Luteolin-7-O-ß-d-glucuronide Ameliorates Cerebral Ischemic Injury: Involvement of RIP3/MLKL Signaling Pathway.

Luteolin-7-O-ß-d-glucuronide (LGU) is a major active flavonoid glycoside compound that is extracted from Ixeris sonchifolia (Bge.) Hance, and it is a Chinese medicinal herb mainly used for the treatment of coronary heart disease, angina pectoris, cerebral infarction, etc. In the present study, the neuroprotective effect of LGU was investigated in an oxygen glucose deprivation (OGD) model and a middle cerebral artery occlusion (MCAO) rat model. In vitro, LGU was found to effectively improve the OGD-induced decrease in neuronal viability and increase in neuronal death by a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and a lactate dehydrogenase (LDH) leakage rate assay, respectively. LGU was also found to inhibit OGD-induced intracellular Ca2+ overload, adenosine triphosphate (ATP) depletion, and mitochondrial membrane potential (MMP) decrease. By Western blotting analysis, LGU significantly inhibited the OGD-induced increase in expressions of receptor-interacting serine/threonine-protein kinase 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL). Moreover, molecular docking analysis showed that LGU might bind to RIP3 more stably and firmly than the RIP3 inhibitor GSK872. Immunofluorescence combined with confocal laser analyses disclosed that LGU inhibited the aggregation of MLKL to the nucleus. Our results suggest that LGU ameliorates OGD-induced rat primary cortical neuronal injury via the regulation of the RIP3/MLKL signaling pathway in vitro. In vivo, LGU was proven, for the first time, to protect the cerebral ischemia in a rat middle cerebral artery occlusion (MCAO) model, as shown by improved neurological deficit scores, infarction volume rate, and brain water content rate. The present study provides new insights into the therapeutic potential of LGU in cerebral ischemia.

Iron-electrolysis assisted anammox/denitrification system for intensified nitrate removal and phosphorus recovery in low-strength wastewater treatment.

Two iron-electrolysis assisted anammox/denitrification (EAD) systems, including the suspended sludge reactor (ESR) and biofilm reactor (EMR) were constructed for mainstream wastewater treatment, achieving 84.51±4.38 % and 87.23±3.31 % of TN removal efficiencies, respectively. Sludge extracellular polymeric substances (EPS) analysis, cell apoptosis detection and microbial analysis demonstrated that the strengthened cell lysate/apoptosis and EPS production acted as supplemental carbon sources to provide new ecological niches for heterotrophic bacteria. Therefore, NO3--N accumulated intrinsically during anammox reaction was reduced. The rising cell lysis and apoptosis in the ESR induced the decline of anammox and enzyme activities. In contrast, this inhibition was scavenged in EMR because of the more favorable environment and the significant increase in EPS. Moreover, ESR and EMR achieved efficient phosphorus removal (96.98±5.24 % and 96.98±4.35 %) due to the continued release of Fe2+ by the in-situ corrosion of iron anodes. The X-ray diffraction (XRD) indicated that vivianite was the dominant P recovery product in EAD systems. The anaerobic microenvironment and the abundant EPS in the biofilm system showed essential benefits in the mineralization of vivianite.

The effect of Tai Chi exercise intervention on sleep quality in community residing older adults: a systematic review and meta-analysis.

PURPOSE: While clinical research has shown that Tai Chi exercise may improve the sleep quality of older adults, there is a lack of robust evidence-based verification. Therefore, this study conducted a systematic review of published research on the effect of Tai Chi exercise on the sleep quality of community-dwelling older adults, aiming to provide solid evidence-based medicine to enhance their sleep quality. METHODS: A systematic search was conducted on PubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, VIP, and SinoMed databases from their inception to December 9, 2022. The Cochrane risk of bias assessment tool 2.0 was used to assess the risk of bias in the included studies. RESULTS: This systematic review included 12 original articles, involving a total of 1,058 community-dwelling older adults, with 553 in the Tai Chi group and 505 in the control group. The meta-analysis results revealed a significant improvement in the sleep quality of community-dwelling older adults who practiced Tai Chi compared to the control group [WMD = - 1.96 (95% CI: - 3.02 to - 0.90, z = 3.62, P < 0.001)]. Subgroup analysis showed that Tai Chi had significantly beneficial effects regardless of age, country/region, intervention time, and Tai Chi type. CONCLUSIONS: Tai Chi exercise can serve as an effective non-medication approach for addressing sleep problems in this demographic. Among the various types of Tai Chi exercises, the 24-form Tai Chi exercise emerges as a preferred option. Moreover, Tai Chi exercise proves to be an excellent choice for older people in their later years, promoting their overall well-being and health.

