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Objective@#To evaluate the radiological tumor response patterns and compare the response assessments based on immunebased therapeutics Response Evaluation Criteria in Solid Tumors (iRECIST) and RECIST 1.1 in metastatic clear-cell renal cell carcinoma (mccRCC) patients treated with programmed cell death-1 (PD-1) inhibitors. @*Materials and Methods@#All mccRCC patients treated with PD-1 inhibitors at Henan Cancer Hospital, China, between January 2018 and April 2019, were retrospectively studied. A total of 30 mccRCC patients (20 males and 10 females; mean age, 55.6 years; age range, 37–79 years) were analyzed. The target lesions were quantified on consecutive CT scans during therapy using iRECIST and RECIST 1.1. The tumor growth rate was calculated before and after therapy initiation. The response patterns were analyzed, and the differences in tumor response assessments of the two criteria were compared. The intra- and inter-observer variabilities of iRECIST and RECIST 1.1 were also analyzed. @*Results@#The objective response rate throughout therapy was 50% (95% confidence interval [CI]: 32.1–67.9) based on iRECIST and 30% (95% CI: 13.6–46.4) based on RECIST 1.1. The time-to-progression (TTP) based on iRECIST was longer than that based on RECIST 1.1 (median TTP: not reached vs. 170 days, p = 0.04). iRECIST and RECIST 1.1 were discordant in 8 cases, which were evaluated as immune-unconfirmed PD based on iRECIST and PD based on RECIST 1.1. Six patients (20%, 6/30) had pseudoprogression based on iRECIST, of which four demonstrated early pseudoprogression and two had delayed pseudoprogression.Significant differences in the tumor response assessments based on the two criteria were observed (p < 0.001). No patients demonstrated hyperprogression during the study period. @*Conclusion@#Our study confirmed that the iRECIST criteria are more capable of capturing immune-related atypical responses during immunotherapy, whereas conventional RECIST 1.1 may underestimate the benefit of PD-1 inhibitors. Pseudoprogression is not rare in mccRCC patients during PD-1 inhibitor therapy, and it may last for more than the recommended maximum of 8 weeks, indicating a limitation of the current strategy for immune response monitoring.
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Objective To explore the related factors and clinical significance of the effect of irrigation on infant with dacryocystitis. Methods A total of 318 eyes of 262 infant were treated with dacryocystitis, and their overall curative effect was observed. Single factor correlation analysis and multivariate Logistic regression were used to analyze 8 factors related to efficacy, such as age of children, length of medical history, severity of symptoms, degree of operation of nurses, degree of parental cooperation, compliance with medication, massage therapy and treatment methods. The effect of each factor on the curative effect. Results It was found that the total effective rate was 90.56 percent of the lacrimal passage in children with 318 tear channel obstruction and dacryocystitis.Single factor analysis results show that the factors influencing the curative effect of single in treatment (χ2= 88.984, P < 0.01), symptom severity (χ2=14.185,P < 0.05) length of history (χ2=18.783, P < 0.05) difference and massage therapy (χ2=10.081, P < 0.05) was statistically significant, the three factors of multiariable Logistic regression analysis results showed that the treatment (P=0.000, OR=0.148,95％ CI 0.052- 0.419) and massage therapy (P=0.012, OR=3.390, 95％ CI 1.309- 8.777) affected infant lacrimal duct flushing out main factors influencing the efficacy of tong. Conclusions The main influencing factors are the different treatment modalities, severity of symptoms the length of medical history and massage therapy in the related factors that affect the effect of infantwith dacryocystitis.
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AIM:To detect the changes of active status of bypass signaling pathways in EML4-ALK positive lung cancer cell line H3122 treated with alectinib, hepatocyte growth factor (HGF), epidermal growth factor (EGF) and transforming growth factor-α (TGF-α), and to explore the potential mechanisms.METHODS:EML4-ALK positive cell line H3122 was treated with increasing concentrations of alectinib or/and induced by HGF, EGF and TGF-α.The cell viability was measured by CCK-8 assay.The cell apoptosis was analyzed by flow cytometry.The protein levels and phosphorylation status of ALK, c-Met and EGFR, and the downstream molecules AKT, ERK, p-AKT and p-ERK were examined by Western blot.RESULTS:The viability of the H3122 cells was inhibited by alectinib in a dose-dependent manner after administrated for 72 h, and the IC50 value was 0.042 μmol/L.The concentration-growth curves of the H3122 cells shifted to the right after induced by HGF, EGF and TGF-α.After treatment with alectinib at 0.05 μmol/L for 48 h, the apoptotic rate of H3122 cells was (20.12±1.36)%, while the apoptotic rates of the cells in the groups of alectinib combined with HGF, EGF or TGF-α were (7.85±1.03)%, (5.60±0.79)% and (4.58±1.00)%, respectively.Those values were remarkably lower than those in alectinib single treatment group (P<0.05).Alectinib inhibited the protein levels of p-ALK and its downstream signaling pathway molecules, while HGF significantly up-regulated the protein levels of p-Met and its downstream p-AKT and p-ERK.Besides, EGF and TGF-α remarkablely up-regulated the protein levels of p-EGFR and its downstream p-AKT and p-ERK.Combined treatment with crizotinib and 17-DMAG successfully inhibited the viability of the H3122 cells even in the presence of the HGF and EGFR ligands, respectively.CONCLUSION:Bypass signaling pathways are activated by HGF, EGF and TGF-α in EML4-ALK positive lung cancer cell line H3122, which may be linked to alectinib resistance.
