its natural and human causes were studied. It was found that western Hunan province is a high regional geochemical abnormal region on mercury and lead. The concentrations of mercury and lead in soils in mercury deposit areas were 1 315 and 3.1 times higher than that of the average background of soils in China respectively, while those in soils in lead-zinc deposit areas were 14.8 and 16.1 times higher. Using geoaccumulation index developed by Muller, it was found that either mercury deposit area or lead-zinc deposit area in western Hunan province is polluted by the two elements, the majority soils in mercury deposit areas are seriously polluted by mercury with middle polluted or light polluted by lead, while the majority soils in lead-zinc deposit areas are middle polluted or middle-heavily polluted by lead and middle-heavily polluted by mercury. The sources of metal pollutants in soils in the deposit areas are natural and human causal, the spatial distribution of mercury and lead are dominated by original geochemical situation but seriously affected by human mining activities.

[Pilot experiment of fluorine fixing ratio of coated lump stone coal fuel].

The pilot experiment on coated lump stone coal fuel selected from 16 families in Haoping Shanxi were studied. 8 families burned coating high fluorine lump stone coal with lime, clay and low fluorine anthracite, 8 families burned untreated lump stone coal. The results show that the fluorine-fixing ratio at treated group was 75.0% when coal fluorine compared with coal cinder fluorine. In comparison with untreated group, the concentration of door air fluoride lowered 85.7%, SO2 lowered 75.0%, dust lowered 55.3%.

[Regularity of flourine release from fluorine-rich coal combustion in the fluorine poisoning area].

Laboratory experiments and in situ measurements inside farmer's houses indicate that the fluorine concentration of indoor air was positively related with the fluorine content in the consumed coal (R = 0.612, P<0.01), but fluorine content in the coal had no effect on the release rate of coal fluorine under the usual combustion temperature of about 1000 degrees C. The release rate of coal fluorine varied versus combustion temperature ranging from 200 to 1200 degrees C, following a "S" curve pattern, increasing slowly under 300 to 700 degrees C, but quickly under 700 to 1000 degrees C, and then slowly again before finally reaching 100% under 1100 to 1200 degrees C, this curve can be fit by Logistic equation. The release rate of coal fluorine usually depends upon the existence status of fluorine and the chemical and mineral components of the coal. The fluorine in soft coal or anthracite from Guizhou is released more quickly than in bone coal from Southern Shanxi, with the former almost completely released under 1100 degrees C but the later almost completely released under 1200 degrees C. The combustion temperature of civil stoves is at most 1000 degrees C, under which averagely 86.9% of the fluorine in coal from Guizhou and 80.6% of that in bone coal from Southern Shanxi is released.

[The application of GIS to environmental health informatics].

In order to improve the management of environment and human health, this paper presented the new concept of human health, and developed the environmental health informatics. Its features, structure and major approach for application have been summarized. The future development of environmental health informatics was discussed.