Associations between artificial sweetener intake from cereals, coffee, and tea and the risk of type 2 diabetes mellitus: A genetic correlation, mediation, and mendelian randomization analysis.

BACKGROUND: Previous studies have emphasized the association between the intake of artificial sweeteners (AS) and type 2 diabetes mellitus (T2DM), but the causative relationship remains ambiguous. METHODS: This study employed univariate Mendelian randomization (MR) analysis to assess the causal link between AS intake from various sources and T2DM. Linkage disequilibrium score (LDSC) regression was used to evaluate the correlation between phenotypes. Multivariate and mediation MR were applied to investigate confounding factors and mediating effects. Data on AS intake from different sources (N = 64,949) were sourced from the UK Biobank, while T2DM data were derived from the DIAbetes Genetics Replication And Meta-analysis.The primary method adopted was inverse variance weighted (IVW), complemented by three validation techniques. Additionally, a series of sensitivity analyses were performed to evaluate pleiotropy and heterogeneity. RESULTS: LDSC analysis unveiled a significant genetic correlation between AS intake from different sources and T2DM (rg range: -0.006 to 0.15, all P < 0.05). After correction by the false discovery rate (FDR), the primary IVW method indicated that AS intake in coffee was a risk factor for T2DM (OR = 1.265, 95% CI: 1.035-1.545, P = 0.021, PFDR = 0.042). Further multivariable and mediation MR analyses pinpointed high density lipoprotein-cholesterol (HDL-C) as mediating a portion of this causal relationship. In reverse MR analysis, significant evidence suggested a positive correlation between T2DM and AS intake in coffee (ß = 0.013, 95% CI: 0.004-0.022, P = 0.004, PFDR = 0.012), cereal (ß = 0.007, 95% CI: 0.002-0.012, P = 0.004, PFDR = 0.012), and tea (ß = 0.009, 95% CI: 0.001-0.017, P = 0.036, PFDR = 0.049). No other causal associations were identified (P > 0.05, PFDR > 0.05). CONCLUSION: The MR analysis has established a causal relationship between AS intake in coffee and T2DM. The mediation by HDL-C emphasizes potential metabolic pathways underpinning these relationships.

Cadmium negatively affects the growth and physiological status and the alleviation effects by exogenous selenium in silage maize (Zea mays L.).

Increasing soil cadmium (Cd) contamination is a serious threat to human food health and safety. In order to reduce Cd uptake and Cd toxicity in silage maize, hydroponic tests were conducted to investigate the effect of exogenous Cd on the toxicity of silage maize in this study. In the study, a combination of Cd (5, 20, 50, 80, and 10 µM) treatments was applied in a hydroponic system. With increasing Cd concentration, Cd significantly inhibited the total root length (RL), root surface area (SA), root volume (RV), root tip number (RT), and branching number (RF) of maize seedlings, which were reduced by 28.1 to 71.3%, 20.2 to 64.9%, 11.2 to 56.5%, 43.7 to 63.4%, and 38.2 to 72.6%, respectively. The excessive Cd accumulation inhibited biomass accumulation and reduced silage maize growth, photosynthesis, and chlorophyll content and activated the antioxidant systems, including increasing lipid peroxidation and stimulating catalase (CAT) and peroxidase (POD), but reduced the activity of superoxide dismutase (SOD) and ascorbate peroxidase (APX) in the root. Besides, selenium (Se) significantly decreased the Cd concentration of the shoot and root by 27.1% and 35.1% under Cd50, respectively. Our results reveal that exogenously applied Cd reduced silage maize growth and impaired photosynthesis. Whereas silage maize can tolerate Cd by increasing the concentration of ascorbate and glutathione and activating the antioxidant defense system, the application of exogenous selenium significantly reduced the content of Cd in silage maize.

Holistic Assessment Based On Hepatocyte Mitochondria: Lycopene Repairs Oxidized mtDNA to Alleviate Mitochondrial Stress Induced by Atrazine.

