Two different mutational types of familial gastrointestinal stromal tumors: Two case reports.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract, and cases of GISTs tend to be of the disseminated type, with a global incidence of 10 to 15 cases/million each year. The rarer familial GISTs, which often represent a population, differ in screening, diagnosis, and treatment. Familial GISTs include primary familial GISTs with predominantly KIT/PDGFRA mutations and wild-type GISTs. However, whether the same genetic family has different phenotypes has not been reported. CASE SUMMARY: We report two cases of rare GISTs in the same family: A male patient with the V561D mutation in exon 12 of the PDGFRA gene, who has been taking the targeted drug imatinib since undergoing surgery, and a female patient diagnosed with wild-type GIST, who has been taking imatinib for 3 years since undergoing surgery. The favorable prognosis of these patients during the 7-year follow-up period validates the accuracy of our treatment strategy, and we have refined the entire process of diagnosis and treatment of familial GISTs in order to better manage this rare familial disease. CONCLUSION: Different mutation types of familial GISTs in the same family are very rare, thus it is very important to make the correct diagnosis and treatment strategies according to the results of molecular detection for the management of familial GISTs.

Advances in immunotherapy of M2 macrophages and gastrointestinal stromal tumor.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal-derived tumors of the GI tract. They can occur throughout the GI tract, and the survival time of some patients can be improved by first-line targeted therapy with imatinib. However, there are some limitations with imatinib treatment. Immunotherapy for GIST has attracted much attention in recent years, and as one of the most abundant cells in the GIST microenvironment, M2 macrophages play an important role in disease progression. They have unique anti-inflammatory and pro-tumorigenic effects and are one target for immunotherapy. This review summarizes the connection between different factors and the programmed death receptor-1/programmed death ligand-1 pathway and M2 macrophages to reactivate or enhance anti-tumor immunity and improve imatinib efficacy, and to provide new ideas for GIST immunotherapy.

Evaluation of the horizontal approach to the medial malleolar facet in sagittal talar fractures through dorsiflexion and plantarflexion positions.

BACKGROUND: Talar fractures often require osteotomy during surgery to achieve reduction and screw fixation of the fractured fragments due to limited visualization and operating space of the talar articular surface. The objective of this study was to evaluate the horizontal approach to the medial malleolus facet by maximizing exposure through dorsiflexion and plantarflexion positions. METHODS: In dorsiflexion, plantarflexion, and functional foot positions, we respectively obtained the anterior and posterior edge lines of the projection of the medial malleolus on the medial malleolar facet. The talar model from Mimics was imported into Geomagic software for image refinement. Then Solidworks software was used to segment the medial surface of the talus and extend the edge lines from the three positions to project them onto the "semicircular" base for 2D projection. The exposed area in different positions, the percentage of total area it represents, and the anatomic location of the insertion point at the groove between the anteroposternal protrusions of the medial malleolus were calculated. RESULTS: The mean total area of the "semicircular" region on the medial malleolus surface of the talus was 542.10 ± 80.05 mm2. In the functional position, the exposed mean area of the medial malleolar facet around the medial malleolus both anteriorly and posteriorly was 141.22 ± 24.34 mm2, 167.58 ± 22.36mm2, respectively. In dorsiflexion, the mean area of the posterior aspect of the medial malleolar facet was 366.28 ± 48.12 mm2. In plantarflexion, the mean of the anterior aspect of the medial malleolar facet was 222.70 ± 35.32 mm2. The mean overlap area of unexposed area in both dorsiflexion and plantarflexion was 23.32 ± 5.94 mm2. The mean percentage of the increased exposure area in dorsiflexion and plantarflexion were 36.71 ± 3.25% and 15.13 ± 2.83%. The mean distance from the insertion point to the top of the talar dome was 10.69 ± 1.24 mm, to the medial malleolus facet border of the talar trochlea was 5.61 ± 0.96 mm, and to the tuberosity of the posterior tibiotalar portion of the deltoid ligament complex was 4.53 ± 0.64 mm. CONCLUSIONS: Within the 3D model, we measured the exposed area of the medial malleolus facet in different positions and the anatomic location of the insertion point at the medial malleolus groove. When the foot is in plantarflexion or dorsiflexion, a sufficiently large area and operating space can be exposed during surgery. The data regarding the exposed visualization area and virtual screws need to be combined with clinical experience for safer reduction and fixation of fracture fragments. Further validation of its intraoperative feasibility will require additional clinical research.

