Radiomics analysis of dual-layer spectral-detector CT-derived iodine maps for predicting tumor deposits in colorectal cancer.

OBJECTIVE: To investigate the value of radiomics analysis of dual-layer spectral-detector computed tomography (DLSCT)-derived iodine maps for predicting tumor deposits (TDs) preoperatively in patients with colorectal cancer (CRC). MATERIALS AND METHODS: A total of 264 pathologically confirmed CRC patients (TDs + (n = 80); TDs - (n = 184)) who underwent preoperative DLSCT from two hospitals were retrospectively enrolled, and divided into training (n = 124), testing (n = 54), and external validation cohort (n = 86). Conventional CT features and iodine concentration (IC) were analyzed and measured. Radiomics features were derived from venous phase iodine maps from DLSCT. The least absolute shrinkage and selection operator (LASSO) was performed for feature selection. Finally, a support vector machine (SVM) algorithm was employed to develop clinical, radiomics, and combined models based on the most valuable clinical parameters and radiomics features. Area under receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis were used to evaluate the model's efficacy. RESULTS: The combined model incorporating the valuable clinical parameters and radiomics features demonstrated excellent performance in predicting TDs in CRC (AUCs of 0.926, 0.881, and 0.887 in the training, testing, and external validation cohorts, respectively), which outperformed the clinical model in the training cohort and external validation cohorts (AUC: 0.839 and 0.695; p: 0.003 and 0.014) and the radiomics model in two cohorts (AUC: 0.922 and 0.792; p: 0.014 and 0.035). CONCLUSION: Radiomics analysis of DLSCT-derived iodine maps showed excellent predictive efficiency for preoperatively diagnosing TDs in CRC, and could guide clinicians in making individualized treatment strategies. CLINICAL RELEVANCE STATEMENT: The radiomics model based on DLSCT iodine maps has the potential to aid in the accurate preoperative prediction of TDs in CRC patients, offering valuable guidance for clinical decision-making. KEY POINTS: Accurately predicting TDs in CRC patients preoperatively based on conventional CT features poses a challenge. The Radiomics model based on DLSCT iodine maps outperformed conventional CT in predicting TDs. The model combing DLSCT iodine maps radiomics features and conventional CT features performed excellently in predicting TDs.

P T symmetry in a superconducting hybrid quantum system with longitudinal coupling.

We propose a scheme consisting of coupled nanomechanical cantilever resonators and superconducting flux qubits to engineer a parity-time- (P T-) symmetric phononic system formed by active and passive modes. The effective gain (loss) of the phonon mode is achieved by the longitudinal coupling of the resonator and the fast dissipative superconducting qubit with a blue-sideband driving (red-sideband driving). A P T-symmetric to broken-P T-symmetric phase transition can be observed in both balanced gain-to-loss and unbalanced gain-to-loss cases. Applying a resonant weak probe field to the dissipative resonator, we find that (i) for balanced gain and loss, the acoustic signal absorption to amplification can be tuned by changing the coupling strength between resonators; (ii) for unbalanced gain and loss, both acoustically induced transparency and anomalous dispersion can be observed around Δ = 0, where the maximum group delay is also located at this point. Our work provides an experimentally feasible scheme to design P T-symmetric phononic systems and a powerful platform for controllable acoustic signal transmission in a hybrid quantum system.

Home-based rehabilitation versus hospital-based rehabilitation for stroke patients in post-acute care stage: Comparison on the quality of life.

BACKGROUND: This study focused on the integrated post-acute care (PAC) stage of stroke patients, and employed a retrospective study to examine the satisfaction with life quality in two groups, one that received home-based rehabilitation and one that received hospital-based rehabilitation. A secondary purpose was to analyze the correlations among the index and components concerning their quality of life (QOL) and compare the advantages and disadvantages of these two approaches to PAC. METHODS: This research was a retrospective study of 112 post-acute stroke patients. The home-based group received rehabilitation for one to two weeks, and two to four sessions per week. The hospital-based group received the rehabilitation for three to six weeks, and 15 sessions per week. The home-based group mainly received the training and guidance of daily activities at the patients' residence. The hospital-based group mainly received physical facilitation and functional training in the hospital setting. RESULTS: The mean scores of QOL assessment for both groups were found to be significantly improved after intervention. Between-group comparisons showed that the hospital-based group had better improvement than the home-based group in mobility, self-care, pain/discomfort and depression/anxiety. In the home-based group, the MRS score and the participant's age can explain 39.4% of the variance of QOL scores. CONCLUSION: The home-based rehabilitation was of lower intensity and duration than the hospital-based one, but it still achieved a significant improvement in QOL for the PAC stroke patients. The hospital-based rehabilitation offered more time and treatment sessions. Therefore hospital-based patients responded with better QOL outcomes than the home-based patients.

