[ Objective] The paper was to operate the application and promotion of non-pesticide replacing high-toxic pesticides techniques in Kunming City, and to analyze its benefit. [ Method ] Through application and promotion...[ Objective] The paper was to operate the application and promotion of non-pesticide replacing high-toxic pesticides techniques in Kunming City, and to analyze its benefit. [ Method ] Through application and promotion of frequency trembler grid lamps, sticking plate trapping technology, construction of treatment ponds for field waste vegetable leaves, standardized (accurate) cultivation techniques, cultivation techniques of disease-resistant varieties and diverse cultivation technologies, the promotion benefit of non-pesticide replacing high-toxic pesticides techniques was comprehensively investigated and evaluated. [ Result ] The appli- cation and promotion area of non-pesticide replacing high-toxic pesticides techniques in Kunming City during 2006 -2010 reached 94 667 hm2. The investigation on control efforts and quantitative analysis of cost/benefit showed that the beneficial result of application and promotion of non-pesticide replacing high-toxic pesticides techniques was higher than the direct benefit of application and promotion of traditional pesticide replacing techniques. This improvement innovated the traditional pesticide replacing method in replacement work of high-toxic pesticides, reducing the usage volume of pesticide in Kunming City. [ Conclusion] The application and promotion of non-pesticide replacing high-toxic pesticides techniques improved the economic, social and ecological benefit of replacement work of high-toxic pesticides, protected the agricultural ecological environment and promoted the sustainable development of agricultural production.展开更多
The stabilization of severely As-polluted soil has been a challenge, especially for the extremely toxic As(Ⅲ) contaminants. In this study, soil with a high As concentration(26084 mg/kg) was availably stabilized by a ...The stabilization of severely As-polluted soil has been a challenge, especially for the extremely toxic As(Ⅲ) contaminants. In this study, soil with a high As concentration(26084 mg/kg) was availably stabilized by a H2O2 pre-oxidation assisted TMT-15(Na3S3C3N3 solution with a mass fraction of 15%) and FeCl3·6 H2O stabilization method. The results showed that the combination of the two stabilizers(i.e., TMT-15 and FeCl3·6 H2O) presented a better stabilization behavior than either stabilizer used individually. The use of the H2O2 pre-oxidation assisted TMT-15 and FeCl3·6 H2O stabilization approach not only converted the As(Ⅲ) to As(Ⅴ) but also reduced the toxic leaching concentration of As to 1.61 mg/L, which is a safe level, when the additions of TMT-15 and FeCl3·6 H2O were 2 mL and 0.20 g, respectively. Thus, using only a simple H2O2 pre-oxidation to combine clean stabilization with non-toxic stabilizers TMT-15 and FeCl3·6 H2O could render the severely As-contaminated soil safe for disposal in a landfill.展开更多
The unusual and remarkable property of parasporin 2 of non-insecticidal Bacillus thuringiensis is specifically recognizing and selectively targeting human leukemic cell lines. The 37-kDa inactive nascent protein is pr...The unusual and remarkable property of parasporin 2 of non-insecticidal Bacillus thuringiensis is specifically recognizing and selectively targeting human leukemic cell lines. The 37-kDa inactive nascent protein is proteolytically cleaved to the 30-kDa active form that loses both the N-terminal and the C-terminal segments. Accumulated cytological and biochemical observations on parasporin-2 imply that the protein is a pore-forming toxin. To confirm the hypothesis, insilico analysis was performed using homology modeling. The resulting model of parasporin 2 protein is unusually elongated and mainly comprises long β-strands aligned with its long axis. It is similar to aerolysin-type β-pore-forming toxins, which strongly reinforce the pore-forming hypothesis. The molecule can be divided into three domains. Domain 1, comprising a small β-sheet sandwiched by short α-helices, is probably the target-binding module. Two other domains are both β-sandwiches and thought to be involved in oligomerization and pore formation. Domain 2 has a putative channel-forming β-hairpin characteristic of aerolysin-type toxins. The surface of the protein has an extensive track of exposed side chains of serine and threonine residues. The track might orient the molecule on the cell membrane when domain 1 binds to the target until oligomerization and pore formation are initiated. The β-hairpin has such a tight structure that it seems unlikely to reform as postulated in a recent model of pore formation developed for aerolysin-type toxins. Parasporin 2 (Accession no: BAD35170) protein sequence analysis indicated two different domains namely, aerolysin toxin and clostridium toxin domain based on different database searches (CDD and Pfam). It showed a close similarity with the available PDB template (PDB id: 2ZTB) of parasporin which has cytocidal activity against MOLT-4, HL60 and Jurkat cell lines. Based on the PSI Blast analysis, 3D structures of the domains were predicted by using Swiss model server. Accuracy of the prediction of 3D structure of different domains of parasporin protein was further validated by Ramachandran plot and PROCHECK (G-value). The structure is dominated by β-strands (67%, S1-12), most of which are remarkably extensive, running all or most of the longer axis of the molecule. This study helped to elucidate the 3D structure of parasporin 2 (Acc. No. BAD35170) which might enable to probe further its specific mechanism of action. Though the similarity is observed in the domain architecture, there is variation in the regions of the domains even among the same group of parasporin 2. Docking of this model structure and experimental structure with specific receptors of the cancer cells will facilitate to explore mechanism of parasporin 2 action and also provide information about its evolutionary relationship with toxic Cry proteins.展开更多