Acute ischemic Stroke combined with Stanford type A aortic dissection: A case report and literature review.

BACKGROUND: Acute aortic dissection (AAD) is a high mortality disease that can lead to acute ischemic strokes (AIS). Some of the patients with AAD combined with AIS initially present with neurological symptoms, which can easily lead to missed or delayed AAD diagnosis. This is attributed to the lack of physician awareness or the urgency of patient thrombolysis. Intravenous administration of thrombolytic therapy (IVT) for AAD is associated with poor prognostic outcomes. We report a patient with AIS combined with AAD who developed a massive cerebral infarction after receiving IVT for a missed AAD diagnosis. CASE SUMMARY: A 49-year-old man was admitted to a local hospital with an acute onset of left-sided limb weakness accompanied by slurred speech. The patient had a history of hypertension that was not regularly treated with medication. Physical examination revealed incomplete mixed aphasia and left limb hemiparesis. Cranial computed tomography (CT) scan showed bilateral basal ganglia and lateral ventricular paraventricular infarct lesions. The patient was diagnosed with AIS and was administered with IVT. After IVT, patient's muscle strength and consciousness deteriorated. From the local hospital, he was referred to our hospital for further treatment. Emergency head and neck CT angiography (CTA) scans were performed. Results showed multiple cerebral infarctions, and aortic dissection in the ascending aorta, innominate artery, as well as in the right common carotid artery. Then, the CTA of thoracoabdominal aorta was performed, which revealed a Stanford type A aortic dissection and aortic dissection extending from the aortic root to the left external iliac artery. Laceration was located in the lesser curvature of the aortic arch. AAD complicated with AIS was considered, and the patient was immediately subjected to cardiovascular surgery for treatment. The next day, the patient underwent aortic arch and ascending aortic replacement and aortic valvuloplasty. CONCLUSION: Clinical manifestations for AAD combined with AIS are diverse. Some patients may not exhibit typical chest or back pains. Therefore, patients should be carefully evaluated to exclude AAD before administering IVT in order to avoid adverse consequences.

Necroptosis Mediates Cigarette Smoke-Induced Inflammatory Responses in Macrophages.

Introduction: Cigarette smoke (CS)-induced inflammation in macrophages is involved in the pathological process of chronic obstructive pulmonary disease (COPD). Necroptosis, which is a form of programmed necrosis, has a close relationship with robust inflammation, while its roles in COPD are unclear. Materials and Methods: Necroptosis markers were measured in mouse alveolar macrophages and cultured bone marrow-derived macrophages (BMDMs). Necroptosis inhibitors were used to block necroptosis in BMDMs, and inflammatory cytokines were detected. We further explored the related signaling pathways. Results: In this study, we demonstrated the way in which necroptosis, in addition to its upstream and downstream signals, regulates CS-induced inflammatory responses in macrophages. We observed that CS exposure caused a significant increase in the levels of necroptosis markers (receptor interacting kinases [RIPK] 1 and 3) in mouse alveolar macrophages and BMDMs. Pharmacological inhibition of RIPK1 or 3 caused a significant suppression in CS extract (CSE)-induced inflammatory cytokines, chemokine ligands (CXCL) 1 and 2, and interleukin (IL)-6 in BMDMs. CSE-induced necroptosis was regulated by mitochondrial reactive oxygen species (mitoROS), which also promoted inflammation in BMDMs. Furthermore, necroptosis regulated CSE-induced inflammatory responses in BMDMs, most likely through activation of the nuclear factor-κB pathway. Conclusion: Taken together, our results demonstrate that mitoROS-dependent necroptosis is essential for CS-induced inflammation in BMDMs and suggest that inhibition of necroptosis in macrophages may represent effective therapeutic approaches for COPD patients.

