Effects of Supercritical CO2 Treatment on Color, Lipid Oxidation, Heme Iron, Non-Heme Iron and Metmyoglobin Contents in Ground Pork.

The color, lipid oxidation, heme iron (HI) and non-heme iron (NHI) contents, metmyoglobin content and Soret band of myoglobin of ground pork subjected to supercritical CO2 treatment under different conditions, or to heat treatment (40°C, 2 h) and subsequent storage at 4°C were evaluated during 9-day period. Supercritical CO2 treatment significantly increased CIE L* and CIE b* values of ground pork during subsequent storage, while the HI content was slightly affected. In general, CIE a* value and metmyoglobin content were decreased. Supercritical CO2 treatment for 2 h could increase the thiobarbituric acid-reactive substances (TBARS) value, while treatment for 1 h or less had no effect. The NHI content could be increased only after treatment at above 40°C or 17.2 MPa for 2 h. The Soret band of myoglobin was shifted to longer wavelength. Increasing treatment temperature from 35°C to 45°C could increase CIE L*, CIE a*, CIE b* and TBARS values, HI and NHI contents of the ground pork, while decreasing metmyoglobin content. As the treatment pressure increased from 13.8 MPa to 20.7 MPa, CIE b* and TBARS values were decreased, while the NHI and metmyoglobin contents were increased. However, the other parameters were unchanged. Extending exposure time from 0.5 h to 2 h could increase CIE L*, CIE b* and TBARS values, HI contents, while decreasing CIE a* value and metmyoglobin content. Correlation analysis showed that the TBARS value was significantly and negatively correlated with the HI content or metmyoglobin content in samples treated at 40°C or above for 2 h.

Prognostic value of pretreatment procalcitonin and neutrophil-lymphocyte ratio in extensive-stage small-cell lung cancer.

BACKGROUND: To investigate the influence of pretreatment neutrophil-to-lymphocyte ratio (NLR) and procalcitonin (PCT) on progression-free survival (PFS) in extensive-stage small-cell lung cancer (SCLC) patients. METHOD: A total of 100 extensive-stage SCLC patients were enrolled in our study. Patients were stratified according to the median values of pretreatment NLR and PCT levels: low NLR group (NLR ≤3.17), high NLR group (NLR＞3.17), low PCT group (PCT ≤0.06; ng/ml), high PCT group (PCT＞0.06; ng/ml). The Kaplan-Meier method and multivariable Cox regression model were used to reveal the prognostic effects of pretreatment NLR and PCT on PFS. RESULTS: The median PFS of the total extensive-stage SCLC patients was 6.0 months. The median PFS of low pretreatment NLR group (NLR ≤3.17) was not significantly different from that of high pretreatment NLR group (6.2 months vs 5.8 months; p = .675). Patients with low pretreatment PCT (PCT ≤0.06; ng/ml) had significantly better PFS than patients with high pretreatment PCT (PCT＞0.06; ng/ml) (6.9 months vs 5.7 months; p = .043). With the multivariable Cox regression analysis, the response to first-line chemotherapy (p ≤ .001) and pretreatment PCT (HR = 0.516; 95%CI 0.326-0.817; p = .005) were identified as independent factors associated with PFS. CONCLUSION: Pretreatment PCT is an independent factor associated with PFS in extensive-stage SCLC patients treated with first-line chemotherapy, but pretreatment NLR reflects no significant prognostic value in our study.

Self-Healing Micro Arc Oxidation and Dicalcium Phosphate Dihydrate Double-Passivated Coating on Magnesium Membrane for Enhanced Bone Integration Repair.

