In Vivo Pharmacokinetic Study of Polygonatum cyrtonema Polysaccharide DPC1 after Oral and Intraperitoneal Administration.

(1) Background: Polygonatum cyrtonema is a medicinal plant, and its polysaccharides are used for immunomodulation and the treatment of hyperglycemia. Investigation of the tissue distribution and pharmacokinetics of P. cyrtonema polysaccharide can further elucidate its pharmacological mechanisms. (2) Methods: A fluorescence-labeling approach using rhodamine B (RhB) as a fluorescent molecular probe was used for the quantitative assessment of the polysaccharide from dried P. cyrtonema (DPC1) samples, and the pharmacokinetics and tissue distribution of DPC1 were evaluated in mice after intraperitoneal or oral administration. (3) Results: DPC1 was successfully labeled with RhB, showing degrees of fluorescence labeling at 0.453% and 0.568% as determined by the ultraviolet and enzyme marker methods, respectively. DPC1-RhB was rapidly absorbed into the bloodstream after oral and intraperitoneal administration. Pharmacokinetic characteristics showed that oral administration and intraperitoneal administration were consistent with the features of a two-compartment model. (4) Conclusion: After administration, DPC1-RhB was primarily distributed in the tissues of the heart, spleen, and lung, indicating that the drug has a targeted effect on these tissues. Overall, the findings provide a comprehensive reference for the in vivo distribution of DPC1, together with a foundation for further elucidation of its pharmacological mechanisms and the development and application of DPC1 formulations.

Evodiae Fructus extract suppresses inflammatory response in HaCaT cells and improves house dust mite-induced atopic dermatitis in NC/Nga mice.

This study was conducted to assess the effect of Evodiae Fructus 70% ethanol extract (EFE) on the pathology of atopic dermatitis using in vitro and in vivo models. The major compounds in EFE were identified by ultra-performance liquid chromatography with tandem mass spectrometry as rutaecarpine, evodiamine, evodol, dehydroevodiamine, limonin, synephrine, evocarpine, dihydroevocarpine, and hydroxyevodiamine. EFE significantly decreased chemokine levels in tumor necrosis factor-α/interferon-γ-stimulated HaCaT cells. In house dust mite-treated NC/Nga mice, topical application of EFE significantly decreased the dermatitis score, epidermal hyperplasia and thickening, mast cell infiltration, and plasma levels of histamine and corticosterone. Thymic stromal lymphopoietin, CD4+ T cells, interleukin-4, and intercellular adhesion molecule-1 expression in the lesioned skin was reduced in the treated mice. The mechanism of EFE was elucidated using transcriptome analysis, followed by experimental validation using Western blotting in HaCaT cells. EFE down-regulated the activation of Janus kinase (JAK)-signal transducers and activators of transcription (STAT) and mitogen-activated protein kinases (MAPK) signaling pathways in HaCaT cells. EFE improves atopic dermatitis-like symptoms by suppressing inflammatory mediators, cytokines, and chemokines by regulating the JAK-STAT and MAPK signaling pathways, suggesting its use as a potential agent for the treatment of atopic dermatitis.

Association between oil spill clean-up work and thyroid cancer: Nine years of follow-up after the Hebei Spirit oil spill accident.

In 2007, an unprecedented oil spill occurred in Taean, Korea. Although crude oil contains chemicals that could increase thyroid cancer risk, few studies have examined the long-term effects of oil exposure during clean-up and thyroid cancer incidence. We investigated the long-term thyroid cancer incidence among participants involved in clean-up work. 1798 participants engaged in at least two surveys since the baseline was tracked from 2008 to 2018. Participants reported the days they participated in oil clean-up works and cancer diagnoses. Cox proportional hazard models were used to estimate the hazard ratios between clean-up work duration and thyroid cancer. Over the 9-year follow-up, 30 thyroid cancer cases were diagnosed. A positive association was observed between clean-up duration and thyroid cancer risk. This effect was more pronounced among residents living <50 m from traffic roads. Our results indicate that crude oil clean-up work participation may increase the thyroid cancer risk.

Long-term effects of the Hebei Spirit oil spill on the prevalence and incidence of allergic disorders.