Increased PIT1 and PIT2 Expression in Streptozotocin (STZ)-induced Diabetic Mice Contributes to Uptake of iAs(V).

OBJECTIVE: This study aimed to investigate the susceptibility of mice with streptozotocin(STZ)-induced diabetes mellitus (TIDM) to the uptake of pentavalent inorganic arsenic (iAsV) and the possible molecular mechanism. METHODS: TIDM was induced in mice by STZ. TIDM and normal mice were treated with 15.0 mg/kg Na2HAsO4·12H2O by intragastric administration. Then, the concentrations of arsenic in various tissues were measured by atomic fluorescence spectrometry. The gene expression levels of Pit1 and Pit2 were quantified by real-time RT-PCR, and their protein levels were detected by Western blotting in mouse heart, kidney, and liver tissues. RESULTS: The concentrations of arsenic in STZ-induced TIDM mouse tissues were higher at 2 h after intragastric administration of Na2HAsO4·12H2O. Compared with the levels in normal mice, PIT1 and PIT2, which play a role in the uptake of iAsV, were upregulated in the livers and hearts of TIDM mice. PIT1 but not PIT2 was higher in TIDM mouse kidneys. The upregulation of Pit1 and Pit2 expression could be reversed by insulin treatment. CONCLUSION: The increased uptake of iAsV in TIDM mouse tissues may be associated with increased PIT1 and/or PIT2 expression.

[Greenhouse gas emissions, carbon leakage and net carbon sequestration from afforestation and forest management: A review.] / æ£®æž—ç»è¥ä¸Žç®¡ç†ä¸‹çš„æ¸©å®¤æ°”ä½“æŽ’æ”¾ã€ç¢³æ³„æ¼å’Œå‡€å›ºç¢³é‡ç ”ç©¶è¿›å±•.

Forests play an important role in climate change mitigation and concentration of CO2 reduction in the atmosphere. Forest management, especially afforestation and forest protection, could increase carbon stock of forests significantly. Carbon sequestration rate of afforestation ranges from 0.04 to 7.52 t C·hm-2·a-1, while that of forest protection is 0.33-5.20 t C·hm-2·a-1. At the same time, greenhouse gas (GHG) is generated within management boundary due to the production and transportation of the materials consumed in relevant activities of afforestation and forest management. In addition, carbon leakage is also generated outside boundary from activity shifting, market effects and change of environments induced by forest management. In this review, we summarized the definition of emission sources of GHG, monitoring methods, quantity and rate of greenhouse gas emissions within boundary of afforestation and forest management. In addition, types, monitoring methods and quantity of carbon leakage outside boundary of forest management were also analyzed. Based on the reviewed results of carbon sequestration, we introduced greenhouse gas emissions within boundary and carbon leakage, net carbon sequestration as well as the countervailing effects of greenhouse gas emissions and carbon leakage to carbon sequestration. Greenhouse gas emissions within management boundary counteract 0.01%-19.3% of carbon sequestration, and such counteraction could increase to as high as 95% considering carbon leakage. Afforestation and forest management have substantial net carbon sequestration benefits, when only taking direct greenhouse gas emissions within boundary and measurable carbon leakage from activity shifting into consideration. Compared with soil carbon sequestration measures in croplands, afforestation and forest management is more advantageous in net carbon sequestration and has better prospects for application in terms of net mitigation potential. Along with the implementation of the new stage of key ecological stewardship projects in China as well as the concern on carbon benefits brought by projects, it is necessary to make efforts to increase net carbon sequestration via reducing greenhouse gas emissions and carbon leakage. Rational planning before start-up of the projects should be promoted to avoid carbon emissions due to unnecessary consumption of materials and energy. Additionally, strengthening the control and monitoring on greenhouse gas emissions and carbon leakage during the implementation of projects are also advocated.

