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Problems, such as toxic side effects and drug resistance of chemoradiotherapy, target therapy and immunotherapy accompanying the current anti-cancer treatments, have become bottlenecks limiting the clinical benefit for patients. Therefore, it is urgent to find promising anti-cancer strategies with higher efficacy and lesser side effects. Baicalein, a flavonoid component derived from the Chinese medicine scutellaria baicalensis, has been widely studied for its remarkable anti-cancer activity in multiple types of malignancies both at the molecular and cellular levels. Baicalein exerts its anti-tumor effects by inhibiting angiogenesis, invasion and migration, inducing cell apoptosis and cell cycle arrest, as well as regulating cell autophagy, metabolism, the tumor microenvironment and cancer stem cells with no obvious toxic side effects. The role of classic signaling pathways, such as PI3K/AKT/mTOR, MAPK, AMPK, Wnt/β-catenin, JAK/STAT3, MMP-2/-9, have been highlighted as the major targets for baicalein exerting its anti-malignant potential. Besides, baicalein can regulate the relevant non-coding RNAs, such as lncRNAs, miRNAs and circ-RNAs, to inhibit tumorigenesis and progression. In addition to the mentioned commonalities, baicalein shows some specific anti-tumor characteristics in some specific cancer types. Moreover, the preclinical studies of the combination of baicalein and chemoradiotherapy pave the way ahead for developing baicalein as an adjunct treatment with chemoradiotherapy. Our aim is to summary the role of baicalein in different types of cancer with its mechanisms based on in vitro and in vivo experiments, hoping providing proof for baicalein serving as an effective and safe compound for cancer treatment in clinic in the future.

Objective: Given the significant impact of long-term traditional Chinese medicine (TCM) treatment on the prognosis of patients with non-small cell lung cancer (NSCLC), we aimed to develop nomograms, with or without consideration of TCM treatment duration, to accurately predict the overall survival (OS) of patients with stage IIIB/IV NSCLC treated with TCM. Methods: Nomograms were developed from a training cohort comprised of 292 patients diagnosed with NSCLC, using univariate and multivariate Cox regression analyses to screen for various prognostic factors with and without TCM treatment. The nomograms were evaluated using the concordance index (C-index), calibration curve, and decision curve analysis (DCA), after which they were validated, using the bootstrap self-sampling method for internal validation, and a validation cohort comprised of 175 patients for external validation. Bootstrap validation is a resampling technique that involves randomly selecting and replacing data from the original dataset to make statistical inferences, thereby circumventing the issue of sample reduction that can arise from cross-validation. Results: We identified seven significant prognostic factors for OS. For nomogram A (excluding TCM treatment time), the C-indexes (95 % confidence interval [CI]) were 0.674 (0.635–0.712) and 0.660 (0.596–0.724) for the training and validation cohorts, respectively. For nomogram B (including TCM treatment time), the C-indices (95 % CI) were 0.846 (0.822–0.870) and 0.783 (0.730–0.894), for the training and validation cohorts, respectively, indicating that nomogram B was superior to nomogram A. Both the calibration curves and DCA results exhibited favorable clinical concordance and usefulness. Conclusion: The nomogram B yielded precise prognostic predictions for patients with advanced NSCLC treated with TCM.

Abstract Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation often obtain de novo resistance or develop secondary resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs), which restricts the clinical benefit for the patients. The activation of phosphatidylinositol 3-kinase (PI3K)/AKT signal pathway is one of the most important mechanisms for the EGFR-TKIs resistance beyond T790M mutation. There are currently no drugs simultaneously targeting EGFR and PI3K signal pathways, and combination of these two pathway inhibitors may be a possible strategy to reverse theses resistances. To test whether this combinational strategy works, we investigated the therapeutic effects and mechanisms of combining BYL719, a PI3Kα inhibitor, with gefitinib, an EGFR-TKI inhibitor in EGFR-TKIs resistance NSCLC models induced by PI3K/AKT activation. Our results demonstrated that PIK3CA mutated cells showed increased growth rate and less sensitive or even resistant to gefitinib, associated with increased PI3K/AKT expression. The combination of BYL719 and gefitinib resulted in synergistic effect compared with the single agents alone in EGFR-mutated NSCLC cells with PI3K/AKT activation. The inhibition of AKT phosphorylation by BYL719 increased the antitumor efficacy of gefitinib in these cell lines. Moreover, the combined effect and mechanism of gefitinib and BYL719 were also confirmed in the NSCLC cells and patient-derived organoids under 3D culture condition, as well as in vivo. Taken together, the data indicate that PIK3CA mutation induces more aggressive growth and gefitinib resistance in NSCLC cells, and the combination treatment with gefitinib and BYL719 is a promising therapeutic approach to overcoming EGFR-TKIs resistance induced by PI3K/AKT activation.