Toxic epidermal necrolysis(TEN) is a rare acute life-threatening mucocutaneous disorder that is mostly drug-related(80%-95%). It is clinically characterized as a widespread sloughing of the skin and mucosa. AP regimen...Toxic epidermal necrolysis(TEN) is a rare acute life-threatening mucocutaneous disorder that is mostly drug-related(80%-95%). It is clinically characterized as a widespread sloughing of the skin and mucosa. AP regimen(pemetrexed plus cisplatin) has been the preferred first-line chemotherapy for metastatic non-squamous non-small cell lung cancer(NSCLC). Gefitinib, a small-molecule epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI), has already been recommended as a first-line treatment in EGFR-mutant metastatic NSCLC. We report rare presentation of TEN involving adverse effects of AP and gefitinib combination treatment in a 42-year-old woman diagnosed with metastatic NSCLC harboring an EGFR mutation. On the 21 st day after administration of the first cycle of AP regimen and the 8th day after the initiation of gefitinib treatment, she developed an acne-like rash, oral ulcer, and conjunctivitis, which later became blisters and ultimately denuded. The characteristic clinical courses were decisive for the diagnosis of TEN. Treatment with systemic steroids and immunoglobulin as well as supportive treatment led to an improvement of her general condition and a remarkable recovery.展开更多
Background: Pemetrexed (PEM) is an efficacious multi-targeted antifolate with acceptable toxicities for non-squamous non-small cell lung cancer (non-Sq NSCLC). However, in the clinical setting, PEM has more severe adv...Background: Pemetrexed (PEM) is an efficacious multi-targeted antifolate with acceptable toxicities for non-squamous non-small cell lung cancer (non-Sq NSCLC). However, in the clinical setting, PEM has more severe adverse effects than those reported. The aim of this study was to identify the factors for the toxicities of PEM-containing chemotherapy in non-Sq NSCLC patients in the clinical setting. Patients and Methods: We retrospectively evaluated the factors related to PEM toxicities in chemotherapy-naive patients with non-Sq NSCLC from September 2009 to July 2013 at our hospital. Logistic regression model was used in the univariate and multivariate analyses. Results: In total, 104 patients were analyzed. Grades 3 to 5 hematologic toxicities were frequent and included neutropenia (42%), febrile neutropenia (7%), anemia (18%), thrombocytopenia (17%), and disseminated intravascular coagulation (2%). On multivariate analyses, the predictors were poor performance status (PS) [odds ratio (OR): 4.89, 95% confidence interval (CI): 1.22 - 19.4] and low body mass index (OR: 1.44, 95% CI: 1.05 - 1.98) for febrile neutropenia;concomitant chronic infectious disease (OR: 6.63, 95% CI: 1.59 - 27.5) and bevacizumab use (OR: 3.57, 95% CI: 1.36 - 9.32) for neutropenia;poor PS (OR: 3.02, 95% CI: 1.33 - 6.85) for thrombocytopenia;and low serum albumin level (OR: 0.22, 95% CI: 0.08 - 0.63) for non-hematologic toxicities. Conclusions: In addition to the previously reported predictors of PEM toxicities, the presence of concomitant chronic infectious disease was associated with hematologic toxicities. Patient groups who are not sufficiently evaluated in clinical trials should be carefully monitored for the development of more toxicities than expected.展开更多
Objective: To evaluate the maximum tolerated dose (MTD) of docetaxel (DCT) and cisplatin (DDP) concurrently with three dimensional (3D) conformal radiotherapy or IMRT for patients with locally advanced non-sm...Objective: To evaluate the maximum tolerated dose (MTD) of docetaxel (DCT) and cisplatin (DDP) concurrently with three dimensional (3D) conformal radiotherapy or IMRT for patients with locally advanced non-small cell lung cancer (stage IIIa and IIIb) after 2–4 cycles of induction chemotherapy. Methods: Fourteen patients with histological/cytological proven stage III non–small-cell lung cancer were eligible. 3D or IMRT radiotherapy (60-70Gy in 30-35 fractions, 6-7weeks, 2 Gy/fraction) was delivered concurrently with cisplatin and docetaxel, 2 cycles during concurrent chemoradiotherapy (CCRT). The level I dosage was composed of 56 mg/m2 DCT, on day 1 and 28mg/m2 DDP, on day 1 and day 2. The level II was composed of 60 mg/m2 DCT, on day 1 and 30 mg/ m2 DDP, on day 1 and day 2. The level III was composed of 64 mg/m2 DCT, on day 1 and 32 mg/ m2 DDP, on day 1 and day 2. Results: Fourteen patients were allocated and finished concurrent chemoradiotherapy. The dose-limiting neutropenia was at the dose Level III (64 mg/m2) and occurred in 2 of 5 patients. No dose limiting non-hematologic or hematologic toxicity occurred in the other patients. Conclusions: Patients with locally advanced non-small cell lung cancer may tolerate 60mg/m2 docetaxel and 60mg/m2 cisplatin for 2 cycles during concurrent radiotherapy after 2-3 cycles of induction chemotherapy.展开更多
Pathogenic mutations involving DNA repeat expansions are responsible for over 20 different neuronal and neuromuscular diseases. All result from expanded tracts of repetitive DNA sequences(mostly microsatellites) that ...Pathogenic mutations involving DNA repeat expansions are responsible for over 20 different neuronal and neuromuscular diseases. All result from expanded tracts of repetitive DNA sequences(mostly microsatellites) that become unstable beyond a critical length whentransmitted across generations. Nearly all are inherited as autosomal dominant conditions and are typically associated with anticipation. Pathologic unstable repeat expansions can be classified according to their length, repeat sequence, gene location and underlying pathologic mechanisms. This review summarizes the current contribution of mutant pluripotent stem cells(diseased human embryonic stem cells and patient-derived induced pluripotent stem cells) to the research of unstable repeat pathologies by focusing on particularly large unstable noncoding expansions. Among this class of disorders are Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome, myotonic dystrophy type 1 and myotonic dystrophy type 2, Friedreich ataxia and C9 related amyotrophic lateral sclerosis and/or frontotemporal dementia, Facioscapulohumeral Muscular Dystrophy and potentially more. Common features that are typical to this subclass of conditions are RNA toxic gain-of-function, epigenetic loss-of-function, toxic repeat-associated non-ATG translation and somatic instability. For each mechanism we summarize the currently available stem cell based models, highlight how they contributed to better understanding of the related mechanism, and discuss how they may be utilized in future investigations.展开更多