[Estimations of application dosage and greenhouse gas emission of chemical pesticides in staple crops in China.] / æˆ‘å›½ä¸»ç²®ä½œç‰©çš„åŒ–å­¦å†œè¯ç”¨é‡åŠå ¶æ¸©å®¤æ°”ä½“æŽ’æ”¾ä¼°ç®—.

Chemical pesticides play an important role in improving crop yield in modern agriculture. However, commonly overuse of pesticide in China leads to serious environmental problems and food safety hazards. Based on a national questionnaire survey of farmers across China in 2012, the situation of pesticide applications to rice, wheat, and corn in 2011, and their corresponding greenhouse gas (GHG) emissions were investigated. The survey showed that at least 54 types of insecticide, 24 types of fungicide, and 50 types of herbicide were in use across three crops. 32% of rice farmers applied biological pesticides in China. The amounts of pesticides applied to the three cereal crops were 30.8, 16.5, and 58.3 kt for insecticides, fungicides, and herbicides, respectively. The total GHG emission from these pesticides was 1.5 Tg Ce, and the GHG emissions from these insecticides, fungicides, and herbicides accounted for 23.8%, 16.9%, and 59.3% of the total emission, respectively. In south China, the amounts of pesticides applied occupied 51% of the national total. For the production of each kilogram of grain, the amounts of pesticides applied were 0.22, 0.18, and 0.24 g for rice, wheat, and corn, respectively. Therefore, the sums of pesticides applied by crop types were 44.4 kt for rice, 21.4 kt for wheat, and 39.7 kt for corn. Meanwhile, the GHG emissions of pesticides were 665.5, 250.1, and 547.5 Gg Ce for rice, wheat, and corn, respectively. For pesticide types, organophosphorus insecticides accounted for 69% of total insecticide use in China, while benzimidazole, organophosphorus, azole, and organic sulfur fungicides together contributed 87% of total fungicide use. In addition, the use of anilide, organic heterocyclic, and organophosphorus herbicides contributed 85% of the total herbicide application. Therefore, the reduction of pesticide use would play an important role in food safety and environmental safety, and GHG mitigation in agricultural sector in China.

[Greenhouse gas emissions and net carbon sequestration of "Grain for Green" Program in China.] / 中国退耕还林工程温室气体排放与净固碳量.

Based on the estimation of carbon cost from afforestation in project boundary and carbon leakage out of boundary in the construction period of "Grain for Green" Program (GGP) (2000-2010), the annual variance and composition of the carbon cost and carbon leakage, as well as characters of variance of net carbon sequestration were analyzed for GGP and respective program regions. Results showed that the carbon costs in northwest region, southwest region, northeast region, north region and central south and east region were 3.38, 3.64, 1.03, 1.66 and 4.38 Tg C, respectively, totaling 14.09 Tg C. Meanwhile the carbon leakages of the above regions were 21.33, 4.60, 5.50, 1.32 and 3.78 Tg C, respectively, and 36.53 Tg C in total. The composition characters of the carbon costs of the GGP and the respective regions were similar. Carbon emissions from afforestation were the largest carbon cost, and afforestation on converted farmland was the main carbon emission source. Accordingly, among the materials consumed, fertilizer brought about the largest carbon cost, followed by building materials, while carbon emissions from fuels, irrigation, herbicides and pesticides only accounted for about 10% for respective regions. The carbon cost and carbon leakage of the GGP were 50.62 Tg C in total, which counteracted 19.9% of the sequestered carbon in the program. In northwest region, southwest region, northeast region, north region and central south and east region, carbon emissions (including cost and leakage) accounted for 38.9%, 10.4%, 26.1%, 8.9% and 15.5% of the carbon sequestration, respectively. The net carbon sequestration of the GGP was 203.50 Tg C with an annual average of 18.50 Tg C·a-1. The carbon cost and leakage offset a minor part of the carbon sequestration of the GGP. Therefore, the GGP contributed significantly to greenhouse gas mitigation in China as well as global climate warming mitigation. Adopting precision fertilization in economic forest afforestation and supplying alternative livelihoods to farmers in the program could be the potential measures to reduce carbon cost and carbon leakage.

