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The safety of neoadjuvant chemoimmunotherapy before surgery in patients with non-small cell lung cancer (NSCLC) remains unclear in the perioperative stage. We describe a case of a 63-year-old man with IIIC stage NSCLC who received neoadjuvant chemoimmunotherapy and radical lobectomy. After the second cycle of pembrolizumab and chemotherapy (paclitaxel + carboplatin), the patient was diagnosed with immunologic enterocolitis and relieved by glucocorticoid therapy. Radical lobectomy of the right upper lobe was then performed. On postoperative day 4 (POD 4), the patient suddenly suffered suffocated wheezing during sleep. Interstitial lung disease was, therefore, identified by chest computed tomography scan. Glucocorticoids and mechanical ventilation were applied and the symptoms were relieved. On POD 10, the patient developed a bronchial fistula and underwent emergent repair surgery. This is the first case of multi-organs, multi-time point immune-related adverse events (irAE) in perioperative NSCLC patients who received neoadjuvant chemoimmunotherapy. Clinicians should be on high alert for signs of irAEs in neoadjuvant chemoimmunotherapy patients, promptly requiring multidisciplinary management.

Background Acupuncture has always been a treatment method of Chinese traditional medicine, and while becoming more and more popular, it also faces some risks. The case we reported was a patient who was founded a foreign body in the lung many years after acupuncture. Case Presentation A middle-aged woman who came to our hospital with chest pain found a needle-like foreign body in the middle lobe of her right lung on X-ray. This patient underwent acupuncture in the lower back and lower extremities for local pain many years ago. Based on imaging findings and medical history, we suppose that the foreign body in the lung is the result of a ruptured acupuncture needle that is ectopized. Through preoperative 3-dimension reconstruction and indocyanine green localization, we identified the foreign body located in the lateral segment of right middle lobe and successfully removed the foreign body by wedge resection. The patient recovered smoothly after surgery. Conclusion Acupuncturists and surgeons should be alert to the possible risks of acupuncture.

Drought, which directly affects the yield of crops and trees, is a natural stress with a profound impact on the economy. Improving water use efficiency (WUE) and drought tolerance are relatively effective strategies to alleviate drought stress. OPEN STOMATA1 (OST1), at the core of abscisic acid (ABA) signaling, can improve WUE by regulating stomatal closure and photosynthesis. Methyl jasmonate (MeJA) and ABA crosstalk is considered to be involved in the response to drought stress, but the detailed molecular mechanism is insufficiently known. Here, Populus euphratica, which naturally grows in arid and semiarid regions, was selected as the species for studying MeJA and ABA crosstalk under drought. A yeast two-hybrid assay was performed using PeOST1 as bait and a nucleus-localized factor, JASMONATE ZIM-domain protein 2 (PeJAZ2), was found to participate in MeJA signaling by interacting with PeOST1. Overexpression of PeJAZ2 in poplar notably increased water deficit tolerance and WUE in both severe and mild drought stress by regulating ABA signaling rather than ABA synthesis. Furthermore, a PeJAZ2 overexpression line was shown to have greater ABA-induced stomatal closure and hydrogen peroxide (H2O2) production. Collectively, this evidence establishes a mechanism in which PeJAZ2 acts as a positive regulator in response to drought stress via ABA-induced stomatal closure caused by H2O2 production. Our study presents a new insight into the crosstalk of ABA and jasmonic acid signaling in regulating WUE and drought stress, providing a basis of the drought tolerance mechanism of P. euphratica.