Non-steroidal anti-inflammatory drugs have a fundamental and pivotal position in management of many of the disorders managed by rheumatologists.Promulgation of a false perspective of their toxicity has compromised our...Non-steroidal anti-inflammatory drugs have a fundamental and pivotal position in management of many of the disorders managed by rheumatologists.Promulgation of a false perspective of their toxicity has compromised our ability to advise our patients and participate in the management of their disorders. The literature sources, from which the false perspective derives, do not accurately reflect safety and fail to address the value of appropriate drug use monitoring.We, as rheumatologists, must stand up and proactively address engrained misconceptions-if we are to be able to continue to provide safe, effective care for our patients.展开更多
<strong>Purpose:</strong> <span>Recent studies of radiotherapy</span><span "=""> </span><span>(RT) for stage III non-small-cell lung cancer</span><span...<strong>Purpose:</strong> <span>Recent studies of radiotherapy</span><span "=""> </span><span>(RT) for stage III non-small-cell lung cancer</span><span "=""> </span><span>(NSCLC) have associated high dose to the heart with cardiac toxicity</span><span "=""> </span><span>and decreased overall survival</span><span "=""> </span><span>(OS). We used advanced statistical techniques</span><span "=""> </span><span>to account for correlations between dosimetric variables</span><span "=""> </span><span "=""><span>and more accurately determine the range of heart doses which are associated with reduced OS in patients receiving RT for stage III NSCLC.</span><b><span> Methods: </span></b><span>From 2006 to 2013, 119 patients with stage III NSCLC received definitive RT at our institution. OS</span></span><span "=""> </span><span>data was obtained from institutional tumor registry.</span><span "=""> </span><span>We used multivariate Cox model to determine patient specific covariates predictive for reduced overall survival. We examined age, prescription dose, mean lung dose, lung V20, RT technique, stage, chemotherapy, tumor laterality, tumor volume, and tumor site as candidate covariates.</span><span "=""> </span><span>We</span><span "=""> </span><span>subsequently used novel statistical techniques within multivariate Cox model to</span><span "=""> </span><span>systematically search the whole heart dose-volume histogram</span><span "=""> </span><span>(DVH) for dose parameters</span><span "=""> </span><span "=""><span>associated with OS.</span><b><span> Results: </span></b><span>Patients were followed until death or 2.5 to 81.2 months (median 30.4 months) in those alive at last follow up. On multivariate analysis of whole heart DVH</span></span><span>,</span><span> the dose of</span><span "=""> </span><span>51</span><span "=""> </span><span>Gy was identified as a threshold dose above which the dose volume relationship becomes predictive for OS. We identified</span><span "=""> </span><span>V55Gy (percentage of the whole heart volume receiving at least</span><span "=""> </span><span>55</span><span "=""> </span><span>Gy) as the best single DVH index which can be used to set treatment optimization constraints</span><span "=""> </span><span>(Hazard Ratio = 1.044 per 1% increase in heart volume exposed to at least 55</span><span "=""> </span><span>Gy, P</span><span "=""> </span><span>=</span><span "=""> </span><span>0.03). Additional characteristics correlated with OS on multivariate analysis were</span><span "=""> </span><span "=""><span>age, stage (IIIA/IIIB), and administration of chemotherapy. </span><b><span>Conclusion:</span></b><span> Doses above 51</span></span><span "=""> </span><span>Gy, applied to</span><span "=""> </span><span>small volumes of the heart,</span><span "=""> </span><span>are associated with worse OS in stage III NSCLC patients treated with definitive RT. Higher stage, older age and lack of chemotherapy were also associated with reduced OS</span><span>.</span>展开更多
Background: Comparing the efficacy and safety of gemcitabine at a fixed-dose rate (FDR) infusion (10 mg/m2/min) with the standard dose rate infusion in patients with locally advanced and metastatic non-small squamous ...Background: Comparing the efficacy and safety of gemcitabine at a fixed-dose rate (FDR) infusion (10 mg/m2/min) with the standard dose rate infusion in patients with locally advanced and metastatic non-small squamous cell carcinoma (NSCLC). Methods: The study randomized 60 patients with confirmed diagnosis of NSCLC to receive gemcitabine at a dose of 1000 mg/m2 on days 1 and 8 given as a 30-min infusion (Arm A) or at a rate of 10 mg/m2/min (Arm B). Cisplatin 75 mg/m2 was administered intravenously on day 2 in both arms. Results: No difference in overall response rate (46.6% versus 43.3%). Median time to progression for Arm A was 7 months (95% CI, 6.207 - 7.793 months), versus 6 months for Arm B (95% CI, 4.990 - 7.010 months). Median survival time was comparable [12 months (95% CI, 8.588 - 15.412 months) versus 11 months (95% CI, 9.066 - 12.934 months)] respectively. Two-year survival (18% versus 11%, p = 0.38) was detected. No treatment related deaths occurred. Main hematological toxicities were grade I and II neutropenia, in 36.7% and 53.3% respectively (p = 0.044). Grade III anemia was observed in 10% and 6.7% in both arms respectively (p = 0.024). Grade I and II nausea and vomiting was observed in 50% and 46.7%. Conclusions: FDR gemcitabine in combination with cisplatin had equivalent efficacy and more severe hematologic toxicities compared to the standard 30-min gemcitabine infusion with cisplatin in patients with advanced NSCLC.展开更多
<strong>Purpose:</strong> <span><span><span style="font-family:""><span style="font-family:Verdana;">To examine possible association between heart irradiati...<strong>Purpose:</strong> <span><span><span style="font-family:""><span style="font-family:Verdana;">To examine possible association between heart irradiation and Overall Survival (OS) in lung SBRT patients and to compare observed associations with cardiac toxicity models previously derived in LA-NSCLC patient studies. </span><b><span style="font-family:Verdana;">Materials and Methods: </span></b><span style="font-family:Verdana;">197 Patients treated with lung SBRT at Mayo Clinic Arizona were selected for this IRB</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">approved study. Multivariate Cox model with Akaike Information Criterion (AIC) was used to select patient</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">specific covariates associated with OS. Heart dosimetry was represented by </span></span></span><span><span><i><span style="font-family:""><span style="font-family:Verdana;">V</span><sub><span style="font-family:Verdana;">D</span></sub></span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> indices, which is a percentage of volume exposed to dose D or greater. Multivariate Cox model</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">s</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> with patient</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">specific covariates and single </span></span></span><span><span><i><span style="font-family:""><span style="font-family:Verdana;">V</span><sub><span style="font-family:Verdana;">D</span></sub></span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> index per model was used to find a range of doses which were predictive for OS. A digital subdivision of the heart was further used to determine </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">the </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">spatial distribution of doses which were predictive for OS. A coarse subdivision divided heart into 4 segments, while </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">the </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">fine subdivision divided heart into 64 segments. Knowledge constrained Fused Lasso operator was used to derive a more complete model which correlated heart dosimetry with OS. Results of statistical analysis were compared to predictions of a model of cardiac toxicity in LA-NSCLC patients.</span><b><span style="font-family:Verdana;"> Results: </span></b><span style="font-family:Verdana;">Higher age (p < 0.001), higher stage (p < 0.001) and squamous cell histology (p = 0.001) were associated with reduced OS. Whole heart DVH analysis did not reveal associations between heart irradiation and reduced OS. Coarse subdivision of the heart into four segments revealed that the irradiation of two inferior segments of the heart with low doses was associated with reduced OS, </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">V</span></i></span></span><span><span><sub><span style="font-family:""><span style="font-family:Verdana;">2</span><i><span style="font-family:Verdana;">Gy</span></i></span></sub></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> in the right-inferior segment (HR = 1.012/1%, p = 0.02), and </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">V</span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><sub><span style="font-family:Verdana;">1</span></sub></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><sub><span style="font-family:Verdana;">Gy</span></sub></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> in the left-inferior segment (HR = 1.01/1%, p = 0.04). Maximum dose in the right-inferior segment of the heart was also associated with reduced OS (HR = 1.02/Gy, p = 0.02). Fine subdivision of the heart into 64 segments revealed that approximately 25% of heart volume in the inferior part of the heart (15/64 segments), when irradiated to doses in the 1</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Gy </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> 5</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">Gy range, were predictive for reduced OS (HR = 1.01/1%, p = 0.01). A previously derived model of cardiac toxicity in LA-NSCLC patients did not predict a reduction of OS due to heart irradiation in lung SBRT patients, because of relatively low doses to the heart in most lung SBRT patients. </span><b><span style="font-family:Verdana;">Conclusions:</span></b><span style="font-family:Verdana;"> Doses lower than 5</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Gy in the inferior segments of the heart may be associated with reduced overall survival in patients treated for lung lesions with SBRT. Stage and histology of the disease, as well as patients’ age, were also associated with overall survival. Comparisons of cardiac toxicity patterns in LA-NSCLC patients and lung SBRT patients suggest different etiology of cardiac toxicity in the two groups.</span></span></span>展开更多
Introduction: Satraplatin has been given in combination therapy for lung cancer to utilize its radio-sensitizing properties. The optimal dose of satra-platin given concurrently with radiation therapy for locally advan...Introduction: Satraplatin has been given in combination therapy for lung cancer to utilize its radio-sensitizing properties. The optimal dose of satra-platin given concurrently with radiation therapy for locally advanced non-small cell lung cancer (NSC-LC) has not been defined. This phase I trial attempts to identify a maximally tolerated dose (MTD) and dose limiting toxicity (DLT) for Satraplatin given con-currently with radiation for locally advanced N-SCLC. Patients and Methods: 15 patients with histologically confirmed Stage IIIA/B NSCLC entered onto this study with four dose escalations (10 to 40 mg daily) of Satraplatin. Eligibility included patients with NSCLC and one of the following criteria: 1) previously untreated, inoperable disease and planned to receive radiation therapy to primary disease site;2) previously resected disease with mediastinal relapse;or 3) metastatic disease in no more than one distant site. Results: The most common toxicities reported were all grades of fatigue (n = 9), nausea (n = 9), constipation (n = 7), fever (n = 7), and vomiting (n = 6). No DLT at the 1st, 2nd, and 3rd dose levels was identified. At the 4th dose level, one patient developed grade III elevation of liver function tests (LFTs) and a second patient developed grade III diarrhea with fever requiring hospitalization. There were 8 partial responses out of 11 evaluable patients for response (RR 67%). Conclusion: Elevated LFTs and diarrhea appear to be the principal DLTs of concurrent daily oral Satraplatin and thoracic radiation in the outpatient setting. The MTD of concurrent Satraplatin with thoracic radiation therapy appears to be 40 mg daily.展开更多
