Epidemiology of Sarcoidosis in U.S. Veterans from 2003 to 2019.

Rationale: United States veterans represent an important population to study sarcoidosis. Their unique history of environmental exposures, wide geographic distribution, and long-term enrollment in a single integrated healthcare system provides an unparalleled opportunity to understand the incidence, prevalence, and risk factors for sarcoidosis. Objectives: To determine the epidemiology, patient characteristics, geographic distribution, and associated risk factors of sarcoidosis among U.S. veterans. Methods: We used data from the Veterans Health Administration (VHA) electronic health record system between 2003 and 2019 to evaluate the annual incidence, prevalence, and geographic distribution of sarcoidosis (defined using the International Classification of Diseases codes). We used multivariate logistic regression to examine patient characteristics associated with sarcoidosis incidence. Results: Among more than 13 million veterans who received care through or paid for by the VHA, 23,747 (0.20%) incident diagnoses of sarcoidosis were identified. Compared with selected VHA control subjects using propensity score matching, veterans with sarcoidosis were more likely to be female (13.5% vs. 9.0%), of Black race (52.2% vs. 17.0%), and ever-tobacco users (74.2% vs. 64.5%). There was an increase in the annual incidence of sarcoidosis between 2004 and 2019 (from 38 to 52 cases/100,000 person-years) and the annual prevalence between 2003 and 2019 (from 79 to 141 cases/100,000 persons). In a multivariate logistic regression model, Black race (odds ratio [OR], 4.49; 95% confidence interval [CI], 4.33-4.65), female sex (OR, 1.64; 95% CI, 1.56-1.73), living in the Northeast compared with the western region (OR, 1.57; 95% CI, 1.48-1.67), history of tobacco use (OR, 1.36; 95% CI, 1.31-1.41), and serving in the Army, Air Force, or multiple branches compared with the Navy (OR, 1.08; 95% CI, 1.03-1.13; OR, 1.10; 95% CI, 1.04-1.17; OR, 1.27; 95% CI, 1.16-1.39, respectively) were significantly associated with incident sarcoidosis (P < 0.0001). Conclusions: The incidence and prevalence of sarcoidosis are higher among veterans than in the general population. Alongside traditionally recognized risk factors such as Black race and female sex, we found that a history of tobacco use within the Veterans Affairs population and serving in the Army, Air Force, or multiple service branches were associated with increased sarcoidosis risk.

A Network Pharmacology Approach for Uncovering the Antitumor Effects and Potential Mechanisms of the Sijunzi Decoction for the Treatment of Gastric Cancer.

Background: Sijunzi decoction (SJZD), a classic Chinese formula, has been clinically used for the treatment of gastrointestinal disorders. However, few studies have uncovered its antitumor effects and its potential mechanisms against gastric cancer (GC). Therefore, this work aimed to identify the active compounds and putative targets of the SJZD and to further explore the potential mechanisms involved in the treatment of GC. Materials and Methods: The active compounds and potential targets of the SJZD and related genes for GC treatment were collected from a public database. Traditional Chinese medicine (TCM)-compound-target-disease networks, Venn diagrams, protein-protein interactions (PPIs), gene ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to obtain the bioactive compounds, key targets, and potential pathways. Next, the human gastric adenocarcinoma cell line NUGC-4 was inoculated subcutaneously into the right flank of NCG mice to build a tumor-bearing mouse model to further verify the findings. Results: There were 117 compounds in the SJZD in total. The SJZD and GC had 161 and 3288 potential targets, respectively, among which 123 targets overlapped. The network analysis showed that quercetin, kaempferol formononetin, ginsenoside, atractylenolide III, etc., were bioactive molecules. The tumor necrosis factor (TNF), interleukin-6 (IL-6), cellular tumor antigen p53 (TP53), transcription factor AP-1 (JUN), and vascular endothelial growth factor A (VEGFA) were potential targets. A KEGG pathway enrichment analysis revealed 110 pathways involved in the pathways for cancer, including the PI3K-AKT signaling pathway. Validation experiments showed that the SJZD inhibited tumor growth and induced apoptosis in tumor cells. In addition, the SJZD downregulated expressions of VEGFA, iNOS, COX-2, and Bax/Bcl2 and inhibited the expressions of p-PI3K and p-AKT. Conclusion: The SJZD treats GC by inhibiting blood vessel hyperplasia and inducing cell apoptosis by regulating the PI3K/AKT pathway.