The Hebei Spirit oil spill accident occurred in December 2007, approximately 10 km off the coast of Taean, South Korea, a location notably close to residential areas. Crude oil substances have been detected in various environmental mediums since the accident, yet previous studies have primarily focused on the acute effects of oil exposure due to the short latency period of allergic diseases. Therefore, this study evaluated the long-term effects of oil spill exposure on allergic disorders. Our study included adult residents who had participated in the Health Effects Research on Hebei Spirit Oil Spill (HEROS) study up to five years post-incident, which was a prospective cohort to monitor the health status of Taean residents. We used two indicators to assess oil spill exposure, namely the distance from the initial contaminated coastline to each participant's residence and the number of days participants had engaged in oil clean-up work. Current symptoms such as asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and multimorbidity were considered allergic disorders. In the baseline survey, the prevalence of asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and allergic multimorbidity symptoms was associated with both exposure indicators; however, these associations were not observed in the two consecutive surveys. Significant longitudinal associations between oil spill exposure indicators and the four allergic disorders, as well as multimorbidity incidences, were observed during a five-year follow-up period. Our results suggest that oil spill exposure can affect acute and long-term allergic symptoms in residents near the accident site.

Spectrum-Effect Relationships as an Effective Approach for Quality Control of Natural Products: A Review.

As natural products with biological activity, the quality of traditional Chinese medicines (TCM) is the key to their clinical application. Fingerprints based on the types and contents of chemical components in TCM are an internationally recognized quality evaluation method but ignore the correlation between chemical components and efficacy. Through chemometric methods, the fingerprints represented by the chemical components of TCM were correlated with its pharmacodynamic activity results to obtain the spectrum-effect relationships of TCM, which can reveal the pharmacodynamic components information related to the pharmacodynamic activity and solve the limitations of segmentation of chemical components and pharmacodynamic research in TCM. In the 20th anniversary of the proposed spectrum-effect relationships, this paper reviews its research progress in the field of TCM, including the establishment of fingerprints, pharmacodynamic evaluation methods, chemometric methods and their practical applications in the field of TCM. Furthermore, the new strategy of spectrum-effect relationships research in recent years was also discussed, and the application prospects of this technology were discussed.

Diverse prenylated C6-C3 derivatives from the stems and branches of Illicium ternstroemioides A. C. Smith with anti-inflammatory and antiviral activities.

Fifteen unreported prenylated C6-C3 derivatives (1-15) were isolated from the stems and branches of Illicium ternstroemioides A. C. Smith, including one bis-prenylated C6-C3 derivative (1), three prenylated C6-C3 derivative-shikimic acid ester hybrids (2-4) and 11 prenylated C6-C3 monomers (5-15). The structures of compounds 1-15 were elucidated by spectroscopic analysis (UV, IR, 1D and 2D NMR, and HRESIMS). The absolute configurations of the compounds were determined using electronic circular dichroism (ECD), induced circular dichroism (ICD), and the modified Mosher's method. Among the isolates, compounds 11, 12, and 15 exhibited significant anti-inflammatory activities by inhibiting the nitric oxide with IC50 values ranging from 1.89 to 24.83 µM in lipopolysaccharide-stimulated murine RAW 264.7 macrophages and murine BV2 microglial cells; compounds 2, 3, and 7 exhibited antiviral activitives against Coxsackievirus B3 with an IC50 value of 33.3, 25.9, and 27.8 µM, respectively.

