Radiomic signatures reveal multiscale intratumor heterogeneity associated with tissue tolerance and survival in re-irradiated nasopharyngeal carcinoma: a multicenter study.

BACKGROUND: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. METHODS: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. RESULTS: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity. CONCLUSIONS: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.

Colonization of multidrug-resistant Gram-negative bacteria increases risk of surgical site infection after hemorrhoidectomy: a cross-sectional study of two centers in southern China.

PURPOSE: The present study aims to determine the rectoanal colonization rate and risk factors for the colonization of present multidrug-resistant bacteria (MDRBs). In addition, the relationship between MDRB colonization and surgical site infection (SSI) following hemorrhoidectomy was explored. METHODS: A cross-sectional study was conducted in the Department of Colorectal Surgery of two hospitals. Patients with hemorrhoid disease, who underwent hemorrhoidectomy, were included. The pre-surgical screening of multidrug-resistant Gram-negative bacteria (MDR-GNB) colonization was performed using rectal swabs on the day of admission. Then, the MDRB colonization rate was determined through the rectal swab. Logistic regression models were established to determine the risk factors for MDRB colonization and SSI after hemorrhoidectomy. A p-value of < 0.05 was considered statistically significant. RESULTS: A total of 432 patients met the inclusion criteria, and the MDRB colonization prevalence was 21.06% (91/432). The independent risk factors for MDRB colonization were as follows: patients who received ≥ 2 categories of antibiotic treatment within 3 months (odds ratio (OR): 3.714, 95% confidence interval (CI): 1.436-9.605, p = 0.007), patients with inflammatory bowel disease (IBD; OR: 6.746, 95% CI: 2.361-19.608, p < 0.001), and patients with high serum uric acid (OR: 1.006, 95% CI: 1.001-1.010, p = 0.017). Furthermore, 41.57% (37/89) of MDRB carriers and 1.81% (6/332) of non-carriers developed SSIs, with a total incidence of 10.21% (43/421). Based on the multivariable model, the rectoanal colonization of MDRBs (OR: 32.087, 95% CI: 12.052-85.424, p < 0.001) and hemoglobin < 100 g/L (OR: 4.130, 95% CI: 1.556-10.960, p = 0.004) were independently associated with SSI after hemorrhoidectomy. CONCLUSION: The rectoanal colonization rate of MDRBs in hemorrhoid patients is high, and this was identified as an independent risk factor for SSI after hemorrhoidectomy.

Supervised Object-Specific Distance Estimation from Monocular Images for Autonomous Driving.

Accurate distance estimation is a requirement for advanced driver assistance systems (ADAS) to provide drivers with safety-related functions such as adaptive cruise control and collision avoidance. Radars and lidars can be used for providing distance information; however, they are either expensive or provide poor object information compared to image sensors. In this study, we propose a lightweight convolutional deep learning model that can extract object-specific distance information from monocular images. We explore a variety of training and five structural settings of the model and conduct various tests on the KITTI dataset for evaluating seven different road agents, namely, person, bicycle, car, motorcycle, bus, train, and truck. Additionally, in all experiments, a comparison with the Monodepth2 model is carried out. Experimental results show that the proposed model outperforms Monodepth2 by 15% in terms of the average weighted mean absolute error (MAE).

Targeting PI3K/AKT/mTOR Signaling Pathway as a Radiosensitization in Head and Neck Squamous Cell Carcinomas.

Globally, there are over half a million new patients with head and neck squamous cell carcinomas (HNSCC) every year. The current therapeutic approaches to HNSCC are surgery and adjuvant radiotherapy. These approaches carry a high incidence of metastasis or recurrence from HNSCC cells' radioresistance. Recent studies have revealed that a combination with radiosensitizers can be used to improve the radioresistance in HNSCC; however, few agents are approved as radiosensitizers. The constitutive activation of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is a vitally oncogenic type of signaling that promotes tumorigenesis, metastasis, and radiotherapy resistance in HNSCC. Pharmacological targeting of PI3K/AKT/mTOR signaling pathway is considered a promising strategy of radiosensitization in HNSCC. In this review, we summarize the oncogenic significance of PI3K/AKT/mTOR signaling in HNSCC with radiotherapy resistance and highlight the therapeutic potential of small molecule inhibitors against PI3K/AKT/mTOR signaling for the radiosensitization in HNSCC treatment. It provides a mechanistic framework for the development of new drugs for radiosensitization in HNSCC radiotherapy via targeting PI3K/AKT/mTOR signaling pathway.