Genes Relevant to Tissue Response to Cancer Therapy Display Diurnal Variation in mRNA Expression in Human Oral Mucosa.

BACKGROUND: To address a critical gap for application of cancer chronotherapy of when would be the best time(s) for treating an individual cancer patient, we conducted a pilot study to characterize diurnal variations of gene expression in oral mucosal tissue, which is vulnerable to damage from cancer therapies. METHODS: We conducted RNA-seq assay on individual oral mucosal samples collected from 11 healthy volunteers every 4 hours (6 time points). Using a cosine-based method, we estimated the individual and average values of peak-time and amplitude for each gene. Correlations between gene expression peak-times and age was examined, adjusting for individual's sleep timing. RESULTS: Among candidate gene pathways that are relevant to treatment response, 7 of 16 genes (PER3, CIART, TEF, PER1, PER2, CRY2, ARNTL) involved in circadian regulation and 1 of 118 genes (WEE1) involved in cell cycle regulation achieved p-value ≤ 0.1 and relative amplitude>0.1. The average peak times were approximately 10:15 for PER3, CIART and TEF, 10:45 for PER1, 13:00 for WEE1, PER2 and CRY2, and 19:30 for ARNTL. Ranges in peak times across individuals differed by gene (e.g., 8 hours for PER1; 16.7 hours for WEE1). Older people had later peak times for PER1 (r = 0.77, p = 0.03) and PER3 (r = 0.69, p-value = 0.06). CONCLUSION: In oral mucosa, expression of some genes relevant to treatment response displayed diurnal variation. These genes may be candidates for development of biomarkers for optimizing individual timing of cancer therapy using non-invasively collected oral mucosa.

Bovine Serum Albumin Nanoparticle-Mediated Delivery of Sorafenib for Improving Hepatocellular Carcinoma Therapy.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. The majority of patients with HCC are diagnosed with advanced-stage disease. Sorafenib is a frontline therapy drug approved by the Food and Drug Administration for advanced HCC. However, the poor aqueous solubility of sorafenib limits its applications. The present study aimed to overcome this limitation of sorafenib. Thus, bovine serum albumin (BSA)-based nanoparticles were developed to encapsulate hydrophobic sorafenib. The resultant sorafenib-loaded BSA nanoparticles (Sf-BSA-NPs) were thoroughly characterized for size distribution, encapsulation efficiency and morphology. Previous studies on HepG2 cells in vitro have demonstrated that Sf-BSA-NPs exhibit remarkable superiority to free sorafenib in cytocompatibility, cytotoxicity and proapoptotic effect. The results of the present study demonstrated that Sf-BSA-NPs were effective in improving aqueous solubility, and enhanced drug cytotoxicity, suggesting its therapeutic potential for HCC.

Structural evolution of CrN nanocube electrocatalysts during nitrogen reduction reaction.