Anti-inflammatory effects of Allium cepa L. peel extracts via inhibition of JAK-STAT pathway in LPS-stimulated RAW264.7 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Allium cepa L. (A. cepa) is one of the oldest cultivated plants in the world. A. cepa has been used in traditional folk medicine to treat inflammatory disease in several regions, such as Palestine and Serbia. A. cepa peel has a higher content of flavonoids, such as quercetin, than the edible parts. These flavonoids alleviate inflammatory diseases. However, the anti-inflammatory effects of A. cepa peel extract-obtained using various extraction methods-and their underlying mechanisms require further investigation. AIM OF THE STUDY: Although research to find safe anti-inflammatory substances in various natural products has been actively conducted for many years, it is important to continue identifying potential anti-inflammatory effects in natural materials. The purpose of this study was to investigate the ethnopharmacological properties of the A. cepa peel extract, whose efficacy when obtained through different extraction methods and underlying action mechanisms is not well known. The present study specifically aimed to observe the anti-inflammatory effects of the A. cepa peel extracts obtained using various extraction methods and the related detailed mechanisms of A. cepa peel extracts in lipopolysaccharide (LPS)-induced RAW264.7 cells. MATERIALS AND METHODS: The total flavonoid content of the A. cepa peel extracts was determined the diethylene glycol colorimetric method and measured using a calibration curve prepared using quercetin as a standard solution. The antioxidant activity was evaluated using the ABTS assay, and cytotoxicity was measured using the MTT assay. NO production was measured using Griess reagent. Protein levels were measured by western blotting, and mRNA expression was measured by RT-qPCR. Secreted cytokines were analyzed using ELISA or cytokine arrays. In the GSE160086 dataset, we calculated Z-scores for individual genes of interest and displayed using a heat map. RESULTS: Of the three A. cepa peel extracts obtained using different extraction methods, the A. cepa peel 50% EtOH extract (AP50E) was the most effective at inhibiting LPS-induced nitric oxide (NO) and inducible nitric oxide synthase (iNOS). Furthermore, AP50E significantly reduced the levels of pro-inflammation cytokines interleukin (IL)-1α, IL-1ß, IL-6, and IL-27. Additionally, AP50E directly inhibited the Janus kinase-signaling transducer and activator of transcription (JAK-STAT) pathway. CONCLUSIONS: These results showed that AP50E exhibited an anti-inflammatory effect in LPS-induced RAW264.7 mouse macrophages by directly inhibiting JAK-STAT signaling. Based on these findings, we propose AP50E as a potential candidate for the development of preventive or therapeutic agents against inflammatory diseases.

Pharmacological anti-tumor effects of natural Chamaecyparis obtusa (siebold & zucc.) endl. Leaf extracts on breast cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Chamaecyparis obtusa (C. obtusa, cypress species) is a plant that grows mainly in the temperate Northern Hemisphere and has long been used as a traditional anti-inflammatory treatment in East Asia. C. obtusa contains phytoncides, flavonoids, and terpenes, which have excellent anti-cancer effects and have been reported to prevent the progression of various cancers. However, the detailed mechanisms underlying the anti-cancer effects of C. obtusa extracts are unknown. AIM OF THE STUDY: We sought to confirm the anti-cancer effects of C. obtusa leaf extracts and to reveal the mechanism of action, with the possibility of its application in the treatment or prevention of cancer. MATERIAL &METHODS: The cytotoxicity of C. obtusa leaf extracts was confirmed using an MTT assay. Intracellular changes in protein levels were measured by immunoblotting, and mRNA levels were measured with qRT-PCR. Wound healing assay and transwell migration assay were used to evaluate the metastatic potential of breast cancer cells. The extract-induced apoptosis was observed using IncuCyte Annexin V Red staining analysis. A syngeneic breast cancer mouse model was established by injecting 4T1-Luc mouse breast cancer cells into the fat pad of female BALB/c mice, and the extract was administered orally. Luciferin solution was injected intraperitoneally to assess primary tumor development and metastasis by bioluminescence. RESULTS: C. obtusa leaf extracts were extracted with boiling water, 70% EtOH, and 99% EtOH. Among the extracts, the 99% EtOH extract of C. obtusa leaf (CO99EL) most clearly inhibited the tyrosine phosphorylation of Signal Transducer and Activator of Transcription 3 (pY-STAT3) in MDA-MB-231 breast cancer cells at a concentration of 25 and 50 µg/mL. In addition, CO99EL strongly inhibited not only endogenous pY-STAT3 levels but also IL-6-induced STAT3 activation in various types of cancer cells, including breast cancer. CO99EL inhibited metastatic potential by downregulating the expression of N-cadherin, fibronectin, TWIST, MMP2, and MMP9 in MDA-MB-231 breast cancer cells. CO99EL also induced apoptotic cell death by increasing cleaved caspase-3 and decreasing anti-apoptotic proteins Bcl-2 and Bcl-xL. In an in vivo syngeneic breast cancer mouse model, 100 mg/kg CO99EL suppressed tumor growth and induced apoptosis of cancer cells. Moreover, CO99EL significantly inhibited lung metastasis from primary breast cancer. CONCLUSIONS: Our study demonstrated that 100 mg/kg CO99EL has potent anti-tumor effects against breast cancer, thus suggesting that 100 mg/kg CO99EL has potential applications in the treatment and prevention of breast cancer.

