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Background: Xihuang pill, a Traditional Chinese Medicine (TCM) prescription and a representative of Huoxuehuayu therapy (one of the TCM therapies to promote blood circulation and remove blood stasis), has been widely used in breast cancer treatments. Although some evidence suggests the efficacy and safety of the Xihuang pill in treating certain cancer, the overall efficacy of the Xihuang pill in other cancer treatment is uncertain. Objective: This study aimed to summarize the current clinical literature and provided evidence support for addressing the research question of whether the Xihuang pill is safe and effective in the treatment of various cancers as Huoxuehuayu therapy, and possibly identify the clinical dosage range and therapeutic effect of Xihuang pills. Method: Seven Chinese and English databases such as PubMed, CNKI, and Google Scholar were searched to collect the publications on Xihuang pill and cancer. Then the researchers extracted data from the articles that met the inclusion criteria and used SAS statistical program version 9.4 (by SAS Institute, Cary, North Carolina, USA) for statistical statistics. Results: Our search identified 78 studies, including 69 RCTs (randomized control trials), 6 NRCCs (non-randomized concurrent control trials), and 3 BAS (before-after study), evaluating 3151 patients in total. The daily doses of Xihuang pills/capsule were between 2 g and 60 g, and duration between 2 weeks and 5 years, mostly used in the middle or late stage of cancer. The therapeutic effect of the Xihuang pill was mainly reflected in improving Complete Response (CR, a term from The Response Evaluation Criteria In Solid Tumors) or Partial Response (PR, a term from The Response Evaluation Criteria In Solid Tumors), reducing adverse reactions, promoting quality of life (QoL), regulating immunity, alleviating pain, prolonging survival, reducing metastasis and recurrence, reducing inflammation, regulating estrogen levels, decreasing hypercoagulative status, and reducing tumor markers. Conclusion: Xihuang pill representing Huoxuehuayu therapy has a good prospect in the treatment of cancer.

IntroductionMiR-196a2 and miR-27a play a key role in the regulation of the insulin signaling pathway. Previous studies have indicated that miR-27a rs895819 and miR-196a2 rs11614913 have a strong association with type 2 diabetes (T2DM), but very few studies have investigated their role in gestational diabetes mellitus (GDM).MethodsA total of 500 GDM patients and 502 control subjects were enrolled in this study. Using the SNPscan™ genotyping assay, rs11614913 and rs895819 were genotyped. In the data treatment process, the independent sample t test, logistic regression and chi-square test were used to evaluate the differences in genotype, allele, and haplotype distributions and their associations with GDM risk. One-way ANOVA was conducted to determine the differences in genotype and blood glucose level.ResultsThere were obvious differences in prepregnancy body mass index (pre-BMI), age, systolic blood pressure (SBP), diastolic blood pressure (DBP) and parity between GDM and healthy subjects (P < 0.05). After adjusting for the above factors, the miR-27a rs895819 C allele was still associated with an increased risk of GDM (C vs. T: OR=1.245; 95% CI: 1.011-1.533; P = 0.039) and the TT-CC genotype of rs11614913-rs895819 was related to an increased GDM risk (OR=3.989; 95% CI: 1.309-12.16; P = 0.015). In addition, the haplotype T-C had a positive interaction with GDM (OR=1.376; 95% CI: 1.075-1.790; P=0.018), especially in the 18.5 ≤ pre-BMI < 24 group (OR=1.403; 95% CI: 1.026-1.921; P=0.034). Moreover, the blood glucose level of the rs895819 CC genotype was significantly higher than that of the TT and TC genotypes (P < 0.05). The TT-CC genotype of rs11614913-rs895819 showed that the blood glucose level was significantly higher than that of the other genotypes.DiscussionOur findings suggest that miR-27a rs895819 is associated with increased GDM susceptibility and higher blood glucose levels.

