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Realizing highly efficient organic light‐emitting diodes (OLEDs) based on "hot exciton" emitters is crucial for the widespread use of purely organic electroluminescence. Herein, it is demonstrated that the radiative decay rate, modulated by molecular configuration, plays a vital role in determining the optoelectronic properties of hot exciton materials. The proof‐of‐concept isomers, TPA‐1IPCN and TPA‐3IPCN, and TPA‐1IANCN and TPA‐3IANCN are intentionally designed and successfully synthesized. By employing a novel donor–acceptor–acceptor (D–A'–A) molecular architecture, implementing a molecular isomerization strategy, incorporating diverse steric hindrance moieties, and strategically manipulating the positioning of functional groups, precise modulation of the molecular configuration can be achieved to enable accurate regulation of the radiative decay rate. Consequently, various optoelectronic properties, including photoluminescent wavelength, photoluminescence quantum yield, fluorescence lifetime, packing mode in aggregated state, and molecular horizontal dipole ratios in films, undergo significant modifications. As a result, non‐doped blue OLED based on TPA‐1IPCN exhibits outstanding maximum external quantum efficiency (EQE) of 10.3% with minimal efficiency roll‐off—one of the highest reported values for blue OLEDs based on hot exciton materials. [ABSTRACT FROM AUTHOR]

Objective: The relationship between anaplastic lymphoma kinase ( ALK ) expression in malignant pleural effusion (MPE) samples detected only by Ventana immunohistochemistry (IHC) ALK (D5F3) and the efficacy of ALK -tyrosine kinase inhibitor therapy is uncertain., Methods: Ventana anti-ALK (D5F3) rabbit monoclonal primary antibody testing was performed on 313 cell blocks of MPE samples from Chinese patients with advanced lung adenocarcinoma, and fluorescence in situ hybridization (FISH) was used to verify the ALK gene status in Ventana IHC ALK (D5F3)-positive samples. The follow-up clinical data on patients who received crizotinib treatment were recorded., Results: Of the 313 MPE samples, 27 (8.6%) were confirmed as ALK expression-positive, and the Ventana IHC ALK (D5F3)-positive rate was 17.3% (27/156) in wild-type epidermal growth factor receptor ( EGFR ) MPE samples. Twenty-three of the 27 IHC ALK (D5F3)-positive samples were positive by FISH. Of the 11 Ventana IHC ALK (D5F3)-positive patients who received crizotinib therapy, 2 patients had complete response (CR), 5 had partial response (PR) and 3 had stable disease (SD)., Conclusions: The ALK gene expression status detected by the Ventana IHC ALK (D5F3) platform in MPE samples may predict tumor responsiveness to crizotinib in Chinese patients with advanced lung adenocarcinoma.

Objective: The aim of this study was to establish a standardized protocol for detection of ALK protein expression and gene fusion in cytologic specimens., Methods: Lung adenocarcinoma cytologic specimens were collected from seven hospitals in Beijing city. A detection protocol for ALK protein expression and gene fusion was designed according to the results of comparative experiment. Ventana immunohistochemical (IHC) ALK(D5F3) detecting ALK protein expression was performed in 203 prepared formalin-fixed paraffin-embedded (FFPE) cell blocks. ALK gene fusion in 98 EGFR gene wild type cytologic specimens and in 4 bronchoalveolar lavage fluid (BL) samples was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). ALK gene fusion in the Ventana IHC ALK (D5F3) positive samples was further tested by fluorescence in situ hybridization (FISH). Six patients with ALK IHC-positive result were followed up to analyze the responses of crizotinib therapy. Comparative experiments: (1) Comparison of the results of 4% neutral buffered formalin fixed for different time (24 h, 48 h, 72 h) on the Ventana IHC ALK (D5F3) staining was conducted in two cases of IHC ALK positive FFPE cell blocks; (2) Comparing qRT-PCR results for ALK fusion in samples from FFPE cell blocks and cytospin prepared slides in 10 cases of lung adenocarcinoma cytologic specimens., Results: Among the specimens examined using the standardized protocol recommended by this study, 229 cases of cytologic specimens met the diagnostic criteria of lung adenocarcinoma. Among them, 207 cases obtained ALK gene test results (by at least one method), with an ALK test ratio of 90.4% (207/229). FFPE cell blocks were successfully prepared in 203 cases, Ventana IHC ALK (D5F3) were successfully performed in all the 203 FFPE cell blocks (100%), and the ALK protein positive detection rate was 10.3% (21/203). ALK fusion was tested in 98 FFPE cytologic samples of EGFR wild types by qRT-PCR, and 96 out of 98 (97.96%) cytologic samples were successfully performed.18 out of 19 IHC ALK-positive cases were verified to be of ALK fusion status by qRT-PCR. The concordance rate was 94.7% (Kappa=0.967, P<0.001) between Ventana IHC ALK (D5F3) and qRT-PCR, and the sensitivity of the Ventana IHC ALK (D5F3) assay compared with qRT-PCR was 100% and the specificity was 98.7%. FISH assay was used to verify the positive cases detected by Ventana IHC ALK (D5F3) staining. Two cases of low tumor cell content FFPE samples obtained indefinite results by FISH test. The six patients with positive ALK protein expression received crizotinib therapy, and 5 paitents got treated effectively. For two ALK IHC positive cases, which were 4% neutral buffered formalin fixed for 72 h, the result of Ventana IHC ALK (D5F3) staining became weakened obviously and uneven. In 10 cases of samples, total RNA was extracted from FFPE cytologic sections and cytospin prepared slides, and the results of qRT-PCR test and ALK gene fusion showed good concordance., Conclusions: The standardized protocol recommended in this study expands the detection types and quantity of cytologic specimens for ALK protein expression and gene fusion and increased the detection rate. Ventana IHC ALK (D5F3) is a reliable method for detecting ALK protein expression in FFPE cell blocks. The pathologic quality control procedure prior to Ventana IHC ALK (D5F3) is crucial for the accuracy of testing the ALK gene status. When FFPE cell blocks could not be prepared or prepared unsuccessfully from the cytologic specimens, qRT-PCR may be an alternative option for the detection of ALK gene fusion.