基金Supported by Non-pesticide Replacing High-toxic Pesticides Project in Yunnan Province (ynzz-200733)~~
文摘[ Objective] The paper was to operate the application and promotion of non-pesticide replacing high-toxic pesticides techniques in Kunming City, and to analyze its benefit. [ Method ] Through application and promotion of frequency trembler grid lamps, sticking plate trapping technology, construction of treatment ponds for field waste vegetable leaves, standardized (accurate) cultivation techniques, cultivation techniques of disease-resistant varieties and diverse cultivation technologies, the promotion benefit of non-pesticide replacing high-toxic pesticides techniques was comprehensively investigated and evaluated. [ Result ] The appli- cation and promotion area of non-pesticide replacing high-toxic pesticides techniques in Kunming City during 2006 -2010 reached 94 667 hm2. The investigation on control efforts and quantitative analysis of cost/benefit showed that the beneficial result of application and promotion of non-pesticide replacing high-toxic pesticides techniques was higher than the direct benefit of application and promotion of traditional pesticide replacing techniques. This improvement innovated the traditional pesticide replacing method in replacement work of high-toxic pesticides, reducing the usage volume of pesticide in Kunming City. [ Conclusion] The application and promotion of non-pesticide replacing high-toxic pesticides techniques improved the economic, social and ecological benefit of replacement work of high-toxic pesticides, protected the agricultural ecological environment and promoted the sustainable development of agricultural production.
基金financially supported by the National Key R&D Program of China (No. 2018YFC1802400)the National Natural Science Foundation of China (No. 51604310)+1 种基金the Major Project of Central Research Institute of Building and Construction (No. XAC2017Ky03)the Opening Foundation of State Key Laboratory for Environmental Protection of Iron and Steel Industry (No. 2016YZC02)
文摘The stabilization of severely As-polluted soil has been a challenge, especially for the extremely toxic As(Ⅲ) contaminants. In this study, soil with a high As concentration(26084 mg/kg) was availably stabilized by a H2O2 pre-oxidation assisted TMT-15(Na3S3C3N3 solution with a mass fraction of 15%) and FeCl3·6 H2O stabilization method. The results showed that the combination of the two stabilizers(i.e., TMT-15 and FeCl3·6 H2O) presented a better stabilization behavior than either stabilizer used individually. The use of the H2O2 pre-oxidation assisted TMT-15 and FeCl3·6 H2O stabilization approach not only converted the As(Ⅲ) to As(Ⅴ) but also reduced the toxic leaching concentration of As to 1.61 mg/L, which is a safe level, when the additions of TMT-15 and FeCl3·6 H2O were 2 mL and 0.20 g, respectively. Thus, using only a simple H2O2 pre-oxidation to combine clean stabilization with non-toxic stabilizers TMT-15 and FeCl3·6 H2O could render the severely As-contaminated soil safe for disposal in a landfill.
文摘The unusual and remarkable property of parasporin 2 of non-insecticidal Bacillus thuringiensis is specifically recognizing and selectively targeting human leukemic cell lines. The 37-kDa inactive nascent protein is proteolytically cleaved to the 30-kDa active form that loses both the N-terminal and the C-terminal segments. Accumulated cytological and biochemical observations on parasporin-2 imply that the protein is a pore-forming toxin. To confirm the hypothesis, insilico analysis was performed using homology modeling. The resulting model of parasporin 2 protein is unusually elongated and mainly comprises long β-strands aligned with its long axis. It is similar to aerolysin-type β-pore-forming toxins, which strongly reinforce the pore-forming hypothesis. The molecule can be divided into three domains. Domain 1, comprising a small β-sheet sandwiched by short α-helices, is probably the target-binding module. Two other domains are both β-sandwiches and thought to be involved in oligomerization and pore formation. Domain 2 has a putative channel-forming β-hairpin characteristic of aerolysin-type toxins. The surface of the protein has an extensive track of exposed side chains of serine and threonine residues. The track might orient the molecule on the cell membrane when domain 1 binds to the target until oligomerization and pore formation are initiated. The β-hairpin has such a tight structure that it seems unlikely to reform as postulated in a recent model of pore formation developed for aerolysin-type toxins. Parasporin 2 (Accession no: BAD35170) protein sequence analysis indicated two different domains namely, aerolysin toxin and clostridium toxin domain based on different database searches (CDD and Pfam). It showed a close similarity with the available PDB template (PDB id: 2ZTB) of parasporin which has cytocidal activity against MOLT-4, HL60 and Jurkat cell lines. Based on the PSI Blast analysis, 3D structures of the domains were predicted by using Swiss model server. Accuracy of the prediction of 3D structure of different domains of parasporin protein was further validated by Ramachandran plot and PROCHECK (G-value). The structure is dominated by β-strands (67%, S1-12), most of which are remarkably extensive, running all or most of the longer axis of the molecule. This study helped to elucidate the 3D structure of parasporin 2 (Acc. No. BAD35170) which might enable to probe further its specific mechanism of action. Though the similarity is observed in the domain architecture, there is variation in the regions of the domains even among the same group of parasporin 2. Docking of this model structure and experimental structure with specific receptors of the cancer cells will facilitate to explore mechanism of parasporin 2 action and also provide information about its evolutionary relationship with toxic Cry proteins.