In order to improve the ignition ability of reactive film, in this paper, the effects of copper oxide and silicon nitride on the flame height of the TaN@(Al/Ni) energy exchanger were investigated by using a high-speed photographic system. The insulating layer material was applied to the preparation TaN@(Al/Ni) by the MEMS process. The experimental results showed that the flame height of (Al/Ni)–TaN energy exchanger was obviously higher than that of silicon nitride when copper oxide was used as the insulation layer, which indicates that the oxygen-containing insulation layer could increase the flame height of the energy exchanger.

ObjectivesWe investigated the protective effect of Rehmannia glutinosa oligosaccharides (RGO) on lipopolysaccharide (LPS)-induced intestinal inflammation and barrier injury among mice.MethodsRGO is prepared from fresh rehmannia glutinosa by water extraction, active carbon decolorization, ion exchange resin impurity removal, macroporous adsorption resin purification, and decompression drying. LPS could establish the model for intestinal inflammation and barrier injury in mice. Three different doses of RGO were administered for three consecutive weeks. Then the weight, feces, and health status of the mice were recorded. After sacrificing the mice, their colon length and immune organ index were determined. The morphological changes of the ileum and colon were observed using Hematoxylin-eosin (H&E) staining, followed by measuring the villus length and recess depth. RT-qPCR was utilized to detect the relative mRNA expression of intestinal zonula occludens-1 (ZO-1) and occludin. The expression of inflammatory factors and oxidation markers within ileum and colon tissues and the digestive enzyme activities in the ileum contents were detected using ELISA. The content of short-chain fatty acids (SCFAs) in the colon was determined with GC. The gut microbial composition and diversity changes were determined with 16S-rRNA high-throughput sequencing. The association between intestinal microorganisms and SCFAs, occludins, digestive enzymes, inflammatory factor contents, and antioxidant indexes was also analyzed.ResultsRGO significantly increased the weight, pancreatic index, thymus index, and colon length of mice compared with the model group. Moreover, it also improved the intestinal tissue structure and increased the expression of intestinal barrier-related junction proteins ZO-1 and Occludin. The contents of IL-6, IL-17, IL-1β, and TNF-α in the intestinal tissues of mice were significantly reduced. Additionally, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were elevated. In contrast, the malondialdehyde (MDA) content decreased. Trypsin and pancreatic lipase activities in the ileum enhanced, and the SCFA contents such as acetic acid, propionic acid, and butyric acid in the colon increased. The study on intestinal flora revealed that RGO could enhance the abundance of intestinal flora and improve the flora structure. After RGO intervention, the relative abundance of Firmicutes, Lactobacillus, and Akkermania bacteria in the intestinal tract of mice increased compared with the model group, while that of Actinomycetes decreased. The intestinal microbiota structure changed to the case, with probiotics playing a dominant role. The correlation analysis indicated that Lactobacillus and Ackermann bacteria in the intestinal tract of mice were positively associated with SCFAs, Occludin, ZO-1, pancreatic amylase, SOD, and CAT activities. Moreover, they were negatively correlated with inflammatory factors IL-6, IL-17, IL-1β, and TNF-α.ConclusionsRGO can decrease LPS-induced intestinal inflammation and intestinal barrier injury in mice and protect their intestinal function. RGO can ameliorate intestinal inflammation and maintain the intestinal barrier by regulating intestinal flora.

