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Abstract Background Radiotherapy is regarded as a milestone for the cure of cervical cancer. However, clinical outcome heavily be hindered by radioresistance. So, exploring the underlying mechanism of radioresistance, and find potential target, well deserve fully emphasis. Methods In this study, we developed two novel radiation resistance cervical cancer cell lines, which could mimic clinical radioresistance. In order to find new potential targets, RNA-Seq, database analysis, streptavidin-agarose and LC/MS were used. Pull-down, luciferase and rescue assays were conducted to explore the regulatory mechanisms. To further evaluate the correlation between therapeutic responses and HMGB3/hTERT expression, 172 cervical cancer patients were recruited. Results Knockdown of HMGB3 significantly inhibit the DNA damage repair and induced more γH2AX foci, leading to enhanced chemo- and radio-sensitivity in vitro and in vivo, whereas HMGB3 overexpression has the opposite effects. HMGB3 promotes cell growth and radioresistance by transcriptionally up-regulating hTERT via the specifical binding of HMGB3 at the hTERT promoter region from − 902 to − 321. HMGB3 knockdown-mediated radiosensitization could be reversed by the overexpressed hTERT in both cervical cancer cell lines and xenograft tumor mouse model. Furthermore, clinical data from 172 cervical cancer patients proved that there was a positive correlation between HMGB3 and hTERT expression, and high expression of HMGB3/hTERT predicted poor response to radiotherapy, worse TNM stages and shorter survival time. Conclusion Here, we have identified HMGB3/hTERT signaling axis as a new target for cervical cancer radioresistance. Our results provide new insights into the mechanism of cervical cancer radioresistance and indicate that targeting the HMGB3/hTERT signaling axis may benefit cervical cancer patients.

This study investigated the factors that caused the differences in egg production during the development of ovarian follicles in Leizhou black ducks. Leizhou black ducks population was divided into 2 groups as high-yield group (HG) and low-yield group (LG). The number of eggs (NE), age at first egg (AFE), weight at first egg, and egg weight (EW) of both groups were recorded, and differences were analyzed using the t test. The logistic model was used to simulate the egg production curves to analyze the production rules. The ovarian follicles of both duck groups were collected to count the number of different grades sized follicles, weigh the ovaries, and observe follicular sections to analyze the developmental differences. Ovarian transcriptomic sequencing was performed to investigate differentially expressed genes and signal pathways in both duck groups. The results revealed a significant difference (P

In complex electromagnetic environments, a clutter covariance matrix is required to estimate in the on-line manner, so as to adaptively adjust the filter weight to effectively suppress clutter, thereby improving target estimation, detection, location, and tracking. In this paper, a non-Gaussian clutter model is considered, while apart of the clutter data maybe contaminated by subspace interference, wherein the signal of interest is located in the subspace. To this end, we propose a knowledge-aided hierarchical Bayesian model and obtain the approximated posterior distribution of the clutter covariance matrix by exploiting variational Bayesian inference methods. The target detection performance can be enhanced using a clutter-suppression filter that is designed based on the posterior mean of the clutter covariance matrix. A comparison of the computer simulation results with real clutter data confirms that the proposed method can suppress the clutter and improve detection performance.

Abstract Background The Microplasty (MP) instrumentation designed for the Phase III Oxford mobile-bearing unicompartmental knee arthroplasty (UKA) system is considered a better option to achieve more accurate component positioning and alignment. In the present study, we focused on short-term clinical and radiological outcomes to determine whether the MP instrumentation can reduce the short-term revision rate and occurrence of outliers of metallic components. Methods The literature in PubMed, Embase, the Cochrane Library, and Web of Science was searched up to May 2020. Studies were scrutinized by two independent authors, and the revision rate, complication spectrum, and radiological assessment with outlier rates were specifically analyzed. RevMan 5.3 was used for the statistical analysis. Results Seven studies were included in the meta-analysis. Four studies reported both clinical and radiological outcomes, two reported only radiological outcomes, and one reported only clinical outcomes. The pooled analysis showed that the revision rate in the MP instrumentation group was 0.866 per 100 component years, while that in the control group was 1.124 (odds ratio, 0.77; p < 0.05). The subgroup analysis of the bearing dislocation rate showed a significantly greater reduction in the Korean population than in the populations of other countries (p < 0.05). The radiological assessment showed that the alignment of the femoral component was significantly improved (p < 0.05), while that of the tibial component was not (p > 0.05). Conclusion The newly developed MP instrumentation for Oxford UKA significantly reduced the revision rate of this treatment. The positioning of the femoral component was also proven to be better by radiological assessments.

Abstract This study determined the growth performance, correlations of linear body dimensions, slaughter performance and the fitting model of two generations of Leizhou Black Ducks. Fifteen (15) male and 225 female parents forming generation 0 were selected from the Leizhou duck population. Fifteen (15) families were created in the ratio of 1 male:15 females. Eggs from all the families were collected and numbered according to the family. Generation 1 ducklings were selected and grouped into families in the same ratio. Body weights (BWs) and linear body dimensions were recorded every 2 weeks from weeks 0 to 16. Logistic, Gompertz and Von Bertalanffy models were employed to ascertain the growth model of both sexes of Leizhou Black Ducks. Except for weeks 0–2, generation 1 families had greater BWs than the generation 0 families (p .05) were observed for males at week 10 and females at 16 weeks old. There was a significant negative correlation (p

Abstract Background Hypertension is highly prevalent and is the primary risk factor for cardiovascular disease (CVD) and chronic kidney disease (CKD). While declining in some developed countries, it is increasing rapidly in some developing countries. Sichuan province is the largest and underdeveloped region in southwest China, with 486 thousand square kilometers, more than 80 million residents, unbalanced economic development, and high prevalence, low awareness, low treatment and low control rate of hypertension. We forecasted the death burden due to high systolic blood pressure (SBP) in Sichuan from 1990 to 2030, to raise the awareness of public and government of the importance and benefits of hypertension control. Methods We conducted secondary analysis based on data of Global Burden of Disease (GBD) 1990–2015, and predicted the population SBP level, population attributable fraction, and death burden for people aged 30–69 under different scenarios in 2030. Results Comparing with natural trend, if the prevalence of high SBP can be reduced relatively by 25% by 2030, the deaths of non-communicable chronic diseases (NCDs), CVD and CKD would be reduced by 27.1 thousand, 26.2 thousand and 0.8 thousand for people aged 30–69; the mortality would be reduced by 10.8, 32.8 and 16.0%; and the premature mortality would be reduced by 9.9, 32.0 and 16.0%, respectively. Conclusions Controlling or decreasing the prevalence of high SBP can significantly reduce the deaths, death rate and premature mortality of NCDs, CVD and CKD for the 30–69 years old population in Sichuan. There would be huge benefits for the governments to take cost-effective measures to control or reduce the prevalence of hypertension.

