Phylogenomics of mulberries (Morus, Moraceae) inferred from plastomes and single copy nuclear genes.

Mulberries (genus Morus), belonging to the order Rosales, family Moraceae, are important woody plants due to their economic values in sericulture, as well as for nutritional benefits and medicinal values. However, the taxonomy and phylogeny of Morus, especially for the Asian species, remains challenging due to its wide geographical distribution, morphological plasticity, and interspecific hybridization. To better understand the evolutionary history of Morus, we combined plastomes and a large-scale nuclear gene analyses to investigate their phylogenetic relationships. We assembled the plastomes and screened 211 single-copy nuclear genes from 13 Morus species and related taxa. The plastomes of Morus species were relatively conserved in terms of genome size, gene content, synteny, IR boundary and codon usage. Using nuclear data, our results elucidated identical topologies based on coalescent and concatenation methods. The genus Morus was supported as monophyletic, with M. notabilis as the first diverging lineage and the two North American Morus species, M. microphylla and M. rubra, as sister to the other Asian species. In the Asian Morus species, interspecific relationships were completely resolved. However, cyto-nuclear discordances and gene tree-species tree conflicts were detected in the phylogenies of Morus, with multiple evidences supporting hybridization/introgression as the main cause of discordances between nuclear and plastid phylogenies, while gene tree-species tree conflicts were mainly caused by ILS.

Reconsidering N component of cancer staging for T1-2N0-2M0 small-cell lung cancer: a retrospective study based on multicenter cohort.

BACKGROUND: The current nodal (pN) classification still has limitations in stratifying the prognosis of small cell lung cancer (SCLC) patients with pathological classifications T1-2N0-2M0. Thus. This study aimed to develop and validate a modified nodal classification based on a multicenter cohort. MATERIALS AND METHODS: We collected 1156 SCLC patients with pathological classifications T1-2N0-2M0 from the Surveillance, Epidemiology, and End Results database and a multicenter database in China. The X-tile software was conducted to determine the optimal cutoff points of the number of examined lymph nodes (ELNs) and lymph node ratio (LNR). The Kaplan-Meier method, the Log-rank test, and the Cox regression method were used in this study. We classified patients into three pathological N modification categories, new pN#1 (pN0-#ELNs > 3), new pN#2 (pN0-#ELNs ≤ 3 or pN1-2-#LNR ≤ 0.14), and new pN#3 (N1-2-#LNR > 0.14). The Akaike information criterion (AIC), Bayesian Information Criterion, and Concordance index (C-index) were used to compare the prognostic, predictive ability between the current pN classification and the new pN component. RESULTS: The new pN classification had a satisfactory effect on survival curves (Log-rank P < 0.001). After adjusting for other confounders, the new pN classification could be an independent prognostic indicator. Besides, the new pN component had a much more accurate predictive ability in the prognostic assessment for SCLC patients of pathological classifications T1-2N0-2M0 compared with the current pN classification in the SEER database (AIC: 4705.544 vs. 4731.775; C-index: 0.654 vs. 0.617, P < 0.001). Those results were validated in the MCDB from China. CONCLUSIONS: The multicenter cohort developed and validated a modified nodal classification for SCLC patients with pathological category T1-2N0-2M0 after surgery. Besides, we propose that an adequate lymph node dissection is essential; surgeons should perform and consider the situation of ELNs and LNR when they evaluate postoperative prognoses of SCLC patients.

Preparation of Lamivudinyl palmitate nanoemulsome for liver-targeting delivery.