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Objective To investigate the clinical effects of different dosages of Shenfu injection for treatment of elderly patients with refractory chronic congestive heart failure (CHF).Methods A prospective study was conducted, 360 patients with CHF from Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine were enrolled, and they were randomly divided into low dose, middle dose and high dose Shenfu injection groups. In the three groups, the patients received the same conventional medicine therapy, and additionally they were treated by low, medium and high dose Shenfu injection (60, 80, 100 mL/d, respectively), once a day. The therapeutic course was 10 days in the three groups. After treatment, the clinic therapeutic effect, left ventricular diastolic end diameter (LVEDD), left ventricular ejection fraction (LVEF), stroke volume (SV), cardiac output (CO), cardiac index (CI) and plasma B type natriuretic peptide (BNP) were observed in the three groups.Results The total therapeutic effective rate in middle dose Shenfu injection group was significantly higher than that in low dose and high dose Shenfu injection groups [82.5% (99/120) vs. 54.2% (65/120), 60.0% (72/120), bothP < 0.05]. In high dose Shenfu injection group, increase of blood pressure occurred in 15 cases (12.5%), but no such phenomenon appeared in low and middle dose Shenfu injection groups. In the three groups, no cardiac arrhythmia, liver function abnormality, myocardial enzymogram abnormality, etc. adverse reactions occurred. Compared with those before treatment, after treatment in three groups the LVEDD and BNP were significantly decreased, while LVEF, SV, CO and CI were markedly increased. The changes of above index in middle dose Shenfu injection group were more significant [LVEDD (mm): 46.1±6.3 vs. 58.3±4.4; LVEF: 0.561±0.056 vs. 0.324±0.044, SV (mL): 58.1±6.3 vs. 35.7±5.4, CO (L/min): 5.78±0.60 vs. 4.21±0.78, CI (mL·s-1·m-2): 81.85±7.33 vs. 53.01±9.00, BNP (ng/L): 355.4±76.6 vs. 3 263.2±65.7, allP < 0.05]. Conclusion Shenfu injection 80 mL/d is the best effective dosage for treatment of elderly patients with refractory CHF and its incidence of adverse events is low.
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Objective To investigate the association between genetic polymorphisms of Dectin-2 and pulmonary cryptococcosis.Methods A total of 134 non-human immunodeficiency virus (HIV)patients with pulmonary cryptococcosis and 464 healthy controls were included in this case control study.The peripheral leucocyte DNA was extracted and genotyping was performed by multiplex SNaPshot technology.The single nucleotide polymorphism (SNP)of rs11045418 located at 5′-flanking locus of Dectin-2 gene was genotyped.Patients without predisposing conditions were compared independently.The differences of gene polymorphism distributions compared between pulmonary patients and healthy control, and between patients without predisposing conditions and healthy control.All data were analyzed withχ2 tests.Results Among the total 134 patients,82 patients had no predisposing factors.Thirty two patients met the proven diagnosis criteria and 102 patients were probable pulmonary cryptococcosis.According to the site of infection, 72 patients had local infection in lungs and 62 patients had disseminated cryptococcosis.Three samples failed in genotyping,one of which was a patient without predisposing factor.Compared with the control group,there was a trend of increasing proportion of heterozygote rs11045418 CT in the 131 pulmonary cryptococcosis patients (59% vs 50%,P =0.069,OR=1.44,95%CI :0.97-2.13),and the heterozygote was significantly increased in 81 patients without predisposing conditions(64% vs 50%,P =0.017,OR= 1 .82,95 %CI :1 .11 -2.95 ).No significant difference of genotype distribution was found between the local and disseminated infection patients.Conclusion Our study shows that rs11045418 CT heterozygote in Dectin-2 is associated with the susceptibility of pulmonary cyrptococcosis among non-HIV-infected Chinese patients,which indicated that the change of Dectin-2 receptor may play a role in the pathogenesis of pulmonary cyrptococcosis.
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Objective To compare test results of antinuclear antibodies (ANA ) using different brands kit and methodology . Methods 180 cases who accepted serum ANA detection in hospital from April to December 2012 were choosen ,in which 145 cases of positive serum and 35 cases of healthy control .The 180 cases were tested for ANAs by YHLO ANA-17S ,EUROIMMUN ANA profile 3 and ANA IIFA kits at the same time ,and all parameters about ANA decetion were compared such as sensitivity ,specifici-ty ,positive predictive value ,negative predictive value and the coincidence rate between the two kinds of kits .Results The sensitivi-ty of YHLO ANA-17S ,EUROIMMUN ANA profile 3 and EUROIMMUN ANA IIFA was 94 .8% ,90 .4% ,95 .6% ;specificity was 88 .9% ,91 .1% ,93 .3% ;positive predictive value was 96 .2% ,96 .8% ,97 .7% ;negative predictive value was 85 .1% ,75 .9% , 87 .5% ;the coincidence rate between the EUROIMMUN ANA profile 3 and EUROIMMUN ANA IIFA was 84 .0% (P>0 .05) ,be-tween the YHLO ANA-17S and EUROIMMUN ANA IIFA was 80 .0% (P>0 .05) ,between theYHLO ANA-17S and EUROIM-MUN ANA profile 3 was 93 .0% (P> 0 .05) .Conclusion Three kits for detecting ANAs have good sensitivity and specificity , which can be used for autoimmune disease detection .Laboratory tests result should be combined with clinical symptoms according to the diagnostic criteria to make the final diagnosis .