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Cytochrome P450 26A1 (CYP26A1) plays a vital role in early pregnancy in mice. Our previous studies have found that CYP26A1 affects embryo implantation by modulating natural killer (NK) cells, and that there is a novel population of CYP26A1

Uterine M1/M2 macrophages activation states undergo dynamic changes throughout pregnancy, and inappropriate macrophages polarization can cause adverse pregnancy outcomes, especially during the peri-implantation period. Our previous studies have confirmed that Cytochrome P450 26A1 (CYP26A1) can affect embryo implantation by regulating uterine NK cells and DCs. The aim of this study was to investigate whether CYP26A1 regulates the polarization of uterine macrophages in early pregnancy. Here, we observed that Cyp26a1 was significantly upregulated in M1 as compared with M2 of uterine macrophages, Raw264.7 and iBMDM. Knockdown of CYP26A1 in mice uterine significantly decreased the number of embryo implantation sites and the proportion of CD45+F4/80+CD206− M1-like uterine macrophages. Primary uterine macrophages treated with anti-CYP26A1 antibody expressed significantly lower levels of M1 markers Nos2, Il1b, Il6 and Tnf-a. In CYP26A1 knockout Raw264.7 cells, the protein levels of M1 markers TNF-α, IL-6 and CD86 were significantly decreased as compared with the wild type cells. Moreover, CYP26A1 deficiency decreased the ability to produce nitric oxide and increased the phagocytosis capacity of Raw264.7 cells under M1 stimulation state. The re-introduction of CYP26A1 partially reversed the polarization levels of M1 in CYP26A1 knockout Raw264.7 cells. CYP26A1 may regulate the polarization of uterine macrophages to M1 through Stap1 and Slc7a2. In summary, these results indicate that CYP26A1 plays a significant role in macrophage polarization, and knockdown of CYP26A1 can cause insufficient M1 polarization during the peri-implantation period, which has adverse effects on blastocyst implantation.

Adjuvant chemotherapy (AC) has been proven to yield an approximately 5% improvement in 5-year survival for patients with early-stage non-small-cell lung cancer. With such small gains in survival, the optimal treatment regimen remains to be established. Traditional Chinese medicine (TCM) treatment in combination with AC is frequently used in China. The efficacy and safety of this integrated approach should be scientifically evaluated. We present the rationale and study design of the Combined Adjuvant Chemotherapy and Traditional Chinese Medicine (ACTCM) trial (ChiCTR-IPR-16009062). The ACTCM trial, a prospective multicenter double-blind randomized placebo-controlled study, will recruit 312 patients overall from 5 clinical research centers in China. Within 6 weeks of the thoracic surgery, eligible participants with stages IB-IIIA non-small-cell lung cancer will be randomly assigned in a 1:1 ratio to either the treatment or control group. Patients in the treatment group will receive AC combined with TCM herbal treatment for 4 cycles, then TCM herbal plus injection treatment for 4 cycles. Patients in the control group will receive AC combined with TCM placebo for 4 cycles and then TCM placebo for 4 cycles. Treatment will be discontinued if disease progression or unacceptable toxicity occurs. The primary end point is 2-year disease-free survival. Secondary end points include disease-free survival and quality of life. Other end points are TCM symptoms, performance status, and safety of the regimens. Recruitment started in October 2016 and is ongoing.

Cytochrome P450 26A1 (CYP26A1) plays important roles in the mice peri‐implantation period. Inhibiting its expression or function leads to pregnancy failure. However, little is known about the underlying mechanisms involved, especially the relationship between CYP26A1 and immune cells. In this study, using Cyp26a1‐specific antisense morpholigos (Cyp26a1‐MO) knockdown mice model and pCR3.1‐Cyp26a1 vaccine mice model, we found that the number of uterine CD45+CD11c+MHCIIlo‐hiF4/80− dendritic cells (DCs) was significantly decreased in the treated mice. The percentage of mature DCs (CD86hi) was obviously lower and the percentage of immature DCs (CD86lo) was remarkably higher in uterine DCs in the treatment group than that of the control group. Further experiments found that ID2, a transcription factor associated with DCs development, and CD86, a DC mature marker molecule, were both significantly reduced in mice uteri in the treated group. In vitro, ID2 and CD86 also decreased in bone marrow‐derived DCs under Cyp26a1‐MO treatment. These findings provide novel information that CYP26A1 might affect the embryo implantation via modulating the differentiation and maturation of uterine DCs.