[Protective effect of Shenfu Injection on regulation of autophagy in rats with chronic heart failure based on PI3K/Akt/mTOR pathway].

This study aimed to investigate the mechanism and target sites of Shenfu Injection in the intervention of chronic heart fai-lure based on the PI3K/Akt/mTOR autophagy signaling pathway. The chronic heart failure model was induced in rats by subcutaneous injection of isoproterenol. The model rats were randomly divided into model group, Shenfu Injection group, and 3-methyladenine autophagy inhibitor(3-MA) group. A normal group was also set up. After 15 days of administration, cardiac function indexes of the rats were detected by echocardiography. The serum N-terminal pro-B-type natriuretic peptide(NT-proBNP) levels were measured using the ELISA. HE and Masson staining was performed to observe the morphological changes in myocardial tissues, and electron microscopy was used to observe the autophagosomes in myocardial tissues. Western blot was conducted to measure the changes in autophagy-related proteins(LC3 Ⅱ/Ⅰ and p62), PI3K, Akt, mTOR, and phosphorylation levels. The results showed that compared with normal group, model group in rats led to reduced cardiac function, significant activation of cardiac autophagy, increased fibrotic lesions in myocardial tissues, structural disorder of the myocardium, increased autophagosomes, and cytoplasmic vacuolization. Compared with model group, Shenfu Injection group in rats led to cardiac function significantly improved, myocardial fibrosis decreased, and the number of autophagosomes and cytoplasmic vacuolization decreased. The phosphorylation levels of PI3K, Akt, and mTOR were significantly increased(P<0.01). In the 3-MA group, autophagy was inhibited through the activation of the PI3K/Akt/mTOR signaling pathway, resulting in improved cardiac function, reduced myocardial fibrosis, and no significant cytoplasmic vacuolization. The findings suggest that Shenfu Injection can activate the PI3K/Akt/mTOR signaling pathway and inhibit autophagy, thereby improving cardiac function.

[Processing Magnoliae Officinalis Cortex with ginger juice: process optimization based on AHP-CRITIC weighting method and composition changes after processing].

The weight coefficients of appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol were determined by analytic hierarchy process(AHP), criteria importance though intercrieria correlation(CRITIC), and AHP-CRITIC weighting method, and the comprehensive scores were calculated. The effects of ginger juice dosage, moistening time, proces-sing temperature, and processing time on the quality of Magnoliae Officinalis Cortex(MOC) were investigated, and Box-Behnken design was employed to optimize the process parameters. To reveal the processing mechanism, MOC, ginger juice-processed Magnoliae Officinalis Cortex(GMOC), and water-processed Magnoliae Officinalis Cortex(WMOC) were compared. The results showed that the weight coefficients of the appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol determined by AHP-CRITIC weighting method were 0.134, 0.287, and 0.579, respectively. The optimal processing parameters of GMOC were ginger juice dosage of 8%, moistening time of 120 min, and processing at 100 ℃ for 7 min. The content of syringoside and magnolflorine in MOC decreased after processing, and the content of honokiol and magnolol followed the trend of GMOC>MOC>WMOC, which suggested that the change in clinical efficacy of MOC after processing was associated with the changes of chemical composition. The optimized processing technology is stable and feasible and provides references for the modern production and processing of MOC.

Effects of Tai Chi and Qigong on cognitive and physical functions in older adults: systematic review, meta-analysis, and meta-regression of randomized clinical trials.

BACKGROUND: Older adults experience age-related declines in physical and cognitive functions due to interactions between aging and chronic diseases. Tai Chi and Qigong (TCQ) might be beneficial in improving the physical function and delaying the cognitive decline of this population. The potential underlying mechanism was explored to determine the effects of TCQ on cognitive function via direct or indirect pathways. PURPOSE: The objective of this systematic review was to determine the effects of TCQ on cognitive and physical functions in older adults using meta-analysis, and to determine the impact of TCQ on cognitive function while controlling for physical function using a meta-regression approach. METHODS: A systematic search of 13 electronic databases (in English, Korean, and Chinese languages) identified 10,292 potentially eligible studies published between inception and May 2022. The bias in individual studies was assessed using the Cochrane Risk of Bias (version 2.0) tool. The heterogeneity of the studies was evaluated using a 95% prediction interval, and the meta-analysis and meta-regression were implemented using the Comprehensive Meta-Analysis (version 3) software. RESULTS: Our search identified 17 randomized studies (n = 2,365, mean age = 70.3 years). The results of the meta-analysis that used a random-effects model indicated that TCQ had significant effects on both cognitive (Hedges' g = 0.29, 95% confidence interval [CI] = 0.17 to 0.42) and physical (Hedges' g = 0.32, 95% CI = 0.19 to 0.44) functions. We used meta-regression to explore the effect size of TCQ in association with physical function level. The regression model was significant (Q = 25.01, p = .070), and 55% of the heterogeneity was explained by physical function as a moderator variable. The effects of TCQ on cognitive function remained significant in this model when controlling for the effect of physical function (ß = 0.46, p = .011). CONCLUSION: This meta-regression of 17 randomized studies strongly suggests that TCQ has beneficial effects on physical and cognitive functions in older adults. The effect of TCQ on cognitive function remained significant after taking into account the significant effects of physical function as a moderator. The findings imply the potential health benefits of TCQ by promoting cognitive function in older adults directly and indirectly through enhancing physical function. PROSPERO REGISTRATION NUMBER: *PROSPERO international prospective register of systematic reviews, registration ID CRD42023394358.