Abstract Background Patients with local gastric cancer experience a decline of Health-related quality of life (HRQOL) during adjuvant chemotherapy following gastrectomy. Our previous pilot study has indicated the potential of acupuncture to improve HRQOL and control cancer-related symptoms burden. This full-scale trial will focus on confirming the effect of acupuncture for patients with gastric cancer. Methods A multicenter, open-label, three-arm randomized controlled trial with 249 patients will be conducted in China. Patients will be randomly assigned, in a ratio of 1:1:1, to receive high-dose acupuncture (HA, 7 times each chemo-cycle for 3 cycles), low-dose acupuncture (LA, 3 times each chemo-cycle for 3 cycles), or no acupuncture. The acupoints prescription consisted of bilateral ST36, PC6, SP4, DU20, EX-HN3, and selected Back-shu points. Patients-reported Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) and modified Edmonton Symptom Assessment Scale (mESAS) during the therapy will be recorded. Area under curve (AUC, 21 days/cycle × 3 cycles) and average trajectory of FACT-Ga and mESAS will be calculated. The primary outcome will be the differences in AUC of the FACT-Ga Trial Outcome Index (TOI) between HA and LA versus control groups. Secondary outcomes include AUCs and average trajectory of other FACT-Ga subscales and mESAS scores. Discussion This study aims to assess the effect of acupuncture and to compare the difference between LA and HA groups on HRQOL and symptom burden controlling in gastric cancer patients by an adequately powered trial. Trial registration This study was approved by the Ethics Committee of the Guangdong Provincial Hospital of Traditional Chinese Medicine (approval number: BF2018-118) with registration at ClinicalTrials.gov (identifier: NCT04360577).

Abstract Retinal ischemia–reperfusion (RIR) injury is involved in the pathogenesis of various vision‐threatening diseases. The overproduction of reactive oxygen species (ROS) is thought to be the main cause of RIR injury. A variety of natural products, including quercetin (Que), exhibit potent antioxidant activity. However, the lack of an efficient delivery system for hydrophobic Que and the presence of various intraocular barriers limit the effective retinal delivery of Que in clinical settings. In this study, we encapsulated Que into ROS‐responsive mitochondria‐targeted liposomes (abbreviated to Que@TPP‐ROS‐Lips) to achieve the sustained delivery of Que to the retina. The intracellular uptake, lysosome escape ability, and mitochondria targeting ability of Que@TPP‐ROS‐Lips were evaluated in R28 retinal cells. Treating R28 cells with Que@TPP‐ROS‐Lips significantly ameliorated the decrease in ATP content, ROS generation, and increase in the release of lactate dehydrogenase in an in vitro oxygen–glucose deprivation (OGD) model of retinal ischemia. In a rat model, the intravitreal injection of Que@TPP‐ROS‐Lips 24 h after inducing retinal ischemia significantly enhanced retinal electrophysiological recovery and reduced neuroinflammation, oxidative stress, and apoptosis. Que@TPP‐ROS‐Lips were taken up by retina for at least 14 days after intravitreal administration. Molecular docking and functional biological experiments revealed that Que targets FOXO3A to inhibit oxidative stress and inflammation. Que@TPP‐ROS‐Lips also partially inhibited the p38 MAPK signaling pathway, which contributes to oxidative stress and inflammation. In conclusion, our new platform for ROS‐responsive and mitochondria‐targeted drug release shows promise for the treatment of RIR injury and promotes the clinical application of hydrophobic natural products.

Background DNA metabarcoding is rapidly emerging as a cost-effective approach for large-scale biodiversity assessment and pest monitoring. The current study employed metabarcoding to assess insect diversity in citrus orchards in Ganzhou City, Jiangxi, China in both 2018 and 2019. Insects were sampled using Malaise traps deployed in three citrus orchards producing a total of 43 pooled monthly samples. Methods The Malaise trap samples were sequenced following DNA metabarcoding workflow. Generated sequences were curated and analyzed using two cloud databases and analytical platforms, the barcode of life data system (BOLD) and multiplex barcode research and visualization environment (mBRAVE). Results These platforms assigned the sequences to 2,141 barcode index numbers (BINs), a species proxy. Most (63%) of the BINs were shared among the three sampling sites while BIN sharing between any two sites did not exceed 71%. Shannon diversity index (H′) showed a similar pattern of BIN assortment at the three sampling sites. Beta diversity analysis by Jaccard similarity coefficient (J) and Bray-Curtis distance matrix (BC) revealed a high level of BIN similarity among the three sites (J = 0.67–0.68; BC = 0.19–0.20). Comparison of BIN records against all those on BOLD made it possible to identify 40% of the BINs to a species, 57% to a genus, 97% to a family and 99% to an order. BINs which received a species match on BOLD were placed in one of four categories based on this assignment: pest, parasitoid, predator, or pollinator. As this study provides the first baseline data on insect biodiversity in Chinese citrus plantations, it is a valuable resource for research in a broad range of areas such as pest management and monitoring beneficial insects in citrus gardens.

ObjectiveWe aimed to study the cut-off values of estimated glomerular filtration rate (eGFR) and the urinary albumin creatinine ratio (UACR) in the normal range for diabetic kidney disease (DKD).MethodsIn this study, we conducted a retrospective, observational cohort study included 374 type 2 diabetic patients who had baseline eGFR ≥60 mL/min/1.73 m2 and UACR 0.05). The discrimination of eGFR at the cut-off value of 84.80 mL/min/1.73 m2 or UACR at 15.5mg/g with the largest Youden’s index was further confirmed in the validation cohort. The decrease rate of eGFR was faster in patients with UACR ≥15.5mg/g (P

Abstract It is widely acknowledged that efficiency of pediatric critical care transport plays a vital role in treatment of critically-ill children. In developing countries, most critically-ill children were transported by ambulance, and a few by air, such as a helicopter or fixed airplane. High-speed train (HST) transport may be a potential choice for critically-ill children to a tertiary medical center for further therapy. This is a single-center, retrospective cohort study from June 01, 2016 to June 30, 2019. All the patients transported to the Pediatric Intensive Care Unit (PICU) of PLA general hospital were divided into two groups, HST group and ambulance group. The propensity score matching method was performed for the comparison between the two groups. Finally, a 2:1 patient matching was performed using the nearest-neighbor matching method without replacement. The primary outcome was hospital mortality. Secondary outcomes included duration of transport, transport cost, hospital stay, and hospitalization cost. A total of 509 critically-ill children were transported and admitted. Of them, 40 patients were transported by HST, and 469 by ambulance. The hospital mortality showed no difference between the two groups (p > 0.05). The transport distance in the HST group was longer than that in the ambulance group (1894.5 ± 907.09 vs. 902.66 ± 735.74, p 0.05). There was no death during the transport. There was no difference between groups regarding the transport cost, hospital stays, and hospitalization cost (p > 0.05). High-quality tertiary medical centers are usually located in megacities. HST transport network for critically-ill children could be established to cover most regions of the country. Without increasing financial burden, HST medical transport can be a potentially promising option to improve the outcomes of critically-ill children in developing countries with developed HST network. Clinical Trial Registration: This study was registered at http://www.chictr.org.cn/index.aspx (chiCTR.gov; Identifier: ChiCTR2000032306).

Abstract Herbivory is a highly sophisticated feeding behavior that requires abilities of plant defense suppression, phytochemical detoxification, and plant macromolecule digestion. For plant‐sucking insects, salivary glands (SGs) play important roles in herbivory by secreting and injecting proteins into plant tissues to facilitate feeding. Little is known on how insects evolved secretory SG proteins for such specialized functions. Here, we investigated the composition and evolution of secretory SG proteins in the brown marmorated stink bug (Halyomorpha halys) and identified a group of secretory SG phospholipase C (PLC) genes with highest sequence similarity to the bacterial homologs. Further analyses demonstrated that they were most closely related to PLCs of Xenorhabdus, a genus of Gammaproteobacteria living in symbiosis with insect‐parasitizing nematodes. These suggested that H. halys might acquire these PLCs from Xenorhabdus through the mechanism of horizontal gene transfer (HGT), likely mediated by a nematode during its parasitizing an insect host. We also showed that the original HGT event was followed by gene duplication and expansion, leading to functional diversification of the bacterial‐origin PLC genes in H. halys. Thus, this study suggested that an herbivore might enhance adaptation through gaining genes from an endosymbiont of its parasite in the tripartite parasitic and symbiotic interactions.

Aim: Vildagliptin (vild) improves diastolic dysfunction and is associated with a lower relative risk of major adverse cardiovascular events in younger patients. The present study aimed to evaluate whether vild prevents the development of diabetic cardiomyopathy in type 2 diabetic mice and identify its underlying mechanisms.Methods: Type 2 diabetic mouse model was generated using wild-type (WT) (C57BL/6J) and miR-21 knockout mice by treatment with HFD/STZ. Cardiomyocyte-specific miR-21 overexpression was achieved using adeno-associated virus 9. Echocardiography was used to evaluate cardiac function in mice. Morphology, autophagy, and proteins levels in related pathway were analyzed. qRT-PCR was used to detect miR-21. Rat cardiac myoblast cell line (H9c2) cells were transfected with miR-21 mimics and inhibitor to explore the related mechanisms of miR-21 in diabetic cardiomyopathy.Results: Vild restored autophagy and alleviated fibrosis, thereby enhancing cardiac function in DM mice. In addition, miR-21 levels were increased under high glucose conditions. miR-21 knockout DM mice with miR-21 knockout had reduced cardiac hypertrophy and cardiac dysfunction compared to WT DM mice. Overexpression of miR-21 aggravated fibrosis, reduced autophagy, and attenuated the protective effect of vild on cardiac function. In high-glucose-treated H9c2 cells, the downstream effectors of sprouty homolog 1 (SPRY1) including extracellular signal-regulated kinases (ERK) and mammalian target of rapamycin showed significant changes following transfection with miR-21 mimics or inhibitor.Conclusion: The results of our study indicate that vild prevents DCM by restoring autophagy through the miR-21/SPRY1/ERK/mTOR pathway. Therefore, miR-21 is a target in the development of DCM, and vild demonstrates significant potential for clinical application in prevention of DCM.

Background: We aimed to determine the role of non-mydriatic fundus examination and artificial intelligence (AI) in screening diabetic retinopathy (DR) in patients with diabetes in the Metabolic Disease Management Center (MMC) in Tianjin, China. Methods: Adult patients with type 2 diabetes mellitus who were first treated by MMC in Tianjin First Central Hospital and Tianjin 4th Center Hospital were divided into two groups according to the time that MMC was equipped with the non-mydriatic ophthalmoscope and AI system and could complete fundus examination independently (the former was the control group, the latter was the observation group). The observation indices were as follows: the incidence of DR, the fundus screening rate of the two groups, and fundus screening of diabetic patients with different course of disease. Results: A total of 5039 patients were enrolled in this study. The incidence rate of DR was 18.6%, 29.8%, and 49.6% in patients with diabetes duration of ⩽1 year, 1–5 years, and >5 years, respectively. The screening rate of fundus in the observation group was significantly higher compared with the control group (81.3% versus 28.4%, χ 2 = 1430.918, p

Objective. The present study explored the association between insulin resistance (IR) and the clinical characteristics of thyroid nodules in patients with type 2 diabetes mellitus (T2DM). Methods. All the patients were newly diagnosed with T2DM. 201 patients with thyroid nodule disease and 308 patients without the nodular thyroid disease. The participants were evaluated by relevant examination. Correlation analyses and regression analyses were performed to examine the relationships between the two groups. Results. HOMA-IR values, serum FT4 (free thyroxine) levels, and age were higher in the thyroid nodule group than in the control group. The proportion of women in the thyroid nodule group is greater than the proportion of women in the control group. Logistic regression analysis showed that age, sex, FT4, and HOMA-IR were positive factors for thyroid nodule. The volume and size of the thyroid nodule were positively correlated with HOMA-IR, irrespective of gender. The thyroid nodule volume and size and the TSH (thyroid stimulating hormone) were greater in females than in males, whereas FT3 (free triiodothyronine) was lower in females. Conclusion. IR might be a risk factor for thyroid nodule. Whether alleviating the IR might slow the growth, or diminish the volume and size of the thyroid nodules, is yet to be elucidated.

Ferroelectrics have recently attracted attention as a candidate class of materials for use in photovoltaic devices due to their abnormal photovoltaic effect. However, the current reported efficiency is still low. Hence, it is urgent to develop narrow-band gap ferroelectric materials with strong ferroelectricity by low-temperature synthesis. In this paper, the perovskite bismuth ferrite BiFeO3 (BFO) thin films were fabricated on SnO2: F (FTO) substrates by the sol−gel method and they were rapidly annealed at 450, 500 and 550 °C, respectively. The microstructure and the chemical state’s evolution with annealing temperature were investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS), and the relationship between the microstructure and electric, optical and photovoltaic properties were studied. The XRD, SEM and Raman results show that a pure phase BFO film with good crystallinity is obtained at a low annealing temperature of 450 °C. As the annealing temperature increases, the film becomes more uniform and has an improved crystallinity. The XPS results show that the Fe3+/Fe2+ ratio increases and the ratio of oxygen vacancies/lattice oxygen decreases with increasing annealing temperature, which results in the leakage current gradually being reduced. The band gap is reduced from 2.68 to 2.51 eV due to better crystallinity. An enhanced photovoltaic effect is observed in a 550 °C annealed BFO film with a short circuit current of 4.58 mA/cm2 and an open circuit voltage of 0.15 V, respectively.

We have investigated the adsorption of hydrogen of multiwall carbon nanotubes synthesized by the pyrolysis method using a lanthanum nickel hydrogen storage alloy as a catalyst. The mechanism of carbon nanotubes synthesized using a La–Ni alloy catalyst is discussed. In the hydrogen atmosphere and high-temperature process of carbon nanotube preparation, the LaNi[sub 5] alloy particle may be changed into an intermetallic compound of Ni and La by the analysis of the x-ray diffraction patterns and energy-dispersive x-ray spectroscopy of the nanotubes samples using a La–Ni alloy as a catalyst. The H[sub 2] uptake capacity of the carbon nanotubes using a La–Ni alloy catalyst is about 5 wt % through to the pressure of 10 MPa. Using a La–Ni alloy as a catalyst increases the effect of chemistry adsorption in the H[sub 2] adsorption of the La–Ni alloy catalyzed carbon nanotubes. The P–C–T curve has an approximate plateau. The La–Ni alloy catalyzed carbon nanotubes have better activation for H[sub 2] uptake and larger hydrogen uptake in comparison to the carbon nanotubes without using a La–Ni alloy catalyst, and the hydrogen uptake increases with increasing hydrogen pressure from 2 MPa to 8 MPa at room temperature. The hydrogen uptake versus time showing a hydrogen uptake rate of carbon nanotubes using the La–Ni alloy catalyst was raised by the heat treatment from 1.0 wt % (heat treatment temperature 100 °C) to 2.3 wt % (heat treatment temperature 700 °C) at the H[sub 2] pressure of 5 MPa. © 2003 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Tests the hypothesis that apolipoprotein E (apoE) inhibition of cell migration is mediated through the activation of cAMP/protein kinase A pathways. Results showing that apoE increased intracellular cAMP levels after five minutes and that the increase was sustained for more than an hour; Failure of apoE to increase cAMP levels or inhibit migration of LRP-1-negative mouse embryonic fibroblasts and LRP-1-deficient smooth muscle cells.

Platelet-derived growth factor (PDGF) stimulates expression of matrix metalloproteinases (MMPs), including stromelysin-1 (MMP-3). Induction of these expressions is known to occur during the course of atherosclerosis, tumor invasion, and metastasis. We investigated PDGF-alpha receptor (alphaR)- and beta receptor (betaR)-mediated signaling pathways for the expression of MMP-3 and invasion activity using porcine aortic endothelial (PAE) cells with stable expression of normal or mutated PDGF receptors. RT-PCR and Western blot analyses revealed that PDGF-BB induces MMP-3 expression in PAE cells that exclusively express either the PDGF-alphaR or the -betaR, but not in non-transfected control cells. To identify the signals necessary for PDGF receptor-mediated induction of MMP-3 expression, several lines of PAE cells expressing mutant PDGF receptors were further analyzed. Cells expressing mutant PDGF receptors unable to associate with Src or PLCgamma, retained the ability to induce MMP-3 expression as a result of PDGF-BB stimulation. However, incubation with PDGF-BB did not induce MMP-3 expression in cells expressing a mutant PDGF-betaR unable to associate with phosphatidylinositol 3(')-kinase (PI3K). LY294002, a PI3K inhibitor, reduced PDGF-BB-stimulated MMP-3 expression in PAE cells expressing wild-type PDGF receptors. In contrast, PDGF-BB induced MMP-3 expression in the presence of U-73122, a PLCgamma inhibitor. Moreover, PDGF-BB enhanced the invasiveness of cells expressing wild type PDGF-beta receptors, but not of cells expressing mutant PDGF-betaRs impaired in their ability to associate with PI3K. In light of these results, it appears that PDGF-BB is capable of inducing MMP-3 expression through both the PDGF-alphaR and the -betaR, and the effects are contributed by the PI3K-mediated transduction pathways., ((c) 2002 Elsevier Science (USA).)