Advancements in the study of glucose metabolism in relation to tumor progression and treatment.

Sugar serves as the primary energy source for mammals, with glucose metabolism facilitating energy acquisition in human cells. The proper functioning of intracellular glucose metabolism is essential for the maintenance of orderly and healthy physiological activities. Tumor cells, characterized by uncontrolled growth, exhibit dysregulated proliferation and apoptosis processes, leading to abnormal alterations in glucose metabolism. Specifically, tumor cells exhibit a shift towards aerobic glycolysis, resulting in the production of lactic acid that can be utilized as a metabolic intermediate for sustained tumor cell growth. This article provides a comprehensive overview of the enzymes involved in glucose metabolism and the alterations in gene expression that occur during tumor progression. It also examines the current research on targeting abnormal glucose metabolism processes for tumor treatment and discusses potential future directions for utilizing glucose metabolism as a therapeutic target.

Association between Time to Emergent Surgery and Outcomes in Trauma Patients: A 10-Year Multicenter Study.

Background: Research on the impact of reduced time to emergent surgery in trauma patients has yielded inconsistent results. Therefore, this study investigated the relationship between waiting emergent surgery time (WEST) and outcomes in trauma patients. Methods: This retrospective, multicenter study used data from the Tzu Chi Hospital trauma database. The primary clinical outcomes were in-hospital mortality, intensive care unit (ICU) admission, and prolonged hospital length of stay (LOS) of ≥30 days. Results: A total of 15,164 patients were analyzed. The median WEST was 444 min, with an interquartile range (IQR) of 248-848 min for all patients. Patients who died in the hospital had a shorter median WEST than did those who survived (240 vs. 446 min, p < 0.001). Among the trauma patients with a WEST of <2 h, the median time was 79 min (IQR = 50-100 min). No significant difference in WEST was observed between the survival and mortality groups for patients with a WEST of <120 min (median WEST: 85 vs. 78 min, p < 0.001). Multivariable logistic regression analysis revealed that WEST was not associated with an increased risk of in-hospital mortality (adjusted odds ratio [aOR] = 1.05, 95% confidence interval [CI] = 0.17-6.35 for 30 min ≤ WEST < 60 min; aOR = 1.12, 95% CI = 0.22-5.70 for 60 min ≤ WEST < 90 min; and aOR = 0.60, 95% CI = 0.13-2.74 for WEST ≥ 90 min). Conclusions: Our findings do not support the "golden hour" concept because no association was identified between the time to definitive care and in-hospital mortality, ICU admission, and prolonged hospital stay of ≥30 days.

[Liujunzi Decoction treats 4NQO-induced esophageal cancer in mice: a study based on serum metabolomics].

This study aims to explore the mechanism of Liujunzi Decoction in the treatment of 4-nitroquinoline-N-oxide(4NQO)-induced esophageal cancer in mice. One hundred mice of 35-45 days were randomized into blank, model, and low-, medium-, and high-concentration(18.2, 36.4, and 54.6 g·kg~(-1), respectively) Liujunzi Decoction groups. The mice in other groups except the blank group had free access to the water containing 100 µg·mL~(-1) 4NQO for 16 weeks for the modeling of esophageal cancer. The mice in the Liujunzi Decoction groups were fed with the diets supplemented with corresponding concentrations of Liujunzi Decoction. The body weight and organ weights were weighed for the calculation of organ indexes. The pathological changes of the esophageal tissue were observed by hematoxylin-eosin(HE) staining. Ultra performance liquid chromatography-mass spectrometry(UPLC-MS/MS) was employed to collect metabolites from mouse serum samples, screen out potential biomarkers, and predict related metabolic pathways. Compared with the blank group, the model group showed decreased spleen and stomach indexes and increased lung, esophagus, and kidney indexes. Compared with the model group, Liujunzi Decoction groups had no significant changes in the organ indexes. The HE staining results showed that Liujunzi Decoction inhibited the invasive growth and cancerization of the esophageal cancer cells. A total of 9 potential biomarkers of Liujunzi Decoction in treating esophageal cancer were screened out in this study, which were urocanic acid, 1-oleoylglycerophosphoserine, 11-deoxy prostaglandin E1, Leu-Glu-Lys-Glu,(±) 4-hydroxy-5E,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid, ureidosuccinic acid,(2R)-2,4-dihydroxy-3,3-dimethylbutanoic acid, kynurenic acid, and bicyclo prostaglandin E2, which were mainly involved in histidine, pyrimidine, alanine, aspartate, glutamate, pantothenate and tryptophan metabolism and coenzyme A biosynthesis. In summary, Liujunzi Decoction may exert the therapeutic effect on the 4NQO-induced esophageal cancer in mice by regu-lating the amino acid metabolism, inflammation, and immune function.

