Hypokalemic Periodic Paralysis Type 2 Due to SCN4A Val1105Met Mutation: A Case Study.

Hypokalemic Periodic Paralysis Type 2 (HOKPP2) is a rare autosomal dominant disorder characterized by recurrent episodes of muscle weakness, paralysis, and hypokalemia. In this case report, we present the clinical details of a 49-year-old female diagnosed with HOKPP2. Genetic testing revealed a heterozygous mutation in the Sodium Voltage-Gated Channel Alpha Subunit 4 (SCN4A) gene, confirming the diagnosis of HOKPP2. Management strategies, including potassium supplementation and lifestyle modifications, were implemented, resulting in a significant decrease in the frequency of symptomatic episodes. This case highlights the importance of considering HOKPP2 in patients with recurrent muscle weakness, particularly those with a familial history of similar symptoms. Furthermore, it underscores the crucial role of genetic testing in guiding patient management and facilitating genetic counseling.

The effect of physical interventions on pain control after orthodontic treatment: A systematic review and network meta-analysis.

OBJECTIVE: Pain is a frequent adverse reaction during orthodontic treatment, which can significantly reduce treatment compliance and compromise the expected treatment effect. Physical interventions have been used to alleviate pain after orthodontic treatment, but their effectiveness is controversial. This study used a network meta-analysis to assess the efficacy of various physical interventions typically used in managing pain after orthodontic treatment, with a view to provide evidence-based recommendations for representative interventions for orthodontic pain relief during peak pain intensity. METHODS: A systematic search of six electronic databases, from their respective inception dates, was conducted to identify relevant literature on the efficacy of various typical physical interventions for managing pain after orthodontic treatment. Literature screening was performed according to the Cochrane System Evaluator's Manual. Stata 16.0 was used to assess heterogeneity, inconsistency, publication bias, and sensitivity to generate an evidence network diagram and conduct a network meta-analysis. RESULTS: In total, 771 articles were reviewed to collect literature on interventions, including low-level laser therapy (LLLT), vibration, acupuncture, and chewing. Of these, 28 studies using a visual analog scale (VAS) as an outcome indicator were included. The results showed that LLLT, vibration, acupuncture, and chewing effectively relieved the pain symptoms in patients after orthodontic treatment. At 24 h post-treatment, LLLT (surface under the cumulative ranking curve [SUCRA] = 80.8) and vibration (SUCRA = 71.1) were the most effective interventions. After 48 h of treatment, acupuncture (SUCRA = 89.6) showed a definite advantage as the best intervention. CONCLUSION: LLLT, vibration, acupuncture, and chewing can alleviate pain associated with orthodontic treatment. Among these interventions, acupuncture was found to be the most effective at 48 h after orthodontic treatment. In addition, acupuncture demonstrated long-lasting and stable pain-relieving effects. However, further studies are needed to determine the most suitable equipment-specific parameters for acupuncture in relieving pain associated with orthodontic treatment.

Green Starch-Based Hydrogels with Excellent Injectability, Self-Healing, Adhesion, Photothermal Effect, and Antibacterial Activity for Promoting Wound Healing.

Hydrogel materials have proven valuable in wound healing, but improving the safety of these hydrogels is still challenging. Therefore, designing multifunctional natural polymeric-based hydrogels with excellent mechanical properties to replace toxic or potentially risky, refractory chemical polymer-based hydrogels such as polyacrylamide and polyethylene glycol is of particular significance. Here, a green starch-based hydrogel (Starch@Ca/CGC hydrogel) with injectability, self-healing, and instant adhesion was constructed by coordination interaction, electrostatic interaction, and intramolecular and intermolecular hydrogen bonds. Therein, natural bioactive small molecules gallic acid (GA) and carvacrol (CA) were coordinated with metal ions by the ultrasonic-triggered self-assembly and ionic cross-linking codriven strategy to prepare Cu-gallic acid-carvacrol nanospheres (CGC NPs), which conferred the hydrogel with near-infrared light (NIR)-controlled CA release and photothermal synergistic sterilization properties, as well as antioxidant and anti-infection capabilities. More importantly, the multifunctional hydrogel platforms could completely cover an irregular wound shape to prevent secondary injury and significantly accelerate wound healing under NIR with more skin appendages like hair follicles and blood vessels appearing. Therefore, it is expected that this starch-based hydrogel could serve as a competitive multifunctional dressing in the biomedical field, including bacteria-derived wound infection and other tissue repair.