Anion-Recognition Studies of a Rhenium(I) 4-Mercaptopyridine Compound and Its Ligand-Coupling Products.

The reaction of Re(CO)5Cl with 4-mercaptopyridine (4-PySH) led to the formation of [Re(CO)3(4-HPyS)3]Cl (1), showing three hydrogen-bonding donors of 4-PySH ligands as well as a characteristic ligand-to-metal charge-transfer absorption at ca. 380 nm. In this regard, a variety of anions, i.e., CN-, OAc-, F-, Cl-, Br-, I-, PF6-, NO3-, ClO4-, and H2PO4-, were examined to study anion-recognition studies through hydrogen-bonding functionalities. Upon the addition of CN- to a methanolic solution of complex 1, a remarkable spectral change with an isosbestic point at ca. 314 nm in the absorption spectra was observed, with a binding constant (Kb) calculated to be 24770 M-1. Moreover, the OAc- anion also shows a similar trend, but a mild spectral change, with Kb calculated to be 2170 M-1. Unlike those of CN- and OAc-, the addition of F-, Cl-, Br-, and I- anions causes a less pronounced spectral change with an isosbestic point at ca. 350 nm and Kb calculated to be 2863-750 M-1. However, almost no spectral change can be observed for other anions (i.e., PF6-, NO3-, H2PO4-, and ClO4-). Interestingly, the molecular loops of [Re(CO)3Cl(Py2S2)]2 (2; Py2S2 = 4,4'-dipyridyl disulfide) and [Re(CO)3Cl(Py2S)0.35(Py2S2)0.65]2 (3; Py2S = 4,4'-dipyridyl sulfide) can be isolated and structurally characterized by X-ray diffraction, where those crystals were grown from diethyl ether diffusion into a methanolic solution of complex 1 with [Bu4N]CN and [Bu4N]NO3, respectively. It is noted that such unusual ligand-coupling reactions toward the homoligand and hybrid-ligand loops of complexes 2 and 3 can be achieved at room temperature in this study.

Resveratrol ameliorates thymus senescence changes in D-galactose induced mice.

The thymic microenvironment plays an important role in the development of T cells. A decrease of thymic epithelial cells is the main cause of age-related thymic atrophy or degeneration. Resveratrol (RSV), a phytoalexin produced from plants, has been shown to inhibit the adverse effects of dietary obesity on the structure and function of the thymus. D-Galactose (D-gal) can induce accelerated aging in mice. In the present study, young mice (2 months old) were injected with D-gal (120 mg/kg/day) for 8 consecutive weeks to construct an accelerated aging model. Compared with normal control mice, the thymus epithelium of the D-gal treated mice had structural changes, the number of senescent cells increased, the number of CD4+ T cells decreased, and CD8+ T cells increased. After RSV administration by gavage for 6 weeks, it was found that RSV improved the surface phenotypes of D-gal treated mice, and recovered thymus function by maintaining the ratio of CD4+ to CD8+ cells. It also indicated that RSV enhanced the cell proliferation and inhibited cell senescence. Increased autoimmune regulator (Aire) expression was present in the RSV treated mice. The lymphotoxin-beta receptor (LTßR) expression also increased. These findings suggested that RSV intake could restore the alterations caused by D-gal treatment in the thymus via stimulation of Aire expression.

Rosmarinic acid reverses non-small cell lung cancer cisplatin resistance by activating the MAPK signaling pathway.