Abstract Background There has been a growing interest in using diagnosis-related groups (DRGs) payment to reimburse inpatient care worldwide. But its effects on healthcare and health outcomes are controversial, and the evidence from low- and middle- income countries (LMICs) is especially scarce. The objective of this study is to evaluate the effects of DRGs payment on healthcare and health outcomes in China. Method A systematic review was conducted. We searched literature databases of PubMed, Cochrane Library, EMBASE, Web of Science, Chinese National Knowledge Infrastructure and SinoMed for empirical studies examining the effects of DRGs payment on healthcare in mainland China. We performed a narrative synthesis of outcomes regarding expenditure, efficiency, quality and equity of healthcare, and assessed the quality of evidence. Results Twenty-three publications representing thirteen DRGs payment studies were included, including six controlled before after studies, two interrupted time series studies and five uncontrolled before-after studies. All studies compared DRGs payment to fee-for-service, with or without an overall budget, in settings of tertiary (7), secondary (7) and primary care (1). The involved participants varied from specific groups to all inpatients. DRGs payment mildly reduced the length of stay. Impairment of equity of healthcare was consistently reported, especially for patients exempted from DRGs payment, including: patient selection, cost-shifting and inferior quality of healthcare. However, findings on total expenditure, out of pocket payment (OOP) and quality of healthcare were inconsistent. The quality of the evidence was generally low or very low due to the study design and potential risk of bias of included studies. Conclusion DRGs payment may mildly improve the efficiency but impair the equity and quality of healthcare, especially for patients exempted from this payment scheme, and may cause up-coding of medical records. However, DRGs payment may or may not contain the total expenditure or OOP, depending on the components design of the payment. Policymakers should very carefully consider each component of DRGs payment design against policy goals. Well-designed randomised trials or comparative studies are warranted to consolidate the evidence of the effects of DRGs payment on healthcare and health outcomes in LMICs to inform policymaking.

(E)-7-Phenyl-2-hepten-4,6-diyn-1-ol (1) and (Z)-7-Phenyl-2-hepten-4,6-diyn-1-ol (2) are isomeric natural polyacetylenes isolated from the Chinese medicinal plant Bidens pilosa L. This study first revealed the excellent anti-metastasis potential of these two polyacetylenes on human gastric cancer HGC-27 cells and the distinctive molecular mechanisms underlying their activities. Polyacetylenes 1 and 2 significantly inhibited the migration, invasion, and adhesion of HGC-27 cells at their non-toxic concentrations in a dose-dependent manner. The results of a further mechanism investigation showed that polyacetylene 1 inhibited the expressions of Vimentin, Snail, β-catenin, GSK3β, MST1, YAP, YAP/TAZ, and their phosphorylation, and upregulated the expression of E-cadherin and p-LATS1. In addition, the expressions of various downstream metastasis-related proteins, such as MMP2/7/9/14, c-Myc, ICAM-1, VCAM-1, MAPK, p-MAPK, Sox2, Cox2, and Cyr61, were also suppressed in a dose-dependent manner. These findings suggested that polyacetylene 1 exhibited its anti-metastasis activities on HGC-27 cells through the reversal of the EMT process and the suppression of the Wnt/β-catenin and Hippo/YAP signaling pathways.

Exosomes are vesicles secreted by various kinds of cells, and they are rich in cholesterol, sphingomyelin (SM), phosphatidylcholine, and phosphatidylserine. Although cellular sphingolipid-mediated exosome release has been reported, the involvement of other lipid components of cell membranes in the regulation of exosome release is poorly understood. Here, we show that the level of exosome release into conditioned media is significantly reduced in cultured astrocytes prepared from apolipoprotein E (ApoE) knock-out mice when compared to those prepared from wild-type (WT) mice. The reduced level of exosome release was accompanied by elevated levels of cellular cholesterol. The addition of cholesterol to WT astrocytes significantly increased the cellular cholesterol levels and reduced exosome release. PI3K/Akt phosphorylation was enhanced in ApoE-deficient and cholesterol-treated WT astrocytes. In contrast, the depletion of cholesterol in ApoE-deficient astrocytes due to treatment with β-cyclodextrin recovered the exosome release level to a level similar to that in WT astrocytes. In addition, the reduced levels of exosome release due to the addition of cholesterol recovered to the control levels after treatment with a PI3K inhibitor (LY294002). The cholesterol-dependent regulation of exosome release was also confirmed by in vivo experiments; that is, exosome levels were significantly reduced in the CSF and blood serum of WT mice that were fed a high-fat diet and had increased cholesterol levels when compared to those in WT mice that were fed a normal diet. These results suggest that exosome release is regulated by cellular cholesterol via stimulation of the PI3K/Akt signal pathway.

The purpose of this article is to provide a succinct summary of the sleep monitoring efforts that have been used in nocturnal enuresis (NE) and an overview of the knowledge that has accrued. This is not intended to be a comprehensive review, but rather is intended to highlight how polysomnography (PSG), a common sleep detection tool, has contributed to our understanding of NE, as arousal disorder is considered to be one of the important mechanisms. The authors have organized this report by analysis and display of different ingredients of PSG, starting with comparing the electroencephalogram (EEG) of controls and the enuretic children and then moving to evaluation of respiratory patterns of NE and comorbid disease obstructive sleep apnea (OSA). In addition, the authors' goal is to better understand the mechanism of NE by integrating various levels of sleep monitoring; those sleep-related clinical scale scores for NE are presented to date. Finally, we propose further research of NE to explore the microstructure alterations via PSG combined with EEG–fMRI or to use novel technology like portable device internet and deep learning strategy.

Airborne radars are susceptible to a large number of clutter, noise and variable jamming signals in the real environment, especially when faced with active main lobe jamming, as the waveform shortcut technology in the traditional regime can no longer meet the actual battlefield radar anti-jamming requirements. Therefore, it is necessary to study anti-main-lobe jamming techniques for airborne radars in complex environments to improve their battlefield survivability. In this paper, we propose an airborne radar waveform design method based on a deep reinforcement learning (DRL) algorithm under clutter and jamming conditions, after previous research on reinforcement-learning (RL)-based airborne radar anti-jamming waveform design methods that have improved the anti-jamming performance of airborne radars. The method uses a Markov decision process (MDP) to describe the complex operating environment of airborne radars, calculates the value of the radar anti-jamming waveform strategy under various jamming states using deep neural networks and designs the optimal anti-jamming waveform strategy for airborne radars based on the duelling double deep Q network (D3QN) algorithm. In addition, the method uses an iterative transformation method (ITM) to generate the time domain signals of the optimal waveform strategy. Simulation results show that the airborne radar waveform designed based on the deep reinforcement learning algorithm proposed in this paper improves the signal-to-jamming plus noise ratio (SJNR) by 2.08 dB and 3.03 dB, and target detection probability by 26.79% and 44.25%, respectively, compared with the waveform designed based on the reinforcement learning algorithm and the conventional linear frequency modulation (LFM) signal at a radar transmit power of 5 W. The airborne radar waveform design method proposed in this paper helps airborne radars to enhance anti-jamming performance in complex environments while further improving target detection performance.