Survival Benefit from Surgical Resection in Lung Cancer Patients with Brain Metastases: a Single-Center, Propensity-Matched Analysis Cohort Study.

BACKGROUND: Brain metastases (BMs) are the most serious complication of lung cancer, affecting the prognosis of lung cancer patients, and pose distinct clinical challenges. This study was designed to explore the prognostic factors related to lung cancer BM and the value of surgical resection in BMs from lung cancer. METHODS: A retrospective analysis was performed on 714 patients with lung cancer BMs screened between January 2010 and January 2018 at the Sun Yat-sen University Cancer Center. A 1:1 propensity score matching analysis was performed to reduce the potential bias between the surgery and the nonsurgery group. In both the raw and the propensity-score matched dataset, univariate and multivariate Cox proportional hazards regression analyses were used to evaluate risk factors for survival. RESULTS: After matching, 258 patients (129 surgery, 129 no surgery) were analyzed. Multivariate analyses after propensity score matching demonstrated that surgical resection was an independent protective factor for overall survival (OS), and older age, lower Karnofsky Performance Scale (KPS) score, and extracranial metastases were independent risk factors for worse OS. Patients without extracranial metastases, without synchronous BM and with a single BM had a better prognosis. CONCLUSIONS: The findings showed that surgical resection, age, KPS score, and extracranial metastases are independent prognostic factors for predicting the OS of patients with lung cancer BMs, and surgical resection for brain metastatic lesions could significantly improve the OS. However, only certain groups of patients with BMs can benefit from intracranial lesion resection, such as no extracranial metastases and metachronous metastases.

Polycrystalline Few-Layer Graphene as a Durable Anticorrosion Film for Copper.

Corrosion of metals in atmospheric environments is a worldwide problem in industry and daily life. Traditional anticorrosion methods including sacrificial anodes or protective coatings have performance limitations. Here, we report atomically thin, polycrystalline few-layer graphene (FLG) grown by chemical vapor deposition as a long-term protective coating film for copper (Cu). A six-year old, FLG-protected Cu is visually shiny and detailed material characterizations capture no sign of oxidation. The success of the durable anticorrosion film depends on the misalignment of grain boundaries between adjacent graphene layers. Theoretical calculations further found that corrosive molecules always encounter extremely high energy barrier when diffusing through the FLG layers. Therefore, the FLG is able to prevent the corrosive molecules from reaching the underlying Cu surface. This work highlights the interesting structures of polycrystalline FLG and sheds insight into the atomically thin coatings for various applications.

Tunable Chiral Bound States with Giant Atoms.

We propose tunable chiral bound states in a system composed of superconducting giant atoms and a Josephson photonic-crystal waveguide (PCW), with no analog in other quantum setups. The chiral bound states arise due to interference in the nonlocal coupling of a giant atom to multiple points of the waveguide. The chirality can be tuned by changing either the atom-waveguide coupling or the external bias of the PCW. Furthermore, the chiral bound states can induce directional dipole-dipole interactions between multiple giant atoms coupling to the same waveguide. Our proposal is ready to be implemented in experiments with superconducting circuits, where it can be used as a tunable toolbox to realize topological phase transitions and quantum simulations.

Copper-Catalyzed Cascade Annulation of Malonate-Tethered O-Acyl Oximes with Cyclic 1,3-Dicarbonyl Compounds for the Synthesis of Spiro-Pentacyclic Derivatives.