Cisplatin (DDP) is one of the first-line chemotherapeutic agents for non-small cell lung cancer (NSCLC). However, repeated use of cisplatin in clinical practice often induces chemoresistance. The aims of this study were to investigate whether rosmarinic acid (RA) could reverse multidrug resistance (MDR) in NSCLC and to explore the underlying mechanisms. Our data demonstrated that RA significantly inhibited NSCLC cell proliferation and cell colony formation in a dose-dependent manner, induced G1 phase cell cycle arrest and apoptosis, and increased the sensitivity of cell lines resistant to DDP. Mechanistically, RA inhibited NSCLC cell growth, arrested cell cycle, and induced apoptosis by activating MAPK and inhibiting the expression of P-gp and MDR1, which correspondingly enhanced p21 and p53 expression. We observed that the growth of xenograft tumors derived from NSCLC cell lines in nude mice was significantly inhibited by combination therapy. We demonstrate that RA is a potentially effective MDR reversal agent for NSCLC, based on downregulation of MDR1 mRNA expression and P-gp. Together, these results emphasize the putative role of RA as a resistance reversal agent in NSCLC.

Eukaryotic Initiation Factor 5A2 Contributes to the Maintenance of CD133(+) Hepatocellular Carcinoma Cells via the c-Myc/microRNA-29b Axis.

Cancer stem cells (CSCs)/cancer-initiating cells (CICs) are suggested responsible for driving cancer resistance to conventional therapies and for cancer recurrence and/or metastasis. CD133 is served as a key biomarker to identify and characterize this subpopulation of cells in hepatocellular carcinoma (HCC). Our previous study indicated that overexpression of eukaryotic initiation factor 5A2 (EIF5A2) promotes HCC cell metastasis and angiogenesis. In this study, we demonstrated that EIF5A2 might play a crucial role in CSCs regulation and investigated its potential molecular mechanisms. Using quantitative real-time polymerase chain reaction assay, we observed that the expression of EIF5A2 positively correlated with CD133 levels in a cohort of cancerous and noncancerous liver tissues and cells. Next, HCC cells with high expression of EIF5A2 have a strong capacity to form undifferentiated tumor spheres in vitro and show elevated levels of stem cell-related genes, leading to an increased ability to develop tumors when subcutaneously injected into nude mice. Furthermore, differential microRNA expression was profiling between two EIF5A2-depleted HCC cell lines and their control one identified a decreased expression of miR-29b in EIF5A2-depleted cell lines. Further functional studies illustrated that downregulated miR-29b level is responsible for EIF5A2-maintained HCC cell stemness either in vitro or in vivo. Moreover, enforced expression of EIF5A2 in HCC cells largely enhanced the binding of c-Myc on the promoter of miR-29b and downregulation of miR-29b by EIF5A2 was dependent on c-Myc. Our findings, collectively, reveal that EIF5A2 contributes to the maintenance of CD133+ HCC cells via the c-Myc/miR-29b axis. Stem Cells 2018;36:180-191.

Unfolded protein response regulates yeast small GTPase Arl1p activation at late Golgi via phosphorylation of Arf GEF Syt1p.

ADP ribosylation factor (Arf) GTPases are key regulators of membrane traffic at the Golgi complex. In yeast, Arf guanine nucleotide-exchange factor (GEF) Syt1p activates Arf-like protein Arl1p, which was accompanied by accumulation of golgin Imh1p at late Golgi, but whether and how this function of Syt1p is regulated remains unclear. Here, we report that the inositol-requiring kinase 1 (Ire1p)-mediated unfolded protein response (UPR) modulated Arl1p activation at late Golgi. Arl1p activation was dependent on both kinase and endo-RNase activities of Ire1p. Moreover, constitutively active transcription factor Hac1p restored the Golgi localization of Arl1p and Imh1p inIRE1-deleted cells. Elucidating the mechanism of Ire1p-Hac1p axis actions, we found that it regulated phosphorylation of Syt1p, which enhances Arl1p activation, recruitment of Imh1p to the Golgi, and Syt1p interaction with Arl1p. Consistent with these findings, the induction of UPR by tunicamycin treatment increases phosphorylation of Syt1p, resulting in Arl1p activation. Thus, these findings clarify how the UPR influences the roles of Syt1p, Arl1p, and Imh1p in Golgi transport.