The lungs are the most common site of metastasis in patients with gestational trophoblastic neoplasia. We investigated surgical management and prognostic factors of patients with refractory gestational trophoblastic neoplasia to assess the value of lung metastasis resection.The clinical data of patients with refractory gestational trophoblastic neoplasia and lung metastasis treated at Peking Union Medical College Hospital from January 2005 to December 2020 were retrospectively analyzed. Surgical characteristics and survival outcomes were analyzed.In total, 213 patients with refractory gestational trophoblastic neoplasia and lung metastasis were screened, and 148 patients who underwent unilateral lung resection were analyzed. Patients' median age was 32 years. Lobectomy was performed in 65.5% of patients, while wedge resection was performed in 34.5%. The rate of postoperative complications was 12.2%. The pathological rate was 66.2%. Video-assisted thoracoscopic surgery showed better surgical characteristics than thoracotomy did. Compared with lobectomy, wedge resection had a shorter operative time, shorter duration of chest tube placement, shorter postoperative hospital stay, and fewer postoperative complications. The median follow-up period was 36 months. During follow-up, 90.5% of patients achieved complete remission. The 5-year disease-free and overall survival rates were 80.4% and 92.6%, respectively. More previous chemotherapy courses and failure to achieve normal β-human chorionic gonadotropin levels postoperatively were predictors of poor prognosis.Surgical treatment of lung metastasis is valuable and safe for patients with refractory gestational trophoblastic neoplasia. The minimally invasive video-assisted thoracoscopic approach and wedge resection are recommended.

Background The management of ground‐glass opacities (GGOs) depends mainly on personal experience. In clinical practice, benign GGOs are not rare in resected specimens, for which operations may be avoided. We retrospectively compared the clinical features of resected GGOs to identify differential diagnostic characteristics. Methods Among 1456 patients with suspected malignant GGOs who underwent surgical resection, 105 patients (35 with benign GGOs and 70 matched controls with malignant GGOs) were included. Clinical characteristics, including demographics and radiologic, surgical and pathologic characteristics, were collected. Results The smoking index (P = 0.044), frequency of coughing (P = 0.026), GGO size (P = 0.003), size change during follow‐up (P = 0.011), location (P = 0.022), presence of air bronchogram sign (P = 0.004), distance to the pleura (P = 0.021) and positron emission tomography/computed tomography (PET/CT) appearance (P = 0.003) showed significant differences between the benign and malignant groups. Pathologically, the resected benign GGOs included focal fibrosis (17), inflammation or infection (seven), lymphoproliferative disorder (one), hamartoma (three), inflammatory myofibroblastic tumor (two), hemangioma or vascular malformation (two), endometriosis (two) and pulmonary cyst (one). Conclusions A higher smoking index, coughing, larger size, similar or increased size during follow‐up, location in the upper and middle lobes, air bronchogram sign on CT, lesion margin to pleura distance over 1 cm, and malignant tendency on PET/CT reports were associated with malignant GGOs. Relatively active surgical interventions could be considered for GGOs highly suspected of malignancy., A total of 105 patients (35 cases with benign GGOs and 70 matched controls with malignant GGOs) were enrolled to identify characteristics that would help the differential diagnosis. It is shown that a higher smoking index, cough, larger size, similar or increased size during follow‐up, location in the upper and middle lobes, air bronchogram sign on CT, lesion margin to pleura distance over 1 cm, and malignant tendency on PET/CT reports are associated with malignancy. Pathological patterns of benign GGOs are also provided.

Purpose To assess the use of video-assisted thoracoscopic surgery to treat lung metastases from refractory choriocarcinoma. Patients and methods We reviewed patients diagnosed with refractory choriocarcinoma who underwent lung resection by video-assisted thoracoscopic surgery combined with chemotherapy between October 2013 and August 2019 at the Peking Union Medical College Hospital. The surgical records, pathologic findings and survival rates were analyzed. Results The study included 73 patients who underwent 78 thoracoscopic surgeries. Most patients underwent lobectomy (48.7%), and 17 patients (21.8%) underwent resection of more than one lobe. The median operation time and bleeding volume were 95 minutes and 50 mL, respectively. The median duration of chest tube use and hospital stay were 3 days and 4 days, respectively. Postoperative complications were documented in 6 patients (7.7%). The thoracic lymph nodes were harvested in 51 patients (65.4%), but none of these patients had positive nodes. A total of 69.2% of the patients had positive pathologic findings. The mean follow-up time was 30 months. During follow-up, 11 patients experienced disease relapse, and 2 of them died because of brain metastasis. The overall disease-free rate was 83.6%, and the survival rate was 97.0% after excluding those lost to follow-up. Patients with decreased postoperative β-hCG showed a higher disease-free rate during follow up (P Conclusion The minimally invasive video-assisted thoracoscopic approach is a valuable and safe treatment for refractory choriocarcinoma patients with lung metastases. Lymphadenectomy is not suggested for these patients. Patients with decreased postoperative β-hCG levels may achieve a much better prognostic result.