A copper-catalyzed cascade annulation of malonate-tethered O-acyl oximes with cyclic 1,3-dicarbonyl compounds has been developed for the rapid synthesis of spiro-pentacyclic derivatives. This reaction allows the one-step formation of five C-C/N/O bonds and an angular tricyclic core under very mild conditions and shows excellent regioselectivity and stereoselectivity.

Scutebarbatine A induces cytotoxicity in hepatocellular carcinoma via activation of the MAPK and ER stress signaling pathways.

Scutebarbatine A (SBT-A), a diterpenoid alkaloid found in the root of Scutellaria barbata D. Don, has been reported to induce the apoptosis of A549 cells. In this study, we investigated the antitumor activity of SBT-A in human hepatocellular carcinoma (HCC) cells and the potential underlying mechanisms. Our results showed that SBT-A inhibited the growth of HCC cells in a dose-dependent manner. SBT-A treatment caused cell cycle arrest and decreased the expression of cyclin B1, cyclin D1, p-Cdc2, and p-Cdc25C. SBT-A triggered cell apoptosis via a caspase-dependent pathway, and cell viability was partially restored by pretreatment with the pan-caspase inhibitor Z-VAD-FMK. In HCC cells, treatment with SBT-A increased the phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2), c-Jun N-terminal kinase 1 and 2 (JNK1/2), and p38 mitogen-activated protein kinase (p38 MAPK). Moreover, SBT-A activated endoplasmic reticulum (ER) stress through the upregulation of protein kinase RNA-like ER kinase (PERK), activating transcription factor 4 (ATF-4), and CCAAT-enhancer-binding protein (C/EBP) homologous protein (CHOP). Our data indicate that SBT-A inhibits the proliferation of HCC cells and triggers their apoptosis via the activation of MAPK and ER stress. SBT-A is a potential agent for the treatment of HCC.

Neurodevelopmental outcomes of infants of diabetic mothers. / ç³–å°¿ç— æ¯äº²å©´å„¿çš„ç¥žç»å‘è‚²ç»“å±€.

With the increase of the incidence of pre-pregnancy diabetes mellitus and gestational diabetes mellitus, the number of infants of diabetic mothers (IDMs) are increasing year by year. IDMs may be associated with poor perinatal outcomes and may have a negative impact on neurodevelopment, but there are relatively few studies on the neurodevelopmental outcomes of IDMs. This article reviews the relevant literature and summarizes the neurodevelopmental outcomes of IDMs from the aspects of sensory and perception, motor, language, intellectual development, neuropsychiatric disorders, neurological examination and drug effect, so as to provide reference for clinical work. Citation.

Cu(OAc)2-Promoted Oxidative Cross-Dehydrogenative Coupling Reaction of α-Acylmethyl Malonates with Indole Derivatives to Access 3-Functionalized Indoles and Polycyclic Indoles.

A Cu(OAc)2-promoted oxidative cross-dehydrogenative coupling reaction of α-acylmethyl malonates with indole derivatives was developed. In the case of indoles, the regioselective coupling products were formed through a sequential dehydrogenation-addition-dehydrogenation process. When a second nucleophilic center was located in the 2-position of indoles, further successive nucleophilic cyclization occurred to give polycyclic indole derivatives. The Cu(OAc)2 was proved to act as not only an oxidant but also a catalyst.

Bone marrow mesenchymal stem cells overexpressing GATA-4 improve cardiac function following myocardial infarction.