Abstract Introduction Targeted therapies are based on specific gene alterations. Various specimen types have been used to determine gene alterations, however, no systemic comparisons have yet been made. Herein, we assessed alterations in selected cancer‐associated genes across varying sample sites in lung cancer patients. Materials and Methods Targeted deep sequencing for 48 tumor‐related genes was applied to 153 samples from 55 lung cancer patients obtained from six sources: Formalin‐fixed paraffin‐embedded (FFPE) tumor tissues, pleural effusion supernatant (PES) and pleural effusion cell sediments (PEC), white blood cells (WBCs), oral epithelial cells (OECs), and plasma. Results Mutations were detected in 96% (53/55) of the patients and in 83% (40/48) of the selected genes. Each sample type exhibited a characteristic mutational pattern. As anticipated, TP53 was the most affected sequence (54.5% patients), however this was followed by NOTCH1 (36%, across all sample types). EGFR was altered in patient samples at a frequency of 32.7% and KRAS 10.9%. This high EGFR/ low KRAS frequency is in accordance with other TCGA cohorts of Asian origin but differs from the Caucasian population where KRAS is the more dominant mutation. Additionally, 66% (31/47) of PEC samples had copy number variants (CNVs) in at least one gene. Unlike the concurrent loss and gain in most genes, herein NOTCH1 loss was identified in 21% patients, with no gain observed. Based on the relative prevalence of mutations and CNVs, we divided lung cancer patients into SNV‐dominated, CNV‐dominated, and codominated groups. Conclusions Our results confirm previous reports that EGFR mutations are more prevalent than KRAS in Chinese lung cancer patients. NOTCH1 gene alterations are more common than previously reported and reveals a role of NOTCH1 modifications in tumor metastasis. Furthermore, genetic material from malignant pleural effusion cell sediments may be a noninvasive manner to identify CNV and participate in treatment decisions.

Background: In 2018, diagnosis-related group-based prospective payment system (DRG-PPS) was implemented nationwide by China that did not fully consider the additional costs caused by healthcare-associated infections (HAIs). HAIs can increase hospitalization costs, but only a few studies have been conducted in China. We aimed to assess the additional costs caused by HAIs. Methods: A retrospective matched case-control (1:1) study was performed in one of the largest tertiary hospitals in Sichuan Province, China. A multiple linear regression was used to identify confounding factors, and the propensity score matching (PSM) method was used to balance confounding factors between cases and controls. On this basis, we estimated the additional costs caused by HAIs. Results: Of the 109,294 inpatients observed, 1912 had HAI. After the PSM method was implemented, 1686 cases were successfully matched. Median hospitalization costs were €5613.03 for patients with HAIs and €3414.83 for patients without HAIs (P

Abstract Background In the past decade, the rate of cesarean delivery increased dramatically in rural China under the fee-for-service (FFS) system. In September 2011, the New Cooperative Medical Scheme (NCMS) agency in Yong’an county in Fujian province of China adopted a policy of reforming payment for childbirth by transforming the FFS payment into episode-based bundled payment (EBP), which made the cesarean deliveries less profitable. Thus, this study was conducted to determine the effect of EBP policy on reducing cesarean use and controlling delivery costs for rural patients in the NCMS. Methods Data from the inpatient information database of the NCMS agency from January 2010 to March 2013 was collected, in which Yong’an county was employed as a reform county and 2 other counties as controls. We investigated the effects of EBP on cesarean delivery rate, costs of childbirth and readmission for rural patients in the NCMS using a natural experiment design and difference in differences (DID) analysis method. Results The EBP reform was associated with 33.97% (p

Abstract Background ErbB2 overexpression identifies a subset of breast cancer as ErbB2-positive and is frequently associated with poor clinical outcomes. As a membrane-embedded receptor tyrosine kinase, cell surface levels of ErbB2 are regulated dynamically by membrane physical properties. The present study aims to investigate the influence of membrane cholesterol contents on ErbB2 status and cellular responses to its tyrosine kinase inhibitors. Methods The cholesterol abundance was examined in ErbB2-positive breast cancer cells using filipin staining. Cellular ErbB2 localizations were investigated by immunofluorescence with altered membrane cholesterol contents. The inhibitory effects of the cholesterol-lowering drug lovastatin were assessed using cell proliferation, apoptosis, immunoblotting and immunofluorescence assays. The synergistic effects of lovastatin with the ErbB2 inhibitor lapatinib were evaluated using an ErbB2-positive breast cancer xenograft mouse model. Results Membrane cholesterol contents positively correlated with cell surface distribution of ErbB2 through increasing the rigidity and decreasing the fluidity of cell membranes. Reduction in cholesterol abundance assisted the internalization and degradation of ErbB2. The cholesterol-lowering drug lovastatin significantly potentiated the inhibitory effects of ErbB2 kinase inhibitors, accompanied with enhanced ErbB2 endocytosis. Lovastatin also synergized with lapatinib to strongly suppress the in vivo growth of ErbB2-positive breast cancer xenografts. Conclusion The cell surface distribution of ErbB2 was closely regulated by membrane physical properties governed by cholesterol contents. The cholesterol-lowering medications can hence be exploited for potential combinatorial therapies with ErbB2 kinase inhibitors in the clinical treatment of ErbB2-positive breast cancer.

Increasing information capacity is significant for high-speed communication systems in a congested radio frequency sequence. Vortex waves carrying mode orthogonal orbital angular momentum (OAM) have gained considerable attention in recent years, owing to their multiplexing quality. In this study, a broadband Pancharatnam–Berry (PB) metasurface element with a simple structure is proposed, which exhibits an efficient reflection of the co-polarized component and a full 2π phase variation in 10.5–21.5 GHz under circularly polarized wave incidence. By convolution and addition operations, the elaborate phase distribution is arranged and the corresponding metasurface-reflecting dual-mode asymmetric dual-OAM waves is constructed. Under continuous control of the working frequency, the OAM vortex beams with the topological charges 1 and −1 are steered to scan within the angle range of 11.9°–24.9° and 17.9°–39.1° at φ = 315° and 135° planes, respectively. The simulation and measurement results verified the feasibility of generating frequency-controlled asymmetric dual beams and the validity of dual-mode OAM characteristics, both in the near and far fields. This design approach has considerable potential in OAM wave multiplexing and wireless communication system transmission.

Background: Epirubicin is a first-line chemotherapeutic drug for the clinical treatment of diffuse large B cell lymphoma (DLBCL), but the overexpression of multidrug resistance (MDR) transporter proteins, especially P-glycoprotein (P-gp), renders epirubicin ineffective. Some studies reveal the potential role of melatonin in chemotherapeutic synergy and MDR. Methods: The cell viability and apoptosis were determined by CCK-8 assay and acridine orange/ethidium bromide (AO/EB) fluorescence staining assay. Immunofluorescence and immunohistochemical staining were used to detect the expression of P-gp in DLBCL cells and tissues. Rhodamine-123 accumulation assay was used to evaluate the pump function of P-gp. The possible mechanisms of melatonin sensitize DLBCL cells to epirubicin were explored by western blotting, cytochrome C release, and pulldown assay. Results: Melatonin significantly enhanced the epirubicin-induced cell proliferation suppression, epirubicin-induced apoptosis, and reduced the IC50 value of epirubicin. Further, melatonin synergized with epirubicin to promote the activation of the mitochondria-mediated apoptosis pathway and increased the accumulation of epirubicin in DLBCL cells by inhibiting the expression and function of P-gp. Immunohistochemical staining studies revealed that P-gp expression was positively correlated with P65 expression. Epirubicin was subsequently discovered to upregulate the expression of P-gp by activating the NF-κB pathway in the DLBCL cells. Melatonin reduced the amount of P65 protein in the nucleus and abrogated the ability of P65 to bind to the ABCB1 promoter, decisively suppressing P-gp expression. Conclusions: Our results demonstrated that melatonin inactivates the NF-κB pathway and downregulates the expression of P-gp, ultimately sensitizing DLBCL cells to the epirubicin that suppresses their growth.