Magnesium is a revolutionary biomaterial for orthopedic implants, owing to its eminent mechanical properties and biocompatibility. However, its uncontrolled degradation rate remains a severe challenge for its potential applications. In this study, we developed a self-healing micro arc oxidation (MAO) and dicalcium phosphate dihydrate (DCPD) double-passivated coating on a magnesium membrane (Mg-MAO/DCPD) and investigated its potential for bone-defect healing. The Mg-MAO/DCPD membrane possessed a feasible self-repairing ability and good cytocompatibility. In vitro degradation experiments showed that the Mg contents on the coating surface were 0.3, 3.8, 4.1, 6.1, and 7.9% when the degradation times were 0, 1, 2, 3, and 4 weeks, respectively, exhibiting available corrosion resistance. The slow and sustained release of Mg2+ during the degradation process activated extracellular matrix proteins for bone regeneration, accelerating osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). The extract solutions of Mg-MAO/DCPD considerably promoted the activation of the Wnt and PI3K/AKT signaling pathways. Furthermore, the evaluation of the rat skull defect model manifested the outstanding bone-healing efficiency of the Mg-MAO/DCPD membrane. Taken together, the Mg-MAO/DCPD membrane demonstrates an optimized degradation rate and excellent bioactivity and is believed to have great application prospects in bone tissue engineering.

Copper and cuproptosis-related genes in hepatocellular carcinoma: therapeutic biomarkers targeting tumor immune microenvironment and immune checkpoints.

Background: Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, exhibits high immune heterogeneity and mortality. Emerging studies suggest that copper (Cu) plays a key role in cell survival. However, the relationship between Cu and tumor development remains unclear. Methods: We investigated the effects of Cu and cuproptosis-related genes (CRGs) in patients with HCC in the TCGA-LIHC (The Cancer Genome Atlas-Liver cancer, n = 347) and ICGC-LIRI-JP (International Cancer Genome Consortium-Liver Cancer-Riken-Japan, n = 203) datasets. Prognostic genes were identified by survival analysis, and a least absolute shrinkage and selection operator (Lasso) regression model was constructed using the prognostic genes in the two datasets. Additionally, we analyzed differentially expressed genes and signal pathway enrichment. We also evaluated the effects of CRGs on tumor immune cell infiltration and their co-expression with immune checkpoint genes (ICGs) and performed validation in different tumor immune microenvironments (TIMs). Finally, we performed validation using clinical samples and predicted the prognosis of patients with HCC using a nomogram. Results: A total of 59 CRGs were included for analysis, and 15 genes that significantly influenced the survival of patients in the two datasets were identified. Patients were grouped by risk scores, and pathway enrichment analysis suggested that immune-related pathways were substantially enriched in both datasets. Tumor immune cell infiltration analysis and clinical validation revealed that PRNP (Prion protein), SNCA (Synuclein alpha), and COX17 (Cytochrome c oxidase copper chaperone COX17) may be closely correlated with immune cell infiltration and ICG expression. A nomogram was constructed to predict the prognosis of patients with HCC using patients' characteristics and risk scores. Conclusion: CRGs may regulate the development of HCC by targeting the TIM and ICGs. CRGs such as PRNP, SNCA, and COX17 could be promising targets for HCC immune therapy in the future.

Erasable Domain Wall Current-Dominated Resistive Switching in BiFeO3 Devices with an Oxide-Metal Interface.

Electric transport in the charged domain wall (CDW) region has emerged as a promising phenomenon for the development of next-generation ferro-resistive memory with ultrahigh data storage density. However, accurately measuring the conductivity of CDWs induced by polarization reversal remains challenging due to the polarization modulation of the Schottky barrier at the thin film-electrode interface, which could partially contribute to the collected "on" current of the device. Here, we propose carefully selecting an electrode that can suppress the effect of interfacial barrier modulation induced by polarization reversal, allowing the collected current mainly from the conductive CDWs. The experiment was conducted on epitaxial BiFeO3(001) thin-film devices with vertical and horizontal geometries. Piezo-response force microscopy scanning showed the local polarization experienced 180° rotation to form CDWs under the vertical electric field. However, devices with SrRuO3 epitaxial top electrodes still exhibit an interfacial barrier-dominated diode behavior, with the "on" current proportional to the electrode area. To identify the CDW current, more interfacial defects were introduced by the deposition of Pt top electrodes, which significantly enhanced charge injection for the compensation of the reversed polarization driven by the electric field, leading to the suppressed polarization modulation of the Schottky barrier height. It was observed that the current flow through Pt electrodes is significantly lower compared to that of SRO electrodes and appears to be primarily influenced by the electrode perimeter instead of the electrode area, indicating CDW-dominated conduction behavior in these devices. Planar nanodevices were further fabricated to support the quantitative investigation of the Pt electrode size-dependent "on" current with a linear fit of the current magnitude versus the CDW cross-sectional area. This work constitutes an essential part of understanding the role of the CDW current in ferro-resistive memory devices.

Defect-Induced, Ferroelectric-Like Switching and Adjustable Dielectric Tunability in Antiferroelectrics.

Antiferroelectrics, which undergo a field-induced phase transition to ferroelectric order that manifests as double-hysteresis polarization switching, exhibit great potential for dielectric, electromechanical, and electrothermal applications. Compared to their ferroelectric cousins, however, considerably fewer efforts have been made to understand and control antiferroelectrics. Here, it is demonstrated that the polarization switching behavior of an antiferroelectric can be strongly influenced and effectively regulated by point defects. In films of the canonical antiferroelectric PbZrO3 , decreasing oxygen pressure during deposition (and thus increasing adatom kinetic energy) causes unexpected "ferroelectric-like" polarization switching although the films remain in the expected antiferroelectric orthorhombic phase. This "ferroelectric-like" switching is correlated with the creation of bombardment-induced point-defect complexes which pin the antiferroelectric-ferroelectric phase boundaries, and thus effectively delay the phase transition under changing field. The effective pinning energy is extracted via temperature-dependent switching-kinetics studies. In turn, by controlling the concentration of defect complexes, the dielectric tunability of the PbZrO3 can be adjusted, including being able to convert between "positive" and "negative" tunability near zero field. This work reveals the important role and strong capability of defects to engineer antiferroelectrics for new performance and functionalities.

Prognostic value of RILPL2 and its correlation with tumor immune microenvironment and glycolysis in non-small cell lung cancer.

Rab-interacting lysosomal protein - like 2 (RILPL2) has been reported to be associated with prognosis and tumor biological functions in breast cancer and endometrial carcinoma. However, its expression and functional role in non-small cell lung cancer (NSCLC) remain unclear. The expression and clinical data of lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) were downloaded from the TCGA database. The expression of RILPL2 in NSCLC cell lines was verified by the Western blot. We used online databases and bioinformatics analysis tools to explore its prognostic value, potential biological functions, and correlations with tumor immune microenvironment.The expression of RILPL2 was significantly lower in NSCLC compared with adjacent normal tissues. Low RILPL2 expression was associated with worse overall survival (OS) in NSCLC. The GO analysis showed RILPL2 was comprehensively involved in immune activity. RILPL2 expression was significantly positively correlated with the infiltration levels of B cells, CD8+T cells, CD4+T cells, macrophages, neutrophils, dendritic cells (P < 0.001), and it was also significantly positively correlated with programmed cell death ligand 1 (PD-L1/CD274) (P < 0.001). High RILPL2 expression could predict better immunotherapy response and prognosis in the immunotherapy cohort. The GSEA analysis showed low RILPL2 expression was associated with glycolysis process in LUAD, which was verified in vitro.These results showed RILPL2 expression was correlated with prognosis, tumor microenvironment, and immunotherapy response in NSCLC. Besides, RILPL2 may regulate glycolysis in LUAD.

Nanowires-Assembled TiO2 Nanorods Anchored on Multilayer Graphene for High-Performance Anodes of Lithium-Ion Batteries.

Multilayer graphene (MLG) prepared via ultrasonic exfoliation has many advantages such as its low-cost and defect-free nature, high electronic conductivity, and large specific surface area, which make it an apt conductive substrate for TiO2 composites. To synthesize graphene/TiO2 hybrids, traditional methods that greatly depend on the chemical bond of oxygen-containing functional groups on graphene with titanium cations are not applicable due to the absence of these functional groups on MLG. In this work, a facile chemical method is developed to directly deposit TiO2 on the MLG surface without the introduction of chemically active groups. With this method, four types of TiO2 materials, that is pure anatase TiO2 nanoparticles, a mixture of anatase TiO2 nanoparticles and rutile TiO2 nanoflowers, pure rutile TiO2 nanoflowers, and pure rutile TiO2 nanorods, are homogeneously anchored on the MLG surface by controlling the amount of HCl in the reactant. Interestingly, the rutile TiO2 nanorods in the TiO2/MLG composite are assembled by many TiO2 nanowires with an ultra-small diameter and ultra-long length, which provides a better synergetic effect for high performances as LIB anodes than other composites. A specific capacity of 631.4 mAh g-1 after 100 cycles at a current density of 100 mA g-1 is delivered, indicating it to be a valuable LIB anode material with low cost and high electrochemical performances.

Isolation, Identification and Antibacterial Mechanism of the Main Antibacterial Component from Pickled and Dried Mustard (Brassica juncea Coss. var. foliosa Bailey).

Our previous study showed that the ethyl acetate fraction (EAF) from an ethanolic extract of pickled and dried mustard (Brassica juncea Coss. var. foliosa Bailey) had significant antibacterial activity. Here, the EAF was further separated into seven sub-fractions by silica gel column chromatography. The antibacterial activities of the EAF and its sub-fractions against Staphylococcus aureus and Pseudomonas fluorescens were assessed using the agar diffusion method and double dilution method. Among the seven sub-fractions, the third sub-fraction (Fr 3) possessed the strongest antibacterial activity. The main component in Fr 3 was identified by GC-MS, UV-vis, FT-IR, HPLC, 1H NMR and 13C NMR techniques, and was found to be succinic acid. The content of succinic acid in Fr 3 was determined as 88.68% (w/w) by HPLC. Finally, the antibacterial mechanism of succinic acid against the tested strains was explored by determining the intracellular component leakage, measuring the cell particle size and observing the cell morphology. The results showed that succinic acid could damage the cell membrane structure and intracellular structure to increase the leakage of cell components and reduce the cell particle size. Our results suggest that succinic acid could be used in food industry to control bacterial contamination by S. aureus and P. fluorescens.

TGR5 deficiency activates antitumor immunity in non-small cell lung cancer via restraining M2 macrophage polarization.

The bile acid-responsive G-protein-coupled receptor TGR5 is expressed in monocytes and macrophages, and plays a critical role in regulating inflammatory response. Our previous work has shown its role in promoting the progression of non-small cell lung cancer (NSCLC), yet the mechanism remains unclear. Here, using Tgr5-knockout mice, we show that TGR5 is required for M2 polarization of tumor-associated macrophages (TAMs) and suppresses antitumor immunity in NSCLC via involving TAMs-mediated CD8+ T cell suppression. Mechanistically, we demonstrate that TGR5 promotes TAMs into protumorigenic M2-like phenotypes via activating cAMP-STAT3/STAT6 signaling. Induction of cAMP production restores M2-like phenotypes in TGR5-deficient macrophages. In NSCLC tissues from human patients, the expression of TGR5 is associated with the infiltration of TAMs. The co-expression of TGR5 and high TAMs infiltration are associated with the prognosis and overall survival of NSCLC patients. Together, this study provides molecular mechanisms for the protumor function of TGR5 in NSCLC, highlighting its potential as a target for TAMs-centric immunotherapy in NSCLC.

A Predictive Theory for Domain Walls in Oxide Ferroelectrics Based on Interatomic Interactions and its Implications for Collective Material Properties.

Domain walls separating regions of ferroelectric material with polarization oriented in different directions are crucial for applications of ferroelectrics. Rational design of ferroelectric materials requires the development of a theory describing how compositional and environmental changes affect domain walls. To model domain wall systems, a discrete microscopic Landau-Ginzburg-Devonshire (dmLGD) approach with A- and B-site cation displacements serving as order parameters is developed. Application of dmLGD to the classic BaTiO3 , KNbO3, and PbTiO3 ferroelectrics shows that A-B cation repulsion is the key interaction that couples the polarization in neighboring unit cells of the material. dmLGD decomposition of the total energy of the system into the contributions of the individual cations and their interactions enables the prediction of different properties for a wide range of ferroelectric perovskites based on the results obtained for BaTiO3 , KNbO3, and PbTiO3 only. It is found that the information necessary to estimate the structure and energy of domain-wall "defects" can be extracted from single-domain 5-atom first-principles calculations, and that "defect-like" domain walls offer a simple model system that sheds light on the relative stabilities of the ferroelectric, antiferroelectric, and paraelectric bulk phases. The dmLGD approach provides a general theoretical framework for understanding and designing ferroelectric perovskite oxides.

