Heteryunine A, an amidated tryptophan-catechin-spiroketal hybrid with antifibrotic activity from Heterosmilax yunnanensis.

An unprecedented spiro-C-glycoside adduct, heteryunine A (1), along with two uncommon alkaloids featuring a 2,3-diketopiperazine skeleton, heterpyrazines A (2) and B (3), were discovered in the roots of Heterosmilax yunnanensis. The detailed spectroscopic analysis helped to clarify the planar structures of these compounds. Compound 1, containing 7 chiral centers, features a catechin fused with a spiroketal and connects with a tryptophan derivative by a CC bond. Its complex absolute configuration was elucidated by rotating frame overhauser enhancement spectroscopy (ROESY), specific rotation, and the 13C nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculation. The possible biosynthetic routes for 1 were deduced. Compounds 1 and 2 showed significant antifibrotic effects and further research revealed that they inhibited the activation, migration and proliferation of hepatic stellate cells (HSCs) through suppressing the activity of Ras homolog family member A (RhoA).

Fourteen new 2-benzylbenzofuran glycosides with cardioprotective activity from Heterosmilax yunnanensis.

Fourteen new 2-benzylbenzofuran O-glycosides (1-13, 15) and one new key precursor, diarylacetone (14) were isolated from the roots of Heterosmilax yunnanensis Gagnep, which all have characteristic 2,3,4-O-trisubstituted benzyl. Their structures were elucidated by 1D and 2D NMR, HRESIMS, UV and IR. The isolated compounds were assessed for their cardioprotective activities and compounds 1, 3 and 6 could significantly improve cardiomyocytes viability. Moreover, the mechanistic study revealed that these three compounds could significantly decrease intracellular ROS levels and maintain mitochondrial homeostasis upon hypoxia inducement. Consequently, 1, 3 and 6 might serve as potential lead compounds to prevent myocardial ischemia.

Analysis of molecular pathologic and clinical features of 36 patients with pulmonary sarcomatoid carcinoma.

BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is a heterogeneous disease with poor prognosis. It is essential to understand the molecular basis of its progression in order to devise novel therapeutic strategies. The aim of this study was to identify the pathological mutations in PSC through next generation sequencing technology (NGS), and provide reference for the diagnosis and molecular targeted therapy. MATERIALS AND METHODS: Thirty-sex patients with pathologically confirmed PSC who underwent surgical tumor resection at The First Hospital of Jilin University and Jilin Cancer Hospital from June 2011 to June 2017 were enrolled. Thirteen patients were successfully followed up and detailed clinical data were obtained. NGS was performed for the exons of entire oncogenes. Kaplan-Meier method was used for the univariate analysis, and the Cox proportional risk regression model was used for multivariate analysis. RESULTS: A total of 19 highly frequent mutations were identified, of which the KRAS, BRCA1 and ALK mutations were significantly correlated with the overall survival (OS). Multivariate analysis showed that KRAS mutation was an independent factor affecting the OS of PSC patients. CONCLUSION: The KRAS mutation is an independent prognostic factor for PSC, and patients harboring the KRAS mutation had significantly shorter OS compared to patients with wild type KRAS. The characteristic mutation landscape of PSC may guide clinical targeted therapy.

Giant Cardiac Cavernous Hemangioma Diagnosed with Contrast-Enhanced Ultrasound: A Case Report.

Presently, there are few reports in the database about a contrast-enhanced ultrasound-assisted diagnosis of cardiac cavernous hemangioma. We report a case of giant cavernous hemangioma of the heart, which was diagnosed using contrast-enhanced ultrasound. Finally, it was confirmed by surgical pathology. This case demonstrates that contrast-enhanced ultrasound can play an important role in the diagnosis of cardiac cavernous hemangioma.

Chemical precipitation of heavy metals from wastewater by using the synthetical magnesium hydroxy carbonate.