Objective: To describe the clinical features and treatment of imported pulmonary histoplasmosis and therefore to improve the recognition and differential diagnosis of this disease., Methods: The clinical data of 3 patients with imported pulmonary histoplasmosis in our hospital were collected and analyzed. Literatures published since 1989 were retrieved with 'pulmonary histoplasmosis' from PubMed, China National Knowledge Infrastructure (CNKI), Wanfang Data and VIP data, of which all the literatures about imported pulmonary histoplasmosis were reviewed. The clinical manifestations, diagnostic methods and treatment were summarized., Results: All the 3 cases of imported pulmonary histoplasmosis were immunocompetent hosts, all were males, age were from 44-67 years, and had a history of exploring the cave or tunnel inhabited by bats in the epidemic areas. All of them developed influenza-like symptoms varying in severity after the onset of the disease. Pulmonary multiple nodules and mediastinal lymphadenopathy were found on chest images. One patient underwent percutaneous lung biopsy and the other two received video-assisted thoracoscopic lung biopsy. All the 3 patients showed consistent histopathological findings, such as granulomatous inflammation with necrosis. Pathogen culture with lung biopsy in the first case was identified as histoplasma. All the 3 cases were treated with itraconazole, and recovered with good prognosis. Thirteen literatures in English were obtained, which reported 60 cases with imported pulmonary histoplasmosis. Forty-two of them were males, 16 were females and 2 undefined. The range of their age was from 17-64 years. No imported pulmonary histoplasmosis was reported so far in Chinese literature. Common features of imported pulmonary histoplasmosis were consistent with our patients, including epidemiology, influenza-like symptoms and bilateral pulmonary nodules, recovery with or without antifungal therapy., Conclusion: The epidemiologic history, influenza-like symptoms and bilateral pulmonary nodules provide valuable diagnostic clues for imported histoplasmosis. Clinical features with pathologic findings and good response to antifungal therapy could make the diagnosis even without pathogen detection if other etiology is unlikely.

Objective: The aim of this study was to establish a standard protocol for detection of EGFR mutations in cytologic specimens., Methods: 287 cytologic samples were collected from the patients who were suspected of having lung cancer at six hospitals in Beijing. A detection protocol for EGFR mutations was designed. Two comparative experiments were carried out for the coincidence in EGFR mutation rates between direct sequencing (Seq) and amplification refractory mutation system (ARMS) methods, and between 40 matched cytologic samples with formaldehyde-fixed paraffin embedded (FFPE) cytologic blocks and cytospin slides., Results: Tumor cells were found in 236 out of 287 cases (82.2%, 236/287) . Among them, there were 31 cases (13.1%, 31/236) of low tumor cell content samples and 205 cases (86.9%, 205/236) of high tumor cell content samples. 180 cases in the high tumor cell content samples (87.8%, 180/205) were diagnosed to be consistent with NSCLC. 25 out of 194 cases were ruled out or indefinite to be diagnosed as NSCLC by immunohistochemistry. By direct sequencing, the mutation rate of EGFR was 27.8% (50/180) in NSCLC samples and 28.2% (50/177) in adenocarcinoma samples (high tumor content samples) . By ARMS, the mutation rate of EGFR was 45.6% (82/180) in NSCLC samples and 46.3% (82/177) in adenocarcinoma samples (high tumor content samples). The EGFR mutation rate in low tumor content samples was 38.7% (12/31) , there was no significant difference in EGFR mutation rates between the groups of low tumor cell content samples and high tumor cell content samples (P = 0.12). The concordance rate of EGFR mutation rates was 100% between scraping tumor cells from slides samples and from FFEP blocks in the 40 matched samples. Forty-eight out of 180 definitive NSCLC patients received Gefitinib therapy. The FPS was 12 months in the gefitinib-treated ARMS⁺ group and 2 months in the ARMS⁻ group (P < 0.001), and the OS was 19 months in the gefitinib-treated ARMS⁺ group and 7 months in the ARMS⁻ group (P = 0.003), but no significant differences were found in the efficacy (PFS and OS) of Gefitinib between Seq⁺ and Seq⁻ groups (P = 0.227, P = 0.510, respectively), and Seq⁺/ARMS⁺ and Seq⁻/ARMS⁺ groups (P = 0.354, P = 0.334, respectively)., Conclusions: The detection protocol for EGFR mutations in cytological specimens introduced in this study is tested to be reliable and feasible. Pathological evaluation and immunohistochemistry are important in the detection procedure of EGFR mutations in cytologic specimens. High sensitivity methods should be selected for detection of EGFR mutations in cytologic samples.