Objective: Long non-coding RNAs (lncRNAs) have been shown to play an important regulatory roles in cancer biology, and the lncRNA-UCA1 is upregulated in several cancers such as bladder cancer, breast cancer and colorectal cancer, however, the contributions of UCA1 to non-small cell lung cancer (NSCLC) remain largely unknown. Methods: Expression levels of lncRNA-UCA1 in tumor tissues and plasma from NSCLC patients was evaluated by quantitative real-time PCR, and its association with overall survival of patients was analyzed by statistical analysis. Moreover, the UCA1 expression correlation between tumor tissues and plasma was demonstrated by linear regression analysis. Results: the results showed that the expression of UCA1 in NSCLC tissues was obviously higher than that observed in pair-matched adjacent nontumourous tissues, (P < 0.001). The agarose gel electrophoretogram of RT-PCR products further confirmed that UCA1 was increased in NSCLC tissues. To assess the correlation of UCA1 expression with Clinicopathological data, we found that the expression level of UCA1 was associate with histological grade (P < 0.001) and lymph node metastasis (P < 0.001). Intriguingly, the expression of UCA1 was significantly increased in plasma from NSCLC patients. The UCA1 expression measurements obtained from plasma and tumor tissues were strongly correlated in 60 patient samples (r = 0.881). By receiver operating characteristic curve (ROC) analysis, plasma UCA1 provided the highly diagnostic performance for detection of NSCLC (the area under the ROC curve (AUC), 0.886; P < 0.001). In conclusion, the current results indicated that Plasma UCA1 could serve as a potential biomarker for diagnosis of NSCLC. UCA1 as a biomarker in clinical application might significantly improve the efficacy of human NSCLC screening.

Objective: To evaluate the correlation between genetic polymorphisms in x-ray repair cross complementing group 1 (XRCC1) and sensitivity to platinum-based chemotherapy drugs in patients with non-small cell lung cancer. Methods: Reports published before June 2014 were retrieved from the following databases: China Biology Medicine (CBM), China Academic Journal Full-Text Database (CNKI), China Science and Technology Journal Full-Text Database (VIP), Wanfang Data, PubMed and Excerpta Medica dataBASE (EMBASE). After extracting the data and evaluating the quality, meta-analysis was performed using RevMan5.2 software. Results: A total of 29 studies with 4807 patients were included. Two polymorphisms (Arg399Gln and Arg194Trp) were analyzed. Meta-analysis showed that the efficacy of chemotherapy for patients with the TT genotype [TT vs. CC, OR=1.66, 95% OR=1.66, 95 CI (1.30-2.14)] and the CT genotype [CT vs. CC, OR=1.62, 95% CI (1.35-1.93)] at codon 194 of the XRCC1 gene was significantly higher than that for patients with the CC genotype. The efficacy of chemotherapy for patients with mutant (CT+TT) genotypes was significantly higher than for patients with the wild-type (CC) genotype [TT+CT vs. CC, OR=1.63; 95% CI (1.38-1.92)]. The sensitivity to chemotherapy in patients with the AG genotype at codon 399 of the XRCC1 gene was lower than in patients with the GG genotype [AG vs. GG, OR=0.72, 95% CI (0.55-0.92)] in Chinese population. However, we did not found this association in Caucasus population. Conclusion: Genetic polymorphisms in the XRCC1 gene are correlated with sensitivity to platinum-based chemotherapy in patients with non-small cell lung cancer.