Association between minerals intake and childhood obesity: A cross-sectional study of the NHANES database in 2007-2014.

BACKGROUND: The roles of minerals in obesity received increasing attention recently due to its oxidant or antioxidant functions and effects on insulin and glucose metabolism that may be associated with obesity. Herein, this study aims to explore the association between minerals and obesity and body mass index (BMI) in children with different ages, and hope to provide some references for prevention and management in children with high-risk of obesity. METHODS: Data of children aged 2-17 years old were extracted from the National Health and Nutrition Examination Survey (NHANES) database in 2007-2014 in this cross-sectional study. Weighted univariate and multivariate logistic regression and liner regression analyses were used to screen covariates, and explore the association between minerals [including calcium (Ca), phosphorus (P), magnesium (Mg), iron (Fe), zinc (Zn), copper (Cu), sodium (Na), potassium (K) and selenium (Se)] and childhood obesity and BMI. The evaluation indexes were ß, odds ratios (ORs) and 95% confidence intervals (CIs). These relationships were also investigated in age subgroups. RESULTS: Among 10,450 eligible children, 1,988 (19.02%) had obesity. After adjusting for covariates, we found the highest quartile of dietary Fe [OR = 0.74, 95%CI: (0.58, 0.95)] and Zn [OR = 0.70, 95%CI: (0.54, 0.92)] intakes were associated with low odds of childhood obesity, while that of dietary Na intake seemed to be positively linked to childhood obesity [OR = 1.35, 95%CI: (1.05, 1.74)]. High dietary intakes of Ca, Na and K were positively associated with children's BMI, on the contrary, dietary Fe and Zn consumptions had a negative one (all P<0.05). Additionally, these associations were also found in children with different age (all P<0.05). CONCLUSION: Dietary Fe and Zn intakes played positive roles in reducing childhood obesity or BMI, while the intakes of Na should be controlled suitably.

A highly selective and sensitive sensor for promethazine based on molecularly imprinted interface coated Au/Sn bimetal nanoclusters functionalized acupuncture needle microelectrode.

Promethazine (PMZ) is an effective antihistamine that is used as a nerve tranquilizer to treat mental disorders. However, drug abuse causes harm to the human body and also pollutes the environment to a certain extent. Therefore, it is crucial to develop a highly selective and sensitive biosensor for PMZ determination. An acupuncture needle (AN) was used as an electrode in 2015, and further research on the electrode's essence in electrochemistry is needed. In this work, a sensor based on a surface imprinted film coordinated Au/Sn biometal was first fabricated on AN via electrochemistry. The obtained cavities showed complementary and suitable sites for "N atom" electron transfer through the phenyl ring structure in promethazine, which is rigorous for the configuration near the interface. Under the optimal conditions, MIP/Au/Sn/ANE exhibits a good linear relationship in the range of 0.5 µM-500 µM, and the detection limit (LOD) is 0.14 µM (S/N = 3). The sensor exhibits good repeatability, stability, and selectivity and can be successfully used to analyze and detect PMZ in human serum and environmental water. The findings are scientifically significant for AN electrochemistry and the sensors have potential for in vivo medicamentosus monitoring in the future.

Fabrication of an Injectable Star-polylactide/Thiolated Hyaluronate Hydrogel as a Double Drug-Delivery System for Cancer Treatment.