Objective Segmentectomy has been reported as an alternative to lobectomy for small-sized NSCLC without detriment to survival. The long-term benefits of segmentectomy over lobectomy on pulmonary function have not been firmly established. This meta-analysis aims to compare postoperative changes in pulmonary function in NSCLC patients undergoing segmentectomy or lobectomy. Methods Medline, Embase, Web of Science and Scopus were searched through March 2021. Statistical comparisons were made when appropriate. Results Fourteen studies (2412 participants) out of 324 citations were included in this study. All selected studies were high quality, as indicated by the Newcastle–Ottawa scale for assessing the risk of bias. Clinical outcomes were compared between segmentectomy and lobectomy. ΔFEV1 [10 studies, P P P P P P Conclusion Segmentectomy preserves more lung function than lobectomy. There were significantly smaller decreases in FEV1, FVC, FVC%, FEV1/FVC and DLCO in the segmentectomy group than in the lobectomy group.

Background Mediastinal lymphadenectomy is of great importance during esophagectomy for esophageal squamous cell carcinoma. However, recurrent laryngeal nerve (RLN) injury is a severe complication caused by lymphadenectomy along the RLN. Intraoperative nerve monitoring (IONM) can effectively identify the RLN and reduce the incidence of postoperative vocal cord paralysis (VCP). Here, we describe the feasibility and effectiveness of IONM in minimally invasive McKeown esophagectomy. Methods A total of 150 patients who underwent minimally invasive McKeown esophagectomy from 2016 to 2020 were enrolled in this study. We divided the patients into two groups: a neuromonitoring group (IONM, n = 70) and a control group (control, n = 80). Clinical data, surgical variables, and postoperative complications were retrospectively analyzed and compared. Results There was no significant difference in baseline data between the two groups. Postoperative VCP occurred in six cases (8.6%) in the IONM group, which was lower than that in the control group (21.3%, P = 0.032). Postoperative pulmonary complications were found in five cases (7.1%) and 14 in the control group (18.8%, P = 0.037). The postoperative hospital stay in the IONM group was significantly shorter than that in the control group (8 vs. 12, median, P Conclusion IONM is feasible in minimally invasive McKeown esophagectomy. It showed advantages for distinguishing RLN and achieving thorough mediastinal lymphadenectomy with less RLN injury. Abnormal IONM signals can provide an accurate prediction of postoperative VCP incidence.

Background Isolated diaphragmatic metastasis is rarely associated with periosteal osteosarcoma. Case presentation A 24-year-old female patient was found to have periosteal osteosarcoma of the right humerus 11 years ago. Computed tomography showed a mass in her left chest in 2018, and thoracotomy was performed to remove the tumour. The tumour showed the same characteristics as the original periosteal osteosarcoma. Genetic analysis of the tumour sample showed a TP53 point mutation and CCNE1 gene copy number variants. Conclusions We believe this is the first case report of haematogenous metastasis to the diaphragm of periosteal osteosarcoma, and an investigation of the genetic factors may help to unravel the underlying cause of periosteal osteosarcoma.