The water solubility and side effects of lamivudine limit its application for the treatment of viral hepatitis type B and human immunodeficiency virus. In order to increase the solubility of LA and improve the in vivo membrane permeability of the drug, LA was modified with hexadecane acid to prepare the prodrug lamivudine palmitic acid (LAP) and loaded into nanoemulsome (NES). LAP-NES was prepared by the thin film dispersion method. The LAP-NES showed the sustained release performance up to 72h in pH 7.4 PBS. Moreover, the pharmacokinetics of LAP-NES after tail vein injection in rats and the biodistribution characteristics were evaluated. The tmax of LAP-NES was 2.5h. The t1/2, clearance rate and average retention time of LAP-NES obviously prolonged compared with free LAP. The tissue biodistribution behavior of NES in vivo showed the good targeting in the liver and spleen, with the maximum at 4h and then the fluorescence slowly decreased until 72h. LAP-NES could significantly delay the release of LA in vivo, effectively prolong the elimination time and had obvious liver-targeting ability. In summary, LAP-NES shows great potential for liver-targeting delivery to increase the therapeutic effect and decrease the side effects of LA.

Angular dispersion compensation for ultra-broadband pulses by using a cascaded prism and hollow-core fiber configuration.

In this paper, we report that the angular dispersion of the output pulses in a nonlinear process can be efficiently compensated by using a cascaded prism(s) and short hollow-core fiber (HCF) configuration. Here, the prism(s) is used to suppress the angular dispersion and transform it into spatial chirp, while the HCF is used for removing this spatial chirp and the residual angular dispersion, which can also significantly improve the beam quality. The feasibility of this novel method is numerically and experimentally investigated with the ultra-broadband idler pulses centered at 1250 nm wavelength and generated by an LBO crystal based non-collinear optical parametric amplifier. The proof-of-principle experiment shows that the angular dispersion can be effectively removed and ultra-broadband idler pulses with good spectral quality and spatial profile can be obtained. The total transmission efficiency in the experiment is around 67% and the measured M x2 and M y2 can reach 1.12 and 1.04, respectively. To the best of our knowledge, this is the first reported ultra-broadband angular dispersion compensation scheme combining prism(s) and HCF, which can remarkably eliminate the angular dispersion while simultaneously possesses high efficiency, good spectral and beam spatial quality.

Investigation and suppression of pre-pulses on nanosecond time scale in the SULF-1PW laser.

It is of crucial significance to investigate and suppress pre-pulses on nanosecond time scale because the intense pre-plasma generated by them may have enough time to expand and, thus, cause fatal impact on laser-matter interactions. In this research, we analyze the potential origins of pre-pulses on nanosecond time scale in a typical Ti:sapphire chirped pulse amplification laser system. Based on the analysis, the initial status of these generated pre-pulses in the SULF-1PW laser is measured and investigated. Then different measures, including fine control on the time synchronization and the replacement for the Ti:sapphire, are adopted in the SULF-1PW laser to suppress these pre-pulses with respective origins, which can promote the energy ratio between the main pulse and these pre-pulses by 2-3 orders of magnitude. This research not only improves the temporal contrast of the SULF-1PW laser on nanosecond time scale but also provides beneficial guidance for the design and construction of similar laser facilities.

Transcriptome and Metabolite Conjoint Analysis Reveals the Seed Dormancy Release Process in Callery Pear.

Seed dormancy transition is a vital developmental process for seedling propagation and agricultural production. The process is precisely regulated by diverse endogenous genetic factors and environmental cues. Callery pear (Pyrus calleryana Decne) is an important rootstock species that requires cold stratification to break seed dormancy, but the mechanisms underlying pear seed dormancy release are not yet fully understood. Here, we analyzed the transcriptome profiles at three different stages of cold stratification in callery pear seeds using RNA sequencing combined with phytohormone and sugar content measurements. Significant alterations in hormone contents and carbohydrate metabolism were observed and reflected the dormancy status of the seeds. The expressions of genes related to plant hormone metabolism and signaling transduction, including indole-3-acetic acid (IAA) biosynthesis (ASAs, TSA, NITs, YUC, and AAO) genes as well as several abscisic acid (ABA) and gibberellic acid (GA) catabolism and signaling transduction genes (CYP707As, GA2ox, and DELLAs), were consistent with endogenous hormone changes. We further found that several genes involved in cytokinin (CTK), ethylene (ETH), brassionolide (BR), and jasmonic acid (JA) metabolism and signaling transduction were differentially expressed and integrated in pear seed dormancy release. In accordance with changes in starch and soluble sugar contents, the genes associated with starch and sucrose metabolism were significantly up-regulated during seed dormancy release progression. Furthermore, the expression levels of genes involved in lipid metabolism pathways were also up-regulated. Finally, 447 transcription factor (TF) genes (including ERF, bHLH, bZIP, NAC, WRKY, and MYB genes) were observed to be differentially expressed during seed cold stratification and might relate to pear seed dormancy release. Our results suggest that the mechanism underlying pear seed dormancy release is a complex, transcriptionally regulated process involving hormones, sugars, lipids, and TFs.