[Effects of nitrogen application on soil greenhouse gas fluxes in Eucalyptus plantations with different soil organic carbon content].

The effects of nitrogen fertilization or nitrogen deposition on soil greenhouse gases fluxes has been well studied, while little has been piloted about the effects of nitrogen application on soil greenhouse gas fluxes and its discrepancy with different soil organic carbon content. In our study, we conducted field control experiment in a young Eucalyptus plantation in Southeast China. We compared the effects of 4 levels of nitrogen fertilization (Control: 0 kg · hm(-2); Low N: 84.2 kg · hm(-2); Medium N: 166.8 kg · hm(-2); High N: 333.7 kg · hm(-2)) on soil GHGs fluxes from 2 sites (LC and HC) with significantly different soil organic carbon (SOC) content (P < 0.05). The results showed: (1) Fertilization had significant priming effect on CO2 and N2O emission fluxes. One month after fertilization, both CO2 and N2O had the flux peak and decreased gradually, and the difference among the treatments disappeared at the end of the growing season. However, fertilization had no significant effect on CH4 oxidation between the 2 sites. (2) Fertilization and SOC were two crucial factors that had significant effects on CO2 and N2O emission. Fertilization had a significant positive effect on CO2 and N2O emission fluxes (P < 0.001). CH4 oxidation rates decreased with the increasing N addition, but there was no statistical difference (P > 0.05). The CO2 and N2O emission fluxes were significantly higher in HC than those in LC (P < 0.01). (3) Fertilization and SOC had great interactive effect on CO2 and N2O emission (P < 0.05). Compared with fluxes in LC, the fluxes in HC were much more sensitive to N input: low N could remarkably stimulate the CO2 and N2O emission. In conclusion, the effects of nitrogen fertilization on soil GHGs fluxes were not only in connection with the intensify of nitrogen, but also closely tied to the SOC content. When we assess the effects of nitrogen on soil GHGs fluxes, the difference induced by SOC should not be ignored.

Modeling the greenhouse gas budget of straw returning in China: feasibility of mitigation and countermeasures.

Straw returning is considered to be one of the most promising carbon sequestration measures in China's cropland. A compound model, namely "Straw Returning and Burning Model-Expansion" (SRBME), was built to estimate the net mitigation potential, economic benefits, and air pollutant reduction of straw returning. Three scenarios, that is, baseline, "full popularization of straw returning (FP)," and "full popularization of straw returning and precision fertilization (FP + P)," were set to reflect popularization of straw returning. The results of the SRBME indicated that (1) compared with the soil carbon sequestration of 13.37 Tg/yr, the net mitigation potentials, which were 6.328 Tg/yr for the FP scenario and 9.179 Tg/yr for the FP + P scenario, had different trends when the full budget of the greenhouse gases was considered; (2) when the feasibility in connection with greenhouse gas (GHG) mitigation, economic benefits, and environmental benefits was taken into consideration, straw returning was feasible in 15 provinces in the FP scenario, with a total net mitigation potential of 7.192 TgCe/yr and the total benefits of CNY 1.473 billion (USD 216.6 million); (3) in the FP + P scenario, with the implementation of precision fertilization, straw returning was feasible in 26 provinces with a total net mitigation potential of 10.39 TgCe/yr and the total benefits of CNY 5.466 billion (USD 803.8 million); (4) any extent of change in the treatment of straw from being burnt to being returned would contribute to air pollution reduction; (5) some countermeasures, such as CH(4) reduction in rice paddies, precision fertilization, financial support, education and propaganda, would promote the feasibility of straw returning as a mitigation measure.