Atrazine (ATZ) is a highly persistent herbicide that harms organism health. Lycopene (LYC) is an antioxidant found in plants and fruits. The aim of this study is to investigate the mechanisms of atrazine-induced mitochondrial damage and lycopene antagonism in the liver. The mice were divided into seven groups by randomization: blank control (Con group), vehicle control (Vcon group), 5 mg/kg lycopene (LYC group), 50 mg/kg atrazine (ATZ1 group), ATZ1+LYC group, 200 mg/kg atrazine (ATZ2 group), and ATZ2+LYC group. The present study performed a holistic assessment based on mitochondria to show that ATZ causes the excessive fission of mitochondria and disrupts mitochondrial biogenesis. However, the LYC supplementation reverses these changes. ATZ causes increased mitophagy and exacerbates the production of oxidized mitochondrial DNA (Ox-mtDNA) and mitochondrial stress. This study reveals that LYC could act as an antioxidant to repair Ox-mtDNA and restore the disordered mitochondrial function caused by ATZ.

Sanguinarine Improves Intestinal Health in Grass Carp Fed High-Fat Diets: Involvement of Antioxidant, Physical and Immune Barrier, and Intestinal Microbiota.

An eight-week trial was conducted to investigate the effects of sanguinarine supplementation (600 µg and 1200 µg/kg) in high-fat (crude fat: 10%) diets (HF) on the intestinal physiological function of Ctenopharyngodon idellus (initial weight 50.21 ± 0.68 g), based on a basic diet (5% crude fat, CON), which were named HFLS and HFHS, respectively. The results showed that the HF diet significantly impaired the intestinal immune and physical barrier function, and disrupted the balance of the intestinal microbiota in grass carp. Compared to the HF diet, sanguinarine supplementation significantly improved the levels of serum C4, C3, AKP, IgA, and IgM, and enhanced the intestinal antioxidant capacity (gr, CuZnsod, gpx4, cat, gsto, and nrf2 expression were significantly up-regulated). Sanguinarine significantly down-regulated the expression of claudin-15 and up-regulated the expression of claudin-b, claudin-c, occludin, and zo-1 by inhibiting MLCK signaling molecules. Additionally, sanguinarine significantly down-regulated the expression of il-6, il-1ß, and tnf-α and up-regulated the expression of il-10, tgf-ß2, and tgf-ß1 by inhibiting NF-κB signaling molecules, thereby alleviating intestinal inflammation caused by HF diets. Furthermore, compared to the HF diet, the abundance of Fusobacterium and Cetobacterium in the HFHS diet increased significantly, while the abundance of Firmicutes and Streptococcus showed the opposite trend. In conclusion, the HF diet had a negative impact on grass carp, while sanguinarine supplementation enhanced intestinal antioxidant ability, alleviated intestinal barrier damage, and ameliorated the homeostasis of the intestinal microbiota.

Astragaloside IV-mediated inhibition of oxidative stress by upregulation of ghrelin in type 2 diabetes-induced cognitive impairment.

This study is to observe the upregulation effect of astragaloside IV on ghrelin in diabetic cognitive impairment (DCI) rats and to investigate the pathway in prevention and treatment by reducing oxidative stress. The DCI model was induced with streptozotocin (STZ) in conjunction with a high-fat and high-sugar diet and divided into three groups: model, low-dose (40 mg/kg), and high-dose (80 mg/kg) astragaloside IV. After 30 days of gavage, the learning and memory abilities of rats, as well as their body weight and blood glucose levels, were tested using the Morris water maze and then detection of insulin resistance, SOD activity, and serum MDA levels. The whole brain of rats was sampled for hematoxylin-eosin and Nissl staining to observe pathological changes in the hippocampal CA1 region. Immunohistochemistry was used to detect ghrelin expression in the hippocampal CA1 region. A Western blot was used to determine changes in GHS-R1α/AMPK/PGC-1α/UCP2. RT-qPCR was used to determine the levels of ghrelin mRNA. Astragaloside IV reduced nerve damage, increased superoxide dismutase (SOD) activity, decreased MDA levels, and improved insulin resistance. Ghrelin levels and expression increased in serum and hippocampal tissues, and ghrelin mRNA levels increased in rat stomach tissues. According to Western blot, it increased the expression of the ghrelin receptor GHS-R1α and upregulated the mitochondrial function associated-protein AMPK-PGC-1α-UCP2. Astragaloside IV increases ghrelin expression in the brain to reduce oxidative stress and delay diabetes-induced cognitive impairment. It may be related to the promotion of ghrelin mRNA levels.