Arene Ru(II) Complexes Acted as Potential KRAS G-Quadruplex DNA Stabilizer Induced DNA Damage Mediated Apoptosis to Inhibit Breast Cancer Progress.

A series of arene Ru(II) complexes, [(η6-MeC6H5)Ru(L)Cl]Cl, (L=o-ClPIP, 1; m-ClPIP, 2 and p-ClPIP, 3) (o-ClPIP=2-(2-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline; m-ClPIP=2-(3-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline; p-ClPIP=2-(4-chlorophenyl)imidazo[4,5-f][1,10]phenanthroline) was synthesized and investigated as a potential apoptosis inducer in chemotherapy. Spectroscopy and molecular docking simulations show that 1 exhibits moderated binding affinity to KRAS G-quadruplex DNA by groove mode. Further, in vitro studies reveal that 1 displays inhibitory activity against MCF-7 growth with IC50 = 3.7 ± 0.2 µM. Flow cytometric analysis, comet assay, and immunofluorescence confirm that 1 can induce the apoptosis of MCF-7 cells and G0/G1 phase arrest through DNA damage. In summary, the prepared arene Ru(II) complexes can be developed as a promising candidate for targeting G-quadruplex structure to induce the apoptosis of breast cancer cells via binding and stabilizing KRAS G-quadruplex conformation on oncogene promoter.

Arene Ru(II) Complexes with Difluorinated Ligands Act as Potential Inducers of S-Phase Arrest via the Stabilization of c-myc G-Quadruplex DNA.

Here, a series of half-sandwich arene Ru(II) complexes with difluorinated ligands [Ru(η6-arene)(L)Cl] (L1 = 2-(2,3-difluorophenyl)imidazole[4,5f][1,10]-phenanthroline; L2 = 2-(2,4-difluorophenyl)imidazole[4,5f][1,10]-phenanthroline; arene = benzene, toluene, and p-cymene) were synthesized and characterized. Molecular docking analysis showed that these complexes bind to c-myc G-quadruplex DNA through either groove binding or π-π stacking, and the relative difluorinated site in the main ligand plays a role in regulating the binding mode. The binding behavior of these complexes with c-myc G-quadruplex DNA was evaluated using ultraviolet-visible spectroscopy, fluorescence intercalator displacement assay, fluorescence resonance energy transfer melting assay, and polymerase chain reaction. The comprehensive analysis indicated that complex 1 exhibited a better affinity and stability in relation to c-myc G-quadruplex DNA with a DC50 of 6.6 µM and ΔTm values of 13.09 °C, than other molecules. Further activity evaluation results displayed that this class of complexes can also inhibit the growth of various tumor cells, especially complexes 3 and 6, which exhibited a better inhibitory effect against human U87 glioblastoma cells (51.61 and 23.75 µM) than other complexes, even superior to cisplatin (32.59 µM). Owing to a befitting lipophilicity associated with the high intake of drugs by tumor cells, complexes 3 and 6 had favorable lipid-water partition coefficients of -0.6615 and -0.8077, respectively. Moreover, it was found that complex 6 suppressed the proliferation of U87 cells mainly through an induced obvious S phase arrest and slight apoptosis, which may have resulted from the stabilization of c-myc G-quadruplex DNA to block the transcription and expression of c-myc. In brief, these types of arene Ru(II) complexes with difluorinated ligands can be developed as potential inducers of S-phase arrest and apoptosis through the binding and stabilization of c-myc G-quadruplex DNA, and could be used in clinical applications in the future.

