Geniposide from Gardeniae Fructus exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The desiccative ripe fruits of Gardenia (Gardenia jasminoides Ellis) (called Zhizi in China) are known with cold character and the effects of reducing fire except vexed, clearing away heat evil, and cooling blood and eliminating stasis. Zhizi is often clinical formulated to treat various types of fever. Fever is a sign of inflammation and, geniposide from Zhizi has been proved with anti-inflammatory in various inflammatory models. AIM OF STUDY: The aim of this study was to investigate the antipyretic role of geniposide with three classical inflammatory fever models and explore the underlying mechanisms. MATERIALS AND METHODS: Water extract (WE), high polar part (HP), iridoid glycoside part (IG), and gardenia yellow pigment part (GYP) from Gardeniae Fructus (GF) were obtained from Zhizi. The antipyretic activities of these composes were tested with dry yeast induced fever rats. Geniposide was further purified from IG and the antipyretic activity was evaluated by gavage, intraperitoneal injection, and caudal intravenous injection to rats of fever induced by dry yeast, lipopolysaccharide (LPS), and 2, 4-dinitrophenol (DNP) in rats. Then, the mechanism of geniposide by intragastric administration was studied. The contents of thermoregulatory mediators and inflammatory factors relating to TLR4/NF-κB pathway in serum were determined by ELISA and Western blot, and the pathological changes of the hypothalamus were observed by HE staining. RESULTS: The temperature was decreased by geniposide in the three fever model rats. Geniposide can not only inhibit the increase of inflammatory factors in serum but also protect the hypothalamus from fever pathological damage in the three fever models. Western blot showed that geniposide could inhibit the TLR4/NF-κB pathway. CONCLUSION: Geniposide exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.

Thiamine administration may increase survival benefit in critically ill patients with myocardial infarction.

Background: Myocardial infarction (MI) is a common cardiovascular disease (CVD) in critically ill patients, leading to 17% mortality in the intensive care unit (ICU) setting. Patients with CVD frequently suffer from thiamine insufficiency, thereby thiamine supplements may be helpful. Unfortunately, the relationship between thiamine treatment and survival outcomes in ICU patients with MI is still unknown. The purpose of the research is to demonstrate the survival advantage of thiamine application in these patients. Methods: The Medical Information Mart of Intensive Care-IV database served as the foundation for this retrospective cohort analysis. Depending on whether patients were given thiamine therapy during the hospital stay, critically ill MI patients were split into the thiamine and non-thiamine groups. The Kaplan-Meier (KM) method and Cox proportional hazard models were used to evaluate the relationship between thiamine use and the risk of in-hospital, 30-day, and 90-day mortality. To validate the results, a 1:2 closest propensity-score matching (PSM) was also carried out. Results: This study included 1782 patients for analysis with 170 and 1,612 individuals in the thiamine and non-thiamine groups, respectively. The KM survival analyses revealed that the risk of in-hospital, 30-day, and 90-day mortality was significantly lower in the thiamine group than the none-thiamine group. After modifying for a variety of confounding factors, the Cox regression models demonstrated substantial positive impacts of thiamine use on in-hospital, 30-d, and 90-d mortality risk among critically ill patients with MI with hazard ratio being 0.605 [95% confidence interval (CI): 0.397-0.921, p = 0.019], 0.618 (95% CI: 0.398-0.960, p = 0.032), and 0.626 (95% CI: 0.411-0.953, p = 0.028), respectively, in the completely modified model. PSM analyses also obtained consistent results. Conclusion: Thiamine supplementation is related to a decreased risk of mortality risk in critically ill patients with MI who are admitted to the ICU. More multicenter, large-sample, and well-designed randomized controlled trials are needed to validate this finding.

Advances of phytotherapy in ischemic stroke targeting PI3K/Akt signaling.

The pathogenesis of ischemic stroke is complex, and PI3K/Akt signaling is considered to play a crucial role in it. The PI3K/Akt pathway regulates inflammation, oxidative stress, apoptosis, autophagy, and vascular endothelial homeostasis after cerebral ischemia; therefore, drug research targeting the PI3K/Akt pathway has become the focus of scientists. In this review, we analyzed the research reports of antiischemic stroke drugs targeting the PI3K/Akt pathway in the past two decades. Because of the rich sources of natural products, increasing studies have explored the value of natural compounds, including Flavonoids, Quinones, Alkaloids, Phenylpropanoids, Phenols, Saponins, and Terpenoids, in alleviating neurological impairment and achieved satisfactory results. Herbal extracts and medicinal formulas have been applied in the treatment of ischemic stroke for thousands of years in East Asian countries. These precious clinical experiences provide a new avenue for research of antiischemic stroke drugs. Finally, we summarize and discuss the characteristics and shortcomings of the current research and put forward prospects for further in-depth exploration.

New Evidence for Artemisia absinthium as an Alternative to Classical Antibiotics: Chemical Analysis of Phenolic Compounds, Screening for Antimicrobial Activity.

Artemisia absinthium, an important herb of the Artemisia genus, was evaluated in this study for its potential as an alternative to classical antibiotics. The antimicrobial activity of methanol extracts of A. absinthium (MEAA) was evaluated using the broth microdilution method, revealing that A. absinthium exhibited broad-spectrum antibacterial and antifungal activity. Ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS) was used to analyze the chemical profile of the MEAA, with a focus on flavonoids, quinic acids, and glucaric acids. A total of 90 compounds were identified, 69 of which were described for the first time in A. absinthium. Additionally, a new class of caffeoyl methyl glucaric acids was identified. The main active compounds were quantified and screened for antimicrobial activity. A. absinthium was found to be rich in quinic acids and flavonoids. The screening for antimicrobial activity also revealed that salicylic acid, caffeic acid, casticin, and 3,4-dicaffeoylquinic acid had varying degrees of antimicrobial activity. The acute toxicity of MEAA was examined following OECD guidelines. The administration of 5000 mg/kg bw of MEAA did not result in mortality in male and female mice. Furthermore, there were no observed effects on the visceral organs or general behavior of the mice, demonstrating the good safety of MEAA. This study provides new evidence for the use of A. absinthium as an alternative to classical antibiotics in addressing the problem of bacterial resistance.

Synchronously construction of hierarchical porous channels and cationic surface charge on lanthanum-hydrogel for rapid phosphorus removal.

Phosphorus (P) removal from wastewater is critical for ecosystem operation and resource recovery. To facilitate the recycling of the used absorbents through balancing their adsorption and desorption performance on P, in this work, a novel porous magnetic La(OH)3-loaded MAPTAC/chitosan (CTS)/polyethyleneimine (PEI) ternary composite hydrogel (p-MTCH-La(OH)3) with enhanced bifunctional adsorption sites was synthesized by simultaneous dissolution of pre-embedded CaCO3 and CTS powder, followed by grafting PEI and loading La. Hierarchical porous channels promoted good dispersion of La(OH)3, bringing an excellent P adsorption capacity of 107.23 ± 4.96 mg P/g at neutral condition. PEI grafted with CTS increased the surface charge and enhanced the electrostatic attraction, which facilitated the desorption of P. The porous structure and abundant active sites also facilitated rapid adsorption with an adsorption rate constant of 0.1 g mg-1 h-1. p-MTCH-La(OH)3 maintained effective P adsorption despite co-existence with competing substances and after 5 cycles. Further mechanistic analysis indicated that La-P inner sphere complexation and LaPO4 crystalline transformation were the main pathways for P removal. However, electrostatic interactions contributed 17.5%-46.7% of the adsorption amount during the first 30 min of rapid adsorption, enabling 92.8% of the adsorbed P at this stage to be desorbed by alkaline solution. Based on the variations of adsorption and desorption capacity with adsorption time, a rapid unsaturated adsorption of 1-2 h was proposed to facilitate the recycling of the adsorbent. This study proposed a method to promote P adsorption and desorption by enhancing bifunctional adsorption sites, and proved that p-MTCH-La(OH)3 is a promising phosphate adsorbent.

[CiteSpace knowledge map of research status and trends of Croci Stigma].

This study retrieved Croci Stigma related literature from CNKI, Wanfang, VIP, and Web of Science database, and used bibliometrics and CiteSpace 6.1.R2 software to analyze the published Croci Stigma related articles in Chinese and English from 2000 to 2022. The authors, research institutions, and keywords were visualized and analyzed, and the current status and development trend of Croci Stigma research was summarized by combining the information extraction methods. A total of 1 846 Chinese articles and 2 703 English articles were screened out and included. The results showed a generally steady increase in the number of Croci Stigma related articles. The results of the visualization analysis showed that there were more collaborations between researcher teams and major research institutions in English articles than Chinese articles. The Chinese articles was mainly published by China Pharmaceutical University, and most of the inter-institutional collaborations occurred in neighboring regions. The English articles was mainly published by Iranian institutions, and most of the cooperation occurred within the country, with less transnational cooperation. Keywords analysis showed that the research on Croci Stigma was mainly focused on chemical compositions, pharmacological effects, mechanisms, quality control, etc. It was predicted that the future research hotspots of Croci Stigma would mainly focus on pharmacological mechanism and clinical efficacy. The current research related to Croci Stigma still needs to be developed, cooperation should be strengthened, and more in-depth research should be conducted.

Should acupuncture therapy be used for acute facial paralysis? A protocol for systematic review.

BACKGROUND: Peripheral facial paralysis (PFP) results in functional disorder and social dysfunction, when it is under a severe condition at onset, long-term poor outcomes do occur. Different acupuncture methods have been reported to be potentially effective for shortening the disease course and reducing the occurrence of sequelae when they are applied at an early stage. Neuro edema is a common pathological feature in the acute phase, and many clinical studies have suggested its effect of reducing facial nerve edema. It is of value to estimate the effectiveness and safety of acupuncture treatment at the onset, and to assess the most suitable acupuncture method for the acute period. METHODS AND ANALYSIS: All the RCTs and quasi-RCTs on acupuncture therapy for patients who is during acute stage of PFP will be included. The recovery rate of facial function, the time it takes to restore facial function and the odds of sequelae occurring will be the key parts we focus on. Psychological well-being and quality of life will also be evaluated. Literature searching will be conducted until December 31th, 2022 from eight databases systematically. Two reviewers will screen the literature and extract the data independently. RevMan software will be used for data analysis, and the version 2 of the Cochrane risk-of-bias tool (RoB 2) will be used to assess the certainty of evidence. Forest plots and summary findings will be generated. If data permits, a meta-analysis will be conducted. ETHICS AND DISSEMINATION: Since this study will not involve clinical treatment of patients, ethics approval is not required. The result of this study will be submitted to a peer-reviewed journal for publication and as a proposal for clinical practice and further study on acupuncture treatment at the early stage of PFP. DISCUSSION: This review will summarize the evidence on the different type of acupuncture therapy for acute Bell's palsy and Ramsay-Hunt syndrome. We anticipate that it would be safe and effective when applied to the acute phase of PFP, and some specific suitable acupuncture methods would be found resulting from this review. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register for Systematic Reviews (PROSPERO) number CRD42020205127.

Corrigendum: Modulations of static and dynamic functional connectivity among brain networks by electroacupuncture in post-stroke aphasia.

[This corrects the article DOI: 10.3389/fneur.2022.956931.].

Integrated proteomics and metabolomics reveal variations in pulmonary fibrosis development and the potential therapeutic effect of Shuangshen Pingfei formula.

ETHNOPHARMACOLOGICAL RELEVANCE: Shuangshen Pingfei formula (SSPF), a Chinese medicine prescription, has been prescribed to alleviate PF. However, little is known about the molecular mechanism underlying PF progression and the regulatory mechanism in SSPF. AIMS OF THE STUDY: To discriminate the molecular alterations underlying the development of pulmonary fibrosis (PF) and reveal the regulatory mechanism of Shuangshen Pingfei formula (SSPF). MATERIALS AND METHODS: An integrated analysis of a time-course pathology combined with proteomics and metabolomics was performed to investigate changes in body weight, survival rate, lung coefficient, histopathology, proteins, and metabolites of lung tissues at different time points upon bleomycin (BLM) exposure and SSPF treatment. RESULTS: The results showed that PF progression was characterized by gradually aggravated fibrosis accompanied by inflammation with extended exposure (7, 14, and 21 days). SSPF significantly attenuated lung fibrosis, as evidenced by increased weight, and reduced lung coefficients and fibrosis scores. Moreover, 368 common differentially expressed proteins (DEPs) were identified, and 102 DEPs were continuously and monotonically upregulated via proteomics among the three BLM treatments. The DEPs were principally involved in extracellular matrix (ECM) remodeling and arginine and proline (AP) metabolic reprogramming. Additionally, metabolomics analyses revealed that BLM exposure mainly affected six metabolism pathways, including 34 differentially regulated metabolites (DRMs). Furthermore, correlation analysis found that several DEPs and DRMs, including L-ornithine, S-adenosyl-L-methionine, ARG, and AOC1, were associated with arginine and proline metabolism, and 8,9-EET, 8,9-DHET, CYP2B, etc., were involved in arachidonic acid (AA) metabolism, suggesting that these two pathways play a critical role in the development of fibrosis. After SSPF treatment, the related protein expression and metabolic disorders were regulated, implying that SSPF provides potential solutions to target these pathways for benefit in the treatment of PF. CONCLUSION: Our data suggest that ECM remodeling, and metabolic reprogramming of AP and AA are distinctive features of PF development. Simultaneously, we confirmed that SSPF could effectively regulate metabolic disorders, indicating its potential clinical application for PF therapy. Our findings using multiple approaches provide a molecular-scale perspective on the mechanisms of PF progression and the amelioration of SSPF.

Medication rule of traditional Chinese medicine in the treatment of plateau hypoxia based on data mining. / 基于数据挖掘中药治疗高原性缺氧的组方规律.

OBJECTIVES: The development of traditional Chinese medicine (TCM) in the plateau area is relatively backward. There is a lack of system to analyze the effects of the special environment of plateau low pressure and hypoxia on human meridians qi and blood, as well as the etiology and pathogenesis of plateau hypoxic diseases. To analyze the composition rules of anti-hypoxia TCM formulation with data mining methods. METHODS: The experimental literatures related to high altitude hypoxia were searched in China National Knowledge Infrastructure (CNKI), Wanfang Med Online, VIP, China Biology Medicine disc and other databases, a standardized prescription database was established after screening and standardization of prescription data in the literature. The composition rules of these prescription including drug frequency, drug attributes, drug efficacy, drug combination, and core prescription were analyzed and displayed with visual charts. RESULTS: A total of 135 TCM prescriptions were included, and 229 flavored drugs were included. Among these prescriptions, the TCM with high frequency of use were Astragalus, Danshen, Ginseng, and Angelica, etc. Four natures of the TCM were mostly warm and calm. Five flavours of the TCM were mostly sweet, bitter, and pungent. And channel tropism of the TCM mostly entered the heart, lung, and liver meridians. The frequency combination of TCM was Astragalus-Danshen and Astragalus-Angelica. The core medicines of these prescriptions were Astragalus, Danshen, Angelica, Rhodiola, Goji, and Ginseng. TCM could alleviate symptoms such as chest tightness, chest pain, coughing and wheezing, coughing, vomiting, fatigue, and loss of appetite caused by hypoxia at high altitude. CONCLUSIONS: Through data mining, it is concluded that the prevention or treatment of plateau hypoxic diseases mostly utilized products can nourish blood, replenish qi and dispel stasis, and help yang and dispel qi, most of them are compatible with qi tonic drugs and blood circulation and stasis dissolving drugs, and pay attention to the combination of virtual and real, yin and yang.

Exercise performance reduction and preventive measures in highland sports. / 高原运动效能降低及防治措施.

The plateau is a special environment with low pressure, low oxygen, low temperature, and high ultraviolet radiation. The exercise performance of people on the plateau is generally reduced, which seriously affects the life and health of people living in the plateau and entering the plateau. In recent years, the prevention and treatment of injury caused by high altitude hypoxia has attracted wide attention. It has shown that the higher the altitude with the longer the duration of exercise, the faster the stationing, the greater the impact on people's sports performance. Rapid entry into the plateau and long-term stay in the plateau have an impact on people's explosive power, endurance and fine operation. Advances in medical technology enable various prevention methods to be used to acclimate to high altitude environments. However, in vitro intervention methods are costly, easy to rebound and possess limited effects. Therefore, drug prevention and treatment is obviously a more economical choice. Chemical drugs increase the efficiency of high altitude exercise by improving the ischemic and hypoxic symptoms of the heart and brain, increasing lung ventilation and arterial oxygenation capacity, and accelerating the elimination of adverse product accumulation after exercise. Single Chinese medicine, Chinese patent medicine, and compound preparations can improve exercise performance by promoting body metabolism, improving muscle endurance, enhancing immunity, and other mechanisms. Traditional Chinese medicine has unique advantage and application prospect in improving plateau sports performance damage.

Modulations of static and dynamic functional connectivity among brain networks by electroacupuncture in post-stroke aphasia.

Introduction: Post-stroke aphasia (PSA) is a language disorder caused by left hemisphere stroke. Electroacupuncture (EA) is a minimally invasive therapeutic option for PSA treatment. Tongli (HT5) and Xuanzhong (GB39), two important language-associated acupoints, are frequently used in the rehabilitation of patients with PSA. Preliminary evidence indicated functional activation in distributed cortical areas upon HT5 and GB39 stimulation. However, research on the modulation of dynamic and static functional connectivity (FC) in the brain by EA in PSA is lacking. Method: This study aimed to investigate the PSA-related effects of EA stimulation at HT5 and GB39 on neural processing. Thirty-five participants were recruited, including 19 patients with PSA and 16 healthy controls (HCs). The BOLD signal was analyzed by static independent component analysis, generalized psychophysiological interactions, and dynamic independent component analysis, considering variables such as age, sex, and years of education. Results: The results revealed that PSA showed activated clusters in the left putamen, left postcentral gyrus (PostCG), and left angular gyrus in the salience network (SN) compared to the HC group. The interaction effect on temporal properties of networks showed higher variability of SN (F = 2.23, positive false discovery rate [pFDR] = 0.017). The interaction effect on static FC showed increased functional coupling between the right calcarine and right lingual gyrus (F = 3.16, pFDR = 0.043). For the dynamic FC, at the region level, the interaction effect showed lower variability and higher frequencies of circuit 3, with the strongest connections between the supramarginal gyrus and posterior cingulum (F = 5.42, pFDR = 0.03), middle cingulum and PostCG (F = 5.27, pFDR = 0.036), and triangle inferior frontal and lingual gyrus (F = 5.57, pFDR = 0.026). At the network level, the interaction effect showed higher variability in occipital network-language network (LN) and cerebellar network (CN) coupling, with stronger connections between the LN and CN (F = 4.29, pFDR = 0.042). Dynamic FC values between the triangle inferior frontal and lingual gyri were anticorrelated with transcribing, describing, and dictating scores in the Chinese Rehabilitation Research Center for Chinese Standard Aphasia Examination. Discussion: These findings suggest that EA stimulation may improve language function, as it significantly modulated the nodes of regions/networks involved in the LN, SN, CN, occipital cortex, somatosensory regions, and cerebral limbic system.

Physiological changes and gene responses during Ganoderma lucidum growth with selenium supplementation.

Ganoderma lucidum basidiomycota is highly appreciated for its health and nutrition value. In the present study, Ganoderma lucidum was cultivated as selenium transformation carrier, and the physiological changes and gene responses by selenium supplementation were revealed through high-throughput RNA-Seq technology. As a result, selenium supplementation increased the stipe length and the cap size, but decreased the cap thickness of G. lucidum. Mineral salt supplementation could greatly promote the formation of triterpene acids and selenium in G. lucidum. The highest yield was gained in the treatment with selenium content of 200 µg/g. Subsequently, the tissues of G. lucidum at budding and mature stages in this treatment group were sampled for transcriptome analysis and compared to those of a control group without selenium supplementation. A total of 16,113 expressed genes were obtained from the transcriptome of G. lucidum, and GO-annotated unigenes were mainly involved in molecular functions and KEGG-annotated ones were highly expressed in ribosomal pathway. Furthermore, genes involved in carbon metabolism pathway were most promoted by selenium at budding stage of G. lucidum, while gene expression was the highest in the pathway of amino acid biosynthesis at mature stage of G. lucidum. Specially, selenium-related genes in G. lucidum, such as GL23172-G, GL29881-G and GL28298-G, played a regulatory role in oxidoreductase, antioxidant activity and tryptophan synthesis. The results provide a theoretical basis for further study of selenium-enriched mushrooms and aid to development of Se-enriched foodstuff and health products made from fungi.

Ferroptosis-induced anticancer effect of resveratrol with a biomimetic nano-delivery system in colorectal cancer treatment.

Ferroptosis is a novel form of programmed cell death impelled by iron-dependent lipid peroxidation, which may be a potential strategy for cancer therapy. Here we demonstrated for the first time that Resveratrol (RSV), a traditional Chinese medicine (TCM) chemical monomer, could effectually inhibit the growth of colon cancer cells through the ROS-dependent ferroptosis pathway. Mechanistically, RSV evoked the increase of reactive oxygen species and lipid peroxidation in colorectal cancer cells, and eventually lead to ferroptosis. Furthermore, RSV could promote ferroptosis by downregulating the expression of the channel protein solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). To improve the delivery efficiency of RSV, a biomimetic nanocarrier was developed by coating RSV-loaded poly(ε-caprolactone)-poly(ethylene glycol) (PCL-PEG) nanoparticles with erythrocyte membrane (RSV-NPs@RBCm). The RSV-NPs@RBCm provide the possibility to escape macrophage phagocytosis and have a long circulation effect. In addition, when coupled with a tumor-penetrating peptide iRGD, which could trigger enhanced tissue penetration tumor-specifically, the delivery of RSV-NPs@RBCm into tumors would be significantly improved results from the in vivo study demonstrated an excellent treatment efficacy for CRC. Altogether, our study highlighted the therapeutic potential of RSV as a ferroptosis-inducing anticancer agent and when loaded into a biomimetic nanoplatform, it might pave the way for the application of RSV loaded nanosystems for colorectal cancer treatment.

[Comparison of distribution of verbascoside in normoxic and hypoxic rats].

This study established a high performance liquid chromatography(HPLC) method for the simultaneous determination of verbascoside(VB) and its main metabolite caffeic acid(CA) in rat tissue samples. A low-pressure low-oxygen animal experimental chamber was used to simulate the plateau environment for establishing the hypoxic rat model. After intragastric administration of 300 mg·kg~(-1) VB, the normoxic and hypoxic rats were sacrificed for the collection of heart, liver, spleen, lung, kidney, brain, muscle, large intestine, small intestine, and stomach tissue samples at the time points of 30, 60, and 90 min. VB and CA concentrations in each tissue sample were measured by HPLC, and the distribution of VB and CA in normoxic and hypoxic rats was compared. The results showed that after intragastric administration, VB can be rapidly absorbed and distributed into various tissues including brain in both normoxic and hypoxic rats, indicating that VB can pass through the blood-brain barrier. In the gastrointestinal tract, VB was mainly distributed in small intestine, which suggested that the main absorption site of VB was small intestine. A large amount of VB was detected in muscle and lung, and only a small amount in other tissues. CA was detected in other tissues except brain, heart, and muscle. Small intestine had the most abundant CA, followed by stomach, large intestine, and kidney, and only a small amount of CA was detected in the liver, spleen, and lung(<50 ng·mL~(-1)). The results indicated that VB may be mainly absorbed and metabolized in the gastrointestinal tract to produce CA and was possibly excreted through kidney. Compared with normoxic rats, hypoxic rats had reduced and slow distribution of VB and increased ratio of VB concentration in tissue to plasma, which implied that the relative proportion of VB from systemic circulation to tissues was increased in hypoxic rats. This study provides a basis for the application of VB in anti-hypoxia therapy and for the formulation of anti-hypoxia dosing regimens.

Efficacy of Epigallocatechin-3-Gallate in Preventing Dermatitis in Patients With Breast Cancer Receiving Postoperative Radiotherapy: A Double-Blind, Placebo-Controlled, Phase 2 Randomized Clinical Trial.

Importance: Safe and effective prophylactic therapies for radiation-induced dermatitis (RID) remain an unmet need. Objective: To determine if epigallocatechin-3-gallate (EGCG) solution reduces the incidence of RID in patients undergoing radiotherapy after breast cancer surgery. Design, Setting, and Participants: This phase 2 double-blind, placebo-controlled randomized clinical trial enrolled 180 patients with breast cancer receiving postoperative radiotherapy at Shandong Cancer Hospital and Institute in Shandong, China, between November 2014 and June 2019. Data analysis was performed from September 2019 to January 2020. Interventions: Participants were randomly assigned (2:1) to receive either EGCG solution (660 µmol/L) or placebo (0.9% NaCl saline) sprayed to the whole radiation field from day 1 of the radiation until 2 weeks after radiation completion. Main Outcomes and Measures: The primary end point was incidence of grade 2 or worse RID, defined by the Radiation Therapy Oncology Group scale. The secondary end points included RID index (RIDI), symptom index, changes in the skin temperature measured by infrared thermal images, and safety. Results: A total of 180 eligible patients were enrolled, of whom 165 (EGCG, n = 111; placebo, n = 54) were evaluable for efficacy (median [range] age, 46 [26-67] years). The occurrence of grade 2 or worse RID was significantly lower (50.5%; 95% CI, 41.2%-59.8%) in the EGCG group than in the placebo group (72.2%; 95% CI, 60.3%-84.1%) (P = .008). The mean RIDI in the EGCG group was significantly lower than that in the placebo group. Furthermore, symptom indexes were significantly lower in patients receiving EGCG. Four patients (3.6%) had adverse events related to the EGCG treatment, including grade 1 pricking skin sensation (3 [2.7%]) and pruritus (1 [0.9%]). Conclusions and Relevance: In this randomized clinical trial, prophylactic use of EGCG solution significantly reduced the incidence and severity of RID in patients receiving adjuvant radiotherapy for breast cancer. It has the potential to become a new choice of skin care for patients receiving radiotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02580279.

Effect of aqueous extract of Astragalus membranaceus on behavioral cognition of rats living at high altitude.

OBJECTIVE: To investigate the effect of aqueous extract of Astragalus membranaceus on cognitive ability of rats living at high altitude. METHODS: Rats were exposed to a simulated highaltitude hypobaric hypoxia chamber. The behavior of rats was tested by eight-arm maze. The contents of malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS) and activity of total superoxide dismutase (T-SOD) in hippocampus were measured. The expressions of mammalian target of rapamycin (mTOR) and cleaved capase-3 in hippocampus were determined by reverse transcription-polymerase chain reaction and Western blot. RESULTS: The behavioral cognitive ability of the hypoxic control group was significantly lower than that of the normoxic control group. Under hypoxic environment, after the administration of aqueous extract of Astragalus membranaceus, the behavioral cognitive ability of rats was significantly improved. In hippocampal tissue, the content of MDA and ROS were significantly decreased, while the content of GSH and activity of T-SOD in hippocampus were significantly increased. The mRNA expression of mTOR and P70S6K and the protein expression of p-mTOR were significantly increased; the mRNA expression of 4E-binding protein 1 (4E-BP1) and the protein expression of phosphorylated-4E-BP1 (p-4EBP1) and cleaved capase-3 were significantly decreased. CONCLUSION: When the rats are exposed to high altitude hypoxia, the behavioral cognitive ability could be significantly reduced. Aqueous extract of Astragalus membranaceus can significantly improve cognitive function in rats under hypoxia. The potential mechanism is related to improving oxidative stress, reducing the accumulation of free radicals and metabolites, and activating mTOR signaling pathway.

Tea polyphenol/glycerol-treated double-network hydrogel with enhanced mechanical stability and anti-drying, antioxidant and antibacterial properties for accelerating wound healing.

Frequent dressing changes can result in secondary wound damage. Therefore, it is of great significance to construct a wound dressing that can be used for a long time without changing. Here, a double-network hydrogel was synthesized through hydrogen bonding interactions of tea polyphenol (TP)/glycerol with photo-crosslinked N-acryloyl glycinamide (NAGA), gelatin methacrylate (GelMA), and nanoclay hydrogel. The glycerol/water solvent slowed the diffusion of TP into the NAGA/GelMA/Laponite (NGL)hydrogel, thereby avoiding excessive crosslinking, and forming a uniform network. The hydrogel exhibited excellent water retention (84% within 28 days). Additionally, due to the hygroscopicity of glycerol, the hydrogel's mechanical strength (0.73-1.14 MPa) and tensile strain (207%-353%) increased further after 14 days in an open environment. Additionally, the hydrogel exhibited superior anti-ultraviolet and antioxidant properties, which effectively alleviated the wound site's oxidative stress and accelerated wound healing. Moreover, antibacterial activity was observed against both E. coli and S. aureus in the hydrogel wound dressing. Thus, by promoting wound closure, angiogenesis and collagen deposition, the double-network NGLG20/TG hydrogel dressing can successfully accelerate wound healing. The multifunctional double-network hydrogel, therefore, shows immense potential as an ideal candidate for wound dressings because it is long-lasting and prevents secondary damage caused by frequent dressing changes.

Immune Checkpoint Inhibitor-Associated Tumor Lysis Syndrome: A Real-World Pharmacovigilance Study.

Introduction: Immune checkpoint inhibitors (ICIs) have substantially improved the clinical outcomes of various malignancies. However, the adverse event of tumor lysis syndrome (TLS) has not been included in the National Comprehensive Cancer Network guidelines or drug inserts. In this study, we aimed to establish the relationship between ICI therapies and TLS events using data from a real-world pharmacovigilance database. Methods: The MedDRA terms of TLS and both generic and brand names of ICIs were retrieved from the FDA Adverse Event Reporting System. Four frequentist algorithms were employed to confirm the association between the TLS and the ICI regimens, involving anti-cytotoxic T lymphocyte antigen-4 (anti-CTLA-4), anti-programmed death receptor-1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1), and anti-(CTLA-4 + PD-1). A descriptive and statistical analysis was performed according to the case information. Results: One hundred sixty-four TLS cases, where patients underwent anti-CTLA-4 (n = 14), anti-(PD-1)/(PD-L1) (n = 113), or anti-(CTLA-4 + PD-1) (n = 37) therapies, were collected between the first quarter of 2004 and the fourth quarter of 2020. The most coverage-reporting year, age-group, sex, reporter, region, country, and indication were 2020 (n = 62), 60-74 years (n = 65), males (n = 105), physician (n = 66), Asia (n = 80), Japan (n = 67), and lung and thymus malignancies (n = 40), respectively. The median TLS onset time associated with anti-CTLA-4, anti-(PD-1)/(PD-L1), and anti-(CTLA-4 + PD-1) therapies was 6 (IQR: 2-39.5), 9 (IQR: 2-40), and 20 (IQR: 7.5-37.75) days, respectively. Mortality distribution of 71 reported death outcomes among three groups was statistically significant. All four algorithm signal values of anti-(CTLA-4 + PD-1) were higher than those of anti-CTLA-4 and anti-(PD-1)/(PD-L1). Conclusion: Elderly male patients with lung and thymus malignancies are frequently predisposed to TLS. ICI therapies could induce TLS in both solid and hematological malignancies. The rapid onset time and poor outcomes of patients prompt caution from health-care professionals.

Uncommon Behavior of Li Doping Suppresses Oxygen Redox in P2-Type Manganese-Rich Sodium Cathodes.

Utilizing both cationic and anionic oxygen redox reactions is regarded as an important approach to exploit high-capacity layered cathode materials with earth abundant elements. It has been popular strategies to effectively elevate the oxygen redox activities by Li-doping to introduce unhybridized O 2p orbitals in Nax MnO2 -based chemistries or enabling high covalency transition metals in P2-Na0.66 Mnx TM1- x O2 (TM = Fe, Cu, Ni) materials. Here, the effect of Li doping on regulating the oxygen redox activities P2-structured Na0.66 Ni0.25 Mn0.75 O2 materials is investigated. Systematic X-ray characterizations and ab initio simulations have shown that the doped Li has uncommon behavior in modulating the density of states of the neighboring Ni, Mn, and O, leading to the suppression of the existing oxygen and Mn redox reactivities and the promotion of the Ni redox. The findings provide a complementary scenario to current oxygen redox mechanisms and shed lights on developing new routes for high-performance cathodes.