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Objective To retrospectively analyze the clinical data of 47 young NSCLC patients mutation style of EGFR and PD-L1 expression in tumor cells, to understand their clinicopathological and molecular characteristics. Methods We enrolled 47 young (≤40 years old) patients confirmed as NSCLC who underwent surgical resection, and 94 old patients (≥60 years old) were matched as 1:2 by R language. EGFR mutation status was detected by ARMS-PCR, and the expression of PD-L1 was detected by immunohistochemistry. Results The median age of 47 young patients with NSCLC was 37 years old. The disease was more common in women and the majority type was adenocarcinoma. In youth group, the 19del and 20ins were more frequent, but the exon 21 L858R point mutation proportion was higher in elder group. The expression of PD-L1 was significantly increased in the solid predominant histological subtype. The PD-L1 expression in 19del patients was higher than that in the patients with L858R mutation in youth group. Conclusion The majority of young NSCLC patients are female, nonsmokers and suffered from adenocarcinoma cancer. The proportion of EGFR alteration in 19del and 20ins in youth group is higher than that in elder group. The positive rate of PD-L1 expression in solid predominant histological subtype is higher than that with other subtypes. The expression of PD-L1 in young patients with EGFR 19del is higher than that with L858R.
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BACKGROUND@#Small cell lung cancer (SCLC) is a highly aggressive malignancy characterized by rapid growth, early metastasis and acquired therapeutic resistance, and the prognosis is extremely poor. Studies have proved that the stem cell marker CD44 is correlated with tumor recurrence and treatment resistance, however, there are limited reports yet concerning on the CD44 expression and its clinical prognostic significance in SCLC patients. The purpose of this study is to investigate the expression of CD44 in tumor tissues as well as serum of SCLC patients and explore its correlation with the clinical characteristics, therapeutic effect and prognosis.@*METHODS@#The tumor tissues and serum samples of 47 newly diagnosed SCLC patients were collected. Immunohistochemistry and enzyme-linked immunosorbent assay were applied to detect CD44. The relationship between CD44 level and the clinical characteristics as well as prognosis of the patients was analyzed.@*RESULTS@#The stem cell marker CD44 was detectable both in serum sample and tumor tissue of SCLC patients. The positive rate of CD44 in tumor tissue was significantly higher in patients with performance status (PS) 2 than that of patients with PS 0-1 (85.71% vs 30%, P=0.017). Patients were divided in to different groups according to the treatment efficacy. The CD44 immunohistochemical score and serum level in the disease progression group were significantly higher than those in the disease control group, and the differences were statistically significant (P=0.006, P=0.034), Univariate analysis depicted that the progression-free survival (PFS) of CD44 positive patients was significantly shorter than that of CD44 negative patients (5.23 mon vs 9.03 mon, P=0.036).@*CONCLUSIONS@#The positive expression of CD44 in tumor tissues of pre-treatment SCLC patients is correlated with poor PFS. The clinical significance of CD44 is worthy to be further studied.
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With the development of precise medicine, targeted therapy has greatly improved the survival and prognosis of patients in advanced non-small cell lung cancer (NSCLC) with oncogenic drivers. However, no matter which kinds of targeted therapy are inevitable to develop therapeutic resistance, treatment options upon exhaustion of targeted therapies are limited. Immune checkpoint inhibitors (ICIs) can bring long-term survival to some patients with advanced NSCLC because of its unique long tailing effect. More and more studies have shown that ICIs can also benefit NSCLC patients with oncogenic drivers. However, the timing of ICIs intervention, the therapeutic regimen and the predictive biomarkers are actually debated, underscoring the need to explore the potential interest of ICIs in these populations. .