Metal nitrides have been suggested as prospective catalysts for the electrochemical nitrogen reduction reaction (NRR) in order to obtain ammonia at room temperature under ambient pressure. Herein, we report that templated chromium nitride porous microspheres built up by nanocubes (NCs) are an efficient noble-metal-free electrocatalyst for NRR. The CrN NCs catalyst exhibits both a high stability and NH3 yield of 31.11 µg h-1 mgcat.-1 with a Faradaic efficiency (FE) of 16.6% in 0.1 M HCl electrolyte. Complementary physical characterization techniques demonstrate partial oxidation of the pristine CrN NCs during reaction. Structural characterization by means of scanning transmission electron microscopy (STEM) combining electron energy loss spectrum (EELS) and energy dispersive X-ray spectroscopy (EDX) analysis reveals the NC structure to consist of an O-rich core and N-rich shell after NRR. This gradient distribution of nitrogen within the CrN NCs upon completed NRR is distinct to previously reported metal nitride NRR catalysts, because no significant loss of nitrogen occurs at the catalyst surface.

A machine learning method correlating pulse pressure wave data with pregnancy.

Pulse feeling , representing the tactile arterial palpation of the heartbeat, has been widely used in traditional Chinese medicine (TCM) to diagnose various diseases. The quantitative relationship between the pulse wave and health conditions however has not been investigated in modern medicine. In this paper, we explored the correlation between pulse pressure wave (PPW), rather than the pulse key features in TCM, and pregnancy by using deep learning technology. This computational approach shows that the accuracy of pregnancy detection by the PPW is 84% with an area under the curve (AUC) of 91%. Our study is a proof of concept of pulse diagnosis and will also motivate further sophisticated investigations on pulse waves.

Mindfulness training enhances flow state and mental health among baseball players in Taiwan.

OBJECTIVE: To examine the effect of mindfulness-based training on performance and mental health among a group of elite athletes. METHODS: This study aimed to evaluate the effect of mindful sport performance enhancement (MSPE) on mental health, flow state, and competitive state anxiety using a 4-week workshop. We recruited an amateur baseball team (N=21) in Taiwan, and collected information by self-reported questionnaires administered before, immediately after, and at a 4-week follow-up. The primary outcome was to evaluate sports performance by flow state and competitive state anxiety, which included self-confidence, somatic anxiety, and cognitive anxiety. The secondary outcome was to explore whether MSPE intervention can improve anxiety, depression, sleep disturbance, and eating disorders. RESULT: After the workshop and follow-up 1 month later, we found improvements in flow state (P=0.001; P=0.045), cognitive anxiety in competitive anxiety (P=0.056; P=0.008), global eating disorder (P=0.009; P<0.001), marked shape concern (P=0.005; P<0.001), and weight concern (P=0.007; P<0.001). Scores of sleep disturbance (P=0.047) showed significant improvement at follow-up. We also found significant association between flow state and mindfulness ability (P<0.001). CONCLUSION: This is the first mindfulness intervention to enhance athletes' performance in Taiwan, and also the first application of MSPE for team sports. Our study results suggested that mindfulness ability is associated with flow state, and that MSPE is a promising training program for strengthening flow state and mental health.

Chinese herbal extract Su-duxing had potent inhibitory effects on both wild-type and entecavir-resistant hepatitis B virus (HBV) in vitro and effectively suppressed HBV replication in mouse model.

This study aimed to investigate anti-HBV effect and major active compounds of Su-duxing, a medicine extracted from Chinese herbs. HBV-replicating cell lines HepG2.2.15 (wild-type) and HepG2.A64 (entecavir-resistant) were used for in vitro test. C57BL/6 mice infected by adeno-associated virus carrying 1.3 mer wild-type HBV genome were used for in vivo test. Inhibitory rates of Su-duxing (10 µg/mL) on HBV replicative intermediate and HBsAg levels were 75.1%, 51.0% in HepG2.2.15 cells and 65.2%, 42.9% in HepG2.A64 cells. The 50% inhibitory concentration of Su-duxing and entecavir on HBV replicative intermediates had 0.2-fold and 712.5-fold increase respectively for entecavir-resistant HBV compared to wild-type HBV. Su-duxing and entecavir combination showed a better anti-HBV effect than each single of agents. Mice treated with Su-duxing (45.0 mg kg-1 d-1 for 2 weeks) had 1.39 log10 IU/mL decrease of serum HBV DNA, and 48.9% and 51.7% decrease of serum HBsAg and HBeAg levels. GeneChip and KEGG analysis proposed that anti-HBV mechanisms included relief of HBx stability and viral replication, deregulation of early cell cycle checkpoints, and induction of type I interferon. Quantitative RT-PCR verified that CCNA2, ATF4, FAS and CDKN1A expression levels had significant difference between Su-duxing-treated and control groups. Six active compounds (Matrine, Oxymatrine, Chlorogenic acid, Sophocarpine, Baicalein, and Wogonin) against HBV were identified in Su-duxing. Greater anti-HBV effects were observed in some compound pairs compared to each single compound. In conclusion, Su-duxing had potent inhibitory effects on both wild-type and entecavir-resistant HBV. Its effects were associated with coordinated roles of active compounds in its composition.