INTRODUCTION: The present study aimed to examine whether GATA-4 overexpressing bone marrow mesenchymal stem cells can improve cardiac function in a murine myocardial infarction model compared with bone marrow mesenchymal stem cells alone. METHODS: A lentiviral-based transgenic system was used to generate bone mesenchymal stem cells which stably expressed GATA-4 (GATA-4-bone marrow mesenchymal stem cells). Apoptosis and the myogenic phenotype of the bone marrow mesenchymal stem cells were measured using Western blot and immunofluorescence assays co-cultured with cardiomyocytes. Cardiac function, bone marrow mesenchymal stem cell homing, cardiac cell apoptosis, and vessel number following transplantation were assessed, as well as the expression of c-Kit. RESULTS: In GATA-4-bone marrow mesenchymal stem cells-cardiomyocyte co-cultures, expression of myocardial-specific antigens, cTnT, connexin-43, desmin, and α-actin was increased compared with bone marrow mesenchymal stem cells alone. Caspase 8 and cytochrome C expression was lower, and the apoptotic rate was significantly lower in GATA-4 bone marrow mesenchymal stem cells. Cardiac function following myocardial infarction was also increased in the GATA-4 bone marrow mesenchymal stem cell group as demonstrated by enhanced ejection fraction and left ventricular fractional shortening. Analysis of the cardiac tissue revealed that the GATA-4 bone marrow mesenchymal stem cell group had a greater number of DiR-positive cells suggestive of increased homing and/or survival. Transplantation with GATA-4-bone marrow mesenchymal stem cells significantly increased the number of blood vessels, decreased the proportion of apoptotic cells, and increased the mean number of cardiac c-kit-positive cells. CONCLUSION: GATA-4 overexpression in bone marrow mesenchymal stem cells exerts anti-apoptotic effects by targeting cytochrome C and Fas pathways, promotes the aggregation of bone marrow mesenchymal stem cells in cardiac tissue, facilitates angiogenesis, and effectively mobilizes c-kit-positive cells following myocardial infarction, leading to the improvement of cardiac function after MI.

Design, synthesis, and antitumor activity of oleanolic acid derivatives.

Using the techniques of computer-aided drug design, the docking of survivin and known active small molecules was simulated and then the key amino acid residue fragments of the target protein were analyzed. It led to the discovery of active groups capable of binding to the critical sites. Through the use of the natural product, oleanolic acid, as a lead compound, the introduction of the active groups onto the A-ring, and the modification of the carboxyl group at the C-28 position using esterification or amidation, 20 new oleanolic acid derivatives had been designed and synthesized. HepG2 and SGC-7901 cells were used to screen the antitumor activity through the standard MTT method. The compounds, II3, III5 and IV4, exhibited more potent cytotoxicity than positive drugs. Western blot experiment demonstrated that compound II3 can effectively inhibit the proliferation of HepG2 cells.

Development and validation of the cancer self-perceived discrimination scale for Chinese cancer patients.

BACKGROUND: To develop a Cancer Self-Perceived Discrimination Scale (CSPDS) for Chinese cancer patients and to assess its reliability and validity. METHOD: A total of 178 patients were recruited and the classical test theory was used to develop the CSPDS. Item analysis was adapted to improve the preliminary version of the CSPDS, then the reliability, the validity and the acceptability of the final version of CSPDS were assessed. RESULTS: This CSPDS contained 14 items classified into 3 subscales: social withdrawal with 7 items, stigma with 4 and self-deprecation with 3. Good validity (χ2/df = 1.216, GFI = 0.935, AGFI = 0.903, I-CVIs> 0.80) and good reliability (Cronbach's alpha = 0.829, Spearman-Brown coefficient = 0.827, test-retest reliability coefficient = 0.944) were found. The completion time was 6.06 ± 1.80 min. Participants who were female and reported poor self-rated health tended to have higher CSPDS scores (P <  0.05). CONCLUSIONS: The results indicated that this CSPDS could be used to assess the level of self-perceived discrimination and to preliminarily screen perceived discrimination among Chinese cancer patients, especially in Southwest China. It may provide a basis for scientific assessment of targeted patient education, psychological counseling, social interventions, and psychotherapy in the future.

Comparison of multifactor scoring systems and single serum markers for the early prediction of the severity of acute pancreatitis.