Effect of different carriers on in vitro dissolution behavior and physicochemical characterization of glycyrrhetinic acid solid dispersions.

The effect of PEG 4000, PVP K30, poloxamer 407 and urea as carriers glycyrrhetinic acid solid dispersions (GA-SDs) on dissolution behavior and physicochemical properties were investigated. In vitro dissolution test results show that GA-SDs prepared with four different carriers have better dissolution properties compared with pure drug and corresponding physical mixtures. The enhancement effect of four carriers on dissolution rate and equilibrium solubility shows that PVP K30>PEG 4000>P 407>urea. In addition, the dissolution rate and solubility of the GA-SDs with a carrier-drug ratio of 8:1 were better than the samples of 4:1. The DSC and XRD patterns showed that crystallization of GA-SDs prepared by PVP K30 was significantly inhibited and both were transformed to amorphous. Based on FTIR detection, hydrogen-bond between carriers (PVP K30, PEG 4000 and P 407) and GA molecules were formed. SEM results showed that compared to GA-SDs prepared by the other three carriers, GA-PVP K30-SDs have a smoother surface and clearer boundary. In conclusion, the findings of this study demonstrated that the dissolution performance of the GA-SDs prepared by the solvent method is related to carrier type. The samples with PVP K30 as the carrier have the best dissolution performance.

Performance improvement of a nonlinear temporal filter by using cascaded femtosecond optical parametric amplification.

In this paper, we report that the conversion efficiency and spectrum of femtosecond optical parametric amplification (fs-OPA) can be significantly enhanced by employing a compact cascaded femtosecond OPA (CF-OPA) scheme with the self-compensation of the temporal walk-off between two nonlinear gain media. Correspondingly, the gain related temporal contrast can also be improved. The feasibility of the CF-OPA method using three cascaded BBO crystals is numerically and experimentally analyzed. Moreover, by replacing the conventional fs-OPA with the CF-OPA and optimizing the design, the performance of a nonlinear temporal filter combining cross-polarized wave generation and fs-OPA is comprehensively improved. The experimental results demonstrate the superiority of the CF-OPA scheme, which can generate high-performance cleaned pulses at 1 kHz repetition rate with energy of 340µJ, energy fluctuation below 0.9% (RMS), spectral width of 97 nm (FWHM), Fourier-transform-limited pulse width of 12 fs and temporal contrast better than 10-12. To the best of our knowledge, this is the first reported temporal walk-off self-compensated quasi-collinear CF-OPA geometry adopting three cascaded BBO crystals, which can be easily generalized to other wavelengths or nonlinear crystals. The above nonlinear temporal filter with a CF-OPA scheme has the rarest comprehensive parameters, which can provide excellent seed pulses for PW and 10 PW class femtosecond laser systems.

Selective stabilization of multiple promoter G-quadruplex DNA by using 2-phenyl-1H-imidazole-based tanshinone IIA derivatives and their potential suppressing function in the metastatic breast cancer.

The G-quadruplex (G4) DNA, which has been developed as a potential anticancer target in drug screening and design, plays a crucial role in the oncogene transcription and translation. Tanshinone IIA derivatives with a planar heterocycle structure may function as G4 stabilizers. We present an innovative case of imidazole-based tanshinone IIA derivatives (1-8) especially compound 4 that improve the selectivity and the binding affinity with G4 DNA and enhance the target tumor inhibition. Cellular and in vivo experiments indicate that the tanshinone IIA derivative 4 inhibits the growth, metastasis, and angiogenesis of triple-negative breast cancer cells possibly through the stabilization of multiple G4 DNAs (e.g., c-myc, K-ras, and VEGF) to induce DNA damage. Further investigation of the intermolecular interaction and the molecular docking indicates that tanshinone IIA derivatives have better selective binding capability to various G4 DNAs than to double-stranded DNA. These findings provide guidance in modifying the molecular structures of tanshinone IIA derivatives and reveal their potential to function as specific G4 stabilizers.