A new method to treat onychopapilloma with pulsed dye laser irradiation: a 13-case series report.

Purpose: Onychopapilloma is a rare benign nail tumor affecting the distal matrix and the nail bed. Currently, the only available treatment is surgical resection, which has a recurrence rate of 20% and may lead to various complications. Here we report a new method to treat onychopapilloma with pulsed dye laser (PDL).Materials and methods: We retrospectively analyzed 13 cases and evaluated disease classification, dermoscopic examination, laser treatment parameters, photographs before and after treatment, and treatment outcome.Results: The site distribution of onychopapilloma was consistent with previous reports. PDL treatment was performed with 595 nm laser, with 1.5 ms pulse duration, spot diameter 3-5 mm, and 11.5-13.5 J/cm2 fluence. Irradiation covered the telangiectatic area up to the edge of the nail folds, with the terminal response of purpura occurrence. The overall effective rate was 77%; the effective rates for erythronychia, leukonychia, and melanonychia were 88%, 67%, and 50%, respectively.Conclusions: PDL treatment for onychopapilloma provides an alternative to traditional surgery with comparable effectiveness but much less risk for complications.

Pharmacokinetics, absorption and transport mechanism for ginseng polysaccharides.

BACKGROUND: Ginseng polysaccharide (GP) is one of the most abundant components in Panax ginseng. However, the absorption pathways and mechanisms of GPs have not been investigated systematically due to the challenges of their detection. METHODS: The fluorescein isothiocyanate derivative (FITC) was employed to label GP and ginseng acidic polysaccharide (GAP) to obtain target samples. HPLC-MS/MS assay was used to determine the pharmacokinetics of GP and GAP in rats. The Caco-2 cell model was used to investigate the uptake and transport mechanisms of GP and GAP in rats. RESULTS: Our results demonstrated that the absorption of GAP was more than that of GP in rats after gavage administration, while there was no significant difference between both after intravenous administration. In addition, we found that GAP and GP were more distributed in the kidney, liver and genitalia, suggesting that GAP and GP are highly targeted to the liver, kidney and genitalia. Importantly, we explored the uptake mechanism of GAP and GP. GAP and GP are endocytosed into the cell via lattice proteins or niche proteins. Both are transported lysosomally mediated to the endoplasmic reticulum (ER) and then enter the nucleus through the ER, thus completing the process of intracellular uptake and transportation. CONCLUSION: Our results confirm that the uptake of GPs by small intestinal epithelial cells is primarily mediated via lattice proteins and the cytosolic cellar. The discovery of important pharmacokinetic properties and the uncovering of the absorption mechanism provide a research rationale for the research of GP formulation and clinical promotion.

Overlooked pathways of endogenous simultaneous nitrification and denitrification in anaerobic/aerobic/anoxic sequencing batch reactors with organic supplementation.

The anaerobic/aerobic/anoxic (A/O/A) process is a promising biotechnology to intensify denitrification in low carbon/nitrogen (C/N) wastewater treatment, but the neglected typical rate-limiting step-nitrification-would hinder its wider application. Heterotrophic nitrification driven by intracellular carbon (PHAs) could enhance nitrification and achieve endogenous simultaneous nitrification and denitrification (ESND) in the A/O/A process, but its feasibility remains unexamined. Here we established four A/O/A-SBRs at different C/N ratios (3, 7.5, 12, and 16.5) to address the above-mentioned knowledge gaps. The results showed that organic supplementation promoted both nitrification and denitrification (performance and relevant enzymatic activities) until organic overdose (C/N = 16.5) exacerbated niche competitions from other non-functional heterotrophs. qPCR and batch tests indicated that high C/N ratios inhibited autotrophic nitrifiers, and heterotrophic nitrifiers (HNB) dominated in the enhanced nitrification. Given the high HNB contribution (43.7%) and low COD variation (< 10 mg L-1) in the SND (76.4%) of CN12, we proposed a potential SND pathway based on heterotrophic nitrification and denitrification driven by PHAs and verified it with batch tests. Microbial and functional analyses suggested that CN12 favored the intracellular carbon transformation and harbored the minimum autotrophic nitrifiers, supporting the dominance of ESND in the enhanced SND. Our findings expand the understanding of the relationships between intracellular carbon transformation and SND and provide a novel nitrogen removal pathway for the practical application of the A/O/A process.