BACKGROUND: The purpose of this study was to clarify whether the current scoring systems and single serum markers used in pancreatitis remain applicable for the early prediction of infected pancreatic necrosis (IPN) and the severity and mortality of acute pancreatitis (AP) in accordance with the revised Atlanta and determinant-based classifications. METHODS: Demographic, clinical, and laboratory data from 708 consecutive patients with AP were prospectively collected between January 2011 and December 2012. The severity was classified using the revised Atlanta and determinant-based classification systems. The predictive accuracies for moderately severe AP (MSAP), severe AP (SAP), critically severe AP (CAP), IPN, and mortality were measured using area under the receiver operating characteristic curves. RESULTS: The receiver operating characteristic analysis showed that the multifactor scoring systems and single serum markers had a low predictive accuracy regarding moderately severe AP. The Acute Physiology and Chronic Health Evaluation (APACHE) II score had the highest accuracy in predicting SAP with area under the curve (AUC) values of 0.75 (95% CI = 0.71-0.79) and 0.77 (95% CI = 0.73-0.81) at 24 and 48 h after admission, respectively. Procalcitonin was the most accurate predictor for CAP and IPN, with respective AUCs of 0.86 (95% CI = 0.82-0.89) and 0.83 (95% CI = 0.78-0.87) at 48 h after admission. In predicting mortality, both the APACHE II score and blood urea nitrogen had the highest accuracy. CONCLUSIONS: The APACHE II score had the highest predictive accuracy for SAP and mortality as defined by the revised Atlanta classification, whereas procalcitonin was the most accurate predictor for CAP and IPN.

[Clinical and pathological features and the misdiagnosis of childhood Alport syndrome: a retrospective analysis of 91 cases].

OBJECTIVE: To explore the clinical and pathological features and the diagnosis of childhood Alport syndrome (AS). METHODS: A retrospective analysis was performed on clinical data of 91 children with AS. RESULTS: Hematuria was observed in all 91 patients, of whom 86 were accompanied with proteinuria. Sixty-one children with X-Linked AS (XL-AS) had positive family history. Renal biopsy was performed on 82 children. Mild to moderate mesangial proliferation was observed in 74 cases. Small amounts of immune complexes deposits in the glomerular mesangial area were observed in 48 cases. Glomerular basement membrane (GBM) attenuation, thickening and layering were observed in 53 cases by electron microscopy (EM). In 63 cases receiving renal tissue type IV collagen α3 and α5 chain immunofluorescence detection, 58 were diagnosed with AS, including 53 cases of XL-AS and 5 cases of autosomal recessive AS. In 91 cases of AS, 58 were diagnosed as AS by renal tissue type IV collagen α3 and α5 chain immunofluorescence, 21 were diagnosed by EM, one was diagnosed by skin biopsy, and 12 were diagnosed by gene detection. Six novel mutations of COL4A5 gene were found. Forty-five cases were misdiagnosed before the diagnosis of AS. Forty-one of the 45 cases received steroids and/or immunosuppressant therapy. CONCLUSIONS: The clinical manifestations and pathological changes are not specific in children with AS, resulting in a higher rate of misdiagnosis. Typical lesions of GBM under EM are only observed in a part of patients. There is a high novel mutation rate of COL4A5 in the detected AS children.

Evaluation of the in vitro and in vivo metabolic pathway and cytochrome P450 inhibition/induction profile of Huperzine A.

Huperzine A (HupA), one of the reversible and selective acetylcholinesterase inhibitors derived from Chinese herb Huperzia Serrata, possesses affirmative action of ameliorating cognitive dysfunction of Alzheimer's disease. Up to now, the effects of HupA on human cytochrome P450s (CYPs) have not been fully elucidated. The purpose of the present study was to clarify the metabolic pathway of HupA in vitro and in vivo, and to evaluate the CYPs inhibition/induction profile of HupA in vitro. The catalytic activity of CYP enzymes (CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1 and 3A4) was measured by the quantification of specific enzyme substrates using validated liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods. The in vivo metabolic pathway evaluation was performed in an open, single-dose pharmacokinetic study of HupA in fourteen elderly subjects, with urine collecting at certain intervals. In human liver microsomes, HupA (10 ng/mL) was not metabolized within 90 min, and it showed negligible inhibition against these CYP isoforms within 0.2-100 ng/mL. In human liver hepatocytes, the activities of CYP1A2 and CYP3A4 were not significantly altered when incubated at 2 or 20 ng/mL of HupA. After oral administration of 0.1 mg HupA, the total proportion of HupA excreted through urine was relatively high, accounting to 35± 9% at the limited time period of 48 h. These results suggest that HupA is substantially excreted by kidney unchanged rather than metabolized by human liver, and is unlikely to cause clinically relevant drug-drug interaction (DDI) when co-administrated with drugs that are metabolized by CYP isoenzyme system.