Novel biomimetic nanostructured lipid carriers for cancer therapy: preparation, characterization, and in vitro/in vivo evaluation.

Nanostructured lipid carriers (NLC) have become a research hotspot, wherein cancer-targeting effects are enhanced and side effects of chemotherapy are overcome. Usually, accelerated blood clearance (ABC) occurs after repeated injections, without changing the immunologic profile, despite PEGylation which prolongs the circulation function. To overcome these problems, we designed a red blood cell-membrane-coated NLC (RBCm-NLC), which was round-like, with a particle size of 60.33 ± 3.04 nm and a core-shell structure. Its stability was good, the drug paclitaxel (PTX) release from RBCm-PTX-NLC was less than 30% at pH7.4 and pH6.5, and the integrity of RBC membrane surface protein was maintained before and after preparation. Additionally, in vitro assays showed that, with the RBCm coating, the cellular uptake of the NLC by cancer cells was significantly enhanced. RBCm-NLC can avoid recognition by macrophage cells and prolong circulation time in vivo. In S180 tumor-bearing mice, the DiR-labeled RBCm-NLC group showed a stronger fluorescence signal and longer retention in tumor tissues, indicating a prompt tumor-targeting effect and extended blood circulation. Importantly, RBCm-PTX-NLC enhanced the antitumor effect and extended the survival period significantly in vivo. In summary, biomimetic NLC offered a novel strategy for drug delivery in cancer therapy.

A novel design of double chirped pulse amplification laser systems for fourth-order dispersion control.

A novel design of double chirped pulse amplification laser systems implementing a combination of negatively and positively chirped pulse amplification is proposed for the first time. Without utilizing any extra dispersion compensation element, this design can sufficiently cancel out the second-, third- and especially fourth-order dispersion simultaneously, just by optimizing the parameters of the stretcher and compressor in first chirped pulse amplification stage which applies negatively chirped pulse amplification. The numerical results indicate that near Fourier-transform-limited pulse duration about 20fs can be achieved in high-peak-power femtosecond laser systems up to multi-Petawatt level. This design not only provides a feasible solution for the dispersion control in high-contrast and high-peak-power femtosecond laser systems, but also can avoid the degradation of temporal contrast induced by seed energy loss in the presence of additional dispersion compensation components.

Effect of glycosylated hemoglobin protein molecule in treating diabetes.

The object of this study was to observe and analyze the effect of glycosylated hemoglobin in treating diabetes and provide valuable guidance for clinical treatment. For this purpose, 160 patients treated in our hospital who were definitely diagnosed with diabetes after relevant examinations were classified into the study group. 160 cases with healthy physical examinations for the same period were enrolled as a reference group. Fasting blood glucose and glycosylated hemoglobin levels were measured in both groups, and inter-group comparisons were made. The detection results showed that the study group had significantly higher fasting blood glucose and glycosylated hemoglobin levels than the healthy reference group. The difference was statistically significant (p<0.05). Diabetic patients in the study group were also observed. The results showed that patients with complications had significantly higher fasting blood glucose and glycosylated hemoglobin levels than those without complications. Statistical significance existed, p<0.05. For diabetic patients, glycosylated hemoglobin detection is of great significance in profoundly affecting diabetes diagnosis and treatment and providing positive guidance, which means great value for evaluating disease control effects.

[Effect of maternal exposure to Curcumae Rhizoma during pregnancy on neurodevelopment and apoptosis mechanism in offspring].