CLDN14 is epigenetically silenced by EZH2-mediated H3K27ME3 and is a novel prognostic biomarker in hepatocellular carcinoma.

Trimethylation of lysine 27 on histone H3 (H3K27ME3) is a transcription-suppressive histone mark mediated by enhancer of zeste homolog 2 (EZH2). We have previously suggested that EZH2-mediated H3K27ME3 plays a critical oncogenic role in human hepatocellular carcinoma (HCC) aggressiveness. However, the direct downstream targets of EZH2-H3K27ME3 and the molecular mechanisms by which regulates HCC pathogenesis remain unclear. In this study, we used chromatin immunoprecipitation together with high-throughput sequencing (ChIP-seq) and gene expression profiling by microarray analysis to assess genome-wide chromatin occupancy of H3K27ME3 in HCC cells. We identified that claudin14 (CLDN14) is a potentially direct target for EZH2-mediated H3K27ME3 in HCC. In a large cohort of clinical HCC tissues, we found that low expression of CLDN14 was significantly associated with advanced tumor stage and determined to be an independent predictor of shortened survival of HCC patients. Next, functional experiment demonstrated that depletion of CLDN14 substantially restored EZH2-silenced HCC cells motility and invasive capacities and supported cell epithelial-mesenchymal transition (EMT). Furthermore, downregulation of CLDN14 dramatically re-enhanced the wnt/ß-catenin signaling activity in EZH2-silenced HCC cells by increasing the levels of active ß-catenin and promoting the nuclear localization of ß-catenin. These results, collectively, uncover that CLDN14 is a novel direct target of EZH2-mediated H3K27ME3, and provide an explanation for the aggressive nature of HCC with downregulation of CLDN14 and the underling mechanism that links the tumor suppressor CLDN14 to the wnt/ß-catenin signaling pathway.

Elevated levels of plasma D-dimer predict a worse outcome in patients with nasopharyngeal carcinoma.

BACKGROUND: Hemostatic alterations occur during the development of cancer. Plasma D-dimer is a hypercoagulability and fibrinolytic system marker that is increased in patients with various solid tumours. The aim of this study was to evaluate the hemostatic status of nasopharyngeal carcinoma (NPC) patients by assessing plasma D-dimer levels to investigate its value as a prognostic marker. METHODS: We retrospectively analysed 717 patients with nasopharyngeal carcinoma, and we applied Cox regression and log-rank tests to assess the association of D-dimer levels with disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS). D-dimer levels were measured using a quantitative D-dimer latex agglutination assay. RESULTS: Using the 3rd quartile values (0.8 µg/L) as the optimal cut-offs, we found that patients with high D-dimer levels have a shorter 3-year DFS, (79%, 95%CI (73.1-84.9)) vs. (69%, 95%CI (59.2-78.8)), DMFS (87%, 95%CI (83.1-90.9)) vs. (77%, 95%CI (69.2-84.8)), and overall survival (82%, 95%CI (76.1-87.9)) vs. (76%, 95%CI (66.2-85.8)). Multivariate analysis revealed that pre-treatment D-dimer levels and EBV DNA were significant independent factors for DFS, DMFS, and OS in NPC patients. Subgroup analyses indicated that the plasma D-dimer levels could effectively stratify patient prognosis for early cancer, advanced stage cancer, and patients with EBV DNA ≥4000 copies/ml. CONCLUSIONS: High D-dimer levels were associated with poor disease-free survival, distant metastasis-free survival, overall survival, and increased risk of mortality in NPC patients. Prospective trials are required to assess the prognostic value of D-dimer levels.

Anti-Cancer Effects of CDK4/6 Inhibitor LEE011 and Chemotherapy Drugs on Lymphocytic Leukemia L1210 Cells.