文摘Toxic epidermal necrolysis(TEN) is a rare acute life-threatening mucocutaneous disorder that is mostly drug-related(80%-95%). It is clinically characterized as a widespread sloughing of the skin and mucosa. AP regimen(pemetrexed plus cisplatin) has been the preferred first-line chemotherapy for metastatic non-squamous non-small cell lung cancer(NSCLC). Gefitinib, a small-molecule epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI), has already been recommended as a first-line treatment in EGFR-mutant metastatic NSCLC. We report rare presentation of TEN involving adverse effects of AP and gefitinib combination treatment in a 42-year-old woman diagnosed with metastatic NSCLC harboring an EGFR mutation. On the 21 st day after administration of the first cycle of AP regimen and the 8th day after the initiation of gefitinib treatment, she developed an acne-like rash, oral ulcer, and conjunctivitis, which later became blisters and ultimately denuded. The characteristic clinical courses were decisive for the diagnosis of TEN. Treatment with systemic steroids and immunoglobulin as well as supportive treatment led to an improvement of her general condition and a remarkable recovery.
文摘Background: Pemetrexed (PEM) is an efficacious multi-targeted antifolate with acceptable toxicities for non-squamous non-small cell lung cancer (non-Sq NSCLC). However, in the clinical setting, PEM has more severe adverse effects than those reported. The aim of this study was to identify the factors for the toxicities of PEM-containing chemotherapy in non-Sq NSCLC patients in the clinical setting. Patients and Methods: We retrospectively evaluated the factors related to PEM toxicities in chemotherapy-naive patients with non-Sq NSCLC from September 2009 to July 2013 at our hospital. Logistic regression model was used in the univariate and multivariate analyses. Results: In total, 104 patients were analyzed. Grades 3 to 5 hematologic toxicities were frequent and included neutropenia (42%), febrile neutropenia (7%), anemia (18%), thrombocytopenia (17%), and disseminated intravascular coagulation (2%). On multivariate analyses, the predictors were poor performance status (PS) [odds ratio (OR): 4.89, 95% confidence interval (CI): 1.22 - 19.4] and low body mass index (OR: 1.44, 95% CI: 1.05 - 1.98) for febrile neutropenia;concomitant chronic infectious disease (OR: 6.63, 95% CI: 1.59 - 27.5) and bevacizumab use (OR: 3.57, 95% CI: 1.36 - 9.32) for neutropenia;poor PS (OR: 3.02, 95% CI: 1.33 - 6.85) for thrombocytopenia;and low serum albumin level (OR: 0.22, 95% CI: 0.08 - 0.63) for non-hematologic toxicities. Conclusions: In addition to the previously reported predictors of PEM toxicities, the presence of concomitant chronic infectious disease was associated with hematologic toxicities. Patient groups who are not sufficiently evaluated in clinical trials should be carefully monitored for the development of more toxicities than expected.
基金support by the grant of the National Natural Science Foundation of China (No. 30870738)
文摘Objective: To evaluate the maximum tolerated dose (MTD) of docetaxel (DCT) and cisplatin (DDP) concurrently with three dimensional (3D) conformal radiotherapy or IMRT for patients with locally advanced non-small cell lung cancer (stage IIIa and IIIb) after 2–4 cycles of induction chemotherapy. Methods: Fourteen patients with histological/cytological proven stage III non–small-cell lung cancer were eligible. 3D or IMRT radiotherapy (60-70Gy in 30-35 fractions, 6-7weeks, 2 Gy/fraction) was delivered concurrently with cisplatin and docetaxel, 2 cycles during concurrent chemoradiotherapy (CCRT). The level I dosage was composed of 56 mg/m2 DCT, on day 1 and 28mg/m2 DDP, on day 1 and day 2. The level II was composed of 60 mg/m2 DCT, on day 1 and 30 mg/ m2 DDP, on day 1 and day 2. The level III was composed of 64 mg/m2 DCT, on day 1 and 32 mg/ m2 DDP, on day 1 and day 2. Results: Fourteen patients were allocated and finished concurrent chemoradiotherapy. The dose-limiting neutropenia was at the dose Level III (64 mg/m2) and occurred in 2 of 5 patients. No dose limiting non-hematologic or hematologic toxicity occurred in the other patients. Conclusions: Patients with locally advanced non-small cell lung cancer may tolerate 60mg/m2 docetaxel and 60mg/m2 cisplatin for 2 cycles during concurrent radiotherapy after 2-3 cycles of induction chemotherapy.