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BACKGROUND@#In recent years, a number of clinical trials have shown that immunocheckpoint inhibitors (ICI) have brought survival benefits to patients with advanced non-small cell lung cancer (NSCLC), however, such clinical trials comprise cohorts selected based on strict and complex entry and exclusion criteria, and the results cannot fully reflect the real world situation. The purpose of this study was to investigate the clinical efficacy and safety of immunotherapy in the real world, as well as possible prognostic factors.@*METHODS@#Patients with advanced NSCLC receiving immunotherapy in Beijing Chest Hospital from January 2017 to July 2019 were retrospectively collected, and the following information were collected: curative effect, progression-free surival (PFS) and adverse reactions. The occurrence of adverse reactions and clinical curative effect and prognosis factors that may be relevant were explored.@*RESULTS@#34 patients were enrolled in this study, median PFS was 5.66 months (95%CI: 4.48-6.84), grade 1-2 and 3-4 incidence of adverse events was 61.71% (22/34) and 14.71% (5/34), there were 3 patients (8.82%) experienced fatal immune related adverse events (irAE), 2 cases were immune associated pneumonia, 1 case was immune related myocarditis. Univariate analysis showed that tumor-node-metastasis (TNM) stage and metastatic site were correlated with median PFS (P<0.05), and multivariate analysis showed that patients with extrapulmonary metastasis (OR=6.42, P=0.029) and pleural metastasis (OR=14.14, P=0.006) had shorter median PFS.@*CONCLUSIONS@#In the real world, immunotherapy has good efficacy in patients with advanced NSCLC, but the incidence of severe irAE is also higher. Distant metastasis and pleural metastasis are poor prognostic factors for advanced NSCLC patients receiving immunotherapy.
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Objective To identify mutations in NDP,FZD4,LRPS,TSPAN12 in Chinese families with familial exudative vitreoretinopathy (FEVR) and observe the clinical features.Methods Retrospective case series study.The 9 patients (18 eyes) and 5 normal members from 4 unrelated families were included in the study.The patients medical history and family history were collected in detail.All patients underwent best corrected visual acuity (BCVA),slit-lamp biomicroscopy,fundus colorized photography,fundus fluorescein angiography (FFA).Genomic DNA were collected from all the patients.Mutations were detected by directly sequencing to the whole coding region and exon-intron boundaries ofNDP,FZD4,LRP5 and TSPAN12 gene.Polyphen and SWT programs were used to predict the effects on the structure and functional properties of mutant protein.Results There were two affected individuals in the family 2 carried LRP5 gene mutation [c.1330C＞T (p.R444C)] in exon 6 by sequence analysis.A score of 0.882 was acquired by Polyphen program analysis.And the missense change was predicted to be pathogenic by SIFT.Fundus changes of the proband showed angioplasia,tortuosity of peripheral vessels.And temporal dragging of the optic disc,peripheral avascular zone,neovascularization were found in FFA.Brush-like and straight of peripheral vessels were found in I 1.No variant was found in NDP,FZD4 and TSPAN12 gene.Conclusion Our study supports the gene mutation c.1330C＞T (p.R444C) of LRP5 is pathogenesis of FEVR.Patients with the same mutation could have variable phenotypic characteristics.
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Objective To analyze clinical manifestations and histopathological features of 6 subtypes of psoriasis presenting mainly as skin manifestations.Methods Clinical and histopathological data were collected from 313 patients with psoriasis in the Department of Dermatology of Xijing Hospital between 2013 and 2017,and analyzed retrospectively.Results Among the 313 patients,there were 31 patients with guttate-type psoriasis mainly induced by upper respiratory tract infections,60 with plaque psoriasis with the main precipitating factors being upper respiratory tract infections,overexertion,cold weather and so on,42 with erythrodermic psoriasis induced mainly by the withdrawal of systemic glucocorticoids,60 with generalized pustular psoriasis with the main precipitating factors being upper respiratory tract infections,pregnancy,drugs and so on,60 with palmoplantar pustulosis without definite precipitating factors,and 60 with acrodermatitis continua without definite precipitating factors.The 6 subtypes of psoriasis had similar typical pathological manifestations,including parakeratosis,Munro's microabscess and/or spongiform pustules of Kogoj,thinning or absence of the granular layer,psoriasis-like epidermal hyperplasia,capillary ectasia in the dermal papillae,lymphocytic infiltration and so on.Atypical pathological manifestations were observed in 98 (31％) of the 313 patients,which included 4 with guttate type psoriasis (13％),3 with plaque psoriasis (5％),12 with erythrodermic psoriasis (29％),41 with generalized pustular psoriasis (68％),12 with palmoplantar pustulosis (20％) and 26 with acrodermatitis continua (43％).These atypical pathological manifestations included serous fluid exudation,irregular epidermal hyperplasia,non-neutrophilic spongiosis,keratinocyte necrosis,dermal neutrophilic infiltration and dermal eosinophilic infiltration.Conclusions Different subtypes of psoriasis have different clinical manifestations and similar typical histopathological features.Atypical pathological features can interfere with the diagnosis of psoriasis,and attention should be paid to the differential diagnosis.