BACKGROUND/AIM: Chronic lymphocytic leukemia is a slowly-progressing disease in which symptoms often do not manifest until years after disease onset. In advanced stages, infection and bleeding are common. Past studies have shown that the interaction between CDK4/6 inhibitors and chemotherapy drugs can enhance the anti-tumor efficacy of drugs and limit toxicity. Therefore, in this study, the treatment effects of combining the CDK4/6 inhibitor LEE011 with chemotherapy drugs bendamustine or hydroxyurea were investigated in vitro. MATERIALS AND METHODS: The mouse lymphocytic leukemia cell line L1210 was treated with LEE011 combined with hydroxyurea or bendamustine. Western blot and flow cytometry were performed to elucidate the mechanisms behind tumor suppression. RESULTS: LEE011 combined with hydroxyurea or bendamustine significantly inhibited proliferation of L1210 cell lines in a concentration- and time-dependent manner as well as increased the arrest of cells in G1 and S phases. The combination of LEE011 with hydroxyurea also reduced the phosphorylation of Rb while increased the expression of total Rb protein. Furthermore, reduced expression of GPX4, which is a key protein in ferroptosis, indicates that the tumor suppression effects of this drug combination could involve ferroptosis. CONCLUSION: CDK4/6 inhibitor LEE011 treatment alone may not be a suitable treatment option for lymphocytic leukemia; however, our findings in vitro support the combination of LEE011 with chemotherapy drugs to enhance anti-tumor activity in lymphocytic leukemia.

Comparative chemical profiling of leaf essential oils from Cinnamomum kanehirae and related species using steam distillation and solvent extraction: Implications for plant-based classification.

Cinnamomum kanehirae Hayata, belonging to Lauraceae family, is an indigenous and endangered species of considerable economic importance in Taiwan. It plays a crucial role as the host for the economically valuable saprotrophic fungus, Taiwanofungus camphorates. However, accurate species identification poses a challenge due to the similarity in morphological features and frequent natural hybridization with closely related species. Acquiring high-quality and pure leaf oils becomes imperative for precise species identification and producing superior goods. In this study, our objective was to establish methodologies for analyzing the chemical composition of leaf essential oils and subsequently apply this knowledge to differentiate among three Cinnamomum species. Gas chromatography-mass spectrometry (GC/MS) was employed to scrutinize the chemical makeup of leaf essential oils from three closely related species: C. kanehirae, C. micranthum, and C. camphora. We utilized Steam Distillation (SD) and steam distillation-solvent extraction (SDSE) methods, with the SDSE-Hexane approach chosen for optimization, enhancing extraction efficiency and ensuring essential oil purity. Through the SDSE-Hexane method, we identified seventy-four compounds distributed across three major classes: monoterpenes hydrocarbons (0.0-7.0 %), oxygenated monoterpenes (3.8-90.9 %), sesquiterpenes hydrocarbons (0.0-28.3 %), and oxygenated sesquiterpenes (1.6-88.1 %). Our findings indicated the presence of more than one chemotype in both C. kanehirae and C. camphora, whereas no specific chemotype could be discerned in C. micranthum. Furthermore, clustering based on chemotypes allowed for the differentiation of samples from the three species. Notably, we demonstrated that the chemical compositions of grafted C. kanehirae remained largely unaffected by the rootstock. Conversely, natural hybrids between C. kanehirae and C. camphora exhibited profiles more closely aligned with C. kanehirae. The optimized extraction method and the chemotype-based classification system established in this study present valuable tools for essential oil preparation, species identification, and further exploration into the genetic variation of Cinnamomum.

Three species of rape responded to cadmium and melatonin alleviating Cd-toxicity in species-specific strategy.