Heavy metal pollution has become one of the most serious environmental problems today. The preparation of magnesium hydroxy carbonate from low-grade magnesite, and the chemical precipitation of heavy metal wastewater with magnesium hydroxy carbonate as precipitating agent were undertaken. The removal efficiencies of heavy metals were improved by increasing the dose of magnesium hydroxy carbonate, and the applicable dose of magnesium hydroxy carbonate was 0.30 g for 50 mL of the wastewater (6,000 mg/L). The precipitation reactions proceeded thoroughly within 20 min. At this time, the removal efficiencies of heavy metals were above 99.9%. The final pH value was 7.1, the residual VO2 +, Cr3+ and Fe3+ concentrations were 0.01, 0.05 and 1.12 mg/L, respectively, which conformed to the limit of discharge set by China (0.5-2.0 mg/L, GB 8978-1996). The precipitate was mainly composed of Fe2O3, V2O5 and Cr2O3, which can be recycled as secondary raw material for metallurgical industry. The treatment of the heavy metal wastewater with magnesium hydroxy carbonate was successful in decreasing the concentrations of VO2 +, Cr3+ and Fe3+ in wastewater.

Prognostic factors of budesonide therapy for the management of Crohn's disease: A meta-analysis.

BACKGROUND: This study aimed to identify factors that affect the prognosis of budesonide therapy for Crohn's disease patients. METHOD: Change in Crohn's disease activity index (CDAI) scores at latest follow-up after budesonide therapy reported by individual studies were pooled to gain overall effect size under random effects model and then metaregression analyses were performed to identify factors affecting the change in CDAI scores after budesonide treatment. RESULTS: Fifteen studies (1875 patients; age, 35.6 years [95% confidence interval (CI): 34.1, 37.0]; 41.66% [95% CI: 37.44, 45.88] males; 33.3% [95% CI: 24.3, 42.3] smokers; weight, 64.7 kg [95% CI: 62.71 66.6] and height, 168 cm [95% CI: 165, 171]) were included. Disease duration was 7.0 years [95% CI: 5.7, 8.2] and duration of the current episode was 3.1 months [95% CI: 1.7, 4.4]. Proportion of patients with prior resection was 42% [95% CI: 34%, 50%]. The disease was 21% in the ileum, 61% in ileocecum, and 18% in the colon. Budesonide dose was 8.83 mg/d [95% CI: 7.52, 10.14]. In a follow-up duration of 21.0 weeks [95% CI: 15.2, 26.8], budesonide treatment was associated with improvement in CDAI score of -117.8 [95% CI: -134.0, -102.0]. The magnitude of the change in CDAI score at the latest follow-up was significantly inversely associated with the percentage of smokers, but positively associated with the baseline CDAI score and duration of the current episode. CONCLUSION: Budesonide therapy to Crohn's disease patients appears to be more effective in patients with the more serious condition. Smoking may also affect the prognosis.

Arginine inhibits the malignant transformation induced by interferon-gamma through the NF-κB-GCN2/eIF2α signaling pathway in mammary epithelial cells in vitro and in vivo.

Breast cancer is the most common female malignant tumors in the world. It seriously affects women's physical and mental health and the leading cause of cancer death among women. Our previous study demonstrated that diet-derived IFN-γ promoted the malignant transformation of primary bovine mammary epithelial cells by accelerating arginine depletion. The current study aimed to explore whether arginine addition could inhibit the degree of malignant transformation and its molecular mechanism. The results indicate that arginine addition could alleviate the malignant transformation of mammary epithelial cells induced by IFN-γ, including reducing cell proliferation, cell migration and colony formation, through the NF-κB-GCN2/eIF2α pathway. The in vivo experiments also consistently confirmed that arginine supplementation could significantly inhibit tumor growth in tumor-bearing mice. Furthermore, the investigation of the clinical data also revealed that the plasma or tissue from human breast cancer patients owned lower arginine level and higher IFN-γ level than that from patients with benign breast disease, showing IFN-γ may be a potential control target. Our findings demonstrate that arginine supplement could antagonize the malignant transformation of mammary epithelial cells induced by IFN-γ (nutritionally induced) both in vitro and in vivo, and IFN-γ was higher in breast cancer women. This might provide a novel strategy for the prevention and treatment of breast cancer regarding to nutrition.