Nigrosporins B, an anthraquinone derivative obtained from the secondary metabolites of marine fungus Nigrospora oryzae. In this study, we characterized the distinctive anti-cancer potential of Nigrosporins B in vitro and underlying molecular mechanisms in human cervical cancer Ca Ski cells for the first time. The results of MTT assay showed that Nigrosporins B significantly inhibited the proliferation of multiple tumor cells in a dose-dependent manner, especially for the Ca Ski cells with an IC50 of 1.24 µM. Nigrosporins B exerted an apoptosis induction effect on Ca Ski cells as confirmed by flow cytometry, AO/EB dual fluorescence staining, mitochondrial membrane potential analysis and western blot assay. In addition, Nigrosporins B induced obvious autophagy accompanied with the increase of autophagic vacuoles and the acceleration of autophagic flux as indicated by Cyto-ID staining, mRFP-GFP-LC3 adenovirus transfection and western blot analysis. Interestingly, the combination of Nigrosporins B with the three autophagy inhibitors all significantly enhanced the cytotoxicity of Nigrosporins B on Ca Ski cells, indicating that the autophagy induced by Nigrosporins B might protect Ca Ski cells from death. Furthermore, we found that Nigrosporins B inhibited the phosphorylation of PI3K, AKT, mTOR molecules and increased the protein expression levels of PTEN and p-AMPKα in a dose-dependent manner, suggesting that Nigrosporins B induced apoptosis and protective autophagy through the suppression of the PI3K/AKT/mTOR signaling pathway. Together, these findings revealed the anti-cervical cancer effect of Nigrosporins B and the underlying mechanism of action in Ca Ski cells, it might be as a promising alternative therapeutic agent for human cervical cancer.

Fermentation of the endophytic fungus Aplosporella javeedii on solid rice medium in presence of either 3.5% NaNO3 or 3.5% monosodium glutamate caused a significant change of the fungal metabolite pattern compared to fungal controls grown only on rice. Chemical investigation of the former fungal extracts yielded 11 new lactam derivatives, aplosporellins A–K (2–12), in addition to the known compound, pramanicin A (1). All of these compounds were not detected when the fungus was grown on rice medium without these activators thereby indicating the power of this OSMAC approach. The structures of the new compounds were elucidated by one- and two- dimensional NMR spectroscopy, DFT-NMR calculations and by mass spectrometry as well as by comparison with the literature whereas the absolute configuration of the lactam core was determined by TDDFT-ECD and OR calculations. Pramanicin A (1) showed strong cytotoxicity against human lymphoma (Ramos) and leukemia (Jurkat J16) cells with IC50 values of 4.7 and 4.4 μM, respectively. Mechanistic studies indicated that 1 activates caspase-3 and induces apoptotic cell death.

ObjectiveTo examine the association of health insurances on catastrophic health expenditure (CHE), and compares that among different health insurances in the last two decades in China.MethodsThe systematic review was conducted according to the Cochrane Handbook and reported according to PRISMA. We searched English and Chinese literature databases including PubMed, EM base, web of science, CNKI, Wan fang, VIP and CBM (Sino Med) for empirical studies on the association between health insurance and CHE from January 2000 to June 2020. Study selection, data extraction and quality appraisal were conducted by two reviewers. The secular trend of CHE rate and comparisons between population with different health insurances were conducted using meta-analysis, subgroup analysis and meta-regression.ResultsA total of 4874 citations were obtained, and finally 30 eligible studies with 633917 participants were included. The overall CHE rate was 13.6% (95% CI: 13.1% - 14.0%) from Jan 2000 to June 2020, 12.8% (95% CI: 12.2% - 13.3%) for people with health insurance compared with 16.2% (95% CI:15.4% - 16.9%) for people without health insurance. For types of insurance, the CHE rate was 13.0% (95% CI: 12.4% - 13.6%) for people with new rural cooperative medical scheme (NCMS), 11.9% (95% CI: 9.3% - 14.5%) for urban employees health insurance (UEBMI), 12.0% (95% CI: 8.3% - 15.6%) for urban residents health insurance (URBMI), and 18.0% (95% CI: - 4.5% - 31.5%) for commercial insurance. However, the CHE rate in China has increased in the past 20 years, even adjusted for other factors. The CHE rate of people with NCMS has increased significantly more than people with UEBMI and URBMI.ConclusionIn the past 20 years, the basic health insurance plan has reduce the rate of CHE to a certain extent, but due to the rapid increase in medical costs and the release of health needs in recent years, it masks the role of health insurance. More efforts are needed to control unreasonable medical demand and rising costs.

Abstract Background In 2018, the Chinese government demanded nationwide implementation of medical insurance payment methods based on Single-Disease Payment (SDP), but during the operation process the medical insurance system did not fully consider the extra economic burden caused by healthcare-associated infection (HAI). HAIs can prolong the length of stay and increase the hospitalization costs, but only a few studies have been conducted in Sichuan province, China. We evaluated the hospitalization costs and length of stay due to HAI in Sichuan province based on the prevalence survey, and provided data reference for China’s medical insurance reform. Methods In the hospitals surveyed on the prevalence of HAI, a multi-center nested case-control study was performed by a paired method. The study period was from 6 September 2016 to 30 November 2016. Binary outcomes were tested using χ2 test, continuous outcomes were tested using Wilcoxon matched-pairs signed rank test, intra-group comparisons were tested using multiple linear regression analysis. Results A total of 225 pairs/450 patients were selected in 51 hospitals, and 170 pairs/350 patients were successfully matched. The case fatality rate was 5.14% for the HAIs patients and 3.43% for non-HAs patients, there was no significant difference (χ2 = 0.627, P = 0.429); the median length of stay in patients with HAIs was 21 days, longer than that of patients with non-HAI 16 days, the median of the difference between matched-pairs was 5 days, the difference was statistically significant (Z = 4.896, P = 0.000). The median hospitalization costs of patients with HAI were €1732.83, higher than that of patients with non-HAI €1095.29, the median of the difference between matched-pairs were €431.34, the difference was statistically significant (Z = 6.413, P = 0.000). Multiple linear regression results showed that HAIs at different sites have caused different economic burdens, but in different economic regions, the difference was not statistically significant. Conclusions In Sichuan, the hospitalization costs and length of stay caused by HAI should be given special attention in the current medical insurance reform. The proportion and scope of medical payment for patients with HAI at different sites should be different. Efforts need to be taken to incentivize reduction of HAI rates which will reduce hospitalization costs and length of stay.