Holistic immunomodulation for small cell lung cancer.

Small cell lung cancer (SCLC) is characterized by a high mortality rate, rapid growth, and early metastasis, which lead to a poor prognosis. Moreover, limited clinical treatment options further lower the survival rate of patients. Therefore, novel technology and agents are urgently required to enhance clinical efficacy. In this review, from a holistic perspective, we summarized the therapeutic targets, agents and strategies with the most potential for treating SCLC, including chimeric antigen receptor (CAR) T therapy, immunomodulating antibodies, traditional Chinese medicines (TCMs), and the microbiota, which have been found recently to improve the clinical outcomes and prognosis of SCLC. Multiomics technologies can be integrated to develop effective diagnostic methods and identify new targets for new drug discovery in SCLC. We discussed in depth the feasibility, potential, and challenges of these new strategies, as well as their combinational treatments, which may provide promising alternatives for enhancing the clinical efficacy of SCLC in the future.

[Shenfu Injection improves chronic heart failure by regulating pyroptosis based on NLRP3/caspase-1 pathway].

This study investigated the mechanisms and targets of Shenfu Injection in the intervention in chronic heart failure(CHF) through the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/caspase-1 signaling pathway. A CHF model was induced in rats by subcutaneous injection of isoproterenol. Model rats were randomly divided into a model group, a Shenfu Injection group, and a MCC950(NLRP3 inhibitor) group, and a blank group was also set up as a control. After 15 days of treatment, echocardiography was performed to measure cardiac function parameters [left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS)]. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of N-terminal pro-brain natriuretic peptide(NT-proBNP), interleukin(IL)-1ß, and IL-18. Hematoxylin-eosin(HE) and Masson staining were used to observe morphological changes in myocardial tissues, and Western blot was used to measure the expression levels of NLRP3/caspase-1 pathway-related proteins [NLRP3, caspase-1, apoptosis-associated speck-like protein containing a CARD(ASC), gasdermin D(GSDMD), IL-1ß, and IL-18]. The study found that isoproterenol-induced CHF in rats resulted in decreased cardiac function, worsened myocardial fibrosis, increased expression levels of NLRP3, ASC, caspase-1, GSDMD-N, IL-1ß, and IL-18 in myocardial tissues, elevated serum inflammatory factors, and induced myocardial cell pyroptosis. Following Shenfu Injection intervention, the Shenfu Injection group showed significantly improved LVEF and LVFS, a significant decrease in NT-proBNP, a marked downregulation of NLRP3, ASC, caspase-1, GSDMD-N, IL-1ß, and IL-18 protein expression levels, reduced serum inflammatory factors IL-1ß and IL-18 expression in CHF rats, and a decrease in the rate of TUNEL-positive cells. Shenfu Injection can significantly improve cardiac function in CHF, inhibit myocardial fibrosis, and alleviate the progression of myocardial cell pyroptosis through the inhibition of the NLRP3/caspase-1 pathway.

Effects of Tai Chi and Qigong on the mobility of stroke survivors: A systematic review and meta-analysis of randomized trials.