A Rare Case of a Pedicled Mobile Thrombus in Right Atrium.

Pedicled mobile thrombus in the right atrium is an extremely rare condition. Here, we described a case of a 42-year-old male hospitalized with complaints of chest pain and hemoptysis. Computed tomographic angiography of the pulmonary artery showed signs of embolism, and thoracic echocardiography indicated a pedicled mobile cloudy echo in the right atrium, which was initially suspected to be a myxoma. However, it was confirmed to be a thrombus by histopathological examination. Postoperatively, the patient was treated with anticoagulant therapy comprising of low molecular heparin and warfarin, and the patient recovered well. Thoracic echocardiography performed 3 months after surgery ruled out any recurrence of right atrial thrombus.

A case of giant mediastinal cyst initially detected and diagnosed by echocardiography.

Mediastinal cysts are a group of benign mediastinal lesions, and their diagnoses are primarily depended on x-ray and computed tomography. The development of ultrasound instruments and inspection techniques in recent years has led to the ability to use transthoracic echocardiography to clearly display structures surrounding the heart according to the dark fluid space (blood) of the atrium, ventricles, and large vessels as an acoustic window. This technique offers improved detection rates of mediastinal lesions. We report a case of a mediastinal cyst that was first detected and diagnosed on thoracic echocardiography examination and then confirmed by thoracoscopic surgery and pathological analysis.

Enhanced efficacy of nitrifying biomass by modified PVA_SB entrapment technique.

In this study, we developed a novel technique for preparing polyvinyl alcohol (PVA) hydrogel as an immobilizing matrix by the addition of sodium bicarbonate. This resulted in an increase in the specific surface area of PVA_sodium bicarbonate (PVA_SB) hydrogel beads to 65.23 m(2) g(-1) hydrogel beads, which was approximately 85 and 14 % higher than those of normal PVA and PVA_sodium alginate (PVA_SA) hydrogel beads, respectively. The D e value of PVA_SB hydrogel beads was calculated as 7.49 × 10(-4) cm(2) s(-1), which was similar to the D e of PVA_SA hydrogel beads but nearly 38 % higher than that of the normal PVA hydrogel beads. After immobilization with nitrifying biomass, the oxygen uptake rate and the ammonium oxidation rate of nitrifying biomass entrapped in PVA_SB hydrogel beads were determined to be 19.53 mg O2 g MLVSS(-1) h(-1) and 10.59 mg N g MLVSS(-1) h(-1), which were 49 and 43 % higher than those of normal PVA hydrogel beads, respectively. Scanning electron microscopy observation of the PVA_SB hydrogel beads demonstrated relatively higher specific surface area and revealed loose microstructure that was considered to provide large spaces for microbial growth. This kind of structure was also considered beneficial for reducing mass transfer resistance and increasing pollutant uptake.

Game analysis on PPP model operation of abandoned mines ecological restoration under the innovation of central government's reward and punishment system in China.

There is a huge funding gap in the abandoned mines ecological restoration in China. It is of great research value to explore how PPP model can better introduce social capital into the low-profit ecological restoration of abandoned mines. Based on the innovation perspective of the central government's reward and punishment system, this paper constructs an evolutionary game model of "local government-social capital", analyzes the interaction and behavior mechanism of core stakeholders in the operation process of abandoned mines ecological restoration PPP mode, and discusses the influence of evolutionary equilibrium strategy and parameters change on evolutionary strategy under different scenarios by Matlab simulation. The research shows that the abandoned mines ecological restoration needs the support of the central government. When the local government lightly punishes the low-quality service of social capital, the central government needs to pay higher costs to promote all parties to actively participate in the operation and supervision of the PPP project. The revenue and cost of government supervision, the operating subsidy for social capital and the cost saved by social capital in providing bad service are the key factors affecting the evolution of the game between government and social capital. Punishment can effectively spur social capital to keep the contract and operate in the project, but the punishment effect will be ineffective without government supervision. Finally, some suggestions are put forward, such as establishing a long-term supervision mechanism and a reasonable income mechanism for PPP projects, increasing penalties for violations, attracting third parties to reduce supervision costs and strengthening communication between the two parties, so as to make the project take into account the economic performance of social capital and the social welfare of government departments, and achieve dual Pareto improvement.