文摘Pathogenic mutations involving DNA repeat expansions are responsible for over 20 different neuronal and neuromuscular diseases. All result from expanded tracts of repetitive DNA sequences(mostly microsatellites) that become unstable beyond a critical length whentransmitted across generations. Nearly all are inherited as autosomal dominant conditions and are typically associated with anticipation. Pathologic unstable repeat expansions can be classified according to their length, repeat sequence, gene location and underlying pathologic mechanisms. This review summarizes the current contribution of mutant pluripotent stem cells(diseased human embryonic stem cells and patient-derived induced pluripotent stem cells) to the research of unstable repeat pathologies by focusing on particularly large unstable noncoding expansions. Among this class of disorders are Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome, myotonic dystrophy type 1 and myotonic dystrophy type 2, Friedreich ataxia and C9 related amyotrophic lateral sclerosis and/or frontotemporal dementia, Facioscapulohumeral Muscular Dystrophy and potentially more. Common features that are typical to this subclass of conditions are RNA toxic gain-of-function, epigenetic loss-of-function, toxic repeat-associated non-ATG translation and somatic instability. For each mechanism we summarize the currently available stem cell based models, highlight how they contributed to better understanding of the related mechanism, and discuss how they may be utilized in future investigations.
文摘Non-steroidal anti-inflammatory drugs have a fundamental and pivotal position in management of many of the disorders managed by rheumatologists.Promulgation of a false perspective of their toxicity has compromised our ability to advise our patients and participate in the management of their disorders. The literature sources, from which the false perspective derives, do not accurately reflect safety and fail to address the value of appropriate drug use monitoring.We, as rheumatologists, must stand up and proactively address engrained misconceptions-if we are to be able to continue to provide safe, effective care for our patients.
文摘<strong>Purpose:</strong> <span>Recent studies of radiotherapy</span><span "=""> </span><span>(RT) for stage III non-small-cell lung cancer</span><span "=""> </span><span>(NSCLC) have associated high dose to the heart with cardiac toxicity</span><span "=""> </span><span>and decreased overall survival</span><span "=""> </span><span>(OS). We used advanced statistical techniques</span><span "=""> </span><span>to account for correlations between dosimetric variables</span><span "=""> </span><span "=""><span>and more accurately determine the range of heart doses which are associated with reduced OS in patients receiving RT for stage III NSCLC.</span><b><span> Methods: </span></b><span>From 2006 to 2013, 119 patients with stage III NSCLC received definitive RT at our institution. OS</span></span><span "=""> </span><span>data was obtained from institutional tumor registry.</span><span "=""> </span><span>We used multivariate Cox model to determine patient specific covariates predictive for reduced overall survival. We examined age, prescription dose, mean lung dose, lung V20, RT technique, stage, chemotherapy, tumor laterality, tumor volume, and tumor site as candidate covariates.</span><span "=""> </span><span>We</span><span "=""> </span><span>subsequently used novel statistical techniques within multivariate Cox model to</span><span "=""> </span><span>systematically search the whole heart dose-volume histogram</span><span "=""> </span><span>(DVH) for dose parameters</span><span "=""> </span><span "=""><span>associated with OS.</span><b><span> Results: </span></b><span>Patients were followed until death or 2.5 to 81.2 months (median 30.4 months) in those alive at last follow up. On multivariate analysis of whole heart DVH</span></span><span>,</span><span> the dose of</span><span "=""> </span><span>51</span><span "=""> </span><span>Gy was identified as a threshold dose above which the dose volume relationship becomes predictive for OS. We identified</span><span "=""> </span><span>V55Gy (percentage of the whole heart volume receiving at least</span><span "=""> </span><span>55</span><span "=""> </span><span>Gy) as the best single DVH index which can be used to set treatment optimization constraints</span><span "=""> </span><span>(Hazard Ratio = 1.044 per 1% increase in heart volume exposed to at least 55</span><span "=""> </span><span>Gy, P</span><span "=""> </span><span>=</span><span "=""> </span><span>0.03). Additional characteristics correlated with OS on multivariate analysis were</span><span "=""> </span><span "=""><span>age, stage (IIIA/IIIB), and administration of chemotherapy. </span><b><span>Conclusion:</span></b><span> Doses above 51</span></span><span "=""> </span><span>Gy, applied to</span><span "=""> </span><span>small volumes of the heart,</span><span "=""> </span><span>are associated with worse OS in stage III NSCLC patients treated with definitive RT. Higher stage, older age and lack of chemotherapy were also associated with reduced OS</span><span>.</span>
文摘Background: Comparing the efficacy and safety of gemcitabine at a fixed-dose rate (FDR) infusion (10 mg/m2/min) with the standard dose rate infusion in patients with locally advanced and metastatic non-small squamous cell carcinoma (NSCLC). Methods: The study randomized 60 patients with confirmed diagnosis of NSCLC to receive gemcitabine at a dose of 1000 mg/m2 on days 1 and 8 given as a 30-min infusion (Arm A) or at a rate of 10 mg/m2/min (Arm B). Cisplatin 75 mg/m2 was administered intravenously on day 2 in both arms. Results: No difference in overall response rate (46.6% versus 43.3%). Median time to progression for Arm A was 7 months (95% CI, 6.207 - 7.793 months), versus 6 months for Arm B (95% CI, 4.990 - 7.010 months). Median survival time was comparable [12 months (95% CI, 8.588 - 15.412 months) versus 11 months (95% CI, 9.066 - 12.934 months)] respectively. Two-year survival (18% versus 11%, p = 0.38) was detected. No treatment related deaths occurred. Main hematological toxicities were grade I and II neutropenia, in 36.7% and 53.3% respectively (p = 0.044). Grade III anemia was observed in 10% and 6.7% in both arms respectively (p = 0.024). Grade I and II nausea and vomiting was observed in 50% and 46.7%. Conclusions: FDR gemcitabine in combination with cisplatin had equivalent efficacy and more severe hematologic toxicities compared to the standard 30-min gemcitabine infusion with cisplatin in patients with advanced NSCLC.