Curcumae Rhizoma is a Chinese medicinal herb that is contraindicated during pregnancy. Cold-congelation and blood-stasis are corresponding syndromes to Curcumae Rhizoma. Whether syndrome-based treatment is associated with developmental neurotoxicity of Curcumae Rhizoma remains to be unclear. To verify the theory of traditional Chinese medicine of "syndrome-based treatment during pregnancy", the present study induced the mice blood stasis model by immersing mice in ice water. Pregnant C57 BL/6 wild type(WT) mice and pregnant Nrf2 knock out(KO) mice were randomly divided into control groups and Rhizoma Curcumae exposure groups. The mice were exposed to Rhizoma Curcumae during day 5 to day 18 after pregnancy. The neurodevelopment was examined to evaluate the differences of developmental neurotoxicity between normal and blood-stasis pregnant mice exposed to Rhizoma Curcumae. caspase-3 and caspase-9 activity in brain of the offspring were measured by colorimetric assays. Bcl-2 mRNA and protein expression in brain of the offspring were examined by Real-time RT-PCR and Western blot, respectively. According to the findings, C57 BL/6 mice exposed to Rhizoma Curcumae(10.0 g·kg~(-1)) had a longer positive occurring time of the surface righting reflex test of offspring and higher caspase-3 and caspase-9 activities in brain of offspring, compared with the normal control group, but with no significant change in those of blood-stasis pregnant mice offspring. However, mice exposed to Rhizoma Curcumae(10.0 g·kg~(-1)) showed no change in Bcl-2 gene expression and p38 MAPK phosphorylation in brain of the offspring. Nrf2 gene knockout using CRISPR/Cas9 resulted in a longer positive occurring time of the surface righting reflex test of offspring and higher caspase-3 and caspase-9 activities in brain of offspring. In conclusion, developmental neurotoxicity of the blood-stasis pregnant mice exposed to Rhizoma Curcumae was weaker than that of the normal pregnant mice. Nrf2 activation involved in the phenomenon of Rhizoma Curcumae of "syndrome-based treatment during pregnancy", but the upstream signal pathway mechanism value shall be further investigated.

Interaction Between Ezrin and Cortactin in Promoting Epithelial to Mesenchymal Transition in Breast Cancer Cells.

BACKGROUND Epithelial to mesenchymal transition (EMT) contributes to metastases in various types of tumors, and is also the key step in the breast cancer metastatic cascade. In our previous study, a mouse model containing human-derived normal breast tissue was established and allowed EMT/MET process of human breast cancer cells to be mimicked in a humanized mammary microenvironment. MATERIAL AND METHODS Two-dimensional electrophoresis (2-DE) and mass spectrometry were used to detect different proteins between parental MDA-MB-231 and its variant sub-line obtained from tumors grown in transplanted normal human breast tissue (MDA-MB-231br). We knocked down the ezrin in 2 cell lines (MDA-MB-231 and SUM1315). The migration and invasion ability was assessed. EMT markers were examined by real-time reverse transcription PCR analysis and Western blot analysis. The relationship of ezrin with cortactin was tested by tissue microarray and co-immunoprecipitation. RESULTS Proteomic analysis revealed 81 differentially expressed proteins between parental MDA-MB-231 and MDA-MB-231br. Among these proteins, the expression of ezrin and cortactin and the phosphorylation of ezrin were significantly correlated, accompanied with a group of classic EMT makers. Knockdown of ezrin reversed the expression of EMT markers and downregulated cortactin and EMT transcription factors. Ezrin silencing inhibited tumor cell migration and invasion. Breast cancer tissue microarray and immunohistochemistry showed a significant positive association between ezrin and cortactin. CONCLUSIONS These findings indicate that ezrin is correlated with cortactin in facilitating EMT in breast cancer. The interaction between ezrin and cortactin is a novel mechanism contributing to the EMT process in cancer metastases.

Is there a prognostic difference among stage I lung adenocarcinoma patients with different BRAF-mutation status?