MicroRNA-140, a cartilage-specific microRNA, has recently been implicated in the cancer progression. However, the comprehensive role of miR-140 in the invasion and metastasis of colorectal cancer (CRC) is still not fully understood. In this study, we confirmed that miR-140 downregulates SMAD family member 3 (Smad3), which is a key downstream effector of the TGF-β signaling pathway, at the translational level in the CRC cell lines. Ectopic expression of miR-140 inhibits the process of epithelial-mesenchymal transition (EMT), at least partially through targeting Smad3, and induces the suppression of migratory and invasive capacities of CRC cells in vitro. miR-140 also attenuates CRC cell proliferation possibly via downregulating Samd3. Furthermore, overexpression of miR-140 inhibits the tumor formation and metastasis of CRC in vivo, and silenced Smad3 has the similar effect. Additionally, miR-140 expression is decreased in the clinical primary CRC specimens and appears as a progressive reduction in the metastatic specimens, whereas Smad3 is overexpressed in the CRC samples. Taken together, our findings suggest that miR-140 might be a key suppressor of CRC progression and metastasis through inhibiting EMT process by targeting Smad3. miR-140 may represent a novel candidate for CRC treatment.

Background/Aims: PI3KCA and mutant p53 are associated with tumorigenesis and the development of cancers. NVP-BKM120, a selective pan-PI3K inhibitor, exerts the antitumor activity by suppressing the PI3K signaling pathway. Prima-1Met, a low molecular weight compound, can rescue the gain-of-function of mutant p53 by restoring its transcriptional function. In this study, we investigated whether PI3K inhibition combined with mutant p53 reactivation could enhance the antitumor effect in thyroid cancer cells. Methods: The effects of BKM120 and Prima-1Met on the proliferation, apoptosis, migration and invasion of thyroid cancer cells were measured by MTT, colony formation, flow cytometry, wound-healing and transwell assays, respectively. Thyroid differentiation was assessed by detecting the expression levels of specific markers using RT-PCR and Western blot. The in vivo antitumor efficacy was analyzed in a mouse xenograft model. Results: The combinational treatment of BKM120 and Prima-1Met significantly enhanced the inhibitions of cell viability, colony formation, migration and invasion, and the induction of apoptosis in thyroid cell lines, and synergistically suppressed tumor xenograft growth by inhibiting the PI3K/Akt/mTOR and EMT signaling pathways, up-regulating p53 targeted genes, and triggering the release of cytochrome c. Moreover, the combination of BKM120 and Prima-1Met suppressed the stemlike traits of thyroid cancer cells and promoted their differentiation by upregulating the expression of thyroid-specific differentiation markers and repressing the expression of cancer stem cell markers. Furthermore, the mechanism study demonstrated that the combinational treatment synergistically abrogated the binding of CPSF4 at the promoter of hTERT and thus suppressed hTERT expression. Consistently, overexpression of hTERT rescued the inhibitions of cell viability, invasion and stem-like traits mediated by the combination of BKM120 and Prima-1Met. Conclusion: Our results showed that the combination of BKM120 with Prima-1Met synergistically suppressed the growth of thyroid cancer cells and tumor xenografts via inhibiting PI3K/Akt/mTOR and CPSF4/hTERT signaling and reactivating mutant p53.

RCE-4, a steroidal saponin isolated from Reineckia carnea, has been studied previously and has exhibited promising anti-cervical cancer properties by inducing programmed cell death (PCD) of Ca Ski cells. Considering the cancer cells developed various pathways to evade chemotherapy-induced PCD, there is, therefore, an urgent need to further explore the potential mechanisms underlying its actions. The present study focused on targeting the Bcl-2–Beclin 1 complex, which is known as the key regulator of PCD, to deeply elucidate the molecular mechanism of RCE-4 against cervical cancer. The effects of RCE-4 on the Bcl-2–Beclin 1 complex were investigated by using the co-immunoprecipitation assay. In addition, autophagy-related genes (ATG) were also analyzed due to their special roles in PCD. The results demonstrated that RCE-4 inhibited the formation of the Bcl-2–Beclin 1 complex in Ca Ski cells via various pathways, and ATG 4B proteins involved in this process served as a key co-factor. Furthermore, based on the above, the sensitivity of RCE-4 to Ca Ski cells was significantly enhanced by inhibiting the expression of the ATG 4B by applying the ATG 4B siRNA plasmid.

Conveyors are used commonly in industrial production lines and automated sorting systems. Many applications require fast, reliable, and dynamic detection and recognition for the objects on conveyors. Aiming at this goal, we design a framework that involves three subtasks: one-class instance segmentation (OCIS), multiobject tracking (MOT), and zero-shot fine-grained recognition of 3D objects (ZSFGR3D). A new level set map network (LSMNet) and a multiview redundancy-free feature network (MVRFFNet) are proposed for the first and third subtasks, respectively. The level set map (LSM) is used to annotate instances instead of the traditional multichannel binary mask, and each peak of the LSM represents one instance. Based on the LSM, LSMNet can adopt a pix2pix architecture to segment instances. MVRFFNet is a generalized zero-shot learning (GZSL) framework based on the Wasserstein generative adversarial network for 3D object recognition. Multi-view features of an object are combined into a compact registered feature. By treating the registered features as the category attribution in the GZSL setting, MVRFFNet learns a mapping function that maps original retrieve features into a new redundancy-free feature space. To validate the performance of the proposed methods, a segmentation dataset and a fine-grained classification dataset about objects on a conveyor are established. Experimental results on these datasets show that LSMNet can achieve a recalling accuracy close to the light instance segmentation framework You Only Look At CoefficienTs (YOLACT), while its computing speed on an NVIDIA GTX1660TI GPU is 80 fps, which is much faster than YOLACT’s 25 fps. Redundancy-free features generated by MVRFFNet perform much better than original features in the retrieval task.

Abstract Background Circulating tumor cells (CTCs) have been accepted as a prognostic marker in patients with metastatic colorectal cancer (mCRC, UICC stage IV). However, the prognostic value of CTCs in patients with non-metastatic colorectal cancer (non-mCRC, UICC stage I-III) still remains in dispute. A meta-analysis was performed to investigate the prognostic significance of CTCs detected by the RT-PCR method in patients diagnosed with non-mCRC patients. Methods A comprehensive literature search for relevant articles was performed in the EmBase, PubMed, Ovid, Web of Science, Cochrane library and Google Scholar databases. The studies were selected according to predetermined inclusion/exclusion criteria. Using the random-effects model of Stata software, version12.0 (2011) (Stata Corp, College Station, TX, USA), to conduct the meta-analysis, and the hazard ratio (HR), risk ratio (RR) and their 95% confidence intervals (95% CIs) were regarded as the effect measures. Subgroup analyses and meta-regression were also conducted to clarify the heterogeneity. Results Twelve eligible studies, containing 2363 patients with non-mCRC, were suitable for final analyses. The results showed that the overall survival (OS) (HR = 3.07, 95% CI: [2.05–4.624], P