Abstract Background Abnormal expression of splicing factor 3A subunit 3 (SF3A3), a component of the spliceosome, has been confirmed to be related to the occurrence and development of various cancers. However, the expression and function of SF3A3 in bladder cancer (BC) remains unclear. Methods The SF3A3 mRNA and protein level were measured in clinical samples and cell lines by quantitative real-time PCR, Western blot and immunofluorescence staining. Evaluate the clinical correlation between SF3A3 expression and clinicopathological characteristics through statistical analysis in BC patients. The function of SF3A3 in BC cells was determined in vitro using MTT and colony analysis. Co-immunoprecipitation (CoIP) assay was used to detected E2F6 and KDM5C interaction. Luciferase reporter and chromatin immunoprecipitation (ChIP) were used to examine the relationship between E2F6/KDM5C and SF3A3 expression. Results In the present study, we demonstrated that expression of SF3A3 was elevated in BC tissue compared to the normal bladder tissue. Importantly, the upregulation of SF3A3 in patients was correlated with poor prognosis. Additionally, overexpression of SF3A3 promoted while depletion of SF3A3 reduced the growth of BC cells in vivo and in vitro. Data from the TCGA database and clinical samples revealed that hypomethylation of the DNA promoter leads to high expression of SF3A3 in BC tissue. We found that upregulation of lysine-specific demethylase 5C (KDM5C) promotes SF3A3 expression via hypomethylation of the DNA promoter. The transcription factor E2F6 interacts with KDM5C, recruits KDM5C to the SF3A3 promoter, and demethylates the GpC island of H3K4me2, leading to high SF3A3 expression and BC progression. Conclusions The results demonstrated that depletion of the KDM5C/SF3A3 prevents the growth of BC in vivo and in vitro. The E2F6/KDM5C/SF3A3 pathway may be a potential therapeutic target for BC treatment.

Abstract Inflammation plays an important role during sepsis, and excessive inflammation can result in organ damage, chronic inflammation, fibrosis, and scarring. The study aimed to investigate the specific mechanism of emodin by constructing in vivo and in vitro septic lung injury models via inhibition and reduction of NF‐kB and high mobility group box 1 (HMGB1) pathways. A cecal ligation and puncture (CLP) model was built for adult male Sprague–Dawley rats. Concentrations of TNF‐α, IL‐1β, and IL‐6 in bronchoalveolar lavage fluid were determined using commercially available ELISA kits. Hematoxylin and eosin staining was used for the right lung inferior lobes. Myeloperoxidase (MPO) activity of the lung tissue was detected by using the MPO kit. Murine alveolar epithelial cell line (MLE‐12) cells were used for flow cytometry and Western blot to analyze the apoptosis rate and protein expression. Emodin significantly decreased CLP‐induced cell apoptosis, upregulated expression of sirtuin 1 (SIRT1), and inhibited p‐p65/p65 and HMGB1. In lipopolysaccharide (LPS) treated cell model, emodin treatment markedly decreased LPS‐induced release of IL‐1, IL‐6, and tumor necrosis factor (TNF)‐α, inhibited LPS‐induced cell apoptosis and suppressed protein levels of P‐P65/P65 and HMGB1. However, science of SIRT1 reversed the above effects by treatment of emodin. In summarize, this study found that emodin can alleviate sepsis‐induced lung injury in vivo and in vitro through regulation of SIRT1.

This paper aims to solve the limitations of traditional gravity physical property inversion methods such as insufficient depth resolution and difficulties in parameter selection, by proposing an improved 3D gravity inversion method based on deep learning. The deep learning network model is established using the fully convolutional U-net network. To enhance the generalization ability of the sample set, the large-scale training set and test set are generated by the random walk, based on the forward theory. Founded on the traditional loss function’s definition, this paper introduces an improvement incorporating a physical constraint to measure the degree of data fitting between the predicted and the real gravity data. This improvement significantly boosted the accuracy of the deep learning inversion method, as verified through both a single model and an intricate combination model. Finally, we applied this improved inversion method to the gravity data from the Gamburtsev Subglacial Mountains in the interior of East Antarctica, obtaining a comprehensive 3D crustal density structure. The results provide new evidence for the presence of a dense crustal root situated beneath the central Gamburtsev Province near the Gamburtsev Suture.