BACKGROUND: The data of the prognostic role of V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations in early-stage lung adenocarcinoma (LUAD) patients is scarce. This study aimed to investigate the proportion, clinicopathological features, and prognostic significance of patients with stage I LUAD carrying BRAF mutations. METHODS: We collected 431 patients with pathological stage I LUAD from cBioPortal for Cancer Genomics and 1604 LUAD patients tested for BRAF V600E and epidermal growth factor receptor (EGFR) mutations from Shanghai Pulmonary Hospital. Survival curves were drawn by the Kaplan-Meier method and compared by log-rank test. Cox proportional hazard models, propensity-score matching (PSM), and overlap weighting (OW) were performed in this study. The primary endpoint was recurrence-free survival (RFS). RESULTS: The proportion of BRAF mutations was estimated at 5.6% in a Caucasian cohort. BRAF V600E mutations were detected in six (1.4%) patients in Caucasian populations and 16 (1.0%) patients in Chinese populations. Two BRAF V600E-mutant patients were detected to have concurrent EGFR mutations, one for 19-del and one for L858R. For pathological stage I LUAD patients, BRAF mutations were not significantly associated with worse RFS than wild-type BRAF patients (HR = 1.111; p = 0.885). After PSM and OW, similar results were presented (HR = 1.352; p = 0.742 and HR = 1.246; p = 0.764, respectively). BRAF V600E mutation status also lacked predictive significance for RFS (HR, 1.844; p = 0.226; HR = 1.144; p = 0.831 and HR = 1.466; p = 0.450, respectively). CONCLUSIONS: In this study, we demonstrated that BRAF status may not be capable of predicting prognosis in stage I LUAD patients. There is a need for more data to validate our findings.

Clinical-Pathological Characteristics of Adenosquamous Esophageal Carcinoma: A Propensity-Score-Matching Study.

There are few studies on esophageal adenosquamous carcinoma (ADSC). Our study intended to investigate the clinical and survival features of ADSC. We included esophageal cancer (EC) data from the Surveillance, Epidemiology, and End Results program database to explore clinical and survival traits. Propensity score matching (PSM), the multivariate Cox regression model, and survival curves were used in this study. A total of 137 patients with ADSC were included in our analysis. The proportion of ADSC within the EC cohort declined from 2004 to 2018. Besides, results indicated no significant difference in survival between ADSC and SCC groups (PSM-adjusted HR = 1.249, P = 0.127). However, the survival rate of the ADSC group was significantly worse than that of the ADC group (PSM-adjusted HR = 1.497, P = 0.007). For the ADSC group, combined treatment with surgery had a higher survival rate than other treatment methods (all P < 0.001). Surgical resection, radiotherapy, and chemotherapy were independent protective prognostic factors (all P < 0.05). The proportion of ADSC has been declining from 2004 to 2018. The prognosis of ADSC is not significantly different from that of SCC but is worse than that of ADC. Surgery, radiotherapy, and chemotherapy could improve the prognosis of patients. Comprehensive treatment with surgery as the main treatment is more beneficial for some patients.

Prognostic assessment of lung adenocarcinoma patients with early-staging diseases: a nomogram based on coagulation-related factors.

OBJECTIVES: Early-stage lung adenocarcinoma (ADC) has a great heterogeneity in prognosis that is difficult to evaluate effectively. Thus, we developed and validated an effective nomogram prognostic model based on the clinical and laboratory characteristics of stage I-IIA ADC. METHODS: We included 1585 patients with pathologically diagnosed stage I-IIA ADC who underwent surgery at Shanghai Pulmonary Hospital. The nomogram was constructed based on the peripheral blood test and coagulation test indicators and evaluated using Calibration plots, concordance index, decision curve analysis and the X-tile software. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method and the Cox proportional hazard regression model. The primary end point of this study was RFS. RESULTS: Thrombin time and 4 clinical indicators for RFS were integrated into nomograms. A favourable agreement between the nomogram prediction and validation was observed in the calibration curves for RFS probabilities. The concordance index of the nomogram to predict RFS was 0.736 (95% confidence interval, 0.717-0.755). Moreover, significant differences were shown between the high-risk and low-risk groups in RFS and OS (P < 0.001) after effective cut-off values of risk points were found based on the nomogram. CONCLUSIONS: We established and validated a prognostic nomogram including thrombin time to predict RFS and OS of stage I-IIA ADC patients. This nomogram provided an effective prediction ability for the prognosis of stage I-IIA ADC patients.