Cadmium (Cd) pollution has been a significant concern in heavy metal pollution, prompting plants to adopt various strategies to mitigate its damage. While the response of plants to Cd stress and the impact of exogenous melatonin has received considerable attention, there has been limited focus on the responses of closely related species to these factors. Consequently, our investigation aimed to explore the response of three different species of rape to Cd stress and examine the influence of exogenous melatonin in this scenario. The research findings revealed distinctive responses among the investigated rape species. B. campestris showed the resistance to Cd and exhibited lower Cd absorption and sustained its physiological activity under Cd stress. In contrast, B. juncea accumulated much Cd and increased the amount of anthocyanin to mitigate the Cd-damage. Furthermore, B. napus showed the tolerance to Cd and tended to accumulate Cd in vacuoles under Cd stress, thereby decreasing the Cd damage and leading to higher activity of antioxidant enzymes and photosynthesis. Moreover, the application of exogenous melatonin significantly elevated the melatonin level in plants and mitigated Cd toxicity by promoting the activity of antioxidant enzymes, reducing Cd absorption, enhancing the chelating capacity with Cd, decreasing Cd accumulation in organelles, and reducing its fluidity. Specifically, exogenous melatonin increased the FHAc content in B. campestris, elevated the phytochelatins (PCs) level in B. napus, and stimulated photosynthesis in B. juncea. In summary, the findings underscore the species-specific responses of the three species of rape to both Cd stress and exogenous melatonin, highlighting the potential for tailored mitigation strategies based on the unique characteristics of each species.

Radiomic signatures associated with tumor immune heterogeneity predict survival in locally recurrent nasopharyngeal carcinoma.

BACKGROUND: The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma (lrNPC) is limited due to their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in lrNPC. METHODS: This multicenter, retrospective study included 921 patients with lrNPC. A machine learning signature and nomogram based on pretreatment MRI features were developed for predicting overall survival (OS) in a training cohort and validated in two independent cohorts. A clinical nomogram and an integrated nomogram were constructed for comparison. Nomogram performance was evaluated by concordance index (C-index) and receiver operating characteristic curve analysis. Accordingly, patients were classified into risk groups. The biological characteristics and immune infiltration of the signature were explored by RNA sequencing (RNA-seq) analysis. RESULTS: The machine learning signature and nomogram demonstrated comparable prognostic ability to a clinical nomogram, achieving C-indexes of 0.729, 0.718, and 0.731 in the training, internal, and external validation cohorts, respectively. Integration of the signature and clinical variables significantly improved the predictive performance. The proposed signature effectively distinguished patients between risk groups with significantly distinct OS rates. Subgroup analysis indicated the recommendation of local salvage treatments for low-risk patients. Exploratory RNA-seq analysis revealed differences in interferon response and lymphocyte infiltration between risk groups. CONCLUSIONS: An MRI-based radiomic signature predicted OS more accurately. The proposed signature associated with tumor immune heterogeneity may serve as a valuable tool to facilitate prognostic stratification and guide individualized management for lrNPC patients.

[Clinicopathological characteristics and prognosis of malignant pleural mesothelioma].

OBJECTIVE: To investigate the clinicopathological characteristics and prognosis of malignant pleural mesothelioma. METHODS: Thirty patients with malignant pleural mesothelioma diagnosed between January 2006 and June 2012 in our hospital were studied retrospectively. Clinical manifestations, radiological characteristics, endoscopic features, histopathology, and survival status were analyzed. RESULTS: There were 15 males and 15 females, with a median age of 58 years. The commonest clinical symptoms were dyspnea on exertion (26 cases), followed by chest pain (15 cases). The main radiological manifestations were small to large amount of pleural effusions (28 cases), often accompanied by pleural thickening and/or pleural nodules.Of the 30 cases, 25 were diagnosed through medical thoracoscopy and 1 through surgical thoracoscopy. Thoracic lesions manifested as nodules of diffuse distribution on the diaphragmatic pleura and parietal pleura.Some pleural surface was covered with lesions like white tiles.Histopathological examination showed epithelial type in 24 cases, sarcomatoid type in 5 and biphasic type in 1 case.Immonohistological examination showed that the positive rates of calretinin, MC, D2∼40 were 27, 25 and 19 cases respectively.Fifteen patients received chemotherapy, 2 underwent pleurectomy, and 8 were treated with best supportive care. Twenty-four patients were followed for 1 month to 6 years, and 6 patients were lost.Overall survival time was 1-54 months. Those who survived longer than 24 months received chemotherapy with pemetrexed and cisplatin/carboplatin or pleurectomy. CONCLUSIONS: Clinical manifestations of malignant pleural mesotheliome were nonspecific, medical thoracoscopy can make early diagnosis. The pathological diagnosis of malignant pleural mesothelioma was based on immunohistochemical examination, calretinin, MC and D2-40 had positive diagnostic value. Malignant pleural mesothelioma had poor prognosis, chemotherapy with pemetrexed and cisplatin/carboplatin could prolong the survival time of the patients.