Risk factors based vessel-specific prediction for stages of coronary artery disease using Bayesian quantile regression machine learning method: Results from the PARADIGM registry.

BACKGROUND AND HYPOTHESIS: The recently introduced Bayesian quantile regression (BQR) machine-learning method enables comprehensive analyzing the relationship among complex clinical variables. We analyzed the relationship between multiple cardiovascular (CV) risk factors and different stages of coronary artery disease (CAD) using the BQR model in a vessel-specific manner. METHODS: From the data of 1,463 patients obtained from the PARADIGM (NCT02803411) registry, we analyzed the lumen diameter stenosis (DS) of the three vessels: left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA). Two models for predicting DS and DS changes were developed. Baseline CV risk factors, symptoms, and laboratory test results were used as the inputs. The conditional 10%, 25%, 50%, 75%, and 90% quantile functions of the maximum DS and DS change of the three vessels were estimated using the BQR model. RESULTS: The 90th percentiles of the DS of the three vessels and their maximum DS change were 41%-50% and 5.6%-7.3%, respectively. Typical anginal symptoms were associated with the highest quantile (90%) of DS in the LAD; diabetes with higher quantiles (75% and 90%) of DS in the LCx; dyslipidemia with the highest quantile (90%) of DS in the RCA; and shortness of breath showed some association with the LCx and RCA. Interestingly, High-density lipoprotein cholesterol showed a dynamic association along DS change in the per-patient analysis. CONCLUSIONS: This study demonstrates the clinical utility of the BQR model for evaluating the comprehensive relationship between risk factors and baseline-grade CAD and its progression.

Effect of water filtration infrared-A (wIRA) sauna on inorganic ions excreted through sweat from the human body.

Sweat discharged as a result of exposure to sauna plays an important role in removing inorganic ions accumulated in the body, including heavy metals. In this study, inorganic ions (toxic and nutrient elements) excreted in the form of sweat from the body using a water-filtered infrared-A (wIRA) sauna were determined using inductively coupled plasma sector field mass spectrometry. The analyzed elements included eight toxic elements (Al, As, Be, Cd, Ni, Pb, Ti, and Hg) and 10 nutrient elements (Ca, Co, Cr, Cu, Fe, Mg, Mn, Se, V, and Zn), and their correlations were determined. Analysis of the sweat obtained from 22 people using the wIRA sauna showed a higher inorganic ion concentration than that obtained from conventional activities, such as exercise or the use of wet sauna, and the concentration of toxic elements in sweat was higher in females than in males. Correlation analysis of the ions revealed a correlation between the discharge of toxic elements, such as As, Be, Cd, and Ni, and discharge of Se and V, and Ni was only correlated with Mn. This study provides fundamental information on nutritional element supplementation when using wIRA sauna for detoxification.

Effect of melatonin on oxidative stress indicators in animal models of fibrosis: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Imbalance of oxidative stress has been detected in a range of fibrotic diseases. Melatonin as an indoleamine hormone plays an important role in regulating the circadian rhythm of human, while in recent years, its antioxidant effect has also attracted increasing attention. This study aimed to perform a systematic review and meta-analysis to comprehensively evaluate the antioxidant effect of melatonin in animal models of fibrosis. METHODS: The PubMed, Cochrane Library, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang database, China Science and Technology Journal Database (VIP), and SinoMed databases were searched from inception to March 1st, 2022 to retrieve eligible studies that evaluated the effect of melatonin supplementation on the levels of malondialdehyde (MDA), lipid peroxidation (LPO), nitric oxide (NO), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT) in animal models of fibrosis. RESULTS: A total of 64 studies were included in this meta-analysis. The results showed that melatonin supplementation significantly reduced the levels of oxidative indicators including MDA (P < 0.00001), LPO (P < 0.00001) and NO (P < 0.0001), and elevated the levels of antioxidant indicators including GSH (P < 0.00001), GPx (P < 0.00001) and SOD (P < 0.00001) in fibrotic diseases. CONCLUSIONS: Our research findings showed that melatonin supplementation could significantly reduce the levels of oxidative indicators including MDA, LPO and NO and elevate the levels of antioxidant indicators including GSH, GPx and SOD so as to correct oxidative stress in animal models of fibrosis. However, no significant changes were observed in CAT level. More clinical studies are needed to further confirm the beneficial role of melatonin in fibrotic diseases.