Marine soft corals are prolific sources of various natural products that have served as a wealthy reservoir of diverse chemical scaffolds with potential as new drug leads. The genus Litophyton contains almost 100 species but only a small proportion of them has been chemically investigated, which calls for more attentions from global researchers. In the current work, 175 secondary metabolites have been discussed, drawing from published data spanning almost five decades, up to July 2023. The studied species of the genus Litophyton resided in various tropical and temperate regions and encompassed a broad range of biologically active natural products including terpenes, steroids, nitrogen-containing metabolites, lipids, and other metabolites. A wide spectrum of pharmacological effects of these compounds had been evaluated, such as cytotoxic, antiviral, antibacterial, antifungal, anti-malarial, antifeedant, anti-inflammatory, molluscicidal, PTP1B inhibitory, insect growth inhibitory, and neuroprotective activities. This review aims to offer an up-to-date survey of the literature and provide a comprehensive understanding of the chemical structures, taxonomical distributions, and biological activities of the reported metabolites from the title genus whenever available.

Three new cembranoids (1–3) and a new casbanoid (4), along with three known analogues (5–7), have been isolated from the soft coral Sinularia nanolobata collected off Ximao Island. The structures, including the absolute configurations of new compounds, were established using extensive spectroscopic data analysis, time-dependent density functional theory/electronic circular dichroism (TDDFT-ECD) calculations, and the comparison with spectroscopic data of known compounds. In the in vitro bioassay, compounds 1 and 5 exhibited moderate cytotoxic activities against human erythroleukemia (HEL) cell lines, with IC50 values of 37.1 and 42.4 μM, respectively.

To explore the steroidal constituents of the soft coral Lobophytum sp. at the coast of Xuwen County, Guangdong Province, China, a chemical investigation of the above-mentioned soft coral was carried out. After repeated column chromatography over silica gel, Sephadex LH-20, and reversed-phase HPLC, six new steroids, namely lobosteroids A–F (1–6), along with four known compounds 7–10, were obtained. Their structures were determined by extensive spectroscopic analysis and comparison with the spectral data reported in the literature. Among them, the absolute configuration of 1 was determined by X-ray diffraction analysis using Cu Kα radiation. These steroids were characterized by either the presence of an α,β-α′,β′-unsaturated carbonyl, or an α,β-unsaturated carbonyl moiety in ring A, or the existence of a 5α,8α-epidioxy system in ring B, as well as diverse oxidation of side chains. The antibacterial bioassays showed that all isolated steroids exhibited significant inhibitory activities against the fish pathogenic bacteria Streptococcus parauberis FP KSP28, Phoyobacterium damselae FP2244, and Streptococcus parauberis SPOF3K, with IC90 values ranging from 0.1 to 11.0 µM. Meanwhile, compounds 2 and 6–10 displayed potent inhibitory effects against the vancomycin-resistant Enterococcus faecium bacterium G7 with IC90 values ranging from 4.4 to 18.3 µM. Therefore, ten highly oxidized steroids with strong antibacterial activities were isolated from the Chinese soft coral Lobophytum sp., which could be developed as new chemotypes of antibacterial drug leads.

Lipase activity is one of the main causes of the lipid rancidity in wholegrain wheat flour, leading to its short shelf life. Genetically diverse wheat germplasm offers potential for the selection of wheat cultivars with low lipase activity for stable wholegrain end use. This study evaluated 300 European wheat cultivars harvested in 2015 and 2016 on the genetic association of lipase and esterase activities in wholegrain wheat flour. Esterase and lipase activities in wholegrain flour were measured photometrically with p-nitrophenyl butyrate and p-nitrophenyl palmitate as substrates, respectively. Both enzyme activities showed wide ranges among all cultivars within each year, with differences up to 2.5-fold. The two years showed low correlations between each other, indicating a large environmental impact on the enzyme activities. Cultivars ‘Julius’ and ‘Bueno’ were suggested to be better suited for stable wholegrain products, as they had consistently low esterase and lipase activities compared to the other cultivars. A genome-wide association study revealed associations with single nucleotide polymorphisms in genes located on the high-quality wheat genome sequence of the International Wheat Genome Sequencing Consortium. Eight and four candidate genes were tentatively proposed to be associated to esterase and lipase activity, respectively, in wholegrain flour. Our work shows esterase and lipase activities from a new perspective, that combines reverse genetics to understand the underlying causes. This study outlines the possibilities and limitations to improve lipid stability of wholegrain wheat by genomics-assisted breeding methods, thereby offering new opportunities to optimize the quality of wholegrain wheat flour and wholegrain products.