Abstract Background N-myc (and STAT) interactor (NMI) plays vital roles in tumor growth, progression, and metastasis. In this study, we identified NMI as a potential tumor suppressor in lung cancer and explored its molecular mechanism involved in lung cancer progression. Methods Human lung cancer cell lines and a mouse xenograft model was used to study the effect of NMI on tumor growth. The expression of NMI, COX-2 and relevant signaling proteins were examined by Western blot. Tissue microarray immunohistochemical analysis was performed to assess the correlation between NMI and COX-2 expression in lung cancer patients. Results NMI was highly expressed in normal lung cells and tissues, but lowly expressed in lung cancer cells and tissues. Overexpression of NMI induced apoptosis, suppressed lung cancer cell growth and migration, which were mediated by up-regulation of the cleaved caspase-3/9 and down-regulation of phosphorylated PI3K/AKT, MMP2/MMP9, β-cadherin, and COX-2/PGE2. In contrast, knockdown of NMI promoted lung cancer cell colony formation and migration, which were correlated with the increased expression of phosphorylated PI3K/AKT, MMP2/MMP9, β-cadherin and COX-2/PGE2. Further study showed that NMI suppressed COX-2 expression through inhibition of the p50/p65 NF-κB acetylation mediated by p300. The xenograft lung cancer mouse models also confirmed the NMI-mediated suppression of tumor growth by inhibiting COX-2 signaling. Moreover, tissue microarray immunohistochemical analysis of lung adenocarcinomas also demonstrated a negative correlation between NMI and COX-2 expression. Kaplan-Meier analysis indicated that the patients with high level of NMI had a significantly better prognosis. Conclusions Our study showed that NMI suppressed tumor growth by inhibiting PI3K/AKT, MMP2/MMP9, COX-2/PGE2 signaling pathways and p300-mediated NF-κB acetylation, and predicted a favorable prognosis in human lung adenocarcinomas, suggesting that NMI was a potential tumor suppressor in lung cancer.

Trametenolic acid B (TAB) was a lanostane-type triterpenoid isolated from the trametes lactinea (Berk.) Pat. We have previously reported that extract from trametes lactinea (Berk.) Pat and TAB could efficiently improve learning and memory ability of the cerebral ischemia injury rats and suppress mitochondrial-mediated apoptosis in hydrogen peroxide damaged SH-SY5Y cells. However, the potential mechanisms have not been fully understood yet. The current study was to further investigate the protective effect of TAB on oxygen glucose deprivation/reoxygenation (OGD/R)-damaged SH-SY5Y cells and cerebral ischemia/reperfusion (I/R) injury rats, as well as its mechanisms involved. Cell experiments demonstrated that TAB (10, 20 and 40 μg/mL) protected OGD/R-induced SH-SY5Y cell injury by promoting cell proliferation and suppressing LDH leakage; Meanwhile, the results in vivo showed that TAB (20, 40 and 80 mg/kg) might significantly ameliorate the neurological deficit score, cerebral edema, neuronal cell loss and apoptosis, suppress cerebral infarction volume of the cerebral I/R injury rats. Further studies in vitro and in vivo indicated TAB could efficiently reduce OGD/R-damaged SH-SY5Y cell and cerebral I/R rat serum ROS, LDH and MDA levels, elevate SOD, GSH-Px and CAT activities, downregulate miR-10a mRNA and Bax, cytochrome C, cleaved-caspase-3 and cleaved-caspase-9 protein expressions, upregulate p-PIK3CA, p-Akt, p-mTOR, Bcl-2, pro-caspase-9 and pro-caspase-3 protein expressions and p-PIK3CA/PIK3CA, p-Akt/Akt, p-mTOR/mTOR ratios (P

A 2D floor plan (FP) often contains structural, decorative, and functional elements and annotations. Vectorization of floor plans (VFP) is an object detection task that involves the localization and recognition of different structural primitives in 2D FPs. The detection results can be used to generate 3D models directly. The conventional pipeline of VFP often consists of a series of carefully designed complex algorithms with insufficient generalization ability and suffer from low computing speed. Considering the VFP is not suitable for deep learning-based object detection frameworks, this paper proposed a new VFP framework to solve this problem based on a generative adversarial network (GAN). First, a private dataset called ZSCVFP is established. Unlike current public datasets that only own not more than 5000 black and white samples, ZSCVFP contains 10,800 colorful samples disturbed by decorative textures in different styles. Second, a new edge-extracting GAN (EdgeGAN) is designed for the new task by formulating the VFP task as an image translation task innovatively that involves the projection of the original 2D FPs into a primitive space. The output of EdgeGAN is a primitive feature map, each channel of which only contains one category of the detected primitives in the form of lines. A self-supervising term is introduced to the generative loss of EdgeGAN to ensure the quality of generated images. EdgeGAN is faster than the conventional and object-detection-framework-based pipeline with minimal performance loss. Lastly, two inspection modules that are also suitable for conventional pipelines are proposed to check the connectivity and consistency of PFM based on the subspace connective graph (SCG). The first module contains four criteria that correspond to the sufficient conditions of a fully connected graph. The second module that classifies the category of all subspaces via one single graph neural network (GNN) should be consistent with the text annotations in the original FP (if available). The reason is that GNN treats the adjacent matrix of SCG as weights directly. Thus, GNN can utilize the global layout information and achieve higher accuracy than other common classifying methods. Experimental results are given to illustrate the efficiency of the proposed EdgeGAN and inspection approaches.

Finger vein (FV) biometrics is one of the most promising individual recognition traits, which has the capabilities of uniqueness, anti-forgery, and bio-assay, etc. However, due to the restricts of imaging environments, the acquired FV images are easily degraded to low-contrast, blur, as well as serious noise disturbance. Therefore, how to extract more efficient and robust features from these low-quality FV images, remains to be addressed. In this paper, a novel feature extraction method of FV images is presented, which combines curvature and radon-like features (RLF). First, an enhanced vein pattern image is obtained by calculating the mean curvature of each pixel in the original FV image. Then, a specific implementation of RLF is developed and performed on the previously obtained vein pattern image, which can effectively aggregate the dispersed spatial information around the vein structures, thus highlight vein patterns and suppress spurious non-boundary responses and noises. Finally, a smoother vein structure image is obtained for subsequent matching and verification. Compared with the existing curvature-based recognition methods, the proposed method can not only preserve the inherent vein patterns, but also eliminate most of the pseudo vein information, so as to restore more smoothing and genuine vein structure information. In order to assess the performance of our proposed RLF-based method, we conducted comprehensive experiments on three public FV databases and a self-built FV database (which contains 37,080 samples that derived from 1030 individuals). The experimental results denoted that RLF-based feature extraction method can obtain more complete and continuous vein patterns, as well as better recognition accuracy.

Circulating tumor cells (CTCs) have been considered as an alternative to tissue biopsy for providing both germline-specific and tumor-derived genetic variations. Single-cell analysis of CTCs enables in-depth investigation of tumor heterogeneity and individualized clinical assessment. However, common CTC enrichment techniques generally have limitations of low throughput and cell damage. Herein, based on micropore-arrayed filtration membrane and microfluidic chip, we established an integrated CTC isolation platform with high-throughput, high-efficiency, and less cell damage. We observed a capture rate of around 85% and a purity of 60.4% by spiking tumor cells (PC-9) into healthy blood samples. Detection of CTCs from lung cancer patients demonstrated a positive detectable rate of 87.5%. Additionally, single CTCs, ctDNA and liver biopsy tissue of a representative advanced lung cancer patient were collected and sequenced, which revealed comprehensive genetic information of CTCs while reflected the differences in genetic profiles between different biological samples. This work provides a promising tool for CTCs isolation and further analysis at single-cell resolution with potential clinical value.