[Greenhouse gas emission from reservoir and its influence factors].

Reservoirs are significant sources of emissions of the greenhouse gases. Discussing greenhouse gas emission from the reservoirs and its influence factors are propitious to evaluate emission of the greenhouse gas accurately, reduce gas emission under hydraulic engineering and hydropower development. This paper expatiates the mechanism of the greenhouse gas production, sums three approaches of the greenhouse gas emission, which are emissions from nature emission of the reservoirs, turbines and spillways and downstream of the dam, respectively. Effects of greenhouse gas emission were discussed from character of the reservoirs, climate, pH of the water, vegetation growing in the reservoirs and so on. Finally, it has analyzed the heterogeneity of the greenhouse gas emission as well as the root of the uncertainty and carried on the forecast with emphasis to the next research.

[An observation of the effects of the truncated septin2 on mouse epidermal cell and fibroblast].

OBJECTIVE: To construct eukaryotic expression vector of the truncated septin2 and investigate the influence on the cultured mouse epidermal cell and fibroblast in vitro exerted by the transgenic expression product. METHODS: The short splicing fragment was obtained by amplifying the reverse transcription product of the fetal mouse skin mRNA with PCR. Then its recombinant expression vector pcDNA3.1 (-)/septin2s was constructed and used to transfect the mouse epidermal cell and fibroblast cultured in vitro. The expression of the foreign gene was detected with RT-PCR and the changes of cell proliferation were observed and analysed. RESULTS: RT-PCR results indicated that pcDNA3.1/septin2 was expressed in the cultured mouse epidermal cells and fibroblasts in vitro. We found that the epidermal cells accelerated their reproduction, but the fibroblasts had no obvious changes. CONCLUSION: We successfully constructed eukaryotic expressive vectors of pcDNA3.1/ septin2s and transfected it into mouse epidermal cells and fibroblasts in vitro. The results settle a basis for showing effect of septin2s on fetal mouse skin.

[The mutation study of the FOXL2 gene in a big Chinese family with blepharophimosis-ptosis-epicanthus inversus syndrome].

OBJECTIVE: We have studied 4 generations 12 patients in a family which has blepharophimosis-ptosis-epicanthus-inversus syndrome (BPES) for the gene, FOXL2, the group also have 12 normal members in this family and other 80 normal individuals for contrast. METHODS: The FOXL2 gene was amplified by polymerase chain reaction and then analyzed by direct genomic sequencing. RESULTS: A 892C > T at nucleotides in FOXL2 was found in the twelve affected patients. No mutations was found in any of the health members in the family. CONCLUSIONS: FOXL2 may be a important pathogenesis for the disease in this Chinese family.

[The effect of pcDNA 3.1/RPs15 on skin fibroblasts in vitro].

OBJECTIVE: To construct eukaryotic expression vector of ribosomal protein sl5(RPs15) gene and study its effect on mouse skin fibroblasts in vitro. METHODS: The RPs15 cDNA encoding region of fetal mouse skin was amplified by reverse transcription-polymerase chain reaction (RT-PCR) method and cloned into eukaryotic expression vector pcDNA3.1(-). The recombinant plasmid was transfected into adult mouse skin fibroblasts by FuGENE6 transfection reagents. Then the expression of RPs15 gene, was detected and its biological effect on fibroblasts was measured. RESULTS: The DNA sequencing result of pcDNA3.1/RPs15 was identical with the reported. The RPs15 gene was expressed in transfected fibroblasts. The growth density of fibroblasts decreased with the conformation changing accordingly. CONCLUSIONS: The eukaryotic expression vector pcDNA3.1/RPs15 is successively constructed and can be expressed in mouse skin fibroblasts. The results set up a basis for further study of the effect of RPs15 gene on skin fibroblasts.