文摘<strong>Purpose:</strong> <span><span><span style="font-family:""><span style="font-family:Verdana;">To examine possible association between heart irradiation and Overall Survival (OS) in lung SBRT patients and to compare observed associations with cardiac toxicity models previously derived in LA-NSCLC patient studies. </span><b><span style="font-family:Verdana;">Materials and Methods: </span></b><span style="font-family:Verdana;">197 Patients treated with lung SBRT at Mayo Clinic Arizona were selected for this IRB</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">approved study. Multivariate Cox model with Akaike Information Criterion (AIC) was used to select patient</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">specific covariates associated with OS. Heart dosimetry was represented by </span></span></span><span><span><i><span style="font-family:""><span style="font-family:Verdana;">V</span><sub><span style="font-family:Verdana;">D</span></sub></span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> indices, which is a percentage of volume exposed to dose D or greater. Multivariate Cox model</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">s</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> with patient</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">specific covariates and single </span></span></span><span><span><i><span style="font-family:""><span style="font-family:Verdana;">V</span><sub><span style="font-family:Verdana;">D</span></sub></span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> index per model was used to find a range of doses which were predictive for OS. A digital subdivision of the heart was further used to determine </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">the </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">spatial distribution of doses which were predictive for OS. A coarse subdivision divided heart into 4 segments, while </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">the </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">fine subdivision divided heart into 64 segments. Knowledge constrained Fused Lasso operator was used to derive a more complete model which correlated heart dosimetry with OS. Results of statistical analysis were compared to predictions of a model of cardiac toxicity in LA-NSCLC patients.</span><b><span style="font-family:Verdana;"> Results: </span></b><span style="font-family:Verdana;">Higher age (p < 0.001), higher stage (p < 0.001) and squamous cell histology (p = 0.001) were associated with reduced OS. Whole heart DVH analysis did not reveal associations between heart irradiation and reduced OS. Coarse subdivision of the heart into four segments revealed that the irradiation of two inferior segments of the heart with low doses was associated with reduced OS, </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">V</span></i></span></span><span><span><sub><span style="font-family:""><span style="font-family:Verdana;">2</span><i><span style="font-family:Verdana;">Gy</span></i></span></sub></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> in the right-inferior segment (HR = 1.012/1%, p = 0.02), and </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><span style="font-family:Verdana;">V</span></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><sub><span style="font-family:Verdana;">1</span></sub></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><i><sub><span style="font-family:Verdana;">Gy</span></sub></i></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> in the left-inferior segment (HR = 1.01/1%, p = 0.04). Maximum dose in the right-inferior segment of the heart was also associated with reduced OS (HR = 1.02/Gy, p = 0.02). Fine subdivision of the heart into 64 segments revealed that approximately 25% of heart volume in the inferior part of the heart (15/64 segments), when irradiated to doses in the 1</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Gy </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> 5</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">Gy range, were predictive for reduced OS (HR = 1.01/1%, p = 0.01). A previously derived model of cardiac toxicity in LA-NSCLC patients did not predict a reduction of OS due to heart irradiation in lung SBRT patients, because of relatively low doses to the heart in most lung SBRT patients. </span><b><span style="font-family:Verdana;">Conclusions:</span></b><span style="font-family:Verdana;"> Doses lower than 5</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Gy in the inferior segments of the heart may be associated with reduced overall survival in patients treated for lung lesions with SBRT. Stage and histology of the disease, as well as patients’ age, were also associated with overall survival. Comparisons of cardiac toxicity patterns in LA-NSCLC patients and lung SBRT patients suggest different etiology of cardiac toxicity in the two groups.</span></span></span>
文摘Introduction: Satraplatin has been given in combination therapy for lung cancer to utilize its radio-sensitizing properties. The optimal dose of satra-platin given concurrently with radiation therapy for locally advanced non-small cell lung cancer (NSC-LC) has not been defined. This phase I trial attempts to identify a maximally tolerated dose (MTD) and dose limiting toxicity (DLT) for Satraplatin given con-currently with radiation for locally advanced N-SCLC. Patients and Methods: 15 patients with histologically confirmed Stage IIIA/B NSCLC entered onto this study with four dose escalations (10 to 40 mg daily) of Satraplatin. Eligibility included patients with NSCLC and one of the following criteria: 1) previously untreated, inoperable disease and planned to receive radiation therapy to primary disease site;2) previously resected disease with mediastinal relapse;or 3) metastatic disease in no more than one distant site. Results: The most common toxicities reported were all grades of fatigue (n = 9), nausea (n = 9), constipation (n = 7), fever (n = 7), and vomiting (n = 6). No DLT at the 1st, 2nd, and 3rd dose levels was identified. At the 4th dose level, one patient developed grade III elevation of liver function tests (LFTs) and a second patient developed grade III diarrhea with fever requiring hospitalization. There were 8 partial responses out of 11 evaluable patients for response (RR 67%). Conclusion: Elevated LFTs and diarrhea appear to be the principal DLTs of concurrent daily oral Satraplatin and thoracic radiation in the outpatient setting. The MTD of concurrent Satraplatin with thoracic radiation therapy appears to be 40 mg daily.