Diagnostic significance of DOG-1 and PKC-θ expression and c-Kit/PDGFRA mutations in gastrointestinal stromal tumours.

OBJECTIVE: To investigate discovered on gastrointestinal stromal tumor (GIST)-1 (DOG-1) and protein kinase C-θ (PKC-θ) expression in a series of GISTs and determine the sensitivity, specificity, and diagnostic value of these two antigens. METHODS: Immnunohistochemistry (IHC) was used to detect CD117, DOG-1, PKC-θ, CD34, Ki-67, α-smooth muscle actin (SMA), S100, and Desmin expression in 147 GISTs and 51 non-GISTs. c-Kit gene (exons 9, 11, 13, and 17) and platelet-derived growth factor receptor-alpha (PDGFRA) gene (exons 12 and 18) mutations were also detected. RESULTS: About 94.5% GISTs were CD117 positive, 96% were DOG-1 positive, and 90.5% were PKC-θ positive. DOG-1 had a specificity of 100%, while CD117 and PKC-θ had a specificity of 90% and 80%, respectively. There was no significant difference between DOG-1 and PKC-θ expressions when compared to CD117 expression. In 30 out of 42 (71.5%) GISTs, a c-Kit gene mutation was found, and in 3 out of 42 cases (7%), PDGFRA was mutated. Wild-type c-Kit/PDGFRA genes accounted for 21.5% (9/42). Most c-Kit gene mutations were found to be located at exon 11, mainly as in-frame deletions. Mutations in exon 9 were all missense mutations. Most PDGFRA gene mutations were found in exon 18, codon 842. c-Kit gene mutations in exons 13 and 17, and the PDGFRA gene mutation in exon 12 were not detected. CONCLUSIONS: Compared to CD117, DOG-1 is a biomarker with higher sensitivity and specificity. The combination of CD117 and DOG-1 can be used to improve the diagnosis of GIST. Although PKC-θ has a lower specificity than DOG-1, it can be a useful biomarker, especially in CD117(-) and/or DOG-1(-) cases.

Analysis of primary synchronous breast invasive ductal carcinoma and lung adenocarcinoma with next-generation sequencing: A case report.

Multiple primary cancers (MPCs) have an increasing incidence rate due to the detection of early stages of cancer and the development of effective therapeutic strategies. MPCs are less common compared with metachronous cancers. Therefore, distinguishing synchronous primary tumors from metastasis and developing an individualized treatment strategy can be challenging. In the present study, the case of a 70-year-old female who was referred to The First Hospital of Jilin University (Changchun, China) with an enlarged left cervical lymph node and no other clinical manifestations is reported. Radiography revealed distinct lesions in the left breast, left cervical lymph node and bilateral lungs. Subsequently, a biopsy was performed in all three lesions and then each specimen was subjected to immunohistochemistry, fluorescence in situ hybridization, amplification refractory mutation system-PCR and next-generation sequencing (NGS). Disease-related enrichment of lymph node mutant genes and Gene Ontology Biological Process enrichment of breast, as well as lung, mutant genes were performed using the Database for Annotation, Visualization and Integrated Discovery. Based on the molecular assessment, the patient was finally diagnosed with breast invasive ductal carcinoma, primary lung adenocarcinoma and cervical lymph node metastatic lung adenocarcinoma. Since primary synchronous breast and lung cancer (SBLC) is rare, a molecular assessment, particularly using NGS, could provide important information for both the diagnosis and treatment of SBLC.

Significance of FNAC, BRAF mutation, and intraoperative frozen section in surgical decision-making of thyroid nodules.

