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Epidermal growth factor receptor (EGFR) -mutant advanced non-small cell lung cancer (NSCLC) was previously regarded as a cold tumor according to tumor immune microenvironment (TIME) . However, recent studies have found that EGFR-tyrosine kinase inhibitors (EGFR-TKIs) treatment can transform the host immunity from immunosuppressive to immunosupportive state, bringing new hope for immunotherapy. There are four main therapeutic strategies for patients after EGFR-TKIs acquired resistance: immunotherapy alone (Im) , immunotherapy plus chemotherapy (Im+C) , immunotherapy plus antiangiogenic drugs (Im+A) , and immunotherapy combined with antiangiogenic drugs and chemotherapy (Im+A+C) . Among them, the efficacy of Im is extremely limited, being significantly lower than that of chemotherapy alone, while there is still scarce evidence for the efficacy of Im+A with few clinical studies. The combination of Im+C and Im+A+C shows better efficacy than chemotherapy alone. Im+A+C has a superior clinical outcome to Im+C. Additionally, the EGFR L858R mutation subgroup benefits more from Im+C than the EGFR 19 del mutation subgroup. The T790M-negative subgroup has a greater benefit from Im+A+C than the T790M-positive subgroup. In general, the strategy of combining immunotherapy with chemotherapy and/or an antiangiogenic drug represents a novel and promising method for treating EGFR-mutant NSCLC after EGFR-TKI failure.
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<p><b>OBJECTIVE</b>To investigate the changes of genetic damage in patients with arsenism caused by coal-burning in 9 years. To analyze the relationship between the changes of genetic damage and disease progression and provide a basis for condition monitoring.</p><p><b>METHODS</b>Of 206 arsenism patients from the area with endemic arsenism in Guizhou province were tracking surveyed in February 1998 and divided into 4 groups, including suspicious, mild, moderate and severe poisoning group. Another 67 healthy residents from a neighbour township 12 km away where arsenic was not prevalent were surveyed. Over a 9-year follow-up, 131 arsenism patients and 45 controls with the complete biochemical indexes among them were selected as subjects in December 2006. Arsenic (As) concentration of urine and hair were detected by silver diethyldithiocarbamate spectrophotometry (Ag-DDC). Micronucleis (MN) and chromosome aberrations (CA) were analyzed by conventional methods. DNA single-strand breaks of peripheral blood were measured by single cell gel electrophoresis (SCGE), and the tail lengths of comet were used to measure DNA damage.</p><p><b>RESULTS</b>Among the control, suspicious, mild, moderate and severe arsenic poisoning group, the As contents of urine and hair were respectively (34.16 ± 10.25), (52.35 ± 22.41), (62.26 ± 31.13), (71.43 ± 49.92), (78.45 ± 50.64) µg/L and (1.37 ± 0.56), (3.69 ± 1.78), (4.88 ± 3.49), (5.21 ± 3.10), (6.25 ± 4.04) µg/g in 2006, which were lower than that 9 years before (urine as contents were (36.07 ± 20.70), (73.65 ± 41.33) , (90.92 ± 82.14) , (126.55 ± 107.31) and (139.44 ± 90.90) µg/L, and hair As contents were (1.41 ± 1.18), (4.85 ± 4.20), (5.72 ± 4.07) , (6.43 ± 4.32) and (7.19 ± 4.68) µg/g, respectively, F value was 10.63, 7.72, 14.66, 11.00 respectively, all P values were < 0.05). Except for suspicious poisoning group, the differences of urine As contents in the other groups all showed significance (P < 0.05). The incidences of MN were (0.238 ± 0.130) %, (0.268 ± 0.192) %, (0.283 ± 0.157) % and (0.391 ± 0.233)%; the incidences of CA were (14.36 ± 5.44) %, (18.09 ± 6.49) %, (19.38 ± 5.63)% and (19.83 ± 5.84) %; the tail lengths of comet were (29.88 ± 13.81) , (29.84 ± 12.80) , (34.50 ± 9.88) and (41.58 ± 12.98) µm respectively in 2006 for all poisoning groups; which were higher than that 9 years before(the incidences of MN were (0.163 ± 0.051) %, (0.186 ± 0.117) %, (0.196 ± 