Correlation between PTSD and sleep quality in community-dwelling elderly adults in Hunan province of China.

Background: To understand the occurrence of post-traumatic stress disorder (PTSD) and the current status of sleep quality among community-dwelling elderly adults in Hunan Province of China, to explore the correlation between the two, and to analyze the trend of sleep disorders in PTSD elderly adults. Methods: A simple random sample containing 1,173 community-dwelling elderly adults in Hunan Province was established between March and May 2022, and an on-site face-to-face survey was administered using the PTSD Checklist-Civilian Version (PCL-C) with good reliability and validity, the Pittsburgh Sleep Quality Index (PSQI) scale, and a self-designed general condition questionnaire. Results: The incidence of PTSD in the 1,173 participants was 14.3% (168/1,173). The total incidence of sleep disorders was 40.9% (480/1,173); more specifically, the incidence of sleep disorders in participants with no PTSD symptom, in participants with mild-to-moderate PTSD symptoms, and in participants with severe PTSD symptoms was 36.3, 69.8, and 66.7%, respectively. The Spearman's rank correlation analysis showed that the total PTSD score and the scores of each dimension (i.e., re-experiencing symptom cluster, avoidance symptom cluster and hypervigilance symptom cluster) were positively correlated with the total PSQI score and its dimension scores (i.e., sleep quality, time to fall asleep, sleep duration, sleep efficiency, sleep disturbance, hypnotic medication, and daytime function) (P < 0.05). The correlation coefficients ranged from 0.013 to 0.495. For all PSQI dimensions, the differences across participants with different degrees of PTSD were statistically significant (P < 0.05). Conclusions: The overall status of PTSD and sleep quality in community-dwelling elderly adults in Hunan Province was not optimistic. The elderly with PTSD were more prone to sleep disorders, and the more severe the symptoms of PTSD, the poorer the sleep quality was. However, differences were observed in the scores of each dimension of sleep across participants with different degrees of PTSD. Regardless of the degree of PTSD symptoms, the sleep quality of the elderly is severely affected, and the occurrence rate is not unlimited.

Downregulation of ATP1A1 Expression by Panax notoginseng (Burk.) F.H. Chen Saponins: A Potential Mechanism of Antitumor Effects in HepG2 Cells and In Vivo.

The Na+/K+-ATPase α1 subunit (ATP1A1) is a potential target for hepatic carcinoma (HCC) treatment, which plays a key role in Na+/K+ exchange, metabolism, signal transduction, etc. In vivo, we found that Panax notoginseng saponins (PNS) could inhibit tumor growth and significantly downregulate the expression and phosphorylation of ATP1A1/AKT/ERK in tumor-bearing mice. Our study aims to explore the potential effects of PNS on the regulation of ATP1A1 and the possible mechanisms of antitumor activity. The effects of PNS on HepG2 cell viability, migration, and apoptosis were examined in vitro. Fluorescence, Western blot, and RT-PCR analyses were used to examine the protein and gene expression. Further analysis was assessed with a Na+/K+-ATPase inhibitor (digitonin) and sorafenib in vitro. We found that the ATP1A1 expression was markedly higher in HepG2 cells than in L02 cells and PNS exhibited a dose-dependent effect on the expression of ATP1A and the regulation of AKT/ERK signaling pathways. Digitonin did not affect the expression of ATP1A1 but attenuated the effects of PNS on the regulation of ATP1A1/AKT/ERK signaling pathways and enhanced the antitumor effect of PNS by promoting nuclear fragmentation. Taken together, PNS inhibited the proliferation of HepG2 cells via downregulation of ATP1A1 and signal transduction. Our findings will aid a data basis for the clinical use of PNS.