Background: Serum levels of tumor markers are associated with tumor metabolism or apoptosis, changes of which after chemotherapy may reflect tumor response to treatment. The aim of this study was to assess the predictive role of changes in serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21-1) during chemotherapy in patients with advanced non-small cell lung cancer., Methods: Changes in serum levels of CEA and CYFRA 21-1 were investigated retrospectively after one cycle of chemotherapy in 42 patients with advanced NSCLC. Correlations between the changes and radiological objective response were analyzed., Results: After two cycles of chemotherapy, radiological objective response rate was 28.6%. At baseline, gender, age, clinical stage, serum levels of CEA and CYFRA 21-1 were not different between patients with objective response (OR) and no response (NR). After one cycle of chemotherapy, compared to baseline level, declines in serum levels of CEA and CYFRA 21-1 were observed in patients with OR, but have no statistical significance. In contrast, reduction of CEA and CYFRA 21-1 over baseline after one cycle of chemotherapy showed statistically significant difference between OR and NR. When reduction percentages of CEA and CYFRA 21-1 were used to predict objective response of chemotherapy, the area under the ROC curve (AUC) was 0.875 for CEA and 0.919 for CYFRA 21-1. According to the ROC curve, a 22% reduction of CEA yielded a sensitivity of 58.3% and a specificity of 97%, 51% reduction of CYFRA 21-1 with a sensitivity of 83.3% and a specificity of 93.3%. When above reduction percentages were used as cutoffs for prediction of radiological objective response, combination of the CEA and CYFRA 21-1 yielded a sensitivity of 91.7% and a specificity of 86.7%., Conclusions: Reduction percentages of CEA and CYFRA 21-1 during chemotherapy could be used to evaluate chemotherapy efficacy in patients with advanced NSCLC. The cutoffs of reduction percentage need further research.

Background: Improvement of quality of life (QoL) is an important endpoint for assessment of treatment of non-small cell lung cancer (NSCLC). This study is to report the changes of QoL before and during the treatment with epidermal growth factor receptor inhibitor, gefitinib, for patients with advanced NSCLC., Methods: Thirty-one eligible patients with NSCLC, who participated in gefitinib compassionate-use program, were enrolled in the study. One oral gefitinib tablet (250mg) was administered every day without interruption unless disease progression or unacceptable toxicity occurred. The impact of treatment on disease-related symptoms and QoL was evaluated with the Chinese versions of European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ-C30 and QLQ-LC13)., Results: After eight weeks of treatment, the mean scores of four functioning scales (physical, role, emotional and social) and global QoL increased significantly. Mean scores of main general symptoms (fatigue and appetite loss) and disease-related symptoms (dyspnoea, coughing, pain in chest, pain in arm and shoulder and pain in other parts) decreased significantly. Response rate of five functioning and global QoL were all more than 50% after gefitinib treatment. Response rate of main general symptoms and disease-related symptoms varied from 44%-84%. QoL and symptom response correlated with objective tumor response., Conclusions: Gefitinib treatment can improve the QoL and symptoms of advanced NSCLC patients who failed to conventional treatments.

Background: To investigate the antitumor effects and toxicity of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor ZD1839 (Iressa) in patients with advanced non-small cell lung cancer (NSCLC)., Methods: From December 2002 to August 2003, 39 patients with unresectable NSCLC were enrolled for 250 mg once-daily oral treatment with ZD1839. Clinical data was analysed using chi-square test, t test and Kaplan-Meier survival analysis. Quality of Life (QoL) was analyzed using Chinese Version of European Organization for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 and lung cancer related questionnaire QLQ-LC13., Results: Tumor response rate (complete response and partial response) was 28.2% . Disease control rate, which included both tumor responses and stable disease, was 59.0%. Objective tumor response was correlated with gender and pathological type. Time to progress was (6.6±1.6) months (95% CI, 3.4-9.7), and 1 year survival rate was 54.3%. Response rate of global, functional and lung cancer-related symptom scales were 34.8%, 65.2% and 73.9% respectively. The ZD1839 of 250 mg/d was well tolerated by patients. The majority of adverse events were grade I or grade II skin rash and diarrhea, which were manageable and reversible., Conclusions: ZD1839 offers a new treatment option providing meaningful tumor control and symptom relief for many patients with advanced NSCLC.