Population pharmacokinetic modeling and simulation of huperzine A in elderly Chinese subjects.

AIM: Our preliminary results show that huperzine A, an acetylcholinesterase inhibitor used to treat Alzheimer's disease (AD) patients in China, exhibits different pharmacokinetic features in elderly and young healthy subjects. However, its pharmacokinetic data in elderly subjects remains unavailable to date. Thus, we developed a population pharmacokinetic (PPK) model of huperzine A in elderly Chinese people, and identified the covariate affecting its pharmacokinetics for optimal individual administration. METHODS: A total of 341 serum huperzine A concentration records was obtained from 2 completed clinical trials (14 elderly healthy subjects in a phase I pharmacokinetic study; 35 elderly AD patients in a phase II study). Population pharmacokinetic analysis was performed using the non-linear mixed-effect modeling software Phoenix NLME1.1.1. The effects of age, gender, body weight, height, creatinine, endogenous creatinine clearance rate as well as drugs administered concomitantly were analyzed. Bootstrap and visual predictive checks were used simultaneously to validate the final population pharmacokinetics models. RESULTS: The plasma concentration-time profile of huperzine A was best described by a one-compartment model with first-order absorption and elimination. Age was identified as the covariate having significant influence on huperzine A clearance. The final PPK model of huperzine A was: CL (L/h)=2.4649(*)(age/86)((-3.3856)), Ka=0.6750 h(-1), V (L)=104.216. The final PPK model was demonstrated to be suitable and effective by the bootstrap and visual predictive checks. CONCLUSION: A PPK model of huperzine A in elderly Chinese subjects is established, which can be used to predict PPK parameters of huperzine A in the treatment of elderly AD patients.

[Effect of Tongxinluo on Apoptosis of Rat Cardiac Microvascular Endothelial Cells].

OBJECTIVE: To observe the protective effects of Tongxinluo (TXL) on apoptosis of rat cardiac microvascular endothelial cells (RCMECs) resulting from homocysteine (Hcy) induced endoplasmic reticulum stress (ERS), and to determine the signaling pathway behind its protection. METHODS: Primary cultured RCMECs were isolated from neonatal rats using tissue explant method. The morphology of RCMECs was observed using inverted microscope, identified and differentiated by CD31 immunofluorescence method. Selected were well growing 2nd-4th generations of RCMECs. The optimal action time was determined by detecting the expression of glucose regulated protein 78 (GRP78) using immunofluorescence method. In the next experiment RCMECs were divided into 5 groups, i.e., the blank control group, the Hcy induced group (Hcy 10 mmol/L, 10 h), the Hcy + TXL group (Hcy 10 mmol/L + TXL 400 µg/mL), the Hcy +LY294002 group (Hcy 10 mmol/L + LY294002 5 µmol/L, LY294002 as the inhibitor of PI3K), the Hcy + LY294002 + TXL group (Hcy 10 mmol/L + LY294002 5 µmol/L + TXL 400 µg/mL). The apoptosis rate of RCMECs was detected by flow cytometry. mRNA and protein expressions of GRP78, C/ EBP homologous protein (CHOP), and cysteinyl aspartate specific proteinase-12 (caspase12) were detected by real-time reverse transcription PCR (RT-PCR) and Western blot respectively. Expression levels of phosphorylation of phosphatidylinositol 3-kinase (P-PI3K), total phosphatidylinositol 3-kinase (T- P13K) , phosphorylation of kinase B (P-Akt) , and total kinase B (T-Akt) were detected by Western blot. RESULTS: Ten hours Hcy action time was determined. Compared with the blank control group, the apoptosis rate was increased (22.77%), mRNA and protein expressions of GRP78, CHOP, and Caspase-12 were increased, protein expressions of P-PI3K and P-Akt,ratios of P-PI3K/T-PI3K and P-Akt/T-Akt were decreased in the Hcy induced group (P < 0.05, P < 0.01). Compared with the Hcy induced group, the apoptosis rate was decreased (10.17%), mRNA and protein expressions of GRP78, CHOP, and Caspase-12 were decreased, and expression levels of P-PI3K, P-Akt, P-PI3K/T-PI3K, and P-Akt/T-Akt were increased in the Hcy + TXL group (P < 0.05, P < 0.01). Compared with the Hcy + TXL group, the apoptosis rate was increased (17.9%), mRNA and protein expressions of GRP78, CHOP, and Caspase-12 were increased, expression levels of P-PI3K and P-Akt, ratios of P-PI3K/T-PI3K and P-Akt/T-Akt were decreased in the Hcy + TXL + LY294002 group (P < 0.05, P < 0.01). CONCLUSION: TXL could inhibit the apoptosis of RCMECs resulting from Hcy-induced ERS and its mechanism might be associated with activating PI3K/Akt signaling pathway.