BACKGROUND: Stroke survivors often experience impaired mobility and physical functions. Tai Chi and Qigong have been shown to have physical and psychological benefits for stroke patients. PURPOSE: To summarize the evidence on Tai Chi and Qigong for improving mobility in stroke survivors, specifically the ability to walk, dynamic balance, and activities of daily living (ADL). METHODS: Independent searches of 16 electronic databases in English, Korean, and Chinese from their inception until December 2021 were conducted by two research teams. Methodological quality was assessed using Cochrane's risk of bias tool 2.0. Comprehensive Meta-Analysis 3.0 software was used to calculate effect sizes with subgroup analysis and to assess heterogeneity and publication bias. RESULTS: The meta-analysis included 27 randomized trials (18 with Tai Chi and 9 with Qigong) on stroke survivors (N = 1,919). None of the studies were considered at high risk of bias, about 70% had some concerns, and 30% were considered low risk. Meta-analysis of 27 randomized controlled trials with random-effects models indicated that Tai Chi and Qigong effectively improved mobility, specifically on the ability to walk (Hedges'g = 0.81), dynamic balance (Hedges'g = 1.04), and ADL (Hedges'g = 0.43). The effects of Tai Chi and Qigong were significant for short-term and long-term programs (Hedges'g 0.91 vs. 0.75), and when compared with active controls and no treatment group (Hedges'g 0.81 vs. 0.73). CONCLUSION: Tai Chi and Qigong performed for 12 weeks or less were effective in improving the mobility of stroke survivors. Further studies are warranted to assess whether Tai Chi and Qigong work best as an adjunct to rehabilitation, an effective alternative to rehabilitation or as a maintenance strategy, and whether the results could be further optimized by assessing different schools of Tai Chi and Qigong, different types of stroke patients, and different points in the post-stroke recovery process. PROSPERO REGISTRATION NUMBER: This study has been registered on the UK National Institute for Health Research (http://www.crd.york.ac.uk/PROSPERO) PROSPERO registration number: CRD42020220277.

Chelerythrine ameliorates rheumatoid arthritis by modulating the AMPK/mTOR/ULK-1 signaling pathway.

BACKGROUND: Rheumatoid arthritis (RA) is a long-term, progressive, and disabling autoimmune disease. It causes inflammation, swelling and pain in and around the joints and other body organs. Currently, no cure is available for RA. Clinical interventions can only relieve the condition, and at least 30% of RA patients do not respond to first­line therapy. This means that the development of more effective therapies against RA is urgently needed. OBJECTIVE: This study aimed to assess the anti-rheumatoid arthritis effect of chelerythrine (CLT) and explore its mechanism of action. METHODS: The cytotoxic effect of CLT on human rheumatoid arthritis fibroblast-like synoviocyte (HFLS-RA) cells and HFLS-normal cells were measured by MTT assay. The growth and migration of HFLS-RA cells were determined by colony-formation and wound-healing assay. The level of intracellular reactive oxygen species (ROS) was detected using the DCFH-DA reagent. Cell apoptosis was measured by flow cytometry, TUNEL staining, caspase 3 activity, as well as the activation of apoptosis related proteins. In addition, the levels of autophagy related markers such as LC3B and P62 were determined by immunocytochemistry and western blotting. Lastly, the anti-RA effect of CLT was evaluated in an Adjuvant-Induced Arthritis(AIA) rat model and the severity of arthritis was detected and quantified using macroscopic inspection and X­ray imaging. RESULTS: We discovered that treatment with CLT effectively inhibited the migration and colony-formation of the HFLS-RA cells and resulted in cell death. Moreover, CLT increased the intracellular level of ROS and the apoptotic rate of HFLS-RA by activating the AMPK/mTOR/ULK-1 signaling pathways. In vivo study showed CLT effectively ameliorated AIA in rats, protecting them from inflammation and bone damage. CONCLUSION: Our study shows CLT is an effective agent for ameliorating RA in vitro and in vivo by modulation of the AMPK/mTOR/ULK-1 signaling pathway. These findings indicate that CLT is a great potential candidate for development as a therapeutic agent for the prevention and treatment of RA.

Xihuang pills induce apoptosis in hepatocellular carcinoma by suppressing phosphoinositide 3-kinase/protein kinase-B/mechanistic target of rapamycin pathway.