Single-cell RNA sequencing reveals cellular and molecular immune profile in a Pembrolizumab-responsive PD-L1-negative lung cancer patient.

High expression of PD-L1 predicts PD-1/PD-L1 inhibitor benefit, meanwhile a few PD-L1-negative patients still benefit from these drugs. In this study, we aimed to explore the underlying cellular and molecular characteristics via single-cell sequencing. Before and after treatment with Pembrolizumab, peripheral blood mononuclear cells (PBMCs) were isolated via Ficoll gradient. Thereafter, single-cell RNA sequencing was performed, and clinical significance was validated with The Cancer Genome Atlas (TCGA) cohort. All 3423 cells of 16 clusters were classified into eight cell types, including NKG7+ T, NKG7+ NK, Naïve T, CDC1C+ dendritic cells, CD8+ T cells, B cells, macrophages and erythrocytes. Cell proportion, the clinical significance of differentially expressed genes and significant pathways of NKG7+ T, NKG7+ NK, Naïve T and CD8+ T cells were analyzed. Ubiquitin-mediated proteolysis/cell cycle/natural killer cell-mediated cytotoxicity were identified as PD-1 blockage-responsive pathways in NKG7+ NK cells. Apoptosis/Th1 and Th2 cell differentiation were proposed as Pembrolizumab-affected pathways in NKT cells. In gene level, ID2, PIK3CD, UQCR10, MATK, MZB1, IL7R and TRGC2 showed a significant correlation with PD-1 expression after TCGA dataset validation, which could possess potential as predictive markers for patients with PD-L1-negative lung squamous cell carcinoma who can benefit from Pembrolizumab.

Knockdown of LINC02471 Inhibits Papillary Thyroid Carcinoma Cell Invasion and Metastasis by Targeting miR-375.

BACKGROUND: LncRNAs play important roles in papillary thyroid carcinoma (PTC). LINC02471 has been reported to be related to PTC prognosis. The current study aimed to investigate the effects of LINC02471 on human PTC cells. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine LINC02471 expression in PTC tissues and cells and miR-375 expression in PTC cells. SiLINC02471, miR-375 mimic and miR-375 inhibitor were used for cell transfection. Cell proliferation, apoptosis, migration, and invasion were detected by performing Cell Counting Kit-8 (CCK-8), clone formation assay, flow cytometry, scratch assay, and transwell assay. Western blot was carried out to detect protein levels of E-cadherin, N-cadherin and Snail. The target gene for LINC02471 was verified by dual-luciferase reporter assay. RESULTS: LINC02471 was highly expressed in PTC tissues and cells. After silencing LINC02471, cell proliferation, migration and invasion were reduced, but cell apoptosis was increased. SiLINC02471 increased the expressions of E-cadherin and miR-375, and inhibited the expressions of N-Cadherin and Snail. LINC02471 directly targeted miR-375 in PTC cells. Overexpression of miR-375 inhibited the proliferation, migration, invasion of PTC cells and reduced the expressions of N-Cadherin and Snail but promoted the cell apoptosis and increased E-cadherin expression, while miR-375 inhibitor produced opposite effects to overexpressed miR-375. After inhibiting miR-375 expression, siLINC02471 reversed the effect of miR-375 inhibitor. CONCLUSION: LINC02471 could promote the development of PTC. Knocking down LINC02471 could inhibit invasion and metastasis and promote PTC cell apoptosis through directly targeting miR-375.

Diagnostic value of clinical parameters and parathyroid scintigraphy for asymptomatic primary hyperparathyroidism.