To analyze the efficacy and quality of life and safety for paclitaxel and carboplatin (TC) and TC combined with endostar in the treatment of advanced non-small cell lung cancer (NSCLC).This is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical study. A total of 126 cases of untreated advanced NSCLC were enrolled in this study. There were 63 patients in the TC control arm and TC combined endostar arm, respectively. All enrolled patients were continuously followed-up for disease progression and death.The objective response rate (ORR) of TC combined with endostar arm was 39.3%, and that of TC control arm was 23.0%, P = 0.078. The progression-free survival rates for TC combined with endostar arm and TC control arm were 78.3% and 58.8%, respectively, in 24 weeks (P = 0.017). The hazard ratio for the risk of disease progression was 0.35 (95%CI 0.13 to 0.90, P = 0.030). The median time to progression (TTP) of the TC combined with endostar arm was 7.1 months and TC arm 6.3 months (P0.05). The follow-up results showed that the median survival time (mOS) of the TC + Endostar arm was 17.6 months; (95%CI 13.4 to 21.7 months), and the TC + placebo arm 15.8 months (95%CI 9.4 to 22.9 months) (P0.05). The quality of life scores (LCSS patient scale) after treatment of the TC combined with endostar arm was improved, and that of the TC group was improved after completion of two cycles and three cycles of treatment. The quality of life scores compared with baseline after the completion of one cycle treatment was significantly improved for both the TC combined with endostar arm (P = 0.028 and), and TC arm (P = 0.036). It Indicated that TC combined with endostar treatment improved the patient's quality of life in the early treatment. The difference of adverse and serious adverse event rates between the two groups was not significant (P0.05).Compared with TC alone treatmrnt, TC combined with endostar treatment can reduce the risk of disease progression at early time (24 weeks), increase the ORR, and can be used as first-line treatment for advanced NSCLC. The TC combined with endostar treatment has good safety and tolerability, improves the quality of life, and not increases serious adverse effects and toxicity for patients with advanced NSCLC.

To evaluate the diagnostic yield and the safety of endobronchial ultrasound-guided transbronchial needle biopsy (EBUS-TBNA) in mediastinal and hilar lymph nodes and lung tumors.EBUS-TBNA was performed in 70 patients with thoracic masses or mediastinal-hilar lymphoadenopathy proved by CT scan.From July 2009 to January 2010, 70 patients were included in the study. EBUS-guided TBNA was performed to obtain samples from mediastinal and hilar lymph nodes (120 stations) and lung tumors (11 masses). In 46 cases of newly diagnosed lung cancer, 44 were confirmed by EBUS-TBNA without on site cytology assistance, with 2 false negative cases. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EBUS-TBNA in the diagnosis of lung cancer were 96%, 100%, 100%, 92% and 97% respectively. Non-caseous granuloma formed by epithelioid cells was found in EBUS-TBNA histological specimen from 5 out of 10 patients with clinically diagnosed sarcoidosis. TBNA cytological smear showed acid-fast bacilli and histology of the lymph node demonstrated coagulatory necrosis from 1 out of 4 tuberculous cases. The procedure was uneventful, and there were no complications.EBUS-TBNA is an effective and safe method for the diagnosis of bronchogenic carcinoma and unknown mediastinal-hilar lymphadenopathy.

To evaluate the efficacy, median time to progression (TTP), quality of life and toxicity in the patients with advanced non-small cell lung cancer (NSCLC), treated with thalidomide plus vinorelbine and cisplatin (NP) or NP alone.Sixty six patients with advanced NSCLC were divided randomly into two groups, the trial and control groups. The trial group was treated with vinorelbine 25 approximately 30 mg/m(2) i.v. on D1 and D8, cisplatin 70 approximately 80 mg/m(2) i.v. on D1 (NP regimen), and thalidomide 200 mg orally and daily from D1. The control group received vinorelbine and cisplatin as above described.Of 66 assessable patients, the overall response rate was 51.5% in the trial group and 36.4% in the control group (P = 0.22). The median TTP was 6.0 months for the trial group, and 3.6 months for the control group (P0.001). The score of quality of life in trial group was higher than that in the control group, but no significant difference was observed between the two groups (P0.05). There were no significant differences in toxicities between the two groups (P0.05).NP regimen combined with thalidomide can significantly prolong the median time to tumor progression in patients with advanced NSCLC. Thalidomide may have a synergic activity with NP regimen without increased toxicities.