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Objective To observe the characteristic variation of the patients' inner and outer retina who had chronic central serous chorioretinopathy (CSC) after being treated of photodynamic therapy (PDT).Methods Nineteen patients with chronic CSC were recruited,including 15 eye of men and 4 eye of women,logMAR BCVA was 0.1-1.0,0.39 ± 0.30.Meanwhile,24 healthy people were located in the control group.All the patients received PDT for the first time.All subjects including 24 healthy people underwent fourier domain optical coherence tomography (FD-OCT).Retinal thickness were investigated before PDT and 1,4,12,20 weeks after PDT respectively.Data were recorded including inner layer and outer layer.Retinal thickness were compared in fovea (1 mm),parafovea (3 mm)and perifovea(5 mm).Paired-samples t test was used to compare retinal thickness before and after PDT.The statistical differences of patients and control group were evaluated by independent-samples t test.The correlations between the best logMAR corrected visual acuity (BCVA) was analyzed by Pearson statistical analyses.Results The inner(F=13.814,10.095,4.689) and outer(F＝ 9.354,5.878,3.978) layer fovea thickness of CSC subjects in 1,4,12 week was thinner,the difference was statistically significant (P＜0.05).The outer layer fovea thickness at P12 (t =-3.725),parafovea of inner and outer retinal (t =-3.198,-2.722) was reduced when compared with control group,and differences have statistical sense,respectively (P＜0.05).There was correlation between logMAR BCVA and outer retinal thickness in fovea and parafovea (r =0.465,-0.728,-0.687; P＜0.05).Conclusion In our study,the inner and outer layer retinal thickness decreased generally after the first time PDT in CSC patients.
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Retinopathy of prematurity (ROP) is a kind of vasoproliferative disorders,which leads to vision loss even blindness in premature neonates.Major pathogenesis in ROP is vascular occlusion and retinal neovascularization precipitated by ischemia and hypoxia.Proliferative retinopathy is asscioated with several signaling pathways,such as Wnt signaling pathway,CCN1/cysteine-rich 61 (CCN1/Cry61) in pathological neovascularization,JAK/STAT (Janus kinase/signal transducer and activator of transcription) in intravitreous neovascularization,Apelin/ APJ (Apelin/angiotensin type Ⅰ receptor related protein) in pathological retinal angiogenesis.Deep understanding of the pathways is conducive to treat proliferative retinopathy by targeting pathologic neovessels.
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Objective: To observe the efficacy and safety of analgesic drugs in the standardized treatment of cancer pain patients at the pain clinic. Methods: The data of 787 cancer pain patients and their corresponding prescriptions for cancer pain were collected from April, 2012 to April, 2013 at the pain clinic. The obtained information comprise of diseases that lead to cancer pain, cause of pain, pain intensity, and efficacy and side effects of medications. Diseases that caused cancer pain include 658 cases with primary malignant lung cancer. Results: Pain was mainly caused by primary lung cancer in 787 cancer-related patients. An analgesic drug, namely, oxycodone hydrochloride, was administered in 54.6% via single drug therapy. The daily dosage range of this drug was 20 to 90 mg/d in 280 cases. About 35.6% of the studied patients with a daily dosage of 90 mg/d or lower had their pain effectively managed. After the treatment, the number of cases with moderate to severe pain was reduced from 437 (55.5%) to 248 (31.5%). The oral administration of opioid oxycodone hydrochloride tablets ranked first among the prescribed drugs for cancer pain, and single-drug therapy was the choice of medication. The majority of patients had satisfactory pain-relief with a daily dosage of less than 90 mg/d upon the administration of oxycodone hydrochloride sustained-release tablets and morphine sulfate controlled-release tablets. Side effects included mild constipation, nausea, vomiting, dizziness, loss of appetite, urinary retention, somnolence, and so on. Intervention treatment was needed in most of the patients. Conclusion: Pain clinic is critical in the administration of standardized treatment for cancer pain in hospitals. The establishment of pain clinic ensures the standardized treatment of cancer pain.