Lung adenocarcinoma (LUAD) is the most common histological subtype in non-small cell lung cancer, which is the malignant tumor with the highest mortality and morbidity in the world. Herein, ZNF280A, a member of the zinc finger protein family carrying two consecutive Cys2His2 zinc finger domains, was shown by us to act as a tumor driver in LUAD. The immunohistochemical analysis of ZNF280A in LUAD indicated its positive correlation with tumor grade, pathological stage and lymphatic metastasis, and negative relationship with patients’ survival. A loss-of-function study revealed the inhibition of LUAD development by ZNF280A in vitro and in vivo, whereas ZNF280A overexpression induced opposite effects. Statistical analysis of gene expression profiling in LUAD cells with or without ZNF280A knockdown identified EIF3C as a potential downstream of ZNF280A, which possesses similar regulatory effects on phenotypes of LUAD cells with ZNF280A. Moreover, downregulation of EIF3C in ZNF280A-overexpressed cells could attenuate neutralize the ZNF280A-induced promotion of LUAD. In summary, our study demonstrated that ZNF280A may promote the development of LUAD by regulating cell proliferation, apoptosis, cell cycle, and cell migration and probably via interacting EIF3C.

Objective. To investigate the effects of circDENND4C on the malignant biological behavior of lung cancer and its downstream target genes and molecular mechanisms. Methods. The expression of circDENND4C in lung cancer tissues and cells was detected. After transfection with silenced circDENND4C, the expression levels of circDENND4C, miR-141-3p, and BRD4 in lung cancer cells were detected by qRT-PCR. The targeting relationship between circDENND4C and miR-141-3p as well as miR-141-3p and BRD4 was verified. Cell activity was detected by CCK-8 and EdU assay. Transwell assay was used to detect the invasiveness of A549 and NCI-H1299 in each group. Effects of circDENND4C on proliferation and metastasis of lung cancer in nude mice were studied. Results. In vitro and in vivo results showed that circDENND4C silencing reduced the proliferation, invasion, and metastasis of lung cancer cells. Mechanism studies showed that circDENND4C has a targeting relationship with miR-141-3p. However, miR-141-3p has a targeting relationship with BRD4. circDENND4C indirectly upregulated BRD4 through sponge adsorption of miR-141-3p, thereby promoting metastasis and proliferation of NSCLC. Conclusion. circDENND4C, as an oncogene, promotes the proliferation, invasion, and metastasis of lung cancer cells.

Background: Our current study was performed with an attempt to detect the expression of microRNA-22-3p (miR-22-3p) in lung adenocarcinoma, as well as to analyze its role in clinical practice. In addition, its relationship with vascular endothelial growth factor (VEGF) and metastasis related indexes was focused. Material and Method: The trials in which 62 cases of lung adenocarcinoma were received to collect tumor tissue (study group) and normal lung tissue (control group) were eligible for this study. The expression of miR-22-3p in the two groups was detected through RT-PCR. Immunohistochemical method was used to detect the expression of VEGF and leukocyte differentiation antigen 31 (CD31) marked microvessel density (MVD) in lung adenocarcinoma. The expressions of matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-7 (MMP-7) in lung adenocarcinoma were also detected through the use of Western Blot. Results: The present study revealed significant difference in the expression of miR-22-3p between the two groups. No significant difference in the expression of gender, age, neural invasion and the number of lesions were observed between groups. There was significant difference in the expression of miR-22-3p in the maximum diameter of tumor, pleural recidivism, vascular recidivism, lymph node metastasis and different TNM stages. Based on survival analysis, miR-22-3p was linked to survival time. Correlation analysis indicated that there was negative correlation between miR-22-3p and VEGF, miR-22-3p and MVD, miR-22-3p and MMP-3, and miR-22-3p and MMP-7 in lung adenocarcinoma. Conclusion: Our findings provide evidence that miR-22-3p is low expressed in lung adenocarcinoma tissues and the low expression of miR-22-3p is closely associated with clinicopathological characteristics and the prognosis. MiR-22-3p may be involved in the tumor progression of lung adenocarcinoma and may serve as a biomarker for the diagnosis and prognosis of lung adenocarcinoma.

Natural chalcocite (NCC) was chosen as a co-catalyst for activation of persulfate (PS) to degrade organic contaminants in this study. A synergistic effect between NCC and ferrous ions (Fe

CircABCB10 function as an endogenous miRNA sponge plays an important role in various tumors. This experimental design was based on circABCB10 to explore the pathogenesis of non-small cell lung cancer (NSCLC).NSCLC: non-small cell lung cancer; circ RNA: circular RNA; miRNA: micro RNA.

Background: Lung cancer is the most commonly diagnosed malignant tumor worldwide. Lung adenocarcinoma (LUAD) is the most common histological subtype in non-small cell lung cancer (NSCLC). The relationship between ZNF280A and LUAD has not been demonstrated and remains unclear. Methods: In this study, it was demonstrated that ZNF280A was upregulated in LUAD tissues compared with the normal tissues. Further investigations indicated that the overexpression/knockdown of ZNF280A could promote/inhibit proliferation, colony formation and migration of LUAD cells, while inhibiting/promoting cell apoptosis. Moreover, knockdown of ZNF280A could also suppress tumorigenicity of LUAD cells in vivo. RNA-sequencing followed by Ingenuity pathway analysis (IPA) was performed for exploring downstream of ZNF280A and identified EIF3C as the potential target. Results: Furthermore, our study revealed that knockdown of EIF3C could inhibit development of LUAD in vitro, and alleviate the ZNF280A overexpression induced promotion of LUAD. Conclusions: In conclusion, our study showed, as the first time, ZNF280A as a tumor promotor for LUAD, whose function was carried out probably through the regulation of EIF3C.

Additional file 1. Additional data and figures.

In this study, natural molybdenite (MDN) was employed to activate peroxymonosulfate (PMS) to remove organic contaminant orange G (OG). Degradation rate reached up to 100% and 44.4% TOC decayed in the MDN/PMS system within 60 min. The degradation rate increased with the increase of temperature, catalyst and PMS dosages, but initial pH affected little to the system. Moreover, the sensitivity test of coexisting anion and other organic contaminants to the MDN/PMS system was studied to investigated its application in natural water matrix. Through the analysis of electron paramagnetic resonance and quenching experiments, reactive oxygen species including sulfate radicals ( SO 4 ⋅ − ), hydroxyl radical ( ⋅ OH), superoxide radical (O2 ⋅ − ) and singlet oxygen (1O2) had been proven to account for OG degradation in the MDN/PMS process. Surface-bonded Mo(IV) activated PMS producing radicals and it could be regenerated by the reaction with vicinity sulfur element in MDN. This work not only provided a reference for PMS activation by natural sulfide mineral but also elucidated the activation mechanism.

Natural chalcocite (NCC) was chosen as a co-catalyst for activation of persulfate (PS) to degrade organic contaminants in this study. A synergistic effect between NCC and ferrous ions (Fe2+) was found in catalyzing PS for degradation of orange G (OG). The main role of NCC in the NCC/Fe2+/PS system was to facilitate Fe3+ reduction back to Fe2+ and thus improve the stoichiometric efficiency of PS. The results of scavenging experiments and electron paramagnetic resonance tests proved that both sulfate and hydroxyl radicals were the primary reactive oxidants in the NCC/Fe2+/PS system. Twelve potential intermediate products of OG were identified, and the degradation pathway was proposed. Experiment parameters, such as NCC dose, Fe2+ concentration, initial pH, and the presence of anions (H2PO4‒ and Cl‒), all had important impacts on OG degradation. NCC had good reusability in synergistic activation of PS with Fe2+ for OG degradation for five cycles. This study demonstrated a natural sulfide mineral as an efficient co-catalyst towards PS activation for destruction of organic contaminants in water.

This study examined the effects of RNAi-mediated TUSC3 silencing on radiation-induced autophagy and radiation sensitivity of human lung adenocarcinoma cell line A549 under hypoxic condition. Different CoCl2 concentrations were used to treat A549 cells and establish a CoCl2-induced hypoxic model of A549 cells. MTT and clone formation assays were used to determine the effects of different concentrations of CoCl2 on the growth and proliferation of A549 cells treated by different doses of X-ray irradiation. The siRNA-expressing vector was transfected by liposomes and for silencing of TUSC3. Flow cytometry was used to measure cell cycle changes and apoptosis rate. Real-time quantitative polymerase chain reaction (qRT-PCR) assay was performed to detect the expression of TUSC3 mRNA. Western blotting was applied to detect the changes of TUSC3, LC3, and p62 proteins under different CoCl2 concentrations and after siRNA silencing of TUSC3. The TUSC3 levels in A549 cells increased under hypoxic conditions in a dose-dependent manner (P

Lung cancer is the leading cause of cancer-related mortality and non-small cell lung carcinoma (NSCLC) is the most common type. MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. Aberrant expression of miRNAs has been demonstrated to be a prominent feature in NSCLC. The aim of this study was to determine the potential clinical value of serum miR-342-3p in NSCLC. We first evaluated the miR-342-3p levels in NSCLC cell lines, culture media of NSCLC cell lines, and serum samples from NSCLC patients as well as in their respective controls. The associations between serum miR-342-3p levels and clinicopathological parameters as well as clinical outcome were then determined. miR-342-3p expression was significantly downregulated in NSCLC cell lines, culture media of NSCLC cell lines, and the serum samples from NSCLC patients compared to their controls. Serum miR-342-3p discriminated NSCLC patients from healthy individuals. Low expression of serum miR-342-3p was significantly associated with advanced TNM stage and positive lymph node metastasis. In addition, NSCLC patients in the low serum miR-342-3p expression group had remarkably shorter overall survival than those in the high serum miR-342-3p expression group. Serum miR-342-3p was shown to be an independent prognosis factor. In conclusion, serum miR-342-3p might be a promising biomarker for NSCLC that can be used to improve diagnosis and prognosis.

Background Altered miR-148/152 family expression contributes to human carcinogenesis. This study was designed to detect the potential for using miR-148/152 family as biomarkers for NSCLC patients. Material/Methods The relative expression levels of miR-148/152 family (miR-148a, miR-148b, and miR-152) in serum of 36 non-small-cell lung carcinoma (NSCLC) patients, 20 patients with benign pulmonary diseases (BPD), and 10 healthy individuals were assessed by real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results The expression of all three miRNAs were significantly lower in the serum of NSCLC than that of BPD and healthy controls (all p

Aberrantly microRNAs (miRs) expression is reported to be involved in tumorigenesis and development in non-small cell lung cancer (NSCLC). MiR-340 had been identified to be downregulated in NSCLC in the previous study. However, the underlying mechanisms of miR-340 involved in NSCLC progression still needed to be well known. In the present study, we confirmed that miR-340 expression was notably down-regulated in NSCLC tissues compared to matched adjacent noncancerous lung tissues by quantitative real time PCR (qRT-PCR) analyses. Lower miR-340 expression positively related to lymph node metastasis, larger tumor size, advanced TNM stage and poor prognosis of NSCLC patients. In vitro assays, we demonstrated that upregulation of miR-340 expression suppressed cell proliferation ability. Bioinformatics analysis and luciferase reporter assays revealed that miR-340 directly targeted the 3'-untranslated (3'UTR) region of CDK4 mRNA. Over-expression of miR-340 suppressed cell proliferation by regulating CDK4 expression in NSCLC cells. Additionally, we showed that increased miR-340 expression promoted the expression of cell proliferation related protein CDK6 expression, but decreasing the P15 and P21 expression. In vivo, we verified that miR-340 overexpression also inhibited tumor growth by regulating CDK4 expression. Therefore, these findings revealed miR-340 functions as a tumor suppressor in NSCLC cells and may provide a potential target of NSCLC treatment.

Non–small cell lung cancer is one of the most common types of cancer, and the prognosis of non–small cell lung cancer is still poor. Recent evidence has proved that long noncoding RNA is involved in tumorigenesis. For non–small cell lung cancer, the expression profile of long noncoding RNA has been studied. Here, we identified a novel long noncoding RNA TRPM2-AS from published dataset and found TRPM2-AS is widely upregulated in non–small cell lung cancer tissues compared with adjacent non-tumor tissues. Higher expression level of TRPM2-AS was correlated with higher TNM stages and larger tumor size. Patients with high TRPM2-AS expression level had poor survival than those with low TRPM2-AS level. We silenced TRPM2-AS by small interfering RNA and found that cell proliferation was significantly inhibited after knockdown of TRPM2-AS. Annexin V/propidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay confirmed that cell apoptosis increased after TRPM2-AS knockdown. Further experiments showed that silence of TRPM2-AS upregulated SHC1 and silence of SHC1 partially reversed cell apoptosis after TRPM2-AS knockdown. In summary, the novel long noncoding RNA TRPM2-AS upregulated in non–small cell lung cancer, and downregulation of TRPM2-AS promotes apoptosis in vitro.

Epidermal growth factor receptor-targeted tyrosine kinase inhibitors (EGFR-TKIs) have become first-line drugs used for non-small cell lung cancer (NSCLC) treatment. However, drug resistance to EGFR-TKIs will be developed inevitably due to the repeated use of these drugs. In the present study, we isolated cancer stem cells (CSCs) from the PC9 NSCLC cell line. We then observed that the PC9 CSCs showed significant resistance to erlotinib compared with the PC9 non-CSCs. Erlotinib failed to suppress the phosphorylation of PI3K and AKT in PC9 CSCs, although the EGFR was inhibited sufficiently. Mechanically, we observed aberrant upregulation of microRNA-23a (miR-23a) and downregulation of PTEN in PC9 CSCs compared to PC9 non-CSCs. Luciferase reporter assays proved that PTEN was the target of miR-23a in PC9 CSCs. Furthermore, knockdown of miR-23a enhanced the antitumor effect of erlotinib by increasing the expression of PTEN. In addition, transfection with miR-23a inhibitors promoted the erlotinib-dependent inhibition of PI3K/AKT pathway, thus, suppressing the proliferation and inducing apoptosis in PC9 CSCs. These results propose that upregulation of miR-23a is a potential mechanism associated with resistance to EGFR-TKIs in lung cancer stem cells. Inhibition of miR-23a serves as a novel therapeutic strategy to eliminate the EGFR-TKIs resistance of lung cancer stem cells.

The objectives of this study were to determine species distribution and in vitro antifungal susceptibility of Candida isolates identified in the multicentre China-SCAN study of invasive Candida infection (ICI) in intensive care units (ICUs) across China.Candida isolates from patients in the China-SCAN study with documented ICI were evaluated by a central laboratory. Species were identified using chromogenic culture media or the API 20C AUX kit. Susceptibility to fluconazole, voriconazole, itraconazole, caspofungin and amphotericin B was determined using the CLSI broth microdilution method (M27-A3) and updated clinical breakpoints or epidemiological cut-off values.A total of 389 isolates from 244 patients were analysed. Species identified most frequently were Candida albicans (40.1%), Candida parapsilosis (21.3%), Candida tropicalis (17.2%) and Candida glabrata (12.9%). Rarer species such as Lodderomyces elongisporus and Candida ernobii were also identified. Fluconazole susceptibility was evident in 85.9% (134/156) of C. albicans, 62.7% (42/67) of C. tropicalis and 48.2% (40/83) of C. parapsilosis isolates. Susceptibility to voriconazole was ≥ 90% among all species. All isolates were susceptible to amphotericin B and caspofungin except C. glabrata [86.0% (43/50) susceptible to caspofungin]. Cross-resistance between fluconazole and voriconazole was observed for C. parapsilosis and C. glabrata.Although C. albicans was the predominant single species, non-albicans species constituted50% of isolates. Fluconazole susceptibility was lower in most non-albicans species, indicating that fluconazole resistance should be closely monitored. Susceptibility to voriconazole, amphotericin B and caspofungin is encouraging. Differences between these data and those from other regions emphasize the importance of assessing regional variations.

Objectives To describe the epidemiology, microbiology and management of invasive Candida infection (ICI) in intensive care units (ICUs) in China. Methods A multicentre, prospective, observational study in 67 hospital ICUs across China. Patients were ≥18 years old with clinical signs of infection and at least one of the following diagnostic criteria: (i) histopathological, cytopathological or microscopic confirmation of yeast cells from a normally sterile site; (ii) at least one peripheral blood culture positive for Candida; and (iii) positive Candida culture from a normally sterile site. The China-SCAN study is registered with ClinicalTrials.gov (NCT T01253954). Results ICI incidence was 0.32% (306 patients/96,060 ICU admissions) and median time between ICU admission and diagnosis was 10.0 days. Candida albicans was the most prevalent single isolate (41.8% of patients), although non-albicans species accounted for the majority of infections. Diagnostic confirmation was based solely on at least one positive blood culture in 290 (94.8%) cases. Treatment was initiated after diagnostic confirmation in 166/268 (61.9%) patients. Triazoles (62.7%) and echinocandins (34.2%) were the most commonly used antifungal agents; first-line therapy was typically fluconazole (37.7%). The median duration of antifungal therapy was 14 days. The mortality rate was 36.6% (112/306); the median time between diagnosis and death was 14.5 days. Mortality was higher in older individuals, those with solid tumours, those with recent invasive mechanical ventilation and those with a higher sequential organ failure assessment score at diagnostic confirmation. Susceptibility to first-line antifungals was associated with lower mortality than dose-dependent susceptibility or complete resistance (P=0.008). Conclusions More infections were caused by non-albicans than Candida albicans strains. The majority of patients were treated only after diagnostic confirmation, rather than empirically. First-line antifungal susceptibility was associated with lower mortality.

Ye-ye Chen,1 Shan-qing Li,1,2 Hong-sheng Liu,1,2 Ying-zhi Qin,1 Li Li,1 Cheng Huang,1 Ya-lan Bi,3 Yun-xiao Meng,3 Jia He,1 Xiao-yun Zhou,1 Dong-jie Ma11Department of Thoracic Surgery, 2Key Laboratory of Endocrinology,3Department of Pathology,Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, People’s Republic of ChinaBackground and purpose: Thymic neuroendocrine carcinomas (TNECs) are extremely uncommon. Certain cases of TNECs can produce the adrenocorticotropic hormone (ACTH) and cause ectopic ACTH syndrome (EAS). The current literature on this topic consists mainly of case reports, and therapeutic guidelines are lacking. The aim of this study was to discuss the diagnosis, surgical management, and prognosis of EAS caused by TNECs to improve clinical experience with this rare disease.Methods: From June 1984 to June 2014, at the Peking Union Medical College Hospital, the surgical interventions and follow-up outcomes of 16 consecutive patients (eight men and eight women) with EAS caused by TNECs were retrospectively analyzed.Results: The median age was 32.5years (range: 13–47years), and the median disease duration was 8.5months (range: 1–150months). All patients presented with clinical and biochemical evidence indicating a diagnosis of Cushing’s syndrome. Contrast-enhanced thoracic computed tomography scans were critical to locating the ACTH-producing tumor and evaluating the feasibility of resection. All patients underwent surgery. One patient died of septicemia in the intensive care unit 2weeks after surgery. No other morbidity or mortality occurred during the perioperative period. The median overall survival (OS) was 41months (95% CI: 30.3–51.7months), and the progression-free survival was 28months (95% CI:21.6–34.3months). Both overall survival (P=0.002) and progression-free survival (P=0.030) improved significantly after complete resection.Conclusion: TNEC is an extremely aggressive disease that should be considered when treating patients with Cushing’s syndrome due to ectopic ACTH secretion. In particular, all suspected patients should undergo contrast-enhanced thoracic computed tomography scans to facilitate early diagnosis. The current first-line treatment is surgical resection, and complete resection is a favorable prognostic factor. However, additional patients and a longer follow-up will be needed to determine the variables that are predictive of survival and to improve patient prognosis.Keywords: ACTH syndrome, ectopic, neuroendocrine tumors, thymus gland, surgical procedures