BackgroundThere are controversies on the pathophysiological alteration in patients with atrial fibrillation (AF) undergoing pulmonary vein isolation using different energy sources.ObjectivesWe evaluated the changes in plasma proteins in acute phase post-ablation in patients receiving cryoballoon ablation, radiofrequency balloon ablation, or radiofrequency ablation.MethodsBlood samples from eight healthy controls and 24 patients with AF were taken on the day of admission, day 1, and day 2 post-ablation and analyzed by the Olink proximity extension assay. Proteins were identified and performed with enrichment analysis. Protein–protein interaction network and module analysis were conducted using Cytoscape software.ResultsOf 181 proteins, 42 proteins in the cryoballoon group, 46 proteins in the radiofrequency balloon group, and 43 proteins in the radiofrequency group significantly changed after ablation. Most of the proteins altered significantly on the first day after ablation. Altered proteins were mainly involved in cytokine–cytokine receptor interaction. Both balloon-based ablations showed a similar shift toward enhancing cell communication and regulation of signaling while inhibiting neutrophil chemotaxis. However, radiofrequency ablation presented a different trend. Seed proteins, including osteopontin, interleukin-6, interleukin-10, C-C motif ligand 8, and matrix metalloproteinase-1, were identified. More significant proteins associated with hemorrhage and coagulation were selected in balloon-based ablations by machine learning.ConclusionPlasma protein response after three different ablations in patients with AF mainly occurred on the first day. Radiofrequency balloon ablation shared similar alteration in protein profile as cryoballoon ablation compared with radiofrequency ablation, suggesting that lesion size rather than energy source is the determinant in pathophysiological responses to the ablation.

We propose a scheme to enhance phonon blockade effect in a quadratically coupled optomechanical system. By applying a degenerate parametric drive to the mechanical oscillator, we introduce a mechanical parametric amplifier (MPA) to the system. We show that the phonon blockade can be achieved in both the single-phonon resonant regime and multipath interference regime due to the optomechanical nonlinearity and MPA. By combining the two regimes together, we show that the phonon blockade effect is enhanced compared to the regime without MPA. What is more, the two-time second-order correlation function gradually tends to one without rapid oscillations in our scheme, which suggests that high time resolution is not necessary in the detection.

Summary: Background: COVID-19 vaccines are important for patients with heart failure (HF) to prevent severe outcomes but the safety concerns could lead to vaccine hesitancy. This study aimed to investigate the safety of two COVID-19 vaccines, BNT162b2 and CoronaVac, in patients with HF. Methods: We conducted a self-controlled case series analysis using the data from the Hong Kong Hospital Authority and the Department of Health. The primary outcome was hospitalization for HF and the secondary outcomes were major adverse cardiovascular events (MACE) and all hospitalization. We identified patients with a history of HF before February 23, 2021 and developed the outcome event between February 23, 2021 and March 31, 2022 in Hong Kong. Incidence rate ratios (IRR) were estimated using conditional Poisson regression to evaluate the risks following the first three doses of BNT162b2 or CoronaVac. Findings: We identified 32,490 patients with HF, of which 3035 were vaccinated and had a hospitalization for HF during the observation period (BNT162b2 = 755; CoronaVac = 2280). There were no increased risks during the 0–13 days (IRR 0.64 [95% confidence interval 0.33–1.26]; 0.94 [0.50–1.78]; 0.82 [0.17–3.98]) and 14–27 days (0.73 [0.35–1.52]; 0.95 [0.49–1.84]; 0.60 [0.06–5.76]) after the first, second and third doses of BNT162b2. No increased risks were observed for CoronaVac during the 0–13 days (IRR 0.60 [0.41–0.88]; 0.71 [0.45–1.12]; 1.64 [0.40–6.77]) and 14–27 days (0.91 [0.63–1.32]; 0.79 [0.46–1.35]; 1.71 [0.44–6.62]) after the first, second and third doses. We also found no increased risk of MACE or all hospitalization after vaccination. Interpretation: Our results showed no increased risk of hospitalization for HF, MACE or all hospitalization after receiving BNT162b2 or CoronaVac vaccines in patients with HF. Funding: The project was funded by a Research Grant from the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (Ref. No. COVID19F01). F.T.T.L. (Francisco T.T. Lai) and I.C.K.W. (Ian C.K. Wong)'s posts were partly funded by the D24H; hence this work was partly supported by AIR@InnoHK administered by Innovation and Technology Commission.