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Objective To investigate the pregnancy outcome of gestational intrahepatic cholestasis.Methods 70 pregnant women with intrahepatic cholestasis were selected as the study group.70 healthy pregnant women during the same period were selected as the control group.The pregnancy outcomes of two groups were compaind.Results (1) The maternal serum levels of bile acid,alanine aminotransferase,aspartate aminotransferase in study group were (65.61 ± 13.5) μmol/L,(134.31 ± 24.7) U/L,(97.35 ± 21.54) U/L,which were higher than those of the control group (3.34 ± 0.41) μ mol/L,(36.16 ± 4.15) U/L,(23.34 ± 4.45) U/L,and the differences were statistically significant(P ＜0.01).(2) In study group,the incidence rate of maternal gestational hypertension was 21.42％,premature rupture of membranes was 17.14％,incidence rate of postpartum hemorrhage was 15.71％,which were significantly higher than 7.14％,5.71％,4.29％ in the control group,the differences were statistically significant(P ＜ 0.05).(3) In study group,the incidence rate of neonatal asphyxia was 27.14％,therate of amniotic fluid contamination was 35.71％,fetal distress was 22.86％ and 30.00％ of the childrenwith low birth weight,whichwere higher than those of the control group,the differences were statistically significant(P ＜0.01).Conclusion Pre gnancy intrahepatic cholestasis can increase the incidence rate of perinatal complications,has serious impact on the prognosis of the fetus,and to strengthen the monitoring of pregnancy intrahepatic cholestasis has important clinical significance.
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<p><b>BACKGROUND</b>It was reported that tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was a powerful pulmonary carcinogen, predominantly inducing adenocarcinoma of the lung in mouse. The aim of this study is to assay metabolites of NNK, which are 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its O-glucuronide (NNAL-Gluc), and their ratio (NNAL-Gluc/NNAL) in smokers and non-smokers' urine, and to explore the carcinogenicity of NNK among different people.</p><p><b>METHODS</b>Using high pressure liquid chromatograph (HPLC) and gas chromatograph-mass tadom (GC-MS/MS), NNAL-Gluc and NNAL in 24h urine were detected in 8 healthy smokers, 10 lung cancer smokers and 4 healthy non-smokers.</p><p><b>RESULTS</b>Both of the two metabolites were not found in non-smokers' urine. The ratios of urine NNAL-Gluc/NNAL were greatly different among different smokers. The mean ratio of NNAL-Gluc/NNAL in healthy smokers was 4.95, and 0.5 in lung cancer smokers.</p><p><b>CONCLUSIONS</b>The results provide the first evidence for metabolite detection of tobacco-specific nitrosamine in Chinese smokers' urine . The result suggests that detoxification ability of healthy smokers is higher than that of lung cancer smokers. It may provide a detective way to screen high risk people for lung cancer in smokers.</p>
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<p><b>BACKGROUND</b>With the development of antibody technology, more and more immunoconjugates are used in clinical treatment for different cancers. The aim of this study is to investigate the inhibitive effects of 5F11-DOX immunoconjugate on human lung adenocarcinoma cell line LTEP-A2 in vitro and in vivo and to explore the potential mechanism.</p><p><b>METHODS</b>The 5F11-DOX immunoconjugate was produced by diluted glutaraldehyde crosslinking. The killing efficiency of 5F11-DOX was detected by clonogenic assay. The distribution of DOX was observed under fluorescence microscope and the 5F11 location was determined by immunohistochemistry. The therapeutic efficacy of 5F11-DOX and free DOX was detected on subcutaneous or intraperitoneal exnogenic transplanted tumors of human lung adenocarcinoma A2 cells in nude mice.</p><p><b>RESULTS</b>5F11-DOX of 0.04mg/L could kill all the A2 cells in vitro and the killing efficiency was 10 times as that of the free DOX. Fluorescence microscopy showed that fluorescence of DOX in 3mg/L 5F11-DOX group was much stronger than that in 3mg/L free DOX group after treating A2 cells with 3mg/L 5F11-DOX or DOX for 3h, then incubating the cells with fresh medium for another 24 hours. Immunohistochemistry showed that 5F11 located in cell membrane and cytoplasm and fluorescence microscopy proved that DOX located inside the cells. The average sizes of subcutaneous or intraperitoneal exnogenic transplanted tumors in 5F11-DOX group were obviously smaller than those of the control group and free DOX group at the same dosage (P < 0.05), and the anti-tumorogenicity efficacy of 5F11-DOX was 4-8 times as that of free DOX. The HE staining showed that extensive necrosis occurred in the center of tumors and around cancer nests in 5F11-DOX group.</p><p><b>CONCLUSIONS</b>The killing efficacy of 5F11-DOX on human lung adenocarcinoma cell line A2 is obviously higher than that of the free DOX.</p>