BACKGROUND: A preoperative method is desired to discriminate benign from malignant thyroid nodules. This retrospective study evaluated the diagnostic performance of BRAF (B-Raf proto-oncogene) mutation (BRAFV600E ) positivity and fine-needle aspiration cytology (FNAC) relative to intraoperative frozen section pathology. METHODS: Patients underwent preoperative FNAC of thyroid nodules. Cytology specimens were classified according to the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), and analyzed for BRAFV600E using an amplification-refractory mutation system (ARMS). Thyroid tissue was surgically removed and frozen sections processed for histology. The sensitivities and specificities of each analysis were compared, alone and in combination. RESULTS: Among 346 patients, 333/358 FNACs (93%) showed malignant nodules; 322 (93%) patients received a pathological diagnosis of papillary thyroid carcinoma (PTC). The sensitivity and specificity of BSRTC VI for malignancy was the highest among the BSRTC categories. Compared with FNAC, the BRAFV600E analysis had significantly higher sensitivity and specificity. The diagnostic efficacy of frozen section pathology was significantly higher than that of either BSRTC category or BRAFV600E analysis alone. Combining methods variably improved diagnostic performance. BRAFV600E was not associated with capsule infiltration, neurovascular infiltration, mono- or multifocal PTC, lymph node metastasis, or clinical stage. CONCLUSION: The diagnostic performance of preoperative BRAFV600E determination was better than that of the BSRTC-FNAC category; combining both improved sensitivity and specificity. Patients with positive malignancy scores from both should be recommended for surgery; those with negative scores require close monitoring. Surgical treatment should include comprehensive intraoperative frozen section assessment. BRAF mutations cannot indicate aggressive treatment.

Start-up of the ananmmox process from the conventional activated sludge in a hybrid bioreactor.

The anaerobic ammonium oxidation (anammox) process was successfully started up from conventional activated sludge using a hybrid bioreactor within 2 months. The average removal efficiencies of ammonia and nitrite were both over 80%, and the maximum total nitrogen removal rate of 1.85 kg N/(m3 x day) was obtained on day 362 with the initial sludge concentration of 0.7 g mixed liquor suspended solids (MLSS)/L. Scanning electron microscope (SEM) observation of the granular sludge in the hybrid reactor clearly showed a high degree of compactness and cell sphericity, and the cell size was quite uniform. Transmission electron microscope photos showed that cells were round or oval, the cellular diameter was 0.6-1.0 microm, and the percentage of the anammoxosome compartment was 51%-85% of the whole cell volume. Fluorescence in situ hybridization analysis (FISH) indicated that anammox bacteria became the dominant population in the community (accounting for more than 51% of total bacteria on day 250). Seven planctomycete 16S rRNA gene sequences were present in the 16S rRNA gene clone library generated from the biomass and affiliated to Candidatus Kuenenia stuttgartiensis and Candidatus Brocadia sp., a new anammox species. In addition, the average effluent suspended solid (MLSS) concentrations of outlets I (above the non-woven carrier) and II (below the non-woven carrier) were 0.0009 and 0.0035 g/L, respectively. This showed that the non-woven carrier could catch the biomass effectively, which increased biomass and improved the nitrogen removal rate in the reactor.

MiR-135b improves proliferation and regulates chemotherapy resistance in ovarian cancer.