BACKGROUND: The phosphoinositide 3-kinase/protein kinase-B/mechanistic target of rapamycin (PI3K/Akt/mTOR) signalling pathway is crucial for cell survival, differentiation, apoptosis and metabolism. Xihuang pills (XHP) are a traditional Chinese preparation with antitumour properties. They inhibit the growth of breast cancer, glioma, and other tumours by regulating the PI3K/Akt/mTOR signalling pathway. However, the effects and mechanisms of action of XHP in hepatocellular carcinoma (HCC) remain unclear. Regulation of the PI3K/Akt/mTOR signalling pathway effectively inhibits the progression of HCC. However, no study has focused on the XHP-associated PI3K/Akt/mTOR signalling pathway. Therefore, we hypothesized that XHP might play a role in inhibiting HCC through the PI3K/Akt/mTOR signalling pathway. AIM: To confirm the effect of XHP on HCC and the possible mechanisms involved. METHODS: The chemical constituents and active components of XHP were analysed using ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS). Cell-based experiments and in vivo xenograft tumour experiments were utilized to evaluate the effect of XHP on HCC tumorigenesis. First, SMMC-7721 cells were incubated with different concentrations of XHP (0, 0.3125, 0.625, 1.25, and 2.5 mg/mL) for 12 h, 24 h and 48 h. Cell viability was assessed using the CCK-8 assay, followed by an assessment of cell migration using a wound healing assay. Second, the effect of XHP on the apoptosis of SMMC-7721 cells was evaluated. SMMC-7721 cells were stained with fluorescein isothiocyanate and annexin V/propidium iodide. The number of apoptotic cells and cell cycle distribution were measured using flow cytometry. The cleaved protein and mRNA expression levels of caspase-3 and caspase-9 were detected using Western blotting and quantitative reverse-transcription polymerase chain reaction (RT-qPCR), respectively. Third, Western blotting and RT-qPCR were performed to confirm the effects of XHP on the protein and mRNA expression of components of the PI3K/Akt/mTOR signalling pathway. Finally, the effects of XHP on the tumorigenesis of subcutaneous hepatocellular tumours in nude mice were assessed. RESULTS: The following 12 compounds were identified in XHP using high-resolution mass spectrometry: Valine, 4-gingerol, myrrhone, ricinoleic acid, glycocholic acid, curzerenone, 11-keto-ß-boswellic acid, oleic acid, germacrone, 3-acetyl-9,11-dehydro-ß-boswellic acid, 5ß-androstane-3,17-dione, and 3-acetyl-11-keto-ß-boswellic acid. The cell viability assay results showed that treatment with 0.625 mg/mL XHP extract decreased HCC cell viability after 12 h, and the effects were dose- and time-dependent. The results of the cell scratch assay showed that the migration of HCC cells was significantly inhibited in a time-dependent manner by the administration of XHP extract (0.625 mg/mL). Moreover, XHP significantly inhibited cell migration and resulted in cell cycle arrest and apoptosis. Furthermore, XHP downregulated the PI3K/Akt/mTOR signalling pathway, which activated apoptosis executioner proteins (e.g., caspase-9 and caspase-3). The inhibitory effects of XHP on HCC cell growth were determined in vivo by analysing the tumour xenograft volumes and weights. CONCLUSION: XHP inhibited HCC cell growth and migration by stimulating apoptosis via the downregulation of the PI3K/Akt/mTOR signalling pathway, followed by the activation of caspase-9 and caspase-3. Our findings clarified that the antitumour effects of XHP on HCC cells are mediated by the PI3K/Akt/mTOR signalling pathway, revealing that XHP may be a potential complementary therapy for HCC.

Co-occurrence of autotrophic and heterotrophic denitrification in electrolysis assisted constructed wetland packing with coconut fiber as solid carbon source.

Aiming at the problems of lack of carbon sources for nitrogen removal and low phosphorus removal efficiency of constructed wetlands (CWs) in treating wastewater treatment plant (WWTP) effluent, an electrolysis assisted constructed wetland (E-CW) with coconut fiber as substrate and solid carbon sources was constructed. The synthetic secondary effluent was used as the influent of the E-CW with a wastewater treatment capacity of 140 L d-1. The total nitrogen (TN) and the total phosphorus (TP) removal efficiency of the E-CW with coconut fiber treating WWTP effluent were 69.4% and 93.3%, respectively, which were 54.3% and 88.2% higher than those of CW with coconut fiber and no electrolysis. The removal efficiency of TN was 39.9% higher than that of E-CW with gravel. The current intensity had significant effect on nitrogen removal efficiency and the release of carbon sources from coconut fiber. When current intensity increased from 0.25 A to 1.00 A, the TN removal efficiency and nitrate removal rate increased by 21.1% and 0.21 mg L-1 h-1, respectively, and the volatile fatty acids (VFAs) released from coconut fiber increased by 57.7 mg L-1. The 16S rRNA high-throughput sequencing results indicated that the main functional nitrogen-removing microbes were Hydrogenophaga, Thauera, Rhodanobacteraceae_norank, Xanthobacteraceae_norank, etc. Multiple paths including autotrophic denitrification with hydrogen and Fe2+ as electron donors and heterotrophic denitrification were achieved in the system. Meanwhile, the main functional lignocellulose degradation microbes were enriched in the system, including Cytophaga_xylanolytica_group, and Caldilineaceae. Because electrolysis created a favorable environment for them to release carbon sources from coconut fiber. This study provided a new perspective for advanced nutrients removal of WWTP effluent in CWs.

Long-term eltrombopag for bone marrow failure depletes iron.