0.104) % and (0.273 ± 0.142) %; the incidences of CA were (13.18 ± 5.17)%, (14.48 ± 6.61)%, (15.67 ± 8.49) % and (16.90 ± 8.38) %; the tail lengths of comet were (15.07 ± 12.93) , (19.57 ± 8.80) , (27.03 ± 10.77) and (34.71 ± 14.95) µm) , except for the incidences of MN and CA in suspicious poisoning group and of MN in mild poisoning group , the differences of the three indexes in the other groups were significant (P < 0.05) . The state of illness of arsenic poisoning patients aggravated 9 years later. With the increase of urine and hair As contents and the development of arsenism, the incidences of MN, CA and the tail lengths of comet of all poisoning groups increased. There were positive correlations among them (r values were respectively 0.212, 0.316, 0.232, 0.263, 0.321, 0.654 and 0.760) (P < 0.05).</p><p><b>CONCLUSION</b>The exacerbation of genetic damage was related to constantly high arsenic loads. The accumulation of genetic damage and its irreversibility might be one of the important reasons of the development of arsenism and cancer.</p>
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Humans , Arsenic , Arsenic Poisoning , Coal , DNA Damage , Follow-Up StudiesABSTRACT
OBJECTIVE To investigate the drug resistance of ESBLs-producing Escherichia coli and Klebsiella pneumoniae in local nosocomial infection,for guiding the clinical drug resistance. METHODS ATB analysis system was used for identification of bacteria,extra-susceptibility tests were detected by K-B method. RESULTS The isolation rate of ESBLs-producing E. coli and the K. pneumoniae was 29.9% and 30.8%,respectively. The drug susceptibility was indicated the resistance rate of ESBLs producing strains to antibacterial agents except imipenem was higher than that of non-ESBLs producing strains. CONCLUSIONS Detecting drug resistance of ESBLs producing strains is of important significance for guiding the clinical rational use of antibacterials and controling the epidemics.
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OBJECTIVE To investigate the distribution and drug resistance status of extended-spectrum ?-lactamases producing(ESBLs) Klebsiella pneumoniae and to provide the basis for clinic anti-infective treatment.METHODS To use ATB-expression analyzer to identify the microbe.The drug susceptibility was tested with the K-B method and the ESBLs producing strains detected by diffusion confirmed test.RESULTS Among 137 strains of identified K.pneumoniae,34.3% of them(47 strains)produced ESBLs,and most had been shown in geriatrics ward.The drug resistance rate of ESBLs producing K.pneumoniae was higher than that in non-producing ESBLs one.So imipenem should be considered to be a preferred antibiotic when used on K.pneumoniae seriously infected cases.CONCLUSIONS The drug resistance of K.pneumoniae is a serious problem,we should pay attention on the status of ESBLs distribution,based on the susceptibility to choose the reasonable antibacterial to avoid the producing ESBLs bacteria spread out.
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OBJECTIVE To investigate the drug resistance of ESBLs-producing Escherichia coli in community-acquired urinary tract infection for guiding the clinical drug-using.METHODS ATB-Expression analysis system was used for identification of bacteria,extra-susceptibility tests were detected by K-B method.RESULTS Totally 104 E.coli strains were detected,the isolation rate of ESBLs-producing E.coli was 13.5%,the resistant rates of E.coli were up to 70% to ampicillin,piperacillin and Co-trimoxazole,the resistant rate was up to 55% to ciprofloxacin and levofloxacin,and the susceptible rate was 100% to imipenem.CONCLUSIONS The E.coli is a main pathogen in community-acquired urinary tract infection,Its drug resistance is extremely severe.To enhance detecting drug resistance of pathogenic bacteria is of important significance for guiding the clinical rational drug-using and reducing drug-resistant strains.