OBJECTIVE: The purpose of this study was to evaluate the diagnostic value of clinical parameters and parathyroid scintigraphy for asymptomatic primary hyperparathyroidism (aPHPT), including quantitative parameter of laboratory and semiquantitative parameters derived from technetium-99m- metoxyisobutylisonitrile (99mTc-MIBI) single photon emission computed tomography/computed tomography (SPECT/CT). SUBJECTS AND METHODS: Two hundred and fourteen patients who had been diagnosed as PHPT and underwent surgical treatment were enrolled in this study. All patients were divided into two groups: aPHPT and symptomatic PHPT (sPHPT). Dual tracer 99mTc pertechnetate/99mTc-MIBI, dual time point and tomography scintigraphy with 99mTc-MIBI SPECT/CT were performed. Clinical parameters included basic information, serum calcium (Ca), phosphorus (P), parathyroid hormone (PTH) and alkaline phosphatase (ALP) levels. Semiquantitative parameters of parathyroid scintigraphy included the average counts of early parathyroid (PT1), late parathyroid (PT2), early thyroid (T1) and late thyroid (T2), the ratio of PT1/ T1 (R1), the ratio of PT2/ T2 (R2), parathyroid washout (PTW=(PT1-PT2)/PT1) and retention index (RI=(R2-R1)/R1). P<0.05 was considered as statistically significant. RESULTS: A total of 167 aPHPT patients (46 males, 121 females) were studied. One hundred and seventy four One hundred and seventy four174 parathyroid glands were removed after operation: 146 (87.4%) lesions were adenoma, 12 (7.2%) lesions were hyperplasia and 1 (0.6%) lesion was adenocarcinoma. There were significant differences in previous history (P=0.000), echo of parathyroid (P=0.004), thyroid function (P=0.029), clinical course (Z=-3.422, P=0.001), 99mTc-pertechnetat thyroid uptake (TcTU) (Z=-2.126, P=0.033), serum Ca level (t=-2.926, P=0.004) and serum PTH level (Z=-3.028, P=0.002) between aPHPT and sPHPT. For patients with aPHPT, there were significant differences for serum Ca level (t=2.832, P=0.005), R2 (Z=-2.597, P= 0.009) and RI (Z=-2.100, P=0.036) between adenoma and hyperplasia, and serum Ca level in aPHPT patients with adenoma was significantly higher compared with patients with hyperplasia. The areas under the curve (AUC) of clinical course, TcTU, serum Ca and PTH levels were 0.662, 0.399, 0.642 and 0.645 respectively for differential diagnosis of aPHPT and sPHPT. The AUC of R2 and RI were 0.737 and 0.692 respectively for differential diagnosis of adenoma and hyperplasia in patients with aPHPT. The sensitivity, negative predictive value (NPV) and accuracy for diagnosing aPHPT combined 99mTc-MIBI SPECT/CT with ultrasound (US) were significantly higher than dual tracer, dual time point, 99mTc-MIBI SPECT/CT and US, which were 97.5%, 95.2% and 55.6% respectively. CONCLUSION: Laboratory inspection and semi-quantitative parameters of parathyroid scintigraphy had higher value for differential diagnoses of aPHPT and sPHPT, the same for adenoma and hyperplasia in patients with aPHPT. When combined 99mTc-MIBI SPECT/CT with US, the diagnostic efficiency would be significantly improved.

High-Level Patchoulol Biosynthesis in Artemisia annua L.

Terpenes constitute the largest class of secondary metabolites in plants. Some terpenes are essential for plant growth and development, membrane components, and photosynthesis. Terpenes are also economically useful for industry, agriculture, and pharmaceuticals. However, there is very low content of most terpenes in microbes and plants. Chemical or microbial synthesis of terpenes are often costly. Plants have the elaborate and economic biosynthetic way of producing high-value terpenes through photosynthesis. Here we engineered the heterogenous sesquiterpenoid patchoulol production in A. annua. When using a strong promoter such as 35S to over express the avian farnesyl diphosphate synthase gene and patchoulol synthase gene, the highest content of patchoulol was 52.58 µg/g DW in transgenic plants. When altering the subcellular location of the introduced sesquiterpene synthetase via a signal peptide, the accumulation of patchoulol was observably increased to 273 µg/g DW. This case demonstrates that A. annua plant with glandular trichomes is a useful platform for synthetic biology studies.

Detection of Genetic Mutations by Next-Generation Sequencing for Predicting Prognosis of Extensive-Stage Small-Cell Lung Cancer.