Eltrombopag (EPAG) has been approved for the treatment of aplastic anemia and for immune thrombocytopenia, and a subset of patients require long-term therapy. Due to polyvalent cation chelation, prolonged therapy leads to previously underappreciated iron depletion. We conducted a retrospective review of patients treated at the NIH for aplastic anemia, myelodysplastic syndrome, and unilineage cytopenias, comparing those treated with EPAG to a historical cohort treated with immunosuppression without EPAG. We examined iron parameters, duration of therapy, response assessment, relapse rates, and common demographic parameters. We included 521 subjects treated with (n = 315) or without EPAG (n = 206) across 11 studies with multiyear follow-up (3.6 vs. 8.5 years, respectively). Duration of EPAG exposure correlated with ferritin reduction (p = 4 × 10-14 ) regardless of response, maximum dose, or degree of initial iron overload. Clearance followed first-order kinetics with faster clearance (half-life 15.3 months) compared with historical responders (47.5 months, p = 8 × 10-10 ). Risk of iron depletion was dependent upon baseline ferritin and duration of therapy. Baseline ferritin did not correlate with response of marrow failure to EPAG or to relapse risk, and timing of iron clearance did not correlate with disease response. In conclusion, EPAG efficiently chelates total body iron comparable to clinically available chelators. Prolonged use can deplete iron and ultimately lead to iron-deficiency anemia mimicking relapse, responsive to iron supplementation.

Onset and Recurrence Characteristics of Chinese Patients with Noncardiogenic Ischemic Stroke in Chinese Medicine Hospital.

OBJECTIVE: To delineate the onset and recurrence characteristics of noncardiogenic ischemic stroke patients in China. METHODS: A prospective, multicenter and registry study was carried out in 2,558 patients at 7 representative clinical sub-centers during November 3, 2016 to February 17, 2019. A questionnaire was used to collect information of patients regarding CM syndromes and constitutions and associated risk factors. Additionally, stroke recurrence was defined as a primary outcome indicator. RESULTS: A total of 327 (12.78 %) patients endured recurrence events, 1,681 (65.72%) were men, and the average age was 63.33 ± 9.45 years. Totally 1,741 (68.06%) patients suffered first-ever ischemic stroke, 1,772 (69.27%) patients reported to have hypertension, and 1,640 (64.11%) of them reported dyslipidemia, 1,595 (62.35%) patients exhibited small-artery occlusion by The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Specifically, 1,271 (49.69%) patients were considered as qi-deficient constitution, and 1,227 (47.97%) patients were determined as stagnant blood constitution. There were 1,303 (50.94%) patients diagnosed as blood stasis syndrome, 1,280 (50.04%) patients exhibited phlegm and dampness syndrome and 1,012 (39.56%) patients demonstrated qi deficiency syndrome. And 1,033 (40.38%) patients declared intracranial artery stenosis, and 478 (18.69%) patients reported carotid artery stenosis. The plaque in 1,508 (41.36%) patients were of mixed. Particularly, 41.09% of them demonstrated abnormal levels of glycated hemoglobin levels. CONCLUSIONS: Recurrence in minor and small-artery stroke cannot be ignored. Hypertension, dyslipidemia, abnormal HbA1c, intracranial artery stenosis and carotid plaque were more common in stroke patients. Particularly, phlegm-dampness and blood stasis syndromes, as well as qi deficiency and blood stasis constitutions, were still the main manifestations of stroke. (Trial registration at ClinicalTrials.gov No. NCT03174535).

A method establishment and comparison of in vivo lung cancer model development platforms for evaluation of tumour metabolism and pharmaceutical efficacy.

BACKGROUND: Currently, the identification of accurate biomarkers for the diagnosis of patients with early-stage lung cancer remains difficult. Fortunately, metabolomics technology can be used to improve the detection of plasma metabolic biomarkers for lung cancer. In a previous study, we successfully utilised machine learning methods to identify significant metabolic markers for early-stage lung cancer diagnosis. However, a related research platform for the investigation of tumour metabolism and drug efficacy is still lacking. HYPOTHESIS/PURPOSE: A novel methodology for the comprehensive evaluation of the internal tumour-metabolic profile and drug evaluation needs to be established. METHODS: The optimal location for tumour cell inoculation was identified in mouse chest for the non-traumatic orthotopic lung cancer mouse model. Microcomputed tomography (micro-CT) was applied to monitor lung tumour growth. Proscillaridin A (P.A) and cisplatin (CDDP) were utilised to verify the anti-lung cancer efficacy of the platform. The top five clinically valid biomarkers, including proline, L-kynurenine, spermidine, taurine and palmitoyl-L-carnitine, were selected as the evaluation indices to obtain a suitable lung cancer mouse model for clinical metabolomics research by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: The platform was successfully established, achieving 100% tumour development rate and 0% surgery mortality. P.A and CDDP had significant anti-lung cancer efficacy in the platform. Compared with the control group, four biomarkers in the orthotopic model and two biomarkers in the metastatic model had significantly higher abundance. Principal component analysis (PCA) showed a significant separation between the orthotopic/metastatic model and the control/subcutaneous/KRAS transgenic model. The platform was mainly involved in arginine and proline metabolism, tryptophan metabolism, and taurine and hypotaurine metabolism. CONCLUSION: This study is the first to simulate clinical metabolomics by comparing the metabolic phenotype of plasma in different lung cancer mouse models. We found that the orthotopic model was the most suitable for tumour metabolism. Furthermore, the anti-tumour drug efficacy was verified in the platform. The platform can very well match the clinical reality, providing better lung cancer diagnosis and securing more precise evidence for drug evaluation in the future.