MicroRNAs act as regulators in ovarian tumorigenesis and progression by involving different molecular pathways. Here, we examined the role of miR-135b on growth, chemotherapy resistance in OVCAR3 and SKOV3 ovarian cancer cells. MTT assay was performed to examine proliferation. Transwell migration and matrigel invasion assays were used to assess migration and invasion. Caspase-Glo3/7 assay was carried out to evaluate apoptosis. The dual-luciferase reporter assay was performed to validate the putative binding site. Meanwhile, the miR-135b levels in human ovarian cancer tissue were detected by qPCR assay. Overexpression of miR-135b increased growth, and improved migration and invasion in ovarian cancer cells. Meanwhile, overexpression of miR-135b decreased the cisplatin treatment sensitivity in OVCAR3 and SKOV3 cells. The cisplatin-induced apoptosis was decreased by miR-135b. Furthermore, miR-135b could alter epithelial to mesenchymal transition (EMT) associated proteins expression including E-cadherin, N-cadherin, snail and Vimentin in ovarian cancer cells. Further study demonstrated aberrant expression of miR-135b regulated PTEN and p-AKT expression in ovarian cancer cells. The expression level of miR-135b was increased in human ovarian cancer tissue, compared with normal ovary tissue. MiR-135b involves in tumorigenesis and progression in ovarian cancer cells, and might serve as a promising biomarker to predict chemotherapy sensitivity and prognosis in ovarian cancer.

Mechanisms of Compound Kushen Injection for the treatment of bladder cancer based on bioinformatics and network pharmacology with experimental validation.

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.

Effect of MicroRNA-766 Promotes Proliferation, Chemoresistance, Migration, and Invasion of Breast Cancer Cells.

INTRODUCTION: Breast cancer (BCa) remains the most common cancer in women worldwide. It has been shown that microRNAs (miRs) play essential roles in tumorigenesis and progression in many types of cancers, including BCa. We assessed the role of miR-766 on the proliferation, chemosensitivity, migration, and invasion of BCa cells. MATERIALS AND METHODS: The effect of miR-766 on the proliferation of MCF-7 and T47D BCa cells was evaluated using the MTT assay. The function of miR-766 on the migration and invasion of MCF-7 and T47D cells was examined using Transwell migration and Matrigel invasion assays. Protein expression was evaluated by Western blot. The role of miR-766 on 5-fluorouracil-induced apoptosis in MCF-7 and T47D cells was determined using the Caspase-Glo3/7 assay. A subcutaneous tumor xenograft was performed to examine the effect of miR-766 on tumor growth in vivo. RESULTS: Upregulation of miR-766 improved the proliferation, invasion, and migration of BCa cells. Furthermore, miR-766 reduced the sensitivity of MCF-7 and T47D cells to 5-fluorouracil treatment. The tumor xenograft experiment showed that miR-766 promoted BCa growth in vivo. miR-766 decreased 5-flurouracil-induced apoptosis by regulation of BAX and Bcl-2 expression. miR-766 also affected the epithelial-mesenchymal transition by altering E-cadherin, N-cadherin, SNAIL, and vimentin expression in MCF-7 and T47D cells. Further study showed that the expression of phosphatase and tensin homolog and phosphorylated AKT in MCF-7 and T47D cells had changed after aberrant expression of miR-766. CONCLUSION: miR-766 displayed important roles in tumorigenesis and progression in BCa cells and might act as a potential biomarker to predict the chemotherapy response and progression in BCa.

Advanced lung adenocarcinoma with coexistent HER2 mutation and amplification and response to afatinib: a case report.

Human epidermal growth factor receptor 2 (HER2) mutation and amplification are distinct molecular targets in lung cancer, but the specific targeted therapy for their coexistence is undetermined. Personalized targeted therapy is based on mutation type, with different mutations requiring different treatment. A 64-year-old Chinese woman was diagnosed with advanced lung adenocarcinoma. She was determined as having insertion mutations in exon 20 of the HER2 gene (c.2326G > TTGT) by the amplification refractory mutation system (ARMS) and HER2 gene amplification (HER2/CEP17 ratio 2.6) by fluorescence in situ hybridization (FISH). Thereafter, she was treated with afatinib as first-line therapy, to which she responded. After 2 months, the tumor lesion decreased in size. Computed tomography (CT) follow-up showed stable lung lesions, although she later developed multiple brain metastases and subsequently died of brain failure. Lung adenocarcinoma with coexistent HER2 mutation and amplification is relatively uncommon and has no reported cases on targeted therapy. This case was important because it showed effective response to afatinib and provides evidence to help clinicians identify the therapeutic regimen for such patients.