Functionality of Djulis (Chenopodium formosanum) By-Products and In Vivo Anti-Diabetes Effect in Type 2 Diabetes Mellitus Patients.

Djulis (Chenopodium formosanum Koidz.) is a species of cereal grain native to Taiwan. It is rich in dietary fibre and antioxidants and therefore reputed to relieve constipation, suppress inflammation, and lower blood glucose. The aim of this study was to investigate the composition and physicochemical properties of dietary fibre from djulis hull. Meanwhile, determination of the in vivo antidiabetic effect on patients with type 2 diabetes mellitus (T2DM) after consuming the djulis hull powder. Djulis hull contained dietary fibre 75.21 ± 0.17% dry weight, and insoluble dietary fibre (IDF) reached 71.54 ± 0.27% dry weight. The IDF postponed the adsorption of glucose and reduced the activity of α-amylase. Postprandial blood glucose levels in patients with T2DM showed three different tendencies. First, the area under the glucose curve was significantly lower after ingesting 10 or 5 g djulis hull powder, which then postponed the adsorption of glucose, but the area under the glucose curve was similar with the two doses. After consuming 10 g djulis hull before 75 g glucose 30 and 60 min after the meal, patients with T2DM had blood glucose values that were significantly lower at the same postprandial times than those of patients who did not consume djulis hull. In short, patients who consumed djulis hull prior to glucose administration had decreased blood glucose level compared with those who did not. Djulis hull may have benefits for patients with T2DM.

Toward Heteronuclear Molecular Re(I)-Cu(II) Boxes: Structural, Luminescent, and Magnetic Properties.

The bifunctional ligands of isonicotinic acid (Py-4-COOH) and 4-pyrid-4-ylbenzoic acid (Pybz-4-COOH) instead of polypyridines were therefore reacted with (Re(CO)4)3(C3N3S3) (C3N3S3 = cyanurate trianion), resulting in the formation of two trinuclear [(Re(CO)3)3(C3N3S3)(Py-4-COOH)3] (1) and [(Re(CO)3)3(C3N3S3)(Pybz-4-COOH)3] (2), respectively. In the meantime, both complexes 1 and 2 are connected by three bifurcated hydrogen bonds between their carboxylic acid moieties Py-4-COOH and Pybz-4-COOH to form the supramolecular trigonal-prismatic and -antiprismatic structures, respectively. It is noted that complex 1 can further react with copper(II) nitrate upon deprotonation to give nonanuclear [(Re(CO)3)3(C3N3S3)(Py-4-COO)3]2Cu3(H2O)9 (3), where two trinuclear [(Re(CO)3)3(C3N3S3)(Py-4-COO)3] moieties are connected by three penta-coordinate copper(II) ions, each coordinating to two carboxylates and three water molecules, to form the trigonal-prismatic structure. Surprisingly, addition of pyrazine (pz) in the synthetic process of complex 3 resulted in serendipitous isolation of a rare example of octadecanuclear {[(Re(CO)3)3(C3N3S3)(Py-4-COO)3]2Cu3(H2O)6(pz)2}2 (4), which can be regarded as a dimer of complex 3, connected by two bridging pz ligands. Interestingly, both complexes 3 and 4 are heteronuclear molecular Re(I)-Cu(II) boxes, constructed by a complex-as-a-ligand strategy. Furthermore, complexes 1 and 2 can exhibit respective low-energy luminescence at ca. 561 and 534 nm at room temperature upon photoexcitation, and complex 3 is found to display antiferromagnetic coupling of -127.68 and -134.70 cm-1, possibly due to multiple hydrogen bonds inducing significant Cu(II)···Cu(II) coupling.