Increased therapeutic efficacy of combination of azithromycin and ceftazidime on Pseudomonas aeruginosa biofilm in an animal model of ureteral stent infection.

BACKGROUND: Infection caused by ureteral stent indwelling is one of the most difficult medical problems, since once bacteria reside in biofilms they are extremely resistant to antibiotics as well as to the host immune defences. In this study we assessed the in vitro and in vivo efficacy of azithromycin and ceftazidime in preventing ureteral stent infection by Pseudomonas aeruginosa. RESULTS: The susceptibility testing with adherent bacteria showed that the biofilm was strongly inhibited by azithromycin treatment, ceftazidime against adherent bacteria in the presence of azithromycin showed the minimum inhibitory concentrations (MICs) and minimum bacteriocidal concentrations (MBCs) dramatically lower than those obtained in the absence of azithromycin. Moreover, ceftazidime plus azithromycin reduced twitching motility and production of rhamnolipid. For the single-treatment groups, in vivo intravenous injection of ceftazidime showed the highest inhibitory effect on bacterial load. Azithromycin prophylactic injection combined with ceftazidime showed increased inhibitory effect on bacterial load than that of each single antibiotic. CONCLUSIONS: Combination of azithromycin and ceftazidime effectively prevent the formation of biofilm and reduced bacteria load of Pseudomonas aeruginosa compared to separate treatment of either of these two antibiotics. This combined treatment option have the potential to contribute to the success of Pseudomonas biofilm elimination in the clinical environment.

[Analysis of volatile ingredients in Gardeniae Fructus and its processed products by GC-MS].

Gardeniae Fructus contains volatile ingredients, however, the species and proportions in different processed products of Gardeniae Fructus are different. In this experiment, volatile ingredients were separated by steam distillation with content of 1.2, 1.0, 0.9, 0.7 µL · g(-1) in Gardeniae Fructus, fried Gardeniae Fructus, stir-baked Gardeniae Fructus, Gardeniae Fructus fried into carbon respectively. One hundred and twenty-four kinds of volatile components were identified by GC-MS. Fifty-three kinds of volatile ingredients consisted in Gardeniae Fructus accounting for 93.85%, 54 kinds in fried Cardeniae Fructus accounting for 92.01%, 32 kinds in stir-baked Cardeniae Fructus accounting for 91.59% and 43 kinds in Gardeniae Fructus fried into carbon accounting for 90.81%. In this paper, analysis of Gardeniae Fructus by GC-MS provides a scientific basis for elucidating the mechanism of different processed products.

Isolation and purification of six iridoid glycosides from gardenia jasminoides fruit by medium-pressure liquid chromatography combined with macroporous resin chromatography.