Chemical investigation of secondary metabolites from the endophytic fungus Pseudopestalotiopsis theae led to the isolation of eighteen new polyketide derivatives, pestalotheols I−Q (1−9) and cytosporins O−W (15−23), together with eight known analogs (10−14 and 24−26). The structures of the new compounds were elucidated by HRMS and 1D and 2D NMR data, as well as by comparison with literature data. Modified Mosher’s method was applied to determine the absolute configuration of some compounds. Compound 23 showed significant cytotoxicity against the mouse lymphoma cell line L5178Y with an IC50 value of 3.0 μM. Furthermore, compounds 22 and 23 showed moderate antibacterial activity against drug-resistant Acinetobacter baumannii (ATCC BAA-1605) in combination with sublethal colistin concentrations.

OBJECTIVE:To investigate the effect of elemene on the radiosensitivity of A549 cells and its possible molecular mechanism.METHODS:Apoptosis of A549 cells was detected by flow cytometry and fluorescence microscopy. The effect of double-strand break (DSB) damage repair in A549 cells was evaluated using the neutral comet assay. Protein expression levels were detected using western blotting, and the correlation between protein levels was analyzed.RESULTS:Elemene exhibited a radiosensitizing effect on A549 cells. The level of apoptosis induced by elemene combined with radiation was significantly greater (p

Seeking a strategy for triggering the cryptic natural product biosynthesis to yield novel compounds in the plant-associated fungus Xylaria sp., the effect of culture conditions on metabolite production was investigated. A shift in the production of five known cytochalasin-type analogues 1–5 to six new α-pyrone derivatives, xylapyrones A–F (compounds 6–11), from a solid to a liquid medium was observed. These compounds were identified by analysis of 1D and 2D NMR and HRMS data. Compounds 1–3 showed moderate cytotoxicity against HepG2 and Caski cancer cell lines with IC50 values ranging from 25 to 63 μM and compounds 4–11 were found to be inactive, with IC50 values >100 μM.

Background: Unintentional injuries among 0- to 4-year-olds are a major public health problem incurring substantial NHS, individual and societal costs. However, evidence on the effectiveness and cost-effectiveness of preventative interventions is lacking. Aim: To increase the evidence base for thermal injury, falls and poisoning prevention for the under-fives. Methods: Six work streams comprising five multicentre case–control studies assessing risk and protective factors, a study measuring quality of life and injury costs, national surveys of children’s centres, interviews with children’s centre staff and parents, a systematic review of barriers to, and facilitators of, prevention and systematic overviews, meta-analyses and decision analyses of home safety interventions. Evidence from these studies informed the design of an injury prevention briefing (IPB) for children’s centres for preventing fire-related injuries and implementation support (training and facilitation). This was evaluated by a three-arm cluster randomised controlled trial comparing IPB and support (IPB+), IPB only (no support) and usual care. The primary outcome was parent-reported possession of a fire escape plan. Evidence from all work streams subsequently informed the design of an IPB for preventing thermal injuries, falls and poisoning. Results: Modifiable risk factors for falls, poisoning and scalds were found. Most injured children and their families incurred small to moderate health-care and non-health-care costs, with a few incurring more substantial costs. Meta-analyses and decision analyses found that home safety interventions increased the use of smoke alarms and stair gates, promoted safe hot tap water temperatures, fire escape planning and storage of medicines and household products, and reduced baby walker use. Generally, more intensive interventions were the most effective, but these were not always the most cost-effective interventions. Children’s centre and parental barriers to, and facilitators of, injury prevention were identified. Children’s centres were interested in preventing injuries, and believed that they could prevent them, but few had an evidence-based strategic approach and they needed support to develop this. The IPB was implemented by children’s centres in both intervention arms, with greater implementation in the IPB+ arm. Compared with usual care, more IPB+ arm families received advice on key safety messages, and more families in each intervention arm attended fire safety sessions. The intervention did not increase the prevalence of fire escape plans [adjusted odds ratio (AOR) IPB only vs. usual care 0.93, 95% confidence interval (CI) 0.58 to 1.49; AOR IPB+ vs. usual care 1.41, 95% CI 0.91 to 2.20] but did increase the proportion of families reporting more fire escape behaviours (AOR IPB only vs. usual care 2.56, 95% CI 1.38 to 4.76; AOR IPB+ vs. usual care 1.78, 95% CI 1.01 to 3.15). IPB-only families were less likely to report match play by children (AOR 0.27, 95% CI 0.08 to 0.94) and reported more bedtime fire safety routines (AOR for a 1-unit increase in the number of routines 1.59, 95% CI 1.09 to 2.31) than usual-care families. The IPB-only intervention was less costly and marginally more effective than usual care. The IPB+ intervention was more costly and marginally more effective than usual care. Limitations: Our case–control studies demonstrate associations between modifiable risk factors and injuries but not causality. Some injury cost estimates are imprecise because of small numbers. Systematic reviews and meta-analyses were limited by the quality of the included studies, the small numbers of studies reporting outcomes and significant heterogeneity, partly explained by differences in interventions. Network meta-analysis (NMA) categorised interventions more finely, but some variation remained. Decision analyses are likely to underestimate cost-effectiveness for a number of reasons. IPB implementation varied between children’s centres. Greater implementation may have resulted in changes in more fire safety behaviours. Conclusions: Our studies provide new evidence about the effectiveness of, as well as economic evaluation of, home safety interventions. Evidence-based resources for preventing thermal injuries, falls and scalds were developed. Providing such resources to children’s centres increases their injury prevention activity and some parental safety behaviours. Future work: Further randomised controlled trials, meta-analyses and NMAs are needed to evaluate the effectiveness and cost-effectiveness of home safety interventions. Further work is required to measure NHS, family and societal costs and utility decrements for childhood home injuries and to evaluate complex multicomponent interventions such as home safety schemes using a single analytical model. Trial registration: Current Controlled Trials ISRCTN65067450 and ClinicalTrials.gov NCT01452191. Funding: The National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 5, No. 14. See the NIHR Journals Library website for further project information.

Though the risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA) has been established in Western population, little is known about the risk in Chinese people with RA. Our objective was to estimate the risk of CVD in Chinese people with RA using hospital medical records data.The inpatients medical record database 2005-2015 of Sichuan provincial people's hospital was examined. All individuals with a primary diagnosis of RA were included as cases, and those of osteoarthritis (OA) were included as controls, which consisted of the unmatched dataset. Then, RA cases and OA controls were matched by sex and age at 1:1 ratio, forming the matched dataset. The morbidity of CVD (including ischemia heart disease (IHD), congestive heart failure (CHF), et al), stroke and arthrosclerosis were extracted from the database, so as the demographic data and comorbidities related to CVD. Multiple logistic regression analysis was used to estimate the risk of CVD in RA adjusted for demographics and comorbidities using the unmatched dataset. Sensitivity analysis was conducted 1) considering interaction terms between RA and comorbidities, and 2) using multivariable conditional logistic regression for the matched dataset.The unmatched dataset comprised of 1824RA cases and 1995 OA controls and the matched dataset comprised of 1022 pairs of sex and age matched RA and OA patients. RA exhibited increased odds of prevalent CVD compared with OA, and the adjusted ORs (95%CIs) for CVD, stroke, IHD, CHF, and atherosclerosis were1.86(1.42-2.43), 1.11(0.71-1.74), 1.47(0.97-2.24), 2.09(1.03-4.22), and 2.49 (1.97-3.13), respectively, and was 2.26 (1.29-3.96)for IHD further adjusted for interaction term. The matched dataset analysis found similar results.Chinese people with RA were approximated 2 times more likely to have CVD, IHD, CHF and atherosclerosis compared with those with OA. The findings justified the need of further longitudinal study to establish the causal-relationship between RA and CVD and to estimate the precise risk in this population.

Five new 2(5H)-furanone-type derivatives, pestalafuranones F–J (compounds 3–7), together with two known compounds, pestalafuranones A (1) and B (2), were isolated from the ethyl acetate extract from the fermentation broth of the endophytic fungus Nigrospora sp. BM-2 in a hypersaline medium. The structures of these metabolites were elucidated by EIMS, HREIMS and NMR spectroscopic data. Compounds 1–7 exhibited no cytotoxic activities against the MDA-MB-231 and Caski cancer cell lines.

Background: The antitumor activity of CLE-10 (4-epi-isoinuviscolide), a sesquiterpene lactone compound, isolated from Carpesium abrotanoides L. has rarely been reported. The aim of this study is to investigate the antitumor activity of CLE-10 and give a greater explanation of its underlying mechanisms. Methods: The cytotoxicity of CLE-10 was evaluated using MTT assay. Autophagy was detected by the formation of mRFP-GFP-LC3 fluorescence puncta and observed using transmission electron microscopy, while flow cytometry was employed to detect apoptosis. The protein expressions were detected through Western blotting. Results: CLE-10 induced pro-death autophagy and apoptosis in MDA-MB-231 cells by increasing the protein expression of LC3-II, p-ULK1, Bax, and Bad, as well as downregulating p-PI3K, p-Akt, p-mTOR, p62, LC3-I, Bcl-2, and Bcl-xl. CLE-10 that was pretreated with 3-methyladenine (3-MA) or chloroquine (CQ) weakened the upregulation of the protein expression of p-ULK1, or the downregulation of p62, p-mTOR, and decreased the level of cytotoxicity against MDA-MB-231 cells. Meanwhile, rapamycin enhanced the effect of CLE-10 on the expression of autophagy-related protein and its cytotoxicity, with the IC50 value of CLE-10 decreasing from 4.07 µM to 2.38 µM. Conclusion: CLE-10 induced pro-death autophagy and apoptosis in MDA-MB-231 cells by upregulating the protein expressions of LC3-II, p-ULK1, Bax, and Bad and downregulating p-PI3K, p-Akt, p-mTOR, p62, Bcl-2, and Bcl-xl.

Aspergoterpenins A–D (1–4), four new bisabolane sesquiterpenoid derivatives, were obtained from the endophytic fungus, Aspergillus versicolor, together with eight known compounds (5–12), and their structures were elucidated by a comprehensive analysis of their NMR (Nuclear Magnetic Resonance), MS (Mass Spectrum) and CD (Circular Dichroism) spectra. Aspergoterpenin A (1) was the first example with a characteristic ketal bridged-ring part in the degraded natural bisabolane-type sesquiterpene structures. The compounds 1–12 displayed no significant activities against four cancer cell lines (A549, Caski, HepG2 and MCF-7). Further, the antimicrobial activities to Erwinia carotovora sub sp. Carotovora were evaluated, and the results showed that compounds 1–12 displayed antimicrobial activities with MIC values ranging from 15.2 to 85.2 μg/mL.

Two furostanol saponins were obtained from the rhizomes of Tupistra chinensis Bak. Their structures were determined as 5β-furost-δ25(27)-en-1β,2β,3β,4β,5β,7α,22ξ,26- octaol-6-one-26-O-β-D-glucopyranoside (1) and 5β-furost-δ25(27)-en-1β,2β,3β,4β,5β,6β, 7α,22ξ,26-nonaol-26-O-β-D-glucopyranoside (2), on the basis of chemical and spectroscopic evidence. Both compounds displayed marked inhibitory action against NO production in rat abdomen macrophages induced by lipopolysaccharide (LPS) at 40 μg/mL.

Potassium-competitive acid blockers (P-CABs) are highly safe and active drugs targeting H+,K+-ATPase to cure acid-related gastric diseases. In this study, we for the first time investigate the interaction mechanism between the protonated form of P-CABs and human H+,K+-ATPase using homology modeling, molecular docking, molecular dynamics and binding free energy calculation methods. The results explain why P-CABs have higher activities with higher pKa values or at lower pH. With positive charge, the protonated forms of P-CABs have more competitive advantage to block potassium ion into luminal channel and to bind with H+,K+-ATPase via electrostatic interactions. The binding affinity of the protonated form is more favorable than that of the neutral P-CABs. In particular, Asp139 should be a very important binding site for the protonated form of P-CABs through hydrogen bonds and electrostatic interactions. These findings could promote the rational design of novel P-CABs.

Penicitroamide (1), a new metabolite with a new framework, was isolated from the ethyl acetate extract of the PDB (Potato Dextrose Broth) medium of Penicillium sp. (NO. 24). The endophytic fungus Penicillium sp. (NO. 24) was obtained from the healthy leaves of Tapiscia sinensis Oliv. The structure of penicitroamide (1) features a bicyclo[3.2.1]octane core unit with a high degree of carbonylization (four carbonyl groups and one enol group). The chemical structure of penicitroamide (1) was elucidated by analysis of 1D-, 2D-NMR and MS data. In bioassays, penicitroamide (1) displayed antibacterial potency against two plant pathogens, Erwinia carotovora subsp. Carotovora (Jones) Bersey, et al. and Sclerotium rolfsii Sacc. with MIC50 at 45 and 50 μg/mL. Compound 1 also showed 60% lethality against brine shrimp at 10 μg/mL. Penicitroamide (1) exhibited no significant activity against A549, Caski, HepG2 and MCF-7 cells with IC50 > 50 μg/mL. Finally, the possible biosynthetic pathway of penicitroamide (1) was discussed.

Two new thiazole and thiadiazole alkaloids, penicilliumthiamine A and B (2 and 3), were isolated from the culture broth of Penicillium oxalicum, a fungus found in Acrida cinerea. Their structures were elucidated mainly by spectroscopic analysis, total synthesis and X-ray crystallographic analysis. Biological evaluations indicated that compound 1, 3a and 3 exhibit potent cytotoxicity against different cancer cell lines through inhibiting the phosphorylation of AKT/PKB (Ser 473), one of important cancer drugs target.