Emodin induces apoptosis and suppresses non-small-cell lung cancer growth via downregulation of sPLA2-IIa.

BACKGROUND: Lung cancer has become the principal cause of cancer-related deaths. Emodin is a Chinese herb-derived compound extracted from the roots of Rheum officinale that exhibits numerous pharmacological characteristics. Secretory phospholipase A2-IIa (sPLA2-IIa) is overexpressed in cancers and plays an important role in cancer development. PURPOSE: This study aims to investigate the anti-tumor mechanism of emodin in non-small-cell lung cancer (NSCLC). METHODS: MTT assay was applied to detect the sensitivity of emodin to NSCLC cell line. Flow cytometry was used to examine the effect of emodin on cell cycle distribution and evaluate ROS level and apoptosis. Western blot analysis was utilised to examine the expression levels of sPLA2-IIa, PKM2, and AMPK and its downstream pathways induced by emodin. Enzyme inhibition assay was applied to investigate the inhibitory effect of emodin on sPLA2-IIa. The anticancer effect of emodin was also detected using an in vivo model. RESULTS: Emodin significantly inhibited NSCLC proliferation in vivo and in vitro and was relatively less cytotoxic to normal lung cell lines. Most importantly, emodin inhibited the proliferation of KRAS mutant cell lines by decreasing the expression of sPLA2-IIa and NF-κB pathways. Emodin also inhibited mTOR and AKT and activated the AMPK pathway. Furthermore, emodin induced apoptosis, increased the reactive oxygen species (ROS) level, and arrested the cell cycle. CONCLUSION: Emodin exhibited a novel anti-tumor mechanism of inhibiting the proliferation of KRAS mutant cell lines by decreasing the expression levels of sPLA2-IIa and NF-κB pathways. Hence, emodin can potentially serve as a therapeutic target in NSCLC.

Onset and Recurrence Characteristics of Chinese Patients with Noncardiogenic Ischemic Stroke in Chinese Medicine Hospital / 中国结合医学杂志

OBJECTIVE@#To delineate the onset and recurrence characteristics of noncardiogenic ischemic stroke patients in China.@*METHODS@#A prospective, multicenter and registry study was carried out in 2,558 patients at 7 representative clinical sub-centers during November 3, 2016 to February 17, 2019. A questionnaire was used to collect information of patients regarding CM syndromes and constitutions and associated risk factors. Additionally, stroke recurrence was defined as a primary outcome indicator.@*RESULTS@#A total of 327 (12.78 %) patients endured recurrence events, 1,681 (65.72%) were men, and the average age was 63.33 ± 9.45 years. Totally 1,741 (68.06%) patients suffered first-ever ischemic stroke, 1,772 (69.27%) patients reported to have hypertension, and 1,640 (64.11%) of them reported dyslipidemia, 1,595 (62.35%) patients exhibited small-artery occlusion by The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Specifically, 1,271 (49.69%) patients were considered as qi-deficient constitution, and 1,227 (47.97%) patients were determined as stagnant blood constitution. There were 1,303 (50.94%) patients diagnosed as blood stasis syndrome, 1,280 (50.04%) patients exhibited phlegm and dampness syndrome and 1,012 (39.56%) patients demonstrated qi deficiency syndrome. And 1,033 (40.38%) patients declared intracranial artery stenosis, and 478 (18.69%) patients reported carotid artery stenosis. The plaque in 1,508 (41.36%) patients were of mixed. Particularly, 41.09% of them demonstrated abnormal levels of glycated hemoglobin levels.@*CONCLUSIONS@#Recurrence in minor and small-artery stroke cannot be ignored. Hypertension, dyslipidemia, abnormal HbA1c, intracranial artery stenosis and carotid plaque were more common in stroke patients. Particularly, phlegm-dampness and blood stasis syndromes, as well as qi deficiency and blood stasis constitutions, were still the main manifestations of stroke. (Trial registration at ClinicalTrials.gov No. NCT03174535).