Gardeniae fructus is one of the most frequently used herbs in traditional Chinese medicine. In the present study, a process for the enrichment of six iridoid glycosides from Gardeniae fructus was developed using medium-pressure liquid chromatography combined with macroporous resin and reversed-phase chromatography. The purities of different fractions from Gardeniae fructus were assessed using quantitative high-performance liquid chromatography. After fractionation using HPD-100 column chromatography, a 30% ethanol fraction was selected based on high-performance liquid chromatography and liquid chromatography with mass spectrometry qualitative analysis to separate and purify. Based on the orientation analysis results, six compounds-deacetyl asperulosidic acid methyl ester, gardenoside, ixoroside, scandoside methyl ester, genipin-1-O-ß-d-gentiobioside, and geniposide-were successfully isolated and purified in three to four combined steps from Gardeniae fructus. The purities of these compounds were found by high-performance liquid chromatography analysis to be 97.9, 98.1, 95.5, 96.3, 97.1, and 98.7%, respectively. Moreover, their structures were elucidated by NMR spectroscopy and liquid chromatography with tandem mass spectrometry. The separation process was highly efficient, rapid, and accurate, making it a potential approach for the large-scale production of iridoids in the laboratory and providing several marker compounds for quality control. This procedure may be meaningful for the purification of other natural products used in traditional Chinese medicine.

[Research progress on processed Chinese medicine in vivo].

Processed Chinese medicine is the core of traditional Chinese medicine (TCM) industry chain,which directly affects the clinical efficacy and. safety of Chinese patent medicine and clinical formula Decoction pieces. Studied the variation of effective substance in vivo Chinese medicine processing before and after processed, clarifying the effective substance and processing principle is a top priority of the development of Chinese medicine processing. The traditional research method chiefly focus on the variation about chemicals in vitro of processed Chinese medicine, it cannot reveal that the integrity and complexity of processed Chinese medicine efficacy changes, so the change process is the focus of future research in vivo on the base of effective substance of TCM This paper described the research on the base of effective substance of TCM and Processed Chinese medicine research status in vitro, discussed the analytical methods (plasma chemistry, pharmacokinetics, metabonomics) of the dynamic process in vivo about processed Chinese medicine, and pointed out development and related problems in process in vivo on the base of effective substance of TCM, which could provided research ideas and methods for in-depth interpretation of Chinese medicine processing mechanism.

Bioactivity-guided fractionation of physical fatigue-attenuating components from Rubus parvifolius L.

Alleviation of fatigue has been emerging as a serious issue that requires urgent attention. Health professionals and sports physiologists have been looking for active natural products and synthetic compounds to overcome fatigue in humans. This study was designed to define the anti-fatigue property of Rubus parvifolius L. (RPL) by characterization of active constituents using a mouse forced swimming test model. Four RPL fractions with different polarities containing anti-fatigue activity were sequentially isolated from the n-butanol RPL extract, followed by elution of 50% ethanol-water fraction from D101 macroporous resin chromatography to obtain nigaichigoside F1, suavissimoside R1 and coreanoside F1. Active constituents of the 50% ethanol-water eluate of RPL were total saponins. The fractions were examined based on the effect on weight-loaded swimming capacity of mice. Serum levels of urea nitrogen (SUN), triglyceride fatty acids (TG), lactate dehydrogenase (LDH), lactic acid (LA), ammonia and hepatic glycogen (HG) were also examined for potential mechanisms underlying the anti-fatigue effect of RPL extracts. During the experiment, two inflammatory markers, interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) in serum, were measured. We found that total saponins from RPL possess potent capabilities to alleviate mouse fatigue induced by forced swimming and that nigaichigoside F1 was responsible for the pharmacological effect. The underlying mechanisms include delays of SUN and LA accumulation, a decrease in TG level by increasing fat consumption, increases in HG and LDH so that lactic acid accumulation and ammonia in the muscle were reduced, and suppression of increased immune activation and inflammatory cytokine production. Our findings will be helpful for functional identification of novel anti-fatigue components from natural medicinal herbs.

Characterization of the antibacterial activity and the chemical components of the volatile oil of the leaves of Rubus parvifolius L.