A gene expression profile-based approach to screen the occurrence and predisposed host characteristics of drug-induced liver injury: a case study of Psoralea corylifolia Linn.

Drug-induced liver injury (DILI) is one of the most common causes of a drug being withdrawn, and identifying the culprit drugs and the host factors at risk of causing DILI has become a current challenge. Recent studies have found that immune status plays a considerable role in the development of DILI. In this study, DILI-related differentially expressed genes mediated by immunoinflammatory cytokines were obtained from the Gene Expression Omnibus (GEO) database to predict the occurrence of DILI (named the DILI predictive gene set, DILI_PGS), and the predictability of the DILI_PGS was verified using the Connectivity Map (CMap) and LiverTox platforms. The results obtained DILI_PGS from the GEO database could predict 81.25% of liver injury drugs. In addition, the Coexpedia platform was used to predict the DILI_PGS-related characteristics of common host diseases and found that the DILI_PGS mainly involved immune-related diseases and tumor-related diseases. Then, animal models of immune stress (IS) and immunosuppressive (IP) were selected to simulate the immune status of the above diseases. Meanwhile, psoralen, a main component derived from Psoralea corylifolia Linn. with definite hepatotoxicity, was selected as an experimental drug with highly similar molecular fingerprints to three idiosyncratic hepatotoxic drugs (nefazodone, trovafloxacin, and nimesulide) from the same DILI_PGS dataset. The animal experiment results found a single administration of psoralen could significantly induce liver injury in IS mice, while there was no obvious liver function change in IP mice by repeatedly administering the same dose of psoralen, and the potential mechanism of psoralen-induced liver injury in IS mice may be related to regulating the expression of the TNF-related pathway. In conclusion, this study constructed the DILI_PGS with high accuracy to predict the occurrence of DILI and preliminarily identified the characteristics of host factors inducing DILI.

Yin/Yang associated differential responses to Psoralea corylifolia Linn. In rat models: an integrated metabolomics and transcriptomics study.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoralea corylifolia Linn. (BGZ) is a commonly used traditional Chinese medicine (TCM) for the treatment of kidney-yang deficiency syndrome (Yangsyn) with good curative effect and security. However, BGZ was also reported to induce liver injury in recent years. According to TCM theory, taking BGZ may induce a series of adverse reactions in patients with kidney-yin deficiency syndrome (Yinsyn), which suggests that BGZ-induced liver damage may be related to its unreasonable clinical use. AIM OF THE STUDY: Liver injury caused by TCM is a rare but potentially serious adverse drug reaction, and the identification of predisposed individuals for drug-induced liver injury (DILI) remains challenging. The study aimed to investigate the differential responses to BGZ in Yangsyn and Yinsyn rat models and identify the corresponding characteristic biomarkers. MATERIALS AND METHODS: The corresponding animal models of Yangsyn and Yinsyn were induced by hydrocortisone and thyroxine + reserpine respectively. Body weight, organ index, serum biochemistry, and Hematoxylin and Eosin (HE) staining were used to evaluate the liver toxicity effect of BGZ on rats with Yangsyn and Yinsyn. Transcriptomics and metabonomics were used to screen the representative biomarkers (including metabolites and differentially expressed genes (DEGs)) changed by BGZ in Yangsyn and Yinsyn rats, respectively. RESULTS: The level changes of liver organ index, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), suggested that BGZ has liver-protective and liver-damaging effects on Yangsyn and Yinsyn rats, respectively, and the results also were confirmed by the pathological changes of liver tissue. The results showed that 102 DEGs and 27 metabolites were significantly regulated related to BGZ's protective effect on Yangsyn, which is mainly associated with the glycerophospholipid metabolism, arachidonic acid metabolism, pantothenate, and coenzyme A (CoA) biosynthesis pathways. While 28 DEGs and 31 metabolites, related to the pathway of pantothenate and CoA biosynthesis, were significantly regulated for the BGZ-induced liver injury in Yinsyn. Furthermore, 4 DEGs (aldehyde dehydrogenase 1 family member B1 (Aldh1b1), solute carrier family 25 member 25 (Slc25a25), Pim-3 proto-oncogene, serine/threonine kinase (Pim3), out at first homolog (Oaf)) and 4 metabolites (phosphatidate, phosphatidylcholine, N-Acetylleucine, biliverdin) in the Yangsyn group and 1 DEG [galectin 5 (Lgals5)] and 1 metabolite (5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate) in Yinsyn group were significantly correlated to the ALT and AST levels of BGZ treated and untreated groups (receiver operating characteristic (ROC) ≥ 0.9). CONCLUSIONS: Yinsyn and Yangsyn are the predisposed syndromes for BGZ to exert liver damage and liver protection respectively, which are mainly related to the regulation of amino acid metabolism, lipid metabolism, energy metabolism, and metabolism of cofactors and vitamins. The results further suggest that attention should be paid to the selection of predisposed populations when using drugs related to the regulation of energy metabolism, and the Yinsyn/Yangsyn animal models based on the theory of TCM syndromes may be a feasible method for identifying the susceptible population to receive TCM.

[Effect of Gualou Xiebai Decoction on pulmonary fibrosis in rats based on pyroptosis pathway].

This study investigated the effect of Gualou Xiebai Decoction on rats with bleomycin-induced pulmonary fibrosis. The rats were randomly divided into a control group, a model group, a low-dose Gualou Xiebai Decoction group(2.4 g·kg~(-1)), a high-dose Gualou Xiebai Decoction group(4.8 g·kg~(-1)), and pirfenidone group(150 mg·kg~(-1)). The model of pulmonary fibrosis was established by intratracheal instillation of bleomycin in all groups, except the control group. Since the second day of modeling, the corresponding drugs were given to rats by intragastric administration, once a day for 14 d and 28 d. The hematoxylin-eosin(HE) staining was used to evaluate the degree of inflammatory injury in lung tissues. The immunofluorescence staining was used to detect the expression of CD68 and CD163 in lung tissues of rats. The levels of tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) in serum and brochoalveolar lavage fluid(BALF) were detected by enzyme-linked immunosorbent assay(ELISA). The expression of pyroptosis-related genes in lung tissues of rats was detected by qRT-PCR. The results of HE staining and immunofluorescence staining showed that the lung tissue structure was normal in the control group. In addition, there were alveolar collapse or even closure in lung tissues of rats in the model group, with obvious inflammatory cell infiltration, and the expression of CD68 and CD163 was significantly up-regulated. As compared with the model group, the lung tissue structure of rats in the Gualou Xiebai Decoction groups was significantly improved, with alleviated inflammation, and the expression of CD68 and CD163 was decreased. As compared with the control group, the level of TNF-α in serum and BALF of rats in the model group was significantly increased(P<0.01), the mRNA expression levels of alpha smooth muscle actin(α-SMA), collagen type Ⅰ alpha 1 chain(Col1a1), caspase-1, IL-1ß, IL-18, gasdermin D(Gsdmd), and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in lung tissues were significantly increased(P<0.05, P<0.01), and the mRNA expression level of E-cadherin was significantly decreased(P<0.01). As compared with the model group, the level of TNF-α in serum and BALF was significantly down-regulated in the high-dose Gualou Xiebai Decoction group(P<0.05, P<0.01), and that of IL-10 was up-regulated(P<0.05, P<0.01). The mRNA expression levels of α-SMA, Col1a1, caspase-1, IL-18, Gsdmd, NLRP3 and IL-1ß in lung tissues were significantly decreased(P<0.05, P<0.01) in the high-dose Gualou Xiebai Decoction group, and the mRNA expression level of E-cadherin was significantly increased(P<0.05, P<0.01). In conclusion, Gualou Xiebai Decoction can down-regulate the levels of inflammatory factors and related genes and effectively mitigate pulmonary fibrosis by regulating the pyroptosis pathways.

MAGED4B is a Poor Prognostic Marker of Stomach Adenocarcinoma and a Potential Therapeutic Target for Stomach Adenocarcinoma Tumorigenesis.

Background: Gastric cancer is the second most common cause of cancer death worldwide with poor overall prognosis. It is important to study the molecular mechanism of stomach adenocarcinoma (STAD). MAGED4B, a member of the melanoma antigen gene (MAGE) family, is highly expressed in many tumor cells and is associated with tumor progression. Its prognostic value in and the function of the encoded protein are still unclear. Methods: The data of 415 STAD tissues was retrieved from TCGA database, and the expression level of MAGED4B mRNA was evaluated. The correlation between the expression of MAGED4B mRNA and the progression free survival (PFS) time of STAD patients was evaluated by Kaplan Meier analysis. The STAD cell lines with overexpressed and silent MAGED4B were constructed, and the effects of MAGED4B on the viability, migration and proliferation were evaluated by the CCK-8, scratch test and EDU test. The flow cytometry was used to detect apoptosis with overexpressed and silent MAGED4B under the cisplatin treatment, and WB was used to detect the expressions of related proteins, such as TNF-α. Results: The expression level of MAGED4B mRNA in the STAD tissues was higher than that in the normal tissues, and its high expression was related to poor PFS. The overexpression of MAGED4B in the STAD cell lines can promote the vitality, motility and proliferation of the STAD cells, while the silencing of MAGED4B can inhibit the above three cell functions of the STAD cells. The overexpression of MAGED4B can reduce the cisplatin induced apoptosis and increase the cisplatin IC50; the silencing of MAGED4B can promote the cisplatin induced apoptosis and reduce the cisplatin IC50. The overexpression of MAGED4B reduced the protein levels of TRIM27 and TNF- α. Conclusion: MAGED4B could be a valuable prognostic biomarker and a therapeutic target for gastric adenocarcinoma of great interest.

The impact of holiday season and weekend effect on traumatic injury mortality: Evidence from a 10-year analysis.

Objectives: Trauma is one of the leading causes of death and its incidence increases annually. The "weekend effect" and "holiday season effect" on traumatic injury mortality remain controversial, whereby traumatic injury patients admitted during weekends and/or holiday season have a higher risk of in-hospital death. The present study is aimed to explore the association between "weekend effect" and "holiday season effect" and mortality in traumatic injury population. Materials and Methods: This retrospective descriptive study included patients from the Taipei Tzu Chi Hospital Trauma Database between January 2009 and June 2019. The exclusion criterion was age of < 20 years. The primary outcome was the in-hospital mortality rate. The secondary outcomes included intensive care unit (ICU) admission, ICU re-admission, length of stay (LOS) in the ICU, ICU admission duration ≥ 14 days, total hospital LOS, total hospital LOS ≥ 14 days, need for surgery, and re-operation rate. Results: In this study, 11,946 patients were included in the analysis, and 8143 (68.2%) patients were admitted on weekdays, 3050 (25.5%) on weekends, and 753 (6.3%) on holidays. Multivariable logistic regression revealed that the admission day was not associated with an increased risk of in-hospital mortality. In other clinical outcome analyses, we found no significant increase in the risk of in-hospital mortality, ICU admission, ICU LOS ≥ 14 days, or total LOS ≥ 14 days in the weekend and holiday season groups. The subgroup analysis showed that the association between holiday season admission and in-hospital mortality was noted only in the elderly and shock condition populations. The holiday season duration did not differ in terms of in-hospital mortality. Longer holiday season duration was also not associated with an increased risk of in-hospital mortality, ICU LOS ≥14 days, and total LOS ≥14 days. Conclusion: In this study, we did not find any evidence that weekend and holiday season admissions in the traumatic injury population were associated with an increased risk of mortality. In other clinical outcome analyses, there was no significant increase in the risk of in-hospital mortality, ICU admission, ICU LOS ≥ 14 days, or total LOS ≥ 14 days in the weekend and holiday season groups.

New bio-based polyester with excellent spinning performance: poly(tetrahydrofuran dimethanol-co-ethylene terephthalate).

With the excessive consumption of fossil energy, technologies that transform bio-based resources into materials have received more and more attention from researchers in recent decades. In this paper, a series of poly(ethylene 2,5-tetrahydrofuran dimethyl terephthalate; PEFTs) with different components were synthesized from 2,5-tetrahydrofuran dimethanol (THFDM), terephthalic acid (TPA), and ethylene glycol (EG). Their chemical structures and compositions were determined by FTIR, 1H NMR, and 13C NMR. With the increase in THFDM content, the crystallization, T m, and tensile strength of PEFTs gradually decrease because the introduced THFDM breaks the order of molecular chains, while the thermal stability and T g remain stable. PEFTs seem to present a significant shear thinning phenomenon, which was indicated by the rheological test. Electrospinning technology was used to explore the spinnability of PEFT; it was found that PEFTs have better spinning performance than PET. In addition, due to the good hydrophobicity and porosity of PEFT nanofiber films, they have potential application value in the manufacture of hydrophobic nanofiber and filter films.

Transcriptomic and network pharmacology approaches revealed possible mechanisms underlying the 5-fluorouracil (5-FU)-sensitizing effect of Xuan-Fu-Hua decoction treatment on liver cancer cells.

Background: Xuan-Fu-Hua decoction is a traditional Chinese medicine formula widely used for the treatment of inflammation-related disease in the lung and liver. This study aimed to investigate the effect of Xuan-Fu-Hua decoction treatment on liver cancer cells and its mechanism of action. Methods: The impact of Xuan-Fu-Hua decoction treatment on the proliferation and apoptosis of SMMC-7721 liver cancer cells with or without 5-fluorouracil (5-FU) cotreatment was determined in both in vitro and in vivo settings. Alterations in gene expression patterns in SMMC-7721 cells induced by Xuan-Fu-Hua decoction treatment were explored by transcriptomic sequencing. Effective components of Xuan-Fu-Hua decoction and their target proteins were investigated using network pharmacology approaches. Results: Xuan-Fu-Hua decoction alone did not significantly influence SMMC-7721 liver cancer cell growth, but it significantly increased the 5-Fu-induced growth inhibition and apoptosis of SMMC-7721 liver cancer cells in vitro and in vivo. Most differentially expressed genes in SMMC-7721 liver cancer cells with or without Xuan-Fu-Hua decoction treatment were enriched in cell apoptosis-related pathways. Xuan-Fu-Hua decoction treatment significantly increased the transcription levels of DDIT3, PMAIP1, and ZMAT3 genes while decreasing that of WNT4, AXIN2, NFE2L2, TGFBR1, MITF, and IGFBP3 genes. An interaction network between the effective components and their possible target proteins was constructed by predicting compound-target protein and protein-protein interactions. Gene set enrichment analysis revealed the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway as well as Bcl-2 and Mcl-1 proteins as potential regulatory targets of Xuan-Fu-Hua decoction in sensitizing SMMC-7721 cells to the cytotoxicity of 5-FU treatment. Conclusions: Xuan-Fu-Hua decoction increased the sensitivity of liver cancer cells to the cytotoxicity of 5-FU treatment, possibly by potentiating cell apoptosis and inhibiting the prosurvival machinery.

Effects of modified atmosphere packaging on the postharvest quality of mulberry leaf vegetable.

Fresh mulberry leaf vegetable is nutritive and becoming popular. However, available preservation technologies are deficient. In present work, the effects of two kinds of modified atmosphere packaging on postharvest quality of fresh mulberry leaf vegetable stored at 4 °C were evaluated. The respiration rate of samples in the modified polyethylene packages (MP20) was 12.88-22.65% lower than that in normal polyethylene packaging (CK). The content of total soluble solids, soluble protein, and total polyphenol in MP20 was less changed than that in CK, and the vitamin C retention was higher as well. Moreover, the lignin content in MP20 was lower than that in CK during storage (19.79% vs 13.38% at day 8), and that was significantly positively related to the polyphenol oxidase and peroxidase activities inhibition. Taken together, a packaging with moderate gas permeability (MP20) is suitable for nutrition maintenance and lignification inhibition of fresh mulberry leaf vegetable during cold storage.

Functional Differentiation of BMP7 Genes in Zebrafish: bmp7a for Dorsal-Ventral Pattern and bmp7b for Melanin Synthesis and Eye Development.

Bone morphogenetic protein 7 (BMP7) belongs to the transforming growth factor ß (TGF-ß) family, which not only induces cartilage and bone formation, but also regulates eye development and melanoma tumorigenesis in mammals. In teleosts, BMP7 differentiates into two subtypes, bmp7a and bmp7b, which have clearly differentiated structures. To fully understand the functional differentiation of bmp7a and bmp7b in fish species, we successfully constructed bmp7a and bmp7b gene deletion mutants in zebrafish using CRISPR/Cas9-mediated gene editing technology. Our results showed that bmp7a mutation caused abnormal development of the embryo's dorsal-ventral pattern that led to death; bmp7b mutation induced growth inhibition and increased melanin production in the skin and eye of mutants. Histological analysis revealed that melanin in the retina of the eyes in bmp7b mutants increased, and behavioral observation showed that the vision and sensitivity to food of the mutants were reduced. Transcriptome analysis of the skin and eye tissues showed that the expression changes of wnt7ba and gna14 in bmp7b mutants might promote the increase of melanin. Additionally, the eye transcriptome analysis indicated that changes in the structure of the eyes in bmp7b mutants led to defects in phototransduction, and seven DEGs (rgs9a, rgs9b, rcvrn2, guca1d, grk1b, opn1mw4, and gc2) were identified as key candidate genes that affected the photonic response of the eyes. The study revealed the functional differentiation of bmp7a and bmp7b in teleosts and the first report about the inhibitory effect of bmp7b on melanogenesis may provide useful information for the future research on human melanoma-related diseases.

[Polysaccharide of Atractylodis Macrocephalae Rhizoma inhibits expression of immune checkpoint PD-L1 by targeting miR-34a in esophageal carcinoma cells].

The immune checkpoint programmed cell death-ligand 1(PD-L1)-mediated immunosuppression is among the important features of tumor. PD-L1, an immunosuppressant, can induce T cell failure by binding to programmed cell death-1(PD-1). Thus, the key to restoring the function of T cells is inhibiting the expression of PD-L1. The Chinese medicinal Atractylodis Macrocephalae Rhizoma(AMR) has the anti-tumor, anti-inflammatory, antioxidant, and hypoglycemic activities, and the polysaccharide in AMR(PAMR) plays a crucial role in immunoregulation, but the influence on the immune checkpoints which are closely related to immunosuppression has not been reported. MicroRNA-34 a(miR-34 a) expression in esophageal carcinoma tissue is significantly lower than that in normal tissue. This study aims to investigate the inhibitory effect of PAMR on esophageal carcinoma cells, and the relationship between its inhibitory effect on PD-L1 expression and miR-34 a, which is expected to clarify the anti-tumor mechanism of PAMR. Firstly, different human esophageal carcinoma cell lines(EC9706, EC-1, TE-1, EC109 cells) were screend out, and expression of PD-L1 was determined. Then, EC109 cells, with high expression of PD-L1, were selected for further experiment. The result showed that PAMR suppressed EC109 cell growth. According to the real-time quantitative PCR(qPCR) and Western blot, it significantly suppressed the mRNA and protein expression of PD-L1, while promoting the expression of tumor suppressor miR-34 a. The confocal microscopy and luci-ferase assay proved that PAMR alleviated the inhibitory effect of PD-L1 while blocked miR-34 a. Additionally, the expression of PD-L1 was controlled by miR-34 a, and the combination of miR-34 a inhibitor with high-dose PAMR reversed the inhibitory effect of PAMR on PD-L1 protein expression. Thus, the PAMR may inhibit PD-L1 by increasing the expression of miR-34 a and regulating its downstream target genes. In conclusion, PAMR inhibits the expression of PD-L1 mainly by inducing miR-34 a.

[Study on alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury based on network pharmacology and cell experiments].

This study was designed to explore the alleviating effect and mechanism of Glycyrrhizae Radix et Rhizoma against Psora-leae Fructus-induced liver injury based on network pharmacology and cell experiments. The active components of Glycyrrhizae Radix et Rhizoma and Psoraleae Fructus were first retrieved from the Encyclopedia of Traditional Chinese Medicine(ETCM), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Comparative Toxicogenomics Database(CTD), and literature and further screened by SwissADME. The obtained 25 potential toxic components of Psoraleae Fructus and 29 flavonoids in Glycyrrhizae Radix et Rhizoma were input into the SwissTargetPrediction for target predication. A total of 818 targets related to liver injury were screened out based on GeneCards and MalaCards, and 91 common targets of Psoraleae Fructus, Glycyrrhizae Radix et Rhizoma, and liver injury were obtained from Venny. STRING was applied for constructing the PPI network, and Metascape for analyzing the biological processes and signaling pathways that common targets participated in. Cytoscape was used to construct the component-target-disease network and component-target-pathway network for Glycyrrhizae Radix et Rhizoma against Psoraleae Fructus-induced liver injury. The predicted core targets were proto-oncogene tyrosine-protein kinase(SRC), phosphatidylinositol 4,5-bisphosphate 3-kinase subunit alpha(PIK3 CA), RAC-alpha serine/threonine-protein kinase(AKT1), etc, with PI3 K-AKT signaling pathway, MAPK signaling pathway, apoptosis, Toll-like receptor signaling pathway, and NF-κB signaling pathway mainly involved. Following the scree-ning of the main toxic and pharmacodynamic components, the pharmacodynamic effects were investigated by cell experiments. The results showed that licochalcone A was mainly responsible for alleviating coryfolin-induced liver injury, licochalcone B for coryfolin-and psoralidin-induced liver injury, and echinatin for corylifolinin-and bakuchiol-induced liver injury. The preliminary revealing of the alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury and the prediction of related mechanisms will provide reference for further mechanism research and reasonable clinical compatibility.

Pectic polysaccharide from Nelumbo nucifera leaves promotes intestinal antioxidant defense in vitro and in vivo.

In this study, the Nelumbo nucifera leaf polysaccharide (NNLP) was isolated by hot water extraction and ethanol precipitation. DEAE anion exchange chromatography and gel filtration were further performed to obtained the purified fraction NNLP-I-I, the molecular weight of which was 16.4 kDa. The monosaccharide composition analysis and linkage units determination showed that the fraction NNLP-I-I was a pectic polysaccharide. In addition, the NMR spectra analysis revealed that NNLP-I-I mainly consisted of a homogalacturonan backbone and rhamnogalacturonan I, containing a long HG region and short RG-I region, with AG-II and 1-3 linked rhamnose as side chains. The biological studies demonstrated that NNLP-I-I displayed antioxidant properties through mediating the Nrf2-regulated intestinal cellular antioxidant defense, which could protect cultured intestinal cells from oxidative stress and improve the intestinal function of aged mice.

Analysis of Clinical Outcome and Predictors of Mortality in Pediatric Trauma Population: Evidence from a 10 Year Analysis in a Single Center.

The shock index (SI) is a useful tool for predicting the injury severity and mortality in patients with trauma. However, pediatric physiology differs from that of adults. In the pediatric trauma population, the shock status may be obscured within the normal range of vital signs. Pediatric age-adjusted SI (SIPA) is reported more accurately compared to SI. In our study, we conducted a 10 year retrospective cohort study of pediatric trauma population to evaluate the SI and SIPA in predicting mortality, intensive care unit (ICU) admission, and the need for surgery. This retrospective cohort study included 1265 pediatric trauma patients from January 2009 to June 2019 at the Taipei Tzu Chi Hospital, who had a history of hospitalization. The primary outcome of this investigation was in-hospital mortality, and the secondary outcomes were the length of hospital and ICU stay, operation times, and ICU admission times. The SIPA group can detect changes in vital signs early to reflect shock progression. In the elevated SIPA group, more severe traumatic injuries were identified, including high injury severity score (ISS), revised trauma score (RTS), and new injury severity score (NISS) scores than SI > 0.9. The odds ratio of elevated SIPA and SI (>0.9) to predict ISS ≥ 16 was 3.593 (95% Confidence interval [CI]: 2.175-5.935, p < 0.001) and 2.329 (95% CI: 1.454-3.730, p < 0.001). SI and SIPA are useful for identifying the compensatory phase of shock in prehospital and hospital settings, especially in corresponding normal to low-normal blood pressure. SIPA is effective in predicting the mortality and severity of traumatic injuries in the pediatric population. However, SI and SIPA were not significant predictors of ICU admission and the need for surgery analysis.

Pre-operative proteinuria, postoperative acute kidney injury and mortality: A systematic review and meta-analysis.

OBJECTIVE: To investigate the association of pre-operative proteinuria with postoperative acute kidney injury (AKI) development as well as the requirement for a renal replacement therapy (RRT) and mortality at short-term and long-term follow-up. BACKGROUND: Postoperative AKI is associated with surgical morbidity and mortality. Pre-operative proteinuria is potentially a risk factor for postoperative AKI and mortality. However, the results in literature are conflicting. METHODS: We searched PubMed, Embase, Scopus, Web of Science and Cochrane Library from the inception through to 3 June 2020. Observational cohort studies investigating the association of pre-operative proteinuria with postoperative AKI development, requirement for RRT, and all-cause mortality at short-term and long-term follow-up were considered eligible. Using inverse variance method with a random-effects model, the pooled effect estimates and 95% confidence interval (CI) were calculated. RESULTS: Twenty-eight studies were included. Pre-operative proteinuria was associated with postoperative AKI development [odds ratio (OR) 1.74, 95% CI, 1.45 to 2.09], in-hospital RRT (OR 1.70, 95% CI, 1.25 to 2.32), requirement for RRT at long-term follow-up [hazard ratio (HR) 3.72, 95% CI, 2.03 to 6.82], and long-term all-cause mortality (hazard ratio 1.50, 95% CI, 1.30 to 1.73). In the subgroup analysis, pre-operative proteinuria was associated with increased odds of postoperative AKI in both cardiovascular (OR 1.77, 95% CI, 1.47 to 2.14) and noncardiovascular surgery (OR 1.63, 95% CI, 1.01 to 2.63). Moreover, there is a stepwise increase in OR of postoperative AKI development when the quantity of proteinuria increases from trace to 3+. CONCLUSION: Pre-operative proteinuria is significantly associated with postoperative AKI and long-term mortality. Pre-operative anaesthetic assessment should take into account the presence of proteinuria to identify high-risk patients. PROSPERO REGISTRATION: CRD42020190065.

Tiaobu Feishen therapy inhibits inflammation induced by cigarette smoke extracts in a human monocyte/macrophage cell line.

OBJECTIVE: To study the mechanistic effects of Tiaobu Feishen therapy (TBFS) on inflammation induced by cigarette smoke extract (CSE) in a human monocyte/macrophage cell line. METHODS: The human monocyte/macrophage cell line THP-1 was stimulated with 10 % CSE in the presence or absence of Bufei Yishen formula (BYF), Bufei Jianpi formula (BJF) and Yiqi Zishen formula (YZF). All formulations contained serum. Pro-inflammatory cytokines were measured in the supernatants using enzyme-linked immunosorbent assay. The activity of STAT3 DNA binding was detected using electrophoretic mobility shift assay and janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway activation was assessed using Western blotting. RESULTS: The results showed that BYF, BJF and YZF treatment strongly decreased the CSE-induced secretion of interleukin (IL)-6, IL-8, tumor necrosis factor-α and matrix metalloproteinase-9 by THP-1 cells. Furthermore, BYF, BJF and YZF treatment attenuated STAT3 DNA binding capacity and JAK2 and STAT3 were shown to be phosphorylated. CONCLUSION: The data revealed that BYF, BJF and YZF effectively inhibited a CSE-induced inflammatory response in THP-1 cells by limiting activation of the JAK2/STAT3 pathway.

Characterization of an antioxidant pectic polysaccharide from Platycodon grandiflorus.

Platycodonis Radix is widely used as homology of medicine and food in China; polysaccharides are thought to be one of its functional constituents. In this study, a pectic polysaccharide, PGP-I-I, was obtained from the root of the traditional medicine plant Platycodon grandiflorus through ion exchange chromatography and gel filtration. This was characterized being mainly composed of 1,5-α-L-arabinan and both arabinogalactan type I (AG-I) and II chains linked to rhamnogalacturonan I (RG-I) backbone linked to longer galacturonan chains. In vitro bioactivity study showed that PGP-I-I could restore the intestinal cellular antioxidant defense under the condition of hydrogen peroxide (H2O2) treatment through promoting the expressions of cellular antioxidant genes and protect against oxidative damages.

Gastropericardial fistula induced acute purulent pericarditis.

Gastropericardial fistula is a rare but lethal condition. Several etiologies have been reported, including previous gastric or esophageal surgery, malignancy, trauma, infection, and ulcer perforation. Typical symptoms included chest pain, epigastric pain, fever and dyspnea. Gastropericardial fistula can lead to serious complications, including cardiac tamponade, sepsis, hemodynamic compromise and death. Therefore, early diagnosis and timely management are important for physicians to prevent from catastrophic complications. Here, we present a case of a man who presented with acute purulent pericarditis secondary to a gastropericardial fistula to highlight the pathogenesis and suggest therapeutic strategies.