Some studies have revealed that specific genetic mutations could be associated with chemotherapy response or even survival in small-cell lung cancer (SCLC). Our retrospective study aimed to identify the correlation between genetic mutations and progression-free survival (PFS) in extensive-stage SCLC after first-line chemotherapy. A total of 75 patients with extensive-stage SCLC confirmed by histopathology from February 2018 to February 2019 were retrospectively analyzed. The biopsy specimens of all patients were analyzed by Next-Generation Sequencing (NGS). All patients received first-line chemotherapy and follow-up at Shanghai Chest Hospital. Eleven genes were mutated in, at least, 10% of the 75 patients, including TP53 (96%), RB1 (77%), SMAD4 (32%), NOTCH1 (21%), PTEN (16%), FGFR1 (16%), KDR (15%), PIK3CA (15%), ROS1 (15%), BRCA2 (13%), and ERBB4 (10%). The median number of mutated genes among all patients was 5. Patients with more than 5 mutated genes (PFS = 6.7 months, P=0.004), mutant TP53 (PFS = 5.0 months, P=0.011), and mutant BRCA2 (PFS = 6.7 months, P=0.046) had better PFS after first-line chemotherapy than other patients. Multivariate Cox regression analysis showed that patients who achieved a PR (HR 3.729, 95% CI 2.038-6.822), had more than 5 mutated genes (HR 1.929, 95% CI 1.096-3.396), had BRCA2 mutations (HR 4.581, 95% CI 1.721-12.195), and had no liver metastasis (HR 0.415, 95% CI 0.181-0.951) showed improvements in PFS after first-line chemotherapy. In conclusion, the number of mutated genes and BRCA2 mutation status in extensive-stage SCLC were significantly related to PFS after first-line chemotherapy.

Prognostic value of tumor cavitation in extensive-stage small-cell lung cancer patients treated with anlotinib.

PURPOSE: Anlotinib is a novel multi-target tyrosine kinase inhibitor (TKI) for tumor angiogenesis and tumor cell proliferation. The efficacy of anlotinib as a third-line or beyond therapy for SCLC was confirmed in the ALTER1202 trial. For lung cancer patients treated with antiangiogenesis agents, the phenomenon of cavitation is commonly seen in the lung target lesions. The impact of tumor cavitation on survival in lung cancer patients treated with vascular-targeted therapy remains controversial. Our retrospective study was to investigate the prognostic value of tumor cavitation in extensive-stage SCLC patients treated with anlotinib. METHODS: A total of 73 extensive-stage SCLC patients confirmed by histopathology from January 2018 to January 2019 were retrospectively analyzed. All patients received anlotinib therapy at Shanghai Chest Hospital. We defined tumor cavitation of the lung target lesions as that part of solid component was changed to air-filled area according to chest CT. Progression-free survival (PFS) was calculated from the beginning of anlotinib therapy to the disease progression or the last follow-up visit. RESULTS: Eleven (15.0%) patients had tumor cavitation during anlotinib therapy. The ORR of the 73 patients was 15.1%. Multivariate logistic regression analysis showed that tumor cavitation during anlotinib therapy was not associated with gender (P = 0.630), age (P = 0.190), smoking status (P = 0.165), anatomy type (P = 0.641), and the line of anlotinib therapy (P = 0.302). The median PFS of all patients was 2.6 months (95%CI 2.1-3.2). According to the univariate analysis, the median PFS in patients with and without tumor cavitation was 5.0 months and 2.2 months, respectively, and the difference was statistically significant (P = 0.041). According to the multivariate analysis, tumor cavitation was an independent factor for PFS after adjusting gender, age, smoking status, anatomy type, the line of anlotinib therapy, tumor cavitation, and response to anlotinib (adjusted HR 0.316, 95%CI 0.142-0.702; P = 0.005). CONCLUSIONS: In 73 extensive-stage SCLC patients treated with anlotinib, no demographic/clinical characteristic was related to tumor cavitation, and tumor cavitation was an independent factor in predicting better PFS.

The relationship between preliminary efficacy and prognosis after first-line EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment of advanced non-small cell lung cancer.