Rubus parvifolius L. (Rp) is a medicinal herb that possesses antibacterial activity. In this study, we extracted the volatile oil from the leaves of Rp to assess its antibacterial activity and analyze its chemical composition. A uniform distribution design was used to optimize the extraction procedure, which yielded 0.36% (w/w) of light yellowish oil from the water extract of Rp leaves. We found that the extracted oil effectively inhibited the growth of a wide range of Gram positive and negative bacteria, including Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumanii, Bacillus cloacae, and Klebsiella pneumoniae. We further analyzed the components contained in the hydro-distillated Rp volatile oil by gas chromatography-mass spectroscopy. Twenty nine compounds were identified, including 4-hydroxy-3-methoxystyrene (66%), 3,7,11,15-tetramethyl-2-hexadecen-1-ol (10%) and 4-tert-butylbenzoic acid (2%). Our results suggest that one or multiple constituents contained in Rp volatile oil may account for its antibacterial activity.

[Serum cortisol and peripheral blood mononuclear cell glucocorticoid receptor mRNA expression in severe alopecia areata with liver-kidney deficiency syndrome].

OBJECTIVE: To investigate serum cortisol level and glucocorticoid receptors (GR) mRNA expression in peripheral blood mononuclear cells (PBMCs) in patients with severe alopecia areata and liver-kidney deficiency syndrome and their involvement in the pathogenesis of severe alopecia areata. METHODS: In 32 patients with severe alopecia areata, serum cortisol levels were measured by chemiluminescence assay and GR mRNA expression in the PBMCs was detected using reverse transcription real-time fluorescence quantitative PCR before and after treatment, with 20 normal subjects serving as the controls. RESULTS: Serum cortisol level showed no significant difference between the cases and the normal controls (P>0.05). The expression of GR mRNA in the PBMCs was significantly lower in the patients than in the normal controls (P<0.05). The expression of GR mRNA was even lower after treatments in patients with alopecia areata (P<0.01). CONCLUSIONS: GC-GR disorder exists in severe alopecia areata. A decreased GR mRNA expression in the PBMCs can be involved in the pathogenesis of severe alopecia areata, and such pathological changes at the receptor and genetic levels might also serve as the microscopic basis of liver-kidbey deficiency syndrome in severe alopecia areata.

Root plasma membrane H+-ATPase is involved in the adaptation of soybean to phosphorus starvation.

The plasma membrane H+-ATPase plays an important role in the plant response to nutrient and environmental stresses. However, the involvement of plant root plasma membrane H+-ATPase in adaptation to phosphate (P) starvation is not yet fully elucidated. In this study, experiments were performed with soybean roots in low-P nutrient solution (10 microM). Treatment with fusicoccin, an activator of the plasma membrane H+-ATPase, increased P uptake by 35%, while vanadate, an inhibitor of plasma membrane H+-ATPase, severely suppressed it. These results suggested that P uptake might be regulated via the modulation of the activity of plasma membrane H+-ATPase under P starvation. The relationship between P uptake and the activity of plasma membrane H+-ATPase was examined further by using plasma membrane H+-ATPase transgenic Arabidopsis thaliana under low-P conditions. Transgenic plants absorbed more P compared with wild-type Arabidopsis. Results from real-time RT-PCR, western-blotting and immunolocalization analysis indicated that the increase in activity of the plasma membrane H+-ATPase by P starvation was caused by its transcriptional and translational regulation. A higher expression was observed at the translational level than at the transcriptional level. P starvation could induce a transient increase of endogenous indole-3-acetic acid (IAA) in soybean roots. The exogenous application of IAA stimulated the activity of plasma membrane H+-ATPase and P uptake, while naphthylphthalamic acid (NPA), an IAA transport inhibitor, blocked IAA effects. Taken together, these results suggested an involvement of root plasma membrane H+-ATPase in the adaptation of soybean to P starvation. IAA might be involved in signal transduction of P starvation by activating the plasma membrane H+-ATPase in soybean roots.