Serum amyloid A expression in liver promotes synovial macrophage activation and chronic arthritis via NFAT5.

Nuclear factor of activated T-cells 5 (NFAT5), an osmo-sensitive transcription factor, can be activated by isotonic stimuli, such as infection. It remains unclear, however, whether NFAT5 is required for damage-associated molecular pattern-triggered (DAMP-triggered) inflammation and immunity. Here, we found that several DAMPs increased NFAT5 expression in macrophages. In particular, serum amyloid A (SAA), primarily generated by the liver, substantially upregulated NFAT5 expression and activity through TLR2/4-JNK signalling pathway. Moreover, the SAA-TLR2/4-NFAT5 axis promoted migration and chemotaxis of macrophages in an IL-6- and chemokine ligand 2-dependent (CCL2-dependent) manner in vitro. Intraarticular injection of SAA markedly accelerated macrophage infiltration and arthritis progression in mice. By contrast, genetic ablation of NFAT5 or TLR2/4 rescued the pathology induced by SAA, confirming the SAA-TLR2/4-NFAT5 axis in vivo. Myeloid-specific depletion of NFAT5 also attenuated SAA-accelerated arthritis. Of note, inflammatory arthritis in mice strikingly induced SAA overexpression in the liver. Conversely, forced overexpression of the SAA gene in the liver accelerated joint damage, indicating that the liver contributes to bolstering chronic inflammation at remote sites by secreting SAA. Collectively, this study underscores the importance of the SAA-TLR2/4-NFAT5 axis in innate immunity, suggesting that acute phase reactant SAA mediates mutual interactions between liver and joints and ultimately aggravates chronic arthritis by enhancing macrophage activation.

Development of organic three-phase laminar flow microfluidic chip for extraction of ginsenosides from Panax ginseng.

BACKGROUND: Herbal extracts contain multiple active constituents, so the sample preparation based on the liquid-liquid extraction (LLE) is demanding, especially when a study subsequent to extraction is needed. Since the laminar flow occurring in microchannels can be formed between two miscible organic phases, a new method of extracting polar compounds from the crude extract of Panax ginseng Meyer in aqueous ethanol by pure n-butanol in the three-phase laminar flow microfluidic chip was established. METHODS: A new chip consisting of long microchannels with a guide structure was employed to improve the extraction efficiency caused by the low diffusion ability of saponins. The method was evaluated by using the extraction yields and purities of ginsenosides Rg1, Re and Rb1 as the indicators, and extraction conditions such as flow rate, temperature and other governing factors were optimized. RESULTS: Using the new chip method, the extraction efficiencies of ginsenoside Rg1, Re and Rb1 were 63.1%, 69.5% and 71.6%, respectively, which are higher than the 26% achieved in a previous report. The extraction yields of 1.53, 0.51, 0.90 mg/g were also higher than those obtained previously by the successive laminar flow microchip method. CONCLUSION: The proposed new microfluidic chip method has simplified the sample pretreatment steps to improve the yield of ginsenoside extraction from ginseng samples.

Apiaceae Medicinal Plants in China: A Review of Traditional Uses, Phytochemistry, Bolting and Flowering (BF), and BF Control Methods.

Apiaceae plants have been widely used in traditional Chinese medicine (TCM) for the removing dampness, relieving superficies, and dispelling cold, etc. In order to exploit potential applications as well as improve the yield and quality of Apiaceae medicinal plants (AMPs), the traditional use, modern pharmacological use, phytochemistry, effect of bolting and flowering (BF), and approaches for controlling BF were summarized. Currently, about 228 AMPs have been recorded as TCMs, with 6 medicinal parts, 79 traditional uses, 62 modern pharmacological uses, and 5 main kinds of metabolites. Three different degrees (i.e., significantly affected, affected to some extent, and not significantly affected) could be classed based on the yield and quality. Although the BF of some plants (e.g., Angelica sinensis) could be effectively controlled by standard cultivation techniques, the mechanism of BF has not yet been systemically revealed. This review will provide useful references for the reasonable exploration and high-quality production of AMPs.

ZnO-NPs alleviate aflatoxin B1-induced hepatoxicity in ducklings by promoting hepatic metallothionein expression.

Aflatoxin B1 (AFB1) is a mycotoxin widely present in animal feed and human food, posing a serious threat to animal and human health. This study was aim to illustrate the mechanism of the protective role of MT against AFB1-induced hepatotoxicity, as well as to explore the feasibility of enhancing the tolerance of poultry to AFB1 by upregulating the expression of hepatic MT. After being exposed to AFB1 (50 ng/kg) primary duckling hepatocytes, the cell viability, the antioxidant index (SOD and GPx) and the mRNA levels of MT downstream genes (PTGR, p53, TrxR, AR and Bcl-2) significantly (p < 0.05) decreased, while the intracellular formation of (AFBO)-DNA adduct content, apoptosis, and MDA content significantly (p < 0.05) increased. Interestingly, overexpression of MT in primary duckling hepatocytes markedly (p < 0.05) reversed the detrimental impact of AFB1 and increased the expression of MT downstream genes. HepG2 cells were applied to study the mechanism how MT works to relieve the hepatic toxicity of AFB1. The ZnO-NPs (20 µg/mL) + AFB1 (20 µg/mL) group significantly (p < 0.05) increased the cell viability, the expression of NRF2, NQO1 and SOD, and expression of MT and MTF-1, as well as significantly (p < 0.05) decreased LDH, ROS and apoptotic rate, comparing with the AFB1 group. While joint treatment with AFB1 and ZnO-NPs, the hepatic toxicity exerted by AFB1 alone was reversed, along with the translocation of MTF-1 from the cytoplasm to the nucleus and upregulated its expression. Duckling trails were further carried out. A total number of 96 1-day-old healthy Cherry Valley commercial ducklings were randomly allocated according to a 2 by 2 factorial arrangement of treatments with the main factors including oral administration of AFB1 (0 vs. 40 µg/kg) and dietary supplementation of ZnO-NPs (0 vs. 60 mg/kg) for 7 days. It showed that AFB1 exposure caused body weight loss (p < 0.05), impaired liver structure and failure in hepatic function (activity of ALT, AST and concentration of TP and GLU) (p < 0.05), and decreases in antioxidant capacity(activity of SOD, CAT and concentration of GSH) (p < 0.05), along with the decrease in hepatic concentration of Zn, increase in expression of apoptosis-related genes and protein CAS3 and mRNA Bcl-2 expression (p < 0.05), and suppressed mRNA levels of antioxidant-related genes MT, SOD1, NRF2, and NQO1 (p < 0.05). In accordance with the cell test, dietary supplementation with ZnO-NPs mitigated the toxicity exerted by AFB1. In conclusion, ZnO-NPs has the protective effects against AFB1-induced hepatocyte injury by activating the expression of MTF-1 and the ectopic induction of MT expression, providing detailed information on the detoxification ability of MT on AFB1.

Effectiveness of Yishen Tongbi decoction versus methotrexate in patients with active rheumatoid arthritis: A double-blind, randomized, controlled, non-inferiority trial.

BACKGROUND: Yishen Tongbi decoction (YSTB) which is an herbal formula, has been used for the treatment of rheumatoid arthritis (RA) for more than ten years with a better curative effect. Methotrexate (MTX) is an effective anchoring agent used to treat rheumatoid arthritis. There were, however, no head-to-head comparative randomized controlled trials comparing traditional Chinese medicine (TCM) to MTX, Therefore, we performed this double-blind, double-model, randomized controlled trial of the efficacy and safety of YSTB and MTX in the treatment of active RA for 24 weeks. METHODS: Patients who met the enrollment criteria were randomly selected (1:1) to receive either YSTB therapy (YSTB 150 ml once daily + MTX placebo 7.5-15 mg once weekly) or MTX therapy (MTX 7.5-15 mg once weekly + YSTB placebo 150 ml once daily) in treatment cycles lasting 24 weeks. The percentage of patients who achieve a clinical disease activity index (CDAI) response at week 24 is the primary efficacy outcome. A 10% risk differential non-inferiority margin was previously defined. The Chinese Clinical Trials Registry has recorded this trial (ChiCTR-1,900,024,902, registered on August 3rd 2019, http://www.chictr.org.cn/index.aspx). RESULTS: Out of 118 patients whose eligibility was determined from September 2019 to May 2022, 100 patients (n = 50 for each group) were enrolled in the research overall. The 24-week trial was completed by 82% (40/49) of the YSTB group's patients and 86% (42/49) of the MTX group's patients. In the intention-to-treat analysis, 67.4% (33/49) of patients in the YSTB group met the main outcome of CDAI response criteria at week 24, compared to 57.1% (28/49) in the MTX group. The risk difference was 0.102 (95% CI -0.089 to 0.293), which demonstrated the non-inferiority of YSTB to MTX. After further testing for superiority, the ratio of CDAI responses achieved by the YSTB and MTX groups was not statistically significant (p = 0.298). At the same time, in week 24, secondary outcomes such as the ACR 20/50/70 response, the European Alliance of Associations for Rheumatology good or moderate response, remission rate, simplified disease activity index response, and low disease activity rate all showed similar statistically significant patterns. There was statistically significant attainment of ACR20 (p = 0.008) and EULAR good or moderate response (p = 0.009) in two groups at week 4. The intention-to-treat analysis results and the per-protocol analysis results were in agreement. The incidence of drug-related adverse events was not statistically different between the two groups (p = 0.487). CONCLUSIONS: Previous studies have used TCM as an adjunct to conventional therapy, and few of them have directly compared it with MTX. In order to lessen disease activity in RA patients, this trial demonstrated that YSTB compound monotherapy was non-inferior to MTX monotherapy and had superior efficacy following short-term treatment. This study provided evidence-based medicine in the treatment of RA with compound prescriptions of TCM and contributed to promoting phytomedicine use in RA patients.

Acidic electrolyzed water treatment suppresses Phomopsis longanae Chi-induced the decreased storability and quality properties of fresh longans through modulating energy metabolism.

Longan fruit loses its market value rapidly due to postharvest pathogenic infestation and quality deterioration. Here, we hypothesized that acidic electrolyzed water (AEW) could maintain higher quality of P. longanae-inoculated longans via regulating energy metabolism. Results indicated that AEW reduced fruit disease index and decay incidence. Significantly, AEW treatment retained higher levels of ATP, ADP, and energy charge, and higher activities of Ca2+-ATPase, Mg2+-ATPase, and H+-ATPase in the membranes of plasma, vacuole, and mitochondria, which maintained the structural and functional integrity of cell membrane. Furthermore, indirectly sustaining cell membrane function via AEW treatment could maintain the storability and quality properties of longans, including keeping higher values of color chromaticity (L*, a*, and b*), higher amounts of vitamin C, total soluble solids, sucrose, and total soluble sugars, lower titratable acid and reducing sugar contents. This work elucidated the potential regulation of AEW on the balance of energy metabolism and fruit quality.

Dietary glucosamine overcomes the defects in αß-T cell ontogeny caused by the loss of de novo hexosamine biosynthesis.

T cell development requires the coordinated rearrangement of T cell receptor (TCR) gene segments and the expression of either αß or γδ TCR. However, whether and how de novo synthesis of nutrients contributes to thymocyte commitment to either lineage remains unclear. Here, we find that T cell-specific deficiency in glutamine:fructose-6-phosphate aminotransferase 1 (GFAT1), the rate-limiting enzyme of the de novo hexosamine biosynthesis pathway (dn-HBP), attenuates hexosamine levels, blunts N-glycosylation of TCRß chains, reduces surface expression of key developmental receptors, thus impairing αß-T cell ontogeny. GFAT1 deficiency triggers defects in N-glycans, increases the unfolded protein response, and elevates  γδ-T cell numbers despite reducing γδ-TCR diversity. Enhancing TCR expression or PI3K/Akt signaling does not reverse developmental defects. Instead, dietary supplementation with the salvage metabolite, glucosamine, and an α-ketoglutarate analogue partially restores αß-T cell development in GFAT1T-/- mice, while fully rescuing it in ex vivo fetal thymic organ cultures. Thus, dn-HBP fulfils, while salvage nutrients partially satisfy, the elevated demand for hexosamines during early T cell development.

Effects of Zearalenone on Production Performance, Egg Quality, Ovarian Function and Gut Microbiota of Laying Hens.

Zearalenone (ZEN) is a ubiquitous contaminant in poultry feed, since ZEN and its metabolites can interfere with estrogen function and affect the reproductive ability of animals. The estrogen-like effect of ZEN on mammal is widely reported, while little information is available, regarding the effect of relatively low dose of ZEN on estrogen function and production performance of laying hens, and the relationship between them. This work was aimed to investigate the effects of ZEN on the production performance, egg quality, ovarian function and gut microbiota of laying hens. A total of 96 Hy-line brown laying hens aged 25-week were randomly divided into 3 groups including basal diet group (BD group), basal diet supplemented with 250 µg/kg (250 µg/kg ZEN group) and 750 µg/kg (750 µg/kg ZEN group) ZEN group. Here, 750 µg/kg ZEN resulted in a significant increase in the feed conversion ratio (FCR) (g feed/g egg) (p < 0.05), a decrease in the egg production (p > 0.05), albumen height and Haugh unit (p > 0.05), compared to the BD group. The serum Follicle-stimulating hormone (FSH) levels significantly decreased in ZEN supplemented groups (p < 0.05). Serum Luteinizing hormone (LH) and Progesterone (P) levels in the 750 µg/kg ZEN group were significantly lower than those in the BD group (p < 0.05). 16S rRNA sequencing indicated that ZEN reduced cecum microbial diversity (p < 0.05) and altered gut microbiota composition. In contrast to 250 µg/kg ZEN, 750 µg/kg ZEN had more dramatic effects on the gut microbiota function. Spearman's correlation analysis revealed negative correlations between the dominant bacteria of the 750 µg/kg ZEN group and the production performance, egg quality and ovarian function of hens. Overall, ZEN was shown to exert a detrimental effect on production performance, egg quality and ovarian function of laying hens in this study. Moreover, alterations in the composition and function of the gut microbiota induced by ZEN may be involved in the adverse effects of ZEN on laying hens.

Vasicine alleviates 2,4-dinitrochlorobenzene-induced atopic dermatitis and passive cutaneous anaphylaxis in BALB/c mice.

Atopic dermatitis (AD), a type of skin inflammation, is associated with immune response mediated by T-helper 2 (Th2) cells, and mast cells. Vasicine is an alkaloid isolated from Adhatoda vasica, a popular Ayurvedic herbal medicine used for treating inflammatory conditions. In the present study, the anti-AD effects of vasicine were evaluated on 2,4-dinitrochlorobenzene-induced AD-like skin lesions in BALB/c mice. The potential anti-allergic effects of vasicine were also assessed using the passive cutaneous anaphylaxis (PCA) test. The results showed that the oral administration of vasicine improved the severity of AD-like lesional skin by decreasing histopathological changes and restoring epidermal thickness. Vasicine also inhibited the infiltration of mast cells in the skin and reduced the levels of pro-Th2 and Th2 cytokines as well as immunoglobulin E in the serum. Finally, vasicine inhibited the expression of pro-Th2 and Th2 cytokines in skin tissues, indicating the therapeutic potential of vasicine for AD.

Citrus depressa Hayata peel ameliorates nonalcoholic fatty liver and modulates the activity of hepatic drug-metabolizing enzymes and transporters in rats fed a high-fat diet.

Citrus depressa Hayata is a small, green citrus fruit native to Taiwan and Japan. Citrus peel contains polymethoxylated flavones, including nobiletin and tangeretin, and may exhibit strong antioxidant and anti-inflammatory activities. A preliminary study revealed that Citrus depressa Hayata peel (CDHP) ethanolic extract reduced fat accumulation and the concentration of reactive oxygen species in human HepG2 cells exposed to oleic acid. The effects of CDHP on the activity of hepatic drug-metabolizing enzymes and membrane transporters in high-fat (HF) diet-induced fatty liver were investigated. Male rats were fed a low-fat diet, a HF diet, and a HF diet containing 4% CDHP for 11 weeks. The low-fat and HF diet respectively contained 13.5% and 38.1% of daily total calories from dietary fat. CDHP supplementation reduced the HF diet-induced accumulation of triglycerides in the liver and lowered hepatic fatty acid synthase activity. Higher faecal excretions of cholesterol, triglycerides, and total bile acids were observed after CDHP treatment. CDHP lowered the HF diet-induced increase in the mRNA expressions of nuclear factor erythroid 2-related factor 2, aryl hydrocarbon receptor, pregnane X receptor, and peroxisome proliferator-activated receptor-α and the activities of cytochrome P-450 (CYP)1A1, 1A2, 2B, and 2E1. However, increased hepatic CYP3A activity was observed in rats fed the HF diet containing CDHP. A higher hepatic multidrug resistance-associated protein 2 level was observed after CDHP treatment. After CDHP administration (1 g per kg body weight) for 1 h, nobiletin was found in plasma and various tissues and was abundant in the liver. An in vitro study revealed that the activity of various CYP enzymes in liver microsomes was inhibited by CDHP ethanolic extract and nobiletin, with IC50 values ranging from 18.5 to 54.4 µg ml-1 and from 13.0 to 33.2 µM, respectively. The results of this study suggest that CDHP might reduce hepatic steatosis and alter drug-metabolizing enzymes and transporters in HF diet-induced nonalcoholic fatty liver diseases.

Integrated Metabolomic and Transcriptomic Analysis Reveals Differential Mechanism of Flavonoid Biosynthesis in Two Cultivars of Angelica sinensis.

Angelica sinensis is a traditional Chinese medicinal plant that has been primarily used as a blood tonic. It largely relies on its bioactive metabolites, which include ferulic acid, volatile oils, polysaccharides and flavonoids. In order to improve the yield and quality of A. sinensis, the two cultivars Mingui 1 (M1), with a purple stem, and Mingui 2 (M2), with a green stem, have been selected in the field. Although a higher root yield and ferulic acid content in M1 than M2 has been observed, the differences of flavonoid biosynthesis and stem-color formation are still limited. In this study, the contents of flavonoids and anthocyanins were determined by spectrophotometer, the differences of flavonoids and transcripts in M1 and M2 were conducted by metabolomic and transcriptomic analysis, and the expression level of candidate genes was validated by qRT-PCR. The results showed that the contents of flavonoids and anthocyanins were 1.5- and 2.6-fold greater in M1 than M2, respectively. A total of 26 differentially accumulated flavonoids (DAFs) with 19 up-regulated (UR) and seven down-regulated (DR) were obtained from the 131 identified flavonoids (e.g., flavonols, flavonoid, isoflavones, and anthocyanins) in M1 vs. M2. A total 2210 differentially expressed genes (DEGs) were obtained from the 34,528 full-length isoforms in M1 vs. M2, and 29 DEGs with 24 UR and 5 DR were identified to be involved in flavonoid biosynthesis, with 25 genes (e.g., CHS1, CHI3, F3H, DFR, ANS, CYPs and UGTs) mapped on the flavonoid biosynthetic pathway and four genes (e.g., RL1, RL6, MYB90 and MYB114) belonging to transcription factors. The differential accumulation level of flavonoids is coherent with the expression level of candidate genes. Finally, the network of DAFs regulated by DEGs was proposed. These findings will provide references for flavonoid production and cultivars selection of A. sinensis.

Cool Temperature Enhances Growth, Ferulic Acid and Flavonoid Biosynthesis While Inhibiting Polysaccharide Biosynthesis in Angelica sinensis.

Angelica sinensis, a perennial herb that produces ferulic acid and phthalides for the treatment of cardio-cerebrovascular diseases, prefers growing at an altitude of 1800-3000 m. Geographical models have predicted that high altitude, cool temperature and sunshade play determining roles in geo-authentic formation. Although the roles of altitude and light in yield and quality have been investigated, the role of temperature in regulating growth, metabolites biosynthesis and gene expression is still unclear. In this study, growth characteristics, metabolites contents and related genes expression were investigated by exposing A. sinensis to cooler (15 °C) and normal temperatures (22 °C). The results showed that plant biomass, the contents of ferulic acid and flavonoids and the expression levels of genes related to the biosynthesis of ferulic acid (PAL1, 4CLL4, 4CLL9, C3H, HCT, CCOAMT and CCR) and flavonoids (CHS and CHI) were enhanced at 15 °C compared to 22 °C. The contents of ligustilide and volatile oils exhibited slight increases, while polysaccharide contents decreased in response to cooler temperature. Based on gene expression levels, ferulic acid biosynthesis probably depends on the CCOAMT pathway and not the COMT pathway. It can be concluded that cool temperature enhances plant growth, ferulic acid and flavonoid accumulation but inhibits polysaccharide biosynthesis in A. sinensis. These findings authenticate that cool temperature plays a determining role in the formation of geo-authentic and also provide a strong foundation for regulating metabolites production of A. sinensis.

Shenqi Fuzheng Injection () Combined with Chemotherapy for Acute Leukemia: A Meta-Analysis.

OBJECTIVE: To evaluate to the efficacy and safety of Shenqi Fuzheng Injection (, SFI) combined with chemotherapy in the treatment of acute leukemia (AL) by meta-analysis. METHODS: PubMed, Cochrane library, Embase, SinoMed, China National Knowledge Infrastructure (CNKI), VIP Journal Integration Platform, Wanfang Database were searched from establishment to November 1, 2018. The randomized controlled trials (RCTs) of SFI combined with chemotherapy in the treatment of AL were included. The Cochrane risk assessment form (RevMan 5.1) was used to evaluate the quality of included studies. RESULTS: A total of 14 RCTs and 1,088 patients was included. The quality evaluation were mostly low risk or unclear. Meta-analysis showed that compared with chemotherapy alone, SFI combined with chemotherapy can improve the total clinical effective rate in patients with AL (RR=1.15, 95% CI: 1.056-1.177; P=0.0001), and relieve adverse reactions caused by chemotherapy drugs, including infection (RR=0.561, 95% CI: 0.397-0.792; P=0.001), nausea and vomiting (RR=0.662, 95% CI: 0.524-0.835; P=0.001), bleeding (RR=0.548, 95% CI: 0.39-0.768; P=0.0001), cardiotoxicity (RR=0.230, 95% CI: 0.080-0.660; P=0.006) and hyperhidrosis (RR=0.348, 95% CI: 0.208-0.581; P=0.0001). The incidence rates of adverse reactions in SFI combined with chemotherapy group were significantly lower than that of the chemotherapy alone group (P<0.01). CONCLUSIONS: Shenqi Fuzheng Injection combined with chemotherapy has good efficacy and safety for AL, and it can alleviate the adverse reactions caused by chemotherapy. However, subject to the limitations of the methodological quality of the literature, the conclusions of this study need to be further verified by large-scale and multi-center RCTs.

Cinnamic acid inhibits cell viability, invasion, and glycolysis in primary endometrial stromal cells by suppressing NF-κB-induced transcription of PKM2.

BACKGROUND:   Endometriosis is a painful disorder characterized by the growth of endometrial tissue outside the uterine cavity. Here, we investigated the effects of the cinnamic acid isolated from the Chinese medicinal plant Cinnamomum cassia Presl on primary endometrial stromal cells. METHODS:   Immunohistochemistry was used to examine protein expression and cell purity. Quantitative RT-PCR was conducted to assess mRNA expression, and Western blot was performed to determine protein level. Cell viability was assessed using cell counting kit-8 (CCK-8) assay. Glycolysis and mitochondrial function were evaluated by measuring the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR) of cells, respectively. Lastly, plasmid transfection and inhibitor treatment were used for overexpression and inhibition studies. RESULTS: Cinnamic acid inhibited cell viability and cell invasion, as well as decreased ECAR and OCR, in primary endometrial stromal cells. Cinnamic acid suppressed the effects of PKM2 overexpression, and inhibition of PKM2 using Compound 3k mimicked the effects of cinnamic acid. Treatment with Compound 3k and cinnamic acid did not lead to additive effects, but rather displayed effects similar to those of Compound 3k alone, suggesting that cinnamic acid elicits its effects on primary endometrial stromal cells by targeting PKM2. CONCLUSIONS:   Our study identified cinnamic acid as a novel compound from Cinnamomum cassia Presl that displays potent effects on primary endometrial stromal cell viability, invasion, and glycolysis, suggesting its potential use for endometriosis treatment.

Chinese pediatric Tuina on children with acute diarrhea: a randomized sham-controlled trial.

BACKGROUND: Pediatric Tuina has been widely used in children with acute diarrhea in China. However, due to the lack of high-quality clinical evidence, the benefit of Tuina as a therapy is not clear. We aimed to assess the effect of pediatric Tuina compared with sham Tuina as an add-on therapy in addition to usual care for 0-6-year-old children with acute diarrhea. METHODS: Eighty-six participants aged 0-6 years with acute diarrhea were randomized to receive pediatric Tuina plus usual care (n = 43) or sham Tuina plus usual care (n = 43). The primary outcomes were days of diarrhea from baseline and times of diarrhea on day 3. Secondary outcomes included a global change rating (GCR) and the number of days when the stool characteristics returned to normal. Adverse events were assessed. RESULTS: Pediatric Tuina was associated with a reduction in times of diarrhea on day 3 compared with sham Tuina in both ITT (crude RR, 0.73 [95% CI, 0.59-0.91]) and PP analyses (crude RR, 0.66 [95% CI, 0.53-0.83]). However, the results were not significant when we adjusted for social demographic and clinical characteristics. No significant difference was found between groups in days of diarrhea, global change rating, or number of days when the stool characteristics returned to normal. CONCLUSIONS: In children aged 0-6 years with acute diarrhea, pediatric Tuina showed significant effects in terms of reducing times of diarrhea compared with sham Tuina. Studies with larger sample sizes and adjusted trial designs are warranted to further evaluate the effect of pediatric Tuina therapy. TRIAL REGISTRATION: Clinicaltrials.gov, Identifier: NCT03005821 , Data of registration: 2016-12-29.

Qing-Yu-Mu, an Herbal Formula, Reduces Hepatic Oxidative Stress in Rats Fed a High-Frying Oil Diet and Ameliorates Carbon Tetrachloride-Induced Liver Injury.

Qing-Yu-Mu (QYM) is an herbal formula used to prevent and treat liver disease in Taiwan. In this study, the hepatoprotective effects of QYM were evaluated in two experimental models. First, rats were fed a high-frying oil (FO) diet containing 1.25% QYM for 5 weeks to investigate effects of QYM on hepatic oxidative stress and antioxidant enzyme activities. Then, protective effects of QYM on carbon tetrachloride (CCl4)-induced chronic liver injury were evaluated. Results show that QYM treatment reduced FO diet-induced hepatic lipid peroxidation and reactive oxygen species levels and increased glutathione (GSH) S-transferase activity. A higher reduced GSH/oxidized GSH (GSSG) ratio was observed after QYM treatment. Furthermore, QYM ameliorated CCl4-induced liver injury by reducing the activity of plasma alanine aminotransferase and histological lesions in the liver. QYM also increased the level of hepatic GSH and activities of GSH peroxidase and superoxide dismutase. Finally, chlorogenic acid, chrysophanol, and apigenin were found to be present in relative abundance in QYM. Results show that QYM may exhibit a hepatoprotective effect by reducing oxidative stress and increasing antioxidant activity in the liver.

A Diterpenoid, 14-Deoxy-11, 12-Didehydroandrographolide, in Andrographis paniculata Reduces Steatohepatitis and Liver Injury in Mice Fed a High-Fat and High-Cholesterol Diet.

14-Deoxy-11,12-didehydroandrographolide (deAND), a diterpenoid in Andrographis paniculata (Burm. f.) Nees, acts as a bioactive phytonutrient that can treat many diseases. To investigate the protective effects of deAND on reducing fatty liver disease, male mice were fed a high-fat and high-cholesterol (HFHC) diet without or with 0.05% and 0.1% deAND supplementation. Cholesterol accumulation, antioxidant, and anti-inflammatory activities in liver and liver injury were evaluated after deAND treatment. The results show that deAND treatment for seven weeks reduced plasma alanine aminotransferase activity and lowered hepatic cholesterol accumulation, tumor nuclear factor-α, and histological lesions. The 0.1% deAND treatment reduced HFHC diet-induced apoptosis by lowering the caspase 3/pro-caspase 3 ratio. After 11 weeks of deAND treatment, increased NOD-like receptor protein 3 (NLRP3), capase-1, and interleukin-1ß protein levels in liver were suppressed by deAND treatment. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression, heme oxygenase-1 protein expression, and the activities of glutathione peroxidase and glutathione reductase were increased in mice fed the HFHC diet. However, those activities of antioxidant enzymes or proteins were also upregulated by 0.1% deAND treatment. Furthermore, deAND treatment tended to lower hepatic lipid peroxides. Finally, deAND treatment reversed the depletion of hepatic glutamate level induced by the HFHC diet. These results indicate that deAND may ameliorate HFHC diet-induced steatohepatitis and liver injury by increasing antioxidant and anti-inflammatory activities.

Chinese pediatric Tuina on children with acute diarrhea: study protocol for a randomized sham-controlled trial.

BACKGROUND: Acute pediatric diarrhea is one of the most common causes of morbidity and mortality worldwide and seriously affects the health of children. Previous studies have shown that pediatric Tuina, a traditional Chinese medicine therapy, has potential therapeutic benefits for acute pediatric diarrhea. However, the evidence for its effectiveness is insufficient due to the lack of high-quality clinical studies. Our aim is to evaluate the efficacy of Chinese pediatric Tuina for children aged 0-6 years with acute diarrhea. METHODS/DESIGN: This study is a randomized, double-blind, sham-controlled trial. We will include 122 children with acute diarrhea from Dongguan Kanghua Hospital in Guangdong province, China. The patients will be allocated into either the pediatric Tuina group or the sham Tuina group in a 1:1 ratio. The treatment will last for 3 days followed by an 11-day follow-up period. Both groups will receive usual care. In addition, the experimental group will receive 15-25 min of Chinese pediatric Tuina, while the control group will receive 15-25 min of sham pediatric Tuina. Both groups will receive treatments once per day, for 3 consecutive days. Primary outcome measures are diarrhea days from baseline and diarrhea times on the third day. Secondary outcome measures are the global change rating and period of days when the stool character changes to normal. Safety assessments will be monitored during each visit. DISCUSSION: This clinical trial is designed to evaluate the efficacy of pediatric Tuina for children with acute diarrhea. We expect results to provide solid evidence and support for pediatric Tuina as an appropriate treatment for children with acute diarrhea. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03005821. Registered on 29 December 2016.

Food-Drug Interaction between the Adlay Bran Oil and Drugs in Rats.

Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) contains various phytonutrients for treating many diseases in Asia. To investigate whether orally administered adlay bran oil (ABO) can cause drug interactions, the effects of ABO on the pharmacokinetics of five cytochrome P450 (CYP) probe drugs were evaluated. Rats were given a single oral dose (2.5 mL/kg BW) of ABO 1 h before administration of a drug cocktail either orally or intravenously, and blood was collected at various time points. A single oral dose of ABO administration did not affect the pharmacokinetics of five probe drugs when given as a drug cocktail intravenously. However, ABO increased plasma theophylline (+28.4%), dextromethorphan (+48.7%), and diltiazem (+46.7%) when co-administered an oral drug cocktail. After 7 days of feeding with an ABO-containing diet, plasma concentrations of theophylline (+45.4%) and chlorzoxazone (+53.6%) were increased after the oral administration of the drug cocktail. The major CYP enzyme activities in the liver and intestinal tract were not affected by ABO treatment. Results from this study indicate that a single oral dose or short-term administration of ABO may increase plasma drug concentrations when ABO is given concomitantly with drugs. ABO is likely to enhance intestinal drug absorption. Therefore, caution is needed to avoid food-drug interactions between ABO and co-administered drugs.

[Effect of traditional Chinese medicine syndrome differentiation and standard bundle therapy in patients with septic shock].

OBJECTIVE: To evaluate an effective and feasible quantitative evaluation table of traditional Chinese medicine (TCM) syndrome differentiation, and to observe the effect of combination of TCM syndrome differentiation and standard bundle therapy in patients with septic shock. METHODS: A prospective randomized controlled trial was conducted. The septic shock patients with acute deficiency syndrome admitted to department of critical care medicine of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 1st, 2016 to December 31st, 2017 were enrolled. The patients were randomly divided into control group and Shenfu group. The patients in both groups received early application of standardized bundle therapy; those in Shenfu group received 60 mL Shenfu injection infusion in addition for 7 days. The TCM syndrome score was evaluated by classification and scoring method of TCM symptoms. The circulation and tissue perfusion, severity of disease, organ function, inflammation response, adjuvant treatment and 28-day mortality were compared between the two groups. RESULTS: A total of 50 patients with septic shock were enrolled in the analysis, 25 in control group and 25 in Shenfu group. The markedly effective rate of TCM symptoms score in Shenfu group was significantly higher than that in control group [60.0% (15/25) vs. 16.0% (4/25), P < 0.01]. There was no significant difference in all parameters before treatment between the two groups. After treatment, the observation indexes of both groups were improved. Compared with control group, the mean arterial pressure (MAP) in Shenfu group increased more significantly [mmHg (1 mmHg = 0.133 kPa): 13.0 (2.5, 28.5) vs. 6.0 (0, 13.5)], the lactate (Lac) and procalcitonin (PCT) decreased more significantly [Lac (mmol/L): 0.8 (0.1, 3.7) vs. 0.5 (-0.6, 1.7), PCT (µg/L): 2.0 (0.7, 32.3) vs. 0 (-1.8, 3.8)], activated partial thromboplastin time (APTT) was shortened more significantly [s: 8.5 (0, 12.9) vs. 0 (-7.2, 10.0)], and interleukins (IL-2 receptor and IL-6) levels decreased more significantly [IL-2 receptor (ng/L): 1 031.0 (533.0, 1 840.0) vs. 525.5 (186.0, 1 166.8), IL-6 (ng/L): 153.1 (21.4, 406.8) vs. 35.1 (16.3, 110.1)] with significant differences (all P < 0.05). There was no significant difference in the use time of vasoactive drugs, duration of mechanical ventilation, severity of the disease or 28-day mortality between the two groups. However, the use time of vasoactive drugs in Shenfu group was shorter than that in control group (days: 5.48±4.81 vs. 8.28±7.83), and the 28-day mortality was decreased [8.0% (2/25) vs. 20.0% (5/25)]. CONCLUSIONS: TCM syndrome score is helpful to evaluate the effect of TCM syndrome differentiation and treatment, and it is effective and feasible in clinical application. Septic shock patients treated with TCM syndrome differentiation and treatment combined with standard bundle therapy were significantly improved in circulation, tissue perfusion, coagulation function and inflammation reaction.