BACKGROUND: Nowadays, patients with EGFR tyrosine kinase inhibitor (EGFR-TKI)-sensitive advanced non-small cell lung cancer (NSCLC) receive EGFR-TKIs as first-line treatment. We aimed to analyze the relationship between preliminary efficacy (tumor shrinkage within 1 month) and progression-free survival (PFS) after first-line EGFR-TKI treatment. METHODS: A total of 82 patients with EGFR-TKI-sensitive advanced NSCLC confirmed by histopathology from January 2013 to January 2017 were retrospectively analyzed. All patients received first-line EGFR-TKI treatment and follow-up at Shanghai Chest Hospital. RESULTS: Of a total of 82 patients, 42 (51.2%) patients achieved partial response (PR) within 1 month, and 40 (48.8%) patients achieved stable disease (SD: -30% to 0) within 1 month. The median PFS among all patients was 10 months. The median PFS in patients achieving PR within 1 month was 10.0 months. The median PFS in patients achieving SD (-30% to 0) within 1 month was 9.3 months. There was no statistically significant difference between PR within 1 month and SD (-30% to 0) within 1 month (P=0.620). In the EGFR-sensitive mutation subgroup, there was also no statistically significant difference between PR within 1 month and SD (-30% to 0) within 1 month. Univariate and multivariate analysis of first-line EGFR-TKI treatment showed that age, EGFR mutation type, and T staging had effects on PFS. Patients who were more than 65 years old, had EGFR 19del mutation, along with a T staging less than 4, had a longer PFS; these differences were statistically significant. Liver metastasis, bone metastasis, and brain metastasis were not shown to be related to PFS. CONCLUSIONS: For patients with EGFR-TKI-sensitive advanced NSCLC, there is no correlation between preliminary efficacy (tumor shrinkage within 1 month) and PFS after first-line EGFR-TKI treatment.

Prediction of lymph node status in completely resected IIIa/N2 small cell lung cancer: importance of subcarinal station metastases.

BACKGROUND: The aim of this study was to determine the prognostic value of lymph node status in patients with pathologic N2 (pN2) stage IIIA small cell lung cancer (SCLC). METHODS: A total of 163 consecutive pN2 stage IIIA SCLC patients who underwent pulmonary resections and systematic lymphadenectomies at Shanghai Chest Hospital between January 2006 and June 2014 were enrolled. We retrospectively analyzed the potential clinicopathologic factors that influenced survival, including the node levels (single or multiple-station) and the node-spreading patterns (skip N2 or non-skip N2). The prognostic significance was examined by Cox regression analysis. RESULTS: The median overall survival (OS) was 23.7 months. Multiple-station lymph node metastasis indicated a poorer prognosis than single-station involvement (p = 0.003). Skip metastasis did not appear to influence survival (p = 0.099). With respect to the station of lymph node metastasis, the OS was only related to the involvement of the subcarinal node, regardless of tumor location (p < 0.05). Multivariate analysis showed two statistically significant risk factors for survival, including multiple-station lymph node and subcarinal node metastasis (hazard ratio [HR] = 1.76, 95% confidence interval [CI]:1.11-2.78, p = 0.015; HR = 1.61, 95% CI: 1.03-2.50, p = 0.036, respectively). CONCLUSIONS: Multiple-station N2 metastasis and involvement of the subcarinal node predicted poor prognosis in pN2 stage IIIA SCLC patients, which may profoundly influence therapeutic decisions.

Comprehensive characterization of differentially expressed genes in thyroid cancer.

AIM: To explore the patterns of gene expression and functionally characterize the differentially expressed genes (DEGs) in thyroid cancer. METHODS: DEGs were determined between 57 paired thyroid cancer and noncancerous tissues using DESeq2. Subsequently, the main functions of the DEGs were studied by a variety of analyses. RESULTS: We identified a cohort of 752 upregulated and 309 downregulated DEGs in thyroid cancer. Several hub DEGs were found in the protein-protein interaction networks. We also revealed a set of DEGs that were dysmethylated, involved in copy number variations and associated with clinical features in thyroid cancer. CONCLUSION: These results provide some novel findings on DEGs in thyroid cancer, which will be useful to guide further investigation and target therapy for this disease. [Formula: see text].