Unsatisfactory solid-tumor penetration or rapid metabolism of nanomaterials limits their therapeutic efficacy. Here, we designed an injectable thiolated hyaluronate (HA-SH) hydrogel as a stable drug-releasing platform for in situ tumor treatment. Biodegradable star-shaped polylactide (S-PLLA) was first synthesized and fabricated to porous microspheres to encapsulate hydrophobic curcumin (Cur@S-PLLA), which was then blended with hydrophilic doxorubicin (Dox) and the HA-SH precursor to form composite in situ formable hydrogels [Cur@S-PLLA/(Dox)HA-SH]. The results showed that adding the microspheres improved the performance of the hydrogel, such as decreasing the gelation time from 1080 s to 960 s and also the swelling ratio. The mechanical strength increased from 27 to 45 kPa. In addition, the double drug system guaranteed a sustained release of drugs, releasing Dox at the early stage, with the continuous later release of Cur after gel swelling or S-PLLA degradation to achieve long-lasting tumor suppression, which inhibits the survival of cancer cells. The inhibitory effects of the hydrogels on MCF-7 were studied. The cell activity in the double-loaded hydrogel was significantly lower than that of the control groups, and apparent dead cells appeared in 2 days and fewer living cells with time. Flow cytometry revealed that the Cur@S-PLLA/(Dox)HA-SH group had the highest apoptosis ratio of 86.60% at 12 h, and the drugs caused the cell cycle to be blocked in phase M to reduce cell division. In summary, the innovative release platform is expected to be used in long-lasting tumor suppression and provides more ideas for the design of drug carriers.

An electrochemical chlorpromazine sensor based on a gold-copper bimetallic synergetic molecularly imprinted interface on an acupuncture needle electrode.

Chlorpromazine (CPZ) is a medicine for nervous system disorders. Measuring CPZ in vivo can assist doctors in evaluating patients' blood drug concentration and monitoring drug metabolism. Therefore, an accurate in vivo detection of CPZ is crucial. In recent years, the acupuncture needle, traditionally used in Chinese medicine, has emerged as a potential electrode in the field of electrochemistry, with promising applications for in vivo detection. In this study, Au/Cu nanoparticles were electrodeposited onto an acupuncture needle electrode (ANE) to improve electrical conductivity and provide an electro-catalytic surface. Subsequently, 3-aminophenylboronic acid and CPZ were attracted to each other through intermolecular forces; at the same time, the interaction force of Au-S between CPZ and the AuNPs made the polymer layer grow around the CPZ molecules on the modified electrode surface. The imprinted nanocavities showed highly selective and sensitive detection performance for CPZ after elution. Inside the recognizable site and microenvironment of the cavities, the captured CPZ molecule provided a suitable configuration for the fluent electron transfer of the electroactive group within a short range from the Au/Cu bimetal. Under ideal conditions, the MIP/Au/Cu/ANE exhibited two good linear ranges of 0.1-100 µM and 100-1000 µM with a detection limit of 0.07 µM. Moreover, the sensors showed great selectivity, good stability and excellent repeatability, making them suitable for CPZ detection in human serum. This provides a novel idea for real-time and in vivo CPZ detection.

Berberine Ameliorates Obesity by Inducing GDF15 Secretion by Brown Adipocytes.

Berberine (BBR), which is a compound derived from the Chinese medicinal plant Coptis chinensis, promotes weight loss, but the molecular mechanisms are not well understood. Here, we show that BBR increases the serum level of growth differentiation factor 15 (GDF15), which is a stress response cytokine that can reduce food intake and lower body weight in diet-induced obese (DIO) mice. The body weight and food intake of DIO mice were decreased after BBR treatment, and the weight change was negatively correlated with the serum GDF15 level. Further studies show that BBR induced GDF15 mRNA expression and secretion in the brown adipose tissue (BAT) of DIO mice and primary mouse brown adipocytes. In addition, we found that BBR upregulates GDF15 mRNA expression and secretion by activating the integrated stress response (ISR) in primary mouse brown adipocytes. Overall, our findings show that BBR lowers body weight by inducing GDF15 secretion via the activation of the ISR in BAT.

Circadian signatures of anterior hypothalamus in time-restricted feeding.

Background: Meal timing resets circadian clocks in peripheral tissues, such as the liver, in seven days without affecting the phase of the central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Anterior hypothalamus plays an essential role in energy metabolism, circadian rhythm, and stress response. However, it remains to be elucidated whether and how anterior hypothalamus adapts its circadian rhythms to meal timing. Methods: Here, we applied transcriptomics to profile rhythmic transcripts in the anterior hypothalamus of nocturnal female mice subjected to day- (DRF) or night (NRF)-time restricted feeding for seven days. Results: This global profiling identified 128 and 3,518 rhythmic transcripts in DRF and NRF, respectively. NRF entrained diurnal rhythms among 990 biological processes, including 'Electron transport chain' and 'Hippo signaling' that reached peak time in the late sleep and late active phase, respectively. By contrast, DRF entrained only 20 rhythmic pathways, including 'Cellular amino acid catabolic process', all of which were restricted to the late active phase. The rhythmic transcripts found in both DRF and NRF tissues were largely resistant to phase entrainment by meal timing, which were matched to the action of the circadian clock. Remarkably, DRF for 36 days partially reversed the circadian clock compared to NRF. Conclusions: Collectively, our work generates a useful dataset to explore anterior hypothalamic circadian biology and sheds light on potential rhythmic processes influenced by meal timing in the brain (www.circametdb.org.cn).

Resource Utilization of Red Mud from the Solid Waste of Aluminum Industry Used in Geothermal Wells.

It is difficult for the commonly used Class G oil well cement to withstand the high-temperature environment of geothermal wells, and it is easy to deteriorate the mechanical properties and damage the integrity of the cement sheath. Industrial solid waste red mud can be used as supplementary cementing materials (SCMs) to improve its mechanical properties at high temperatures. In addition, compared to Class G oil well cement, high belite cement (HBC) has lower energy consumption and better mechanical properties at high temperatures. In this study, the mechanical properties of HBC as a gel material and quartz sand and red mud as SCMs were studied at high temperatures. The ratio of HBC to SCMs and the ratio of quartz sand to red mud in SCMs were optimized using the response surface method (RSM). The response surface was established using the three-level factorial design model, which fit well with the experimental data. The optimization results show that the best mass ratio of SCMs/HBC is 37.5% and that the best quality ratio of quartz sand/red mud is 9 under the curing conditions of 180 °C. However, the best mass ratio of SCMs/HBC is 49.3%, and the best quality ratio of quartz sand/red mud is 7 under 220 °C. With the addition of SCMs, the silicon-to-calcium ratio of HBC hydration products decreases, and high-temperature-stable xonotlite and tobermorite can be formed. After adding SCMs, the cement sample is denser without obvious cracks.

Amphiphilic nano-delivery system based on modified-chitosan and ovalbumin: Delivery and stability in simulated digestion.

Nano-delivery systems play an important role in the development of nutritional supplements due to their efficient encapsulation and delivery properties for nutrients. Herein, we prepared protein-polysaccharide nanoparticles as a novel amphiphilic nano-delivery system based on gallic acid modified chitosan (GCS) and ovalbumin (OVA) by pH-driven and calcium ion crosslinking. The nanoparticles loaded with hydrophilic riboflavin (Rib) and hydrophobic quercetin (Que) as nutrient models were abbreviated as GCS-OVA-Rib NPs and GCS-OVA-Que NPs, respectively. Their encapsulation efficiencies for Rib and Que. were 66.36 % and 96.61 %, respectively. In addition, GCS-OVA-Rib NPs and GCS-OVA-Que NPs showed antioxidant activity as well as good stability and delivery capacity for Rib and Que. in simulated digestion with release ratios of 78.38 % and 84.15 %, respectively. More importantly, GCS-OVA-Rib/Que. NPs performed good biocompatibility for further applications. Overall, this work provides some useful insights for the design of novel amphiphilic nano-delivery systems based on polysaccharides and proteins.

Highly effective rheumatoid arthritis therapy by peptide-promoted nanomodification of mesenchymal stem cells.

Traditional medication is not satisfied in rheumatoid arthritis (RA) therapy due to its long-term side effects and failure in cartilage repair. Nanomodification of mesenchymal stem cells (MSCs) holds promise for lifting such hurdles but delivering therapeutic nanomaterials (NPs) into MSCs remains challenging in this new strategy. Here, we show that CuS@MnO2 NPs functionalized with a short phage-selected MSC-targeting peptide enabled the NPs to be uptaken by MSCs. The resultant NP-modified MSCs, further loaded with metformin, significantly improved stem cell therapy of RA. Specifically, the NP-modified MSCs survived the RA-associated oxidized stress through regulating the stress by the superoxide dismutase (SOD)- and catalase (CAT)-like activity of the NPs. They also exhibited an increased capability of cell migration, anti-inflammation, and chondrogenesis due to the nanomodification, thereby effectively inhibiting synovial inflammation and reducing cartilage erosion to relieve RA symptoms in two rat models 28 days post intravenous injection. Our peptide-promoted NP-modified MSCs may be used to enhance therapeutic effects in treating not only RA but also other degenerative and inflammatory diseases.

The involvement of PacIRA system of Stenotrophomonas maltophilia in the uptake of Pseudomonas aeruginosa pyochelin and intraspecies competition for iron acquisition.

BACKGROUND: Stenotrophomonas maltophilia, a species of highly genetic diversity, has emerged as an important nosocomial pathogen. S. maltophilia and Pseudomonas aeruginosa are often co-isolated from pneumonia patients. In our previous study, we have demonstrated that the pacIRA cluster present in some but not all clinical S. maltophilia isolates. Proteins encoded by pacIRA operon are an extracytoplasmic function (ECF) sigma factor, a transmembrane anti-sigma regulator, and a TonB-dependent receptor. This study aimed to elucidate PacIRA system function and its significance to S. maltophilia. METHODS: The pacI, pacR, and pacA genes were individually or totally deleted from the chromosome of KJΔEnt, a pacIRA-positive and siderophore-null strain. Growth promotion assay was performed to examine the implication of pacIRA system in iron utilization. Gene expression was quantified by quantitative real time PCR (qRT-PCR). Growth competition assay was executed to investigate the significance of pacIRA operon to S. maltophilia. RESULTS: PacIRA system contributed to utilize ferri-pyochelin of P. aeruginosa as iron sources for growth in an iron-depleted condition, but hardly utilized ferric citrate, hemin, ferri-stenobactin, and ferri-pyoverdine. PacIRA was founded to belong to Fur regulon and upregulated in response to iron-depleted stress. Growth competition assay demonstrated that pacIRA-positive S. maltophilia had a superiority over pacIRA-negative S. maltophilia in iron acquisition when they were co-cultured in P. aeruginosa ferri-pyochelin-supplemented medium. CONCLUSIONS: PacIRA system of S. maltophilia is a xenosiderophore uptake implement, involving in the acquisition of pyochelin of P. aeruginosa.

Evidence-Based Analysis on Observation for Nursing Care of Patients with Intra-Aortic Balloon Pumping.

In this study, data analysis was performed on 52 patients. According to the different outcomes and discharge diagnosis of patients, data on sedative use, emotions, behavioral abnormalities, hearing loss, pain, total time on board the IABP (intra-aortic balloon pumping), and days of hospitalization of patients were collected. The data were subjected to frequency analysis, paired chi-square analysis, chi-square test, Poisson regression analysis, and stepwise regression analysis. Some findings of the analysis included the following: Between outcome and admission diagnosis, the analysis showed that significant differences existed between paired data. Patients with heart failure and acute myocardial infarction are in an unhealed state, and most patients with coronary atherosclerotic heart disease, myocarditis, and heart disease showed improvement. The samples taken by different sedatives showed no significant differences in the emotional and behavioral abnormalities, hearing loss, and pain. A total of 1 item of hospital stay had a significant negative impact on the total operation time of IABP. However, discharge diagnosis and admission diagnosis did not affect the total time on board the IABP. The dorsalis pedis artery pulse condition has a significant negative effect on the total time on board the IABP.

Enhanced antitumor activity of inulin-capped Se nanoparticles synthesized using Jerusalem artichoke tubers.

An inulin polysaccharide with a molecular weight of ~ 2600 Da was derived from Jerusalem artichoke tubers and referred to as "JAP". Previous studies have shown that inulin can improve glucose tolerance and the liver lipid profile; however, its antitumor activity remains to be examined in detail. Therefore, to investigate the possible improvement of the antitumor activity of JAP, a novel nanostructured biomaterial was constructed by capping Se nanoparticles with JAP using sodium selenite, via a redox reaction with ascorbic acid, and referred to as "JAP-SeNPs". Transmission electron microscopy revealed that the average diameter of JAP-SeNPs is ~ 50 nm, and the C:Se mass ratio in JAP-SeNPs was found to be 15.4:1 by energy-dispersive X-ray spectroscopy. The well-dispersed JAP-SeNPs exhibited a significant in vitro antiproliferative effect on mouse forestomach carcinoma cells at a concentration of 400 µg/mL when incubated for 48 h, with an inhibition rate of 41.5%. Moreover, 38.9% of later apoptotic cells were observed. These results reveal that a combination of Se and JAP can effectively enhance the antitumor activity of polysaccharides obtained from Jerusalem artichoke tubers.

Near-Infrared Light-Regulated Drug-Food Homologous Bioactive Molecules and Photothermal Collaborative Precise Antibacterial Therapy Nanoplatform with Controlled Release Property.

Herein, a collaborative precise antibacterial wound healing therapy nanoplatform integrating drug-food homologous bioactive molecule (cinnamaldehyde, CA) with photothermal therapy (PTT) is presented. Copper-gallic acids-cinnamaldehyde-polydopamine nanorods (Cu-GA-CA-PDA NRs) with near-infrared light (NIR)-controlled CA release property are fabricated, which also integrate CA and photothermal synergistic sterilization, as well as antioxidant, anti-inflammatory, and anti-infection capacities. The characteristics of NIR-mediated CA release and photothermal response of Cu-GA-CA-PDA NRs support their excellent sterilization performance in vitro/in vivo. In addition, under the guidance of NIR, Cu-GA-CA-PDA NRs can hinder the formation of inflammatory cells, reduce oxidative stress damage, accelerate the regeneration of skin tissues in S. aureus-infected wound sites, and achieve the goal of promoting wound healing. Therefore, NIR-mediated Cu-GA-CA-PDA NRs with multifunctional biological activities provide a highly competitive strategy for curing bacteria-infected wounds.

[Prediction of anti-liver fibrosis effect of Piperis Longi Fructus based on network pharmacology].

Network pharmacology and liver fibrosis(LF) model in vitro were used to analyze the underly mechanism of anti-liver fibrosis effect that induced by Piperis Longi Fructus and its major active compounds. TCMSP and TCMIP were used to search for the chemical constituents of Piperis Longi Fructus, as well as the oral bioavailability(OB), drug-likeness(DL), intercellular permeability of intestinal epithelial cells(Caco-2) and Drug-likeness grading were set as limiting conditions. The related target genes of Piperis Longi Fructus were queried by TCMSP database, while related targets of LF were screened by GeneCards databases. Interaction network was constructed using Cytoscape 3.7.1. These above data were imported into STRING database for PPI network analysis. Enrichment of gene ontology(GO) and pathway analysis(KEGG) within Bioconductor database were utilized to note functions of related targets of Piperis Longi Fructus. Finally, the core targets and pathways were preliminarily verified by in vitro experiments. The effects of piperlongumine(PL), the major active component of Piperis Longi Fructus, on proliferation of rat liver stellate cells(HSC-T6) and expression of α smooth muscle actin(α-SMA) and collagen Ⅰ were investigated. The major factors TNF-α of tumor necrosis factor(TNF) pathway and NF-κB p65, IL-6 protein expressions of LF process were examined. A total of 12 active compounds such as PL were obtained by analyzing the bioavailability and drug-like properties, which inferred to 48 targets. The functional enrichment analysis of GO obtained 1 240 GO items, mainly involving in process of biology and molecular function. A total of 99 signaling pathways were enriched in the KEGG pathway enrichment analysis, including TNF signaling pathway, cGMP-PKG signaling pathway, calcium signaling pathways. CCK-8 assay showed that PL inhibited proliferation of HSC-T6 induced by transforming growth factor-ß1(TGF-ß1). Western blot analysis found that treated with PL suppressed the protein expressions of α-SMA, collagen Ⅰ, TNF-α and p65 in HSC-T6. Enzyme linked immunosorbent assay(ELISA) showed that PL inhibited the expressions of TNF-α and IL-6 in the cluture supertant of HSC-T6 cells. In conclusion, PL could play an anti-liver fibrosis role by regulating TNF/NF-κB signaling pathway. This study provided the mechanism basis of anti-LF effects induced by Piperis Longi Fructus and its major active compounds, which might help for the further study of the mechanism and key targets of Piperis Longi Fructus.

Screening of hypolipidemic active components in Jiang-Zhi-Ning and its preliminary mechanism research based on "active contribution value" study.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiang-Zhi-Ning (JZN) is a traditional Chinese medicine formula, which has the effect of lowering blood lipid level and softening blood vessels. It is clinically used in the treatment of hyperlipidemia with significant curative effect. AIM OF THE STUDY: This study aims to screen the active components of JZN that are responsible for its blood lipids lowering effect and lay the foundation for elucidating pharmacodynamic material basis of the hypolipidemic effect of the formula. MATERIALS AND METHODS: The hyperlipidemia model was used to evaluate the efficacy of the JZN effective extraction with the TC and TG of rat plasma as evaluation index. Then the established ultra-high performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UPLC-ESI-Q-TOF-MSn) method was utilized to analyze the components of JZN effective extraction and the absorbed components in rat plasma, the potential active components were screened by using the combined analysis results of in vivo and in vitro component identification. Then an established ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-QqQ-MSn) method was used to determine the content of potential active components and its natural ratio in JZN effective extraction, and a potential active components combination (PACC) was formed accordingly. Then a HepG2 cell hyperlipidemia model induced by sodium oleate was used to study the hypolipidemic activity of PACC by detecting the content of TG level in the model. Meanwhile, the real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to conduct preliminary research on its hypolipidemic mechanism. Then combined with the concept of "combination index" in the "median-effect principle", to calculate the half inhibitory concentration (IC50) values of PACC and each monomer component on inhibiting the TG level in the cell model. Subsequently, the "activity contribution study" was carried out, and the components with the sum of the "activity contribution value" of 85% were finally selected as the hypolipidemic active components of JZN. RESULTS: The pharmacodynamics results showed that JZN effective extraction has displayed a good hypolipidemic effect. 45 components were identified in vitro, 108 components were identified from rat plasma, and 17 potential active components were screened out. The content determination result showed that the ratio of each potential active components in PACC as following: cassiaside C: rubrofusarin-6-O-gentiobioside: aurantio-obtusin-6-O-glucoside: hyperoside: isoquercitrin: quercetin-3-O-glucuronide: (E)-2,3,5,4'-tetrahydroxystilbene-2-O-glucoside: rutin: emodin-8-O-glucoside: astragalin: armepavine: N-nornuciferine: coclaurine: O-nornuciferine: nuciferine: N-norarmepavine: higenamine = 3.30: 16.06: 9.15: 23.94: 98.40: 417.45: 189.68: 8.62: 1.28: 5: 3.51: 14.57: 1.06: 1.35: 1: 5.64: 6.06, and the activity study results showed that it has displayed a good hypolipidemic activity. Finally, the hypolipidemic active components screened out by the "activity contribution study" were: quercetin-3-O-glucuronide, (E)-2,3,5,4'-tetrahydroxystilbene-2-O-glucoside, isoquercitrin, O-nornuciferine, hyperoside and rubrofusarin-6-O-gentiobioside. CONCLUSIONS: A scientific and rational approach of screening the hypolipidemic active ingredients of JZN has been developed in the current study. In addition, the research revealed the blood lipid lowering mechanism of those ingredients, which provide a solid basis for further elucidating the hypolipidemic pharmacodynamic material basis and action mechanism of JZN.

Effects of Chinese Herbal Medicine on Acute Exacerbations of COPD: A Randomized, Placebo-Controlled Study.

Purpose: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an essential occurrence in COPD management and is the leading cause of morbidity and mortality. Chinese herbal medicine is widely used in the treatment of AECOPD, but high quality randomized controlled trials are limited. This study aimed to evaluate the efficacy and safety of Chinese herbal medicine as adjuvant therapy for patients with AECOPD. Methods: This was a randomized, double-blind, placebo-controlled study of 378 participants from eight centers in China. Participants were randomly assigned to receive 10 g of Chinese herbal medicine (according to the type of Traditional Chinese medicine syndrome: Sanhanhuayin, Qingrehuatan, or Zaoshihuatan granules) or placebo, two times per day, for 14 days, in addition to conventional medicine. Participants were followed up for 84 days after the treatment. The primary end point was the COPD assessment test (CAT) score. Secondary end points included the Modified British Medical Research Council (mMRC) questionnaire and the COPD patient-reported outcome scale (COPD-PRO). We also assessed treatment failure and treatment success rate, length of hospitalization, number of patients with acute exacerbations, number of patients readmitted due to AECOPD, and number of deaths and intubation. Results: The between-group difference in the change from baseline for CAT on day 14 (end of treatment) was -2.11 (95% confidence interval [CI], -3.198 to -1.050; P<0.001), exceeding the minimal clinically important difference. The mMRC and COPD-PRO scores were lower in the intervention group compared to the control group (between-group difference in the change from baseline, -0.28; 95% CI, -0.48 to -0.08; P=0.007 and -2.51; 95% CI, -4.087 to -0.929; P=0.002, respectively) on day 14. The intervention group had a significantly shorter duration of hospital stay than the control group (mean difference, -1.21days; 95% CI, -2.041 to -0.419; P=0.003), significantly lower of number of exacerbations (risk ratio [RR], 0.60; 95% CI, 0.409 to 0.892; P=0.010), and significantly lower number of readmissions due to AECOPD (RR, 0.41; 95% CI, 0.193 to 0.865; P=0.015). Significant differences in the number of treatment failures or successes, deaths, and intubation were not observed. The difference in safety variables and adverse events between the two groups was not observed. Conclusion: Chinese herbal medicine appears to be safe and beneficial for AECOPD and can be considered a complementary treatment for patients with AECOPD.

1, 6-O, O-Diacetylbritannilactone from Inula britannica Induces Anti-Tumor Effect on Oral Squamous Cell Carcinoma via miR-1247-3p/LXRα/ABCA1 Signaling.

INTRODUCTION: Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy affecting the oral cavity and is associated with severe morbidity and high mortality. 1, 6-O, O-Diacetylbritannilactone (OODBL) isolated from the medicinal herb of Inula britannica has various biological activities such as anti-inflammation and anti-cancer. However, the effect of OODBL on OSCC progression remains unclear. Here, we were interested in the function of OODBL in the development of OSCC. METHODS: The effect of OODBL on OSCC progression was analyzed by MTT assays, colony formation assays, transwell assays, apoptosis analysis, cell cycle analysis, and in vivo tumorigenicity analysis. The mechanism investigation was performed by qPCR assays, Western blot analysis, and luciferase reporter gene assays. RESULTS: We found that OODBL inhibits the proliferation of OSCC cells in vitro. Moreover, the migration and invasion were attenuated by OODBL treatment in the OSCC cells. OODBL arrested cells at the G0/G1 phase and induced cell apoptosis. OODBL was able to up-regulate the expression of LXRα, ABCA1, and ABCG1 in the system. In addition, OODBL activated LXRα/ABCA1 signaling by targeting miR-1247-3p. Furthermore, the expression levels of cytochrome c in the cytoplasm, cleaved caspase-9, and cleaved caspase-3 were dose-dependently reduced by OODBL. Besides, OODBL increased the expression ratio of Bax to Bcl-2. Moreover, OODBL repressed tumor growth of OSCC cells in vivo. DISCUSSION: Thus, we conclude that OODBL inhibits OSCC progression by modulating miR-1247-3p/LXRα/ABCA1 signaling. Our finding provides new insights into the mechanism by which OODBL exerts potent anti-tumor activity against OSCC. OODBL may be a potential anti-tumor candidate, providing a novel clinical treatment strategy of OSCC.