BackgroundPrimary hepatocellular carcinoma is often complicated with hepatitis and liver cirrhosis. Some patients develop different degrees of splenomegaly, hypersplenism and hypohepatia due to the aggravation of liver cirrhosis, which to some extent interfere with the treatment of tumors and even affect the prognosis of patients. In this study, we prospectively evaluate the efficacy and safety of simultaneous CalliSpheres® microspheres transcatheter arterial chemoembolization (CSM-TACE) and partial splenic embolization (PSE) using 8spheres® for hepatocellular carcinoma (HCC) with hypersplenism.MethodsNinety consecutive HCC patients with hypersplenism who underwent CSM-TACE were selected: 32 patients in CSM-TACE+PSE group, and 58 patients in CSM-TACE group. The peripheral blood cell counts (leukocyte, platelet (PLT), liver function and red blood cell (RBC)), CSM-TACE and/or PSE related complications, and the tumor control rate at 1 month after CSM-TACE were compared. The survival time and prognostic factors were also observed.ResultsBefore CSM-TACE, there were no significant differences in sex, age, Child-Pugh grade, tumor size, and alpha-fetoprotein (AFP) between the two groups. After CSM-TACE, the PLT and white blood cell (WBC) counts in CSM-TACE+PSE group were significantly higher than those in the CSM-TACE group (P 0.05). In the CSM-TACE group, there were no significant differences in WBC, PLT, and RBC before and after treatment (P > 0.05). There was no significant difference in liver function at 1 month after treatment between the two groups. The cholinesterase (CHE) level in the CSM-TACE+PSE group after CSM-TACE+PSE was obviously higher than that before CSM-TACE+PSE and higher than that in the CSM-TACE group (P 0.05).ConclusionsSimultaneous CSM-TACE and PSE using domestic embolization particles for HCC with hypersplenism have good safety and efficacy and has a low incidence of PSE-related adverse events, it is conducive to improving liver function reserve, and can further improve the median OS.

Based on a novel integrated intermediate fluid vaporizer with liquefied natural gas (LNG) cold energy utilization proposed by the author's team, a full-power generation integrated system is constructed in this study. It is a two-stage cascade Rankine cycle with two-stage condensation and coupled with a trans-critical CO2 Rankine cycle. This study regards a river–sea direct transportation type of 25,000-ton LNG fuel-powered chemical ship as the application object and considers combined utilization of the medium-temperature waste heat of flue gas from the exhaust turbine power generation cycle outlet and the vaporization cold energy of LNG. Through the simulation and analysis of the scheme, circulating working fluid optimization and operation parameter optimization based on a genetic algorithm are conducted. The overall exergy efficiency of the optimized system reaches 45.1%, while the power generation of the system reaches 72.66 kW. Furthermore, economic analysis shows that the net annual income of the optimized system can reach 280,700 yuan, and the recovery cycle of initial investment cost is expected to be 6.11 years.