The checkpoint 1 kinase inhibitor LY2603618 induces cell cycle arrest, DNA damage response and autophagy in cancer cells.

Chemotherapy- or radiotherapy-induced DNA damage activates the Chk1-dependent DNA damage response (DDR) and cell cycle checkpoints to facilitate cell survival. Numerous attempts have been made to identify specific Chk1 inhibitors to enhance the efficiency of chemotherapy or radiotherapy. In this study, we investigated the molecular mechanisms underlying the antitumor activity of LY2603618, a potent and selective small molecule inhibitor of Chk1 protein kinase, in human lung cancer cells. Treatment of cancer cells with LY2603618 caused cell cycle arrest in the G2/M phase. A marked induction of DDR, including the phosphorylation of ATM, Chk2, p53 and histone H2AX, was observed after LY2603618 treatment. LY2603618 inhibited Chk1 autophosphorylation (S296 Chk1) and increased DNA damage-mediated Chk1 phosphorylation (S345 Chk1). In addition, LY2603618-treated lung cancer cells transitioned from LC3-I to LC3-II, a hallmark of autophagy. Blocking autophagy with chloroquine (CQ) further enhanced LY2603618's inhibitory effect on cell viability/proliferation. LY2603618 also significantly increased p38 and c-Jun N-terminal kinase (JNK) phosphorylation. Pretreatment with the JNK inhibitor reduced cleavage of caspase-3 and PARP levels in LY2603618-treated cells. These results suggest the following: (i) the biological consequences of LY2603618 in lung cancer cells is associated with both inhibition of Chk1 phosphorylation on S296 and activation of the DNA damage response network; and (ii) the anticancer property of LY2603618 might be increased by inhibiting autophagy.

The Value of Radiomics Features Based on HRCT in Predicting whether the Lung Sub-Centimeter Pure Ground Glass Nodule is Benign or Malignant.

OBJECTIVE: In this study, a radiomics model was created based on High-Resolution Computed Tomography (HRCT) images to noninvasively predict whether the sub-centimeter pure Ground Glass Nodule (pGGN) is benign or malignant. METHODS: A total of 235 patients (251 sub-centimeter pGGNs) who underwent preoperative HRCT scans and had postoperative pathology results were retrospectively evaluated. The nodules were randomized in a 7:3 ratio to the training (n=175) and the validation cohort (n=76). The volume of interest was delineated in the thin-slice lung window, from which 1316 radiomics features were extracted. The Least Absolute Shrinkage and Selection Operator (LASSO) was used to select the radiomics features. Univariate and multivariable logistic regression were used to evaluate the independent risk variables. The performance was assessed by obtaining Receiver Operating Characteristic (ROC) curves for the clinical, radiomics, and combined models, and then the Decision Curve Analysis (DCA) assessed the clinical applicability of each model. RESULTS: Sex, volume, shape, and intensity mean were chosen by univariate analysis to establish the clinical model. Two radiomics features were retained by LASSO regression to build the radiomics model. In the training cohort, the Area Under the Curve (AUC) of the radiomics (AUC=0.844) and combined model (AUC=0.871) was higher than the clinical model (AUC=0.773). In evaluating whether or not the sub-centimeter pGGN is benign, the DCA demonstrated that the radiomics and combined model had a greater overall net benefit than the clinical model. CONCLUSION: The radiomics model may be useful in predicting the benign and malignant sub-centimeter pGGN before surgery.