Chamaecyparis obtusa (Siebold & Zucc.) Endl. leaf extracts prevent inflammatory responses via inhibition of the JAK/STAT axis in RAW264.7 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Chamaecyparis obtusa (Siebold & Zucc.) Endl. (C. obtusa) has been used as folk medicine in East Asia and has been reported to alleviate inflammatory diseases. However, the detailed mechanisms for the anti-inflammatory effects of C. obtusa remain unclear. AIM OF THE STUDY: Although the anti-inflammatory mechanisms of natural products have been studied for decades, it is still important to identify the potential anti-inflammatory effects of natural sources. In this study, we investigated the anti-inflammatory effects and underlying mechanism of C. obtusa leaf extracts. MATERIAL &METHODS: The cell viability was determined by MTT and crystal violet staining. NO production in the supernatant was measured using Griess reagent. The cell lysates were analyzed by immunoblotting and RT-qPCR. Secreted cytokines were analyzed using ELISA kit and cytokine array kit. mRNA expression from the GSE9632 database set. Z-scores were calculated for each gene and visualized by heat map. RESULTS: Among the extracts of C. obtusa obtained with different extraction methods, the 99% ethanol leaf extract (CO99EL) strongly inhibited lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and Janus kinase/signaling transducer and activator of transcription (JAK/STAT) phosphorylation in RAW264.7 cells. In addition, CO99EL strongly inhibited LPS-induced interleukin (IL)-1ß, IL-6, IL-27, and C-C motif chemokine ligand (CCL)-1 production and directly inhibited LPS-induced JAK/STAT phosphorylation in RAW264.7 cells. CONCLUSIONS: These findings demonstrate that CO99EL significantly prevents LPS-induced macrophage activation by inhibiting the JAK/STAT axis. Therefore, we suggest the use of C. obtusa extracts as therapeutic approach for inflammatory diseases.

[A new seco-prezizaane-type sesquiterpene lactone from stems and branches of Illicium ternstroemioides].

Three seco-prezizaane-type sesquiterpene lactones, one phenylpropanoid, and two lignans were isolated from the 95% ethanol extract of stems and branches of Illicium ternstroemioides with silica gel column chromatography, ODS column chromatography, and preparative HPLC. Based on the spectral data, they were identified as burmanicumolide D(1), veranisatin A(2), veranisatin B(3), dihydroconiferylalcohol(4), pinoresinol(5),(-)-matairesinol(6), respectively. Among them, compound 1 was a new seco-prezizaane-type sesquiterpene lactone, and 2-6 were obtained from this plant for the first time. None of these compounds display antiviral or cytotoxic activities.

Risk of upper gastrointestinal bleeding in patients on oral anticoagulant and proton pump inhibitor co-therapy.

BACKGROUND: Proton pump inhibitors (PPIs) are known to reduce the risk of upper gastrointestinal bleeding in patients on oral anticoagulants, and patients are increasingly on oral anticoagulants and PPI co-therapy. However, evidence is lacking on the safety and effectiveness of oral anticoagulants when co-administered with PPIs. METHODS: Among patients initiating oral anticoagulants (warfarin and non-vitamin K antagonist oral anticoagulants [NOACs], i.e. rivaroxaban, dabigatran, apixaban, and edoxaban) during 2013-2017, those concomitantly prescribed PPIs were identified (n = 19,851). The primary endpoint was hospitalization for major upper gastrointestinal bleeding, and secondary endpoints were death and ischemic stroke. RESULTS: During a mean 1.4 years of follow-up, the primary endpoint occurred in 512 (2.58%) patients. Overall, NOACs were associated with lower upper gastrointestinal bleeding risk after adjustment for age, sex, comorbidities and concomitant medications (adjusted hazard ratio 0.78, 95% confidence interval 0.65-0.94), compared to warfarin. There was no significant difference in upper gastrointestinal bleeding risk among the individual NOACs. This trend of reduced risk for upper gastrointestinal bleeding in NOACs compared to warfarin was consistent for both regular and reduced doses, throughout bleeding risk groups, and other subgroup analyses. NOACs were also associated with lower risk of death compared to warfarin. The risk for ischemic stroke was not significantly different among the oral anticoagulants in patients with atrial fibrillation. CONCLUSION: In patients on oral anticoagulant and PPI co-therapy, NOACs were associated with lower risk of upper gastrointestinal bleeding and mortality compared to warfarin, while there was no difference among the oral anticoagulants for stroke prevention. In patients on PPI therapy, NOACs may preferred over warfarin for decreasing risk of upper gastrointestinal bleeding and mortality.

Effects of chronic kidney disease and declining renal function on coronary atherosclerotic plaque progression: a PARADIGM substudy.

AIMS: To investigate the change in atherosclerotic plaque volume in patients with chronic kidney disease (CKD) and declining renal function, using coronary computed tomography angiography (CCTA). METHODS AND RESULTS: In total, 891 participants with analysable serial CCTA and available glomerular filtration rate (GFR, derived using Cockcroft-Gault formulae) at baseline (CCTA 1) and follow-up (CCTA 2) were included. CKD was defined as GFR <60 mL/min/1.73 m2. Declining renal function was defined as ≥10% drop in GFR from the baseline. Quantitative assessment of plaque volume and composition were performed on both scans. There were 203 participants with CKD and 688 without CKD. CKD was associated with higher baseline total plaque volume, but similar plaque progression, measured by crude (57.5 ± 3.4 vs. 65.9 ± 7.7 mm3/year, P = 0.28) or annualized (17.3 ± 1.0 vs. 19.9 ± 2.0 mm3/year, P = 0.25) change in total plaque volume. There were 709 participants with stable GFR and 182 with declining GFR. Declining renal function was independently associated with plaque progression, with higher crude (54.1 ± 3.2 vs. 80.2 ± 9.0 mm3/year, P < 0.01) or annualized (16.4 ± 0.9 vs. 23.9 ± 2.6 mm3/year, P < 0.01) increase in total plaque volume. In CKD, plaque progression was driven by calcified plaques whereas in patients with declining renal function, it was driven by non-calcified plaques. CONCLUSION: Decline in renal function was associated with more rapid plaque progression, whereas the presence of CKD was not.

Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets.

Chronic kidney disease (CKD) is a progressive loss of renal function. The gradual decline in kidney function leads to an accumulation of toxins normally cleared by the kidneys, resulting in uremia. Uremic toxins are classified into three categories: free water-soluble low-molecular-weight solutes, protein-bound solutes, and middle molecules. CKD patients have increased risk of developing cardiovascular disease (CVD), due to an assortment of CKD-specific risk factors. The accumulation of uremic toxins in the circulation and in tissues is associated with the progression of CKD and its co-morbidities, including CVD. Although numerous uremic toxins have been identified to date and many of them are believed to play a role in the progression of CKD and CVD, very few toxins have been extensively studied. The pathophysiological mechanisms of uremic toxins must be investigated further for a better understanding of their roles in disease progression and to develop therapeutic interventions against uremic toxicity. This review discusses the renal and cardiovascular toxicity of uremic toxins indoxyl sulfate, p-cresyl sulfate, hippuric acid, TMAO, ADMA, TNF-α, and IL-6. A focus is also placed on potential therapeutic targets against uremic toxicity.

Sex differences in the prognosis of patients with hypertrophic cardiomyopathy.

We investigated sex-related differences in the prognosis of patients with hypertrophic cardiomyopathy (HCM) using the Korea National Health Insurance Service database. From 2010 to 2016, 9524 patients diagnosed with HCM and had more than 1-year follow-up period were analyzed. The primary endpoint was the composite of cardiovascular death or new-onset heart failure (HF) admission. Propensity score-matching analysis was performed to adjust for different baseline characteristics. With a 4.4-years' median follow-up interval (range 2.0-6.6 years) and male predominance (77.6%), women with HCM were older (52.6 ± 9.7 vs. 51.4 ± 9.1, p < 0.001), had lower incomes, more comorbidities based on Charlson comorbidity index. Women with HCM had a higher incidence of the primary endpoint than men (incidence rate: 34.15 vs. 22.83 per 1000 person-years, log-rank p < 0.001). Multivariable Cox analysis showed that female sex was a poor prognostic factor for the primary endpoint (HR 1.43, 95% CI 1.24-1.64, p < 0.001). This was mainly driven by a higher incidence of new-onset HF admission (HR 1.55, 95% CI 1.34-1.80). However, there was no difference in the incidence of cardiovascular death between the sexes. This result was concordant in the propensity score-matched cohort. In conclusion, women with HCM have worse prognosis, which was mainly driven by a higher new-onset HF admission.

Correlation between bone mineral density and endometrial thickness over time in women with breast cancer history.

As the efficacy of chemotherapy and adjuvant endocrine therapy for breast cancer increase, the quality-of-life to cancer survivors could be more important issue in strategies of breast cancer treatment. Bone health has become more compelling in care of breast cancer survivor than ever before. This retrospective study was aimed to evaluate factors relating to the change in BMD and to ascertain the correlation between changes in BMD and EMT of women with breast cancer in follow-up. Records of 164 women who underwent surgery for breast cancer were reviewed in this study. The basal characteristics included parity, menopausal state, medication with vitamin D, bisphosphonate, selective estrogen modulator (SERM), aromatase inhibitor (AI), gonadotrophin releasing hormone agonist (GnRHa), chemotherapy, radiotherapy, cancer type including positivity of estrogen receptor, progesterone receptor and HER2, combined the other gynecologic disease or the other origin cancer. At initial and follow-up visit, all subjective were checked with BMD, endometrial thickness (EMT). The mean age was 52.1 ± 8.5 years old and overall interval between initial and follow-up visits were 17.6 ± 7.5 month in this study. The BMDs of L1-4 (1.040 ± 0.166 g/cm2 vs 1.070 ± 0.181 g/cm2, p < 0.001), femur neck (0.850 ± 0.121 g/cm2 vs 0.870 ± 0.136 g/cm2, p < 0.001), and femur total (0.902 ± 0.132 g/cm2 vs 0.915 ± 0.138 g/cm2, p < 0.001) at follow-up visit were significantly lower than those at initial visit. The change in BMDs of L1-4 (ΔBMDL1-4, r = 0.353, p < 0.001, and r = 0.228, p = 0.003), femur neck (ΔBMDNeck, r = 0.198, p = 0.011, and r = 0.282, p < 0.001), femur total (ΔBMDTotal, r = 0.294, p < 0.001, and r = 0.327, p < 0.001) had positive correlation with age and the change in EMT (ΔEMT). After age correction, ΔEMT had positive correlation with ΔBMDNeck (r = 0.245, p = 0.002) and ΔBMDTotal (r = 0.273, p < 0.001). ΔBMDL1-4 and ΔBMDNeck differed according to menopausal state (p < 0.001 and p = 0.035), bisphosphonate (p < 0.001 and p < 0.001), and GnRHa (p < 0.001 and p < 0.001). In follow-up of women with history of breast cancer, ΔEMT could be an alternative screening marker for BMD decrease.

Rapid and simple colorimetric detection of hydrogen sulfide using an etching-resistant effect on silver nanoprisms.

A fast and sensitive colorimetric paper sensor has been developed using silver nanoprisms (Ag NPRs) with an edge length of ~50 nm for the detection of free H2S gas. We prepared two types of Ag NPRs-coated H2S sensing papers: a multi-zone patterned paper for passive (diffusion mode), and a single-zone patterned paper for pumped mode of H2S gas. The change in color intensity was quantitatively analyzed of Ag NPRs-coated paper after KCl treatment depending on the concentration of H2S gas, from yellow to purplish brown. As a result, Ag NPRs-coated H2S sensing paper showed good sensitivity with a linear range of 1.03 to 32.9 µM H2S, high selectivity, and good reproducibility and stability, together with a fast response time of 1 min. The developed H2S sensing paper was applied to detect the free H2S gas released from three types of garlic including crushed, peeled, and fresh garlic. Therefore, it can be utilized as a simple, fast, and reliable tool for on-site colorimetric detection of free H2S gas for quality control of dietary supplements and exhaled breath analysis.Graphical abstract.

Clinical application of glycyrrhizic acid and its effect on cytochrome P 450 / 中国基层医药

Glycyrrhizic acid, as the main active ingredient of Glycyrrhiza, has anti-inflammatory, antiviral, antitussive, expectorant, immunomodulatory and other pharmacological effects. In recent years, many new clinical uses of glycyrrhizic acid have been found, and glycyrrhizic acid has an effect on human and animal cytochrome P 450. This paper summarizes the clinical application of glycyrrhizic acid and its effect on cytochrome P 450, providing reference for clinical rational use of glycyrrhizic acid preparation.