Protective effects of chlorogenic acid on growth, intestinal inflammation, hepatic antioxidant capacity, muscle development and skin color in channel catfish Ictalurus punctatus fed an oxidized fish oil diet.

Under oxidative stress condition, the protective effects of dietary chlorogenic acid (CGA) supplementation on liver antioxidant capacity, intestinal inflammation and barrier function, muscle development and skin coloration in channel catfish Ictalurus punctatus were explored in the current study. With that purpose, I. punctatus were fed five experimental diets containing 2% fresh fish oil (FFO, 9.2 meqO2/kg) or 2% oxidized fish oil (OFO, 897.4 meqO2/kg) without or with CGA supplementation (0.02%, 0.04% and 0.08%) for 8 weeks. Upon comparative analysis, the oxidized fish oil consumption significantly lowered weight gain rate, decreased intestinal villi length and muscular thickness values and the tight junction proteins mRNA abundance, augmented the intestinal proinflammatory factors, attenuated hepatic antioxidant enzymes activities and related genes mRNA expression levels, influenced the myogenic regulatory factors expression profile and impacted the myocyte density, myocyte area values as well as the skin pigments contents compared to the FFO treatment. Collectively, long-term feeding of the oxidized fish oil diet suppressed the growth performance, destroyed intestinal structural integrity, caused intestinal inflammation and hepatic oxidative stress, impacted the skeletal development and skin color of I. punctatus. Whereas CGA supplementation in oxidized fish oil diets partially counteracted the negative effects of the oxidized fish oil on I. punctatus in terms of increasing the growth performance, improving the intestinal mucosal structure, alleviating hepatic oxidative stress and intestinal inflammation, recompiling the myogenic regulatory factors expression and improving skin color. In conclusion, CGA has great potential to be an aquatic feed additive.

Biotransformation of the saponins in Panax notoginseng leaves mediated by gut microbiota from insomniac patients.

Saponins extracted from Panax notoginseng leaves by methanol or water could be orally administrated for insomnia with very low bioavailability, which might be bio-converted by gut microbiota to generate potential bioactive products. Moreover, gut microbiota profiles from insomniac patients are very different from healthy subjects. We aimed to compare the metabolic characteristics and profiles of the two saponins extract by incubation with gut microbiota from insomniac patients. The ginsenosides, notoginsenosides, and metabolites were identified and relatively quantified by high-performance liquid chromatography-tandem mass spectrometry. Gut microbiota was profiled by 16S ribosomal RNA gene sequencing. The results showed that saponins were very different between methanol or water extract groups, which were metabolized by gut microbiota to generate similar yields. The main metabolites included ginsenoside Rd, ginsenoside F2 , ginsenoside C-Mc or ginsenoside C-Y, ginsenoside C-Mx, ginsenoside compound K, and protopanaxadiol in both groups, while gypenoside XVII, notoginsenoside Fe, ginsenoside Rd2 , and notoginsenoside Fd were the intermediates in the methanol group. Moreover, the microbial, Faecalibacterium prausnitzi, could bio-convert the saponins to obtain the corresponding metabolites. Our study implied that saponins extracted from P. notoginseng leaves by methanol or water could be used for insomniac patients due to gut microbiota biotransformation.

[Research progress of Angelicae Sinensis Radix and predictive analysis on its quality markers].

Angelicae Sinensis Radix, as a medicinal and edible Chinese medicinal herb, is widely used in clinical practice. It is mainly cultivated in Minxian, Tanchang, Zhangxian and Weiyuan counties of Gansu province. In recent years, with the comprehensive and in-depth study of Angelicae Sinensis Radix in China and abroad, its chemical composition, pharmacological effects and application and development have attracted much attention. In this study, the chemical composition, traditional efficacy, and modern pharmacological effects of Angelicae Sinensis Radix were summarized. On this basis, combined with the core concept of quality markers(Q-markers), the Q-markers of Angelicae Sinensis Radix were discussed from the aspects of mass transfer and traceability and chemical composition specificity, availability, and measurability, which provided scientific basis for the quality evaluation of Angelicae Sinensis Radix.

Efficacy and safety of triple therapy containing berberine hydrochloride, amoxicillin, and rabeprazole in the eradication of Helicobacter pylori.

OBJECTIVE: To estimate the effectiveness and safety of triple therapy containing berberine, amoxicillin, and rabeprazole in the eradication of Helicobacter pylori (H. pylori). METHODS: This prospective, randomized controlled, open-label, noninferiority trial included treatment-naive patients with H. pylori infection who were randomly allocated at a ratio of 1:1 into the berberine triple therapy group (berberine hydrochloride 300 mg thrice daily, amoxicillin 1 g twice daily, and rabeprazole 10 mg twice daily) or standard bismuth-containing quadruple therapy group (amoxicillin 1 g twice daily, rabeprazole 10 mg twice daily, clarithromycin 500 mg twice daily, and bismuth tartrate 200 mg twice daily) for 14 days. Negative 13 C/14 C-urea breath test at 4 weeks after completion of the therapy was regarded as successful eradication. RESULTS: Altogether 262 and 262 patients received berberine triple therapy and bismuth-containing quadruple therapy, respectively. Both intention-to-treat (79.8% vs 80.9%, P = 0.742) and per-protocol analyses (83.6% and 85.1%, P = 0.636) showed comparable eradication rate between the two groups, indicating a noninferior eradication rate (the lower limit of the 95% confidence interval over -10% [-7.9% and -7.87%, respectively]). Adverse events more commonly occurred in the bismuth-containing quadruple-therapy group (8.8% vs 16.0%, P = 0.012), while patient compliance and symptom improvement of the two regimens were comparable. CONCLUSION: Triple therapy containing berberine, amoxicillin and rabeprazole is noninferior to bismuth-containing quadruple therapy in the initial treatment for H. pylori eradication.

Lycopene alleviates di(2-ethylhexyl) phthalate-induced splenic injury by activating P62-Keap1-NRF2 signaling.

Di(2-ethylhexyl) phthalate (DEHP) is an omnipresent environmental pollutant. It has been determined that DEHP is involved in multiple health disorders. Lycopene (Lyc) is a natural carotenoid pigment, with anti-inflammatory and antioxidant properties. However, it is not clear whether Lyc can protect the spleen from DEHP-induced oxidative damage. A total of 140 mice were randomly divided into seven groups (n = 20) and continuously gavaged with corn oil, distilled water, DEHP (500 or 1000 mg/kg BW/day) and/or Lyc (5 mg/kg BW/day) for 28 days. Histopathological and ultrastructural results showed a DEHP-induced inflammatory response and mitochondrial injuries. Moreover, DEHP exposure induced redox imbalance, which resulted in the up-regulation of ROS activity and MDA content, and the down-regulation of T-AOC, T-SOD and CAT in the DEHP groups. Simultaneously, our results also demonstrated that DEHP-induced kelch-like ECH-associated protein 1 (Keap1) expression was downregulated, and the expression levels of P62, nuclear factor erythroid 2-related factor (NRF2) and their downstream target genes were up-regulated. However, the supplementary Lyc reverted these changes to normal levels. Together, Lyc prevented DEHP-induced splenic injuries by regulating the P62-Keap1-NRF2 signaling pathway. Hence, the protective effects of Lyc might be a therapeutic strategy to ameliorate DEHP-induced splenic damage.

[Tianma Gouteng Decoction regulates MFN2 expression to delay vascular aging in spontaneously hypertensive rats].

We studied the effect of Tianma Gouteng Decoction on vascular aging in spontaneously hypertensive rats(SHRs) to explore the molecular mechanism of the decoction in improving arterial vascular aging by regulating the expression of mitofusin 2(MFN2).Twenty 64-weeks-old SHRs were randomly assigned into the aging group and the treatment group(Tianma Gouteng Decoction 5.48 mg·kg~(-1)).Wistar-Kyoto(WKY) rats of 64 weeks old were taken as the normal group and SHR rats of 14 weeks old as the young group.The intervention with Tianma Gouteng Decoction lasted for 12 weeks.We then employed HE staining and Masson staining to observe the morphology of thoracic aorta under an electron microscope and measured the malondialdehyde(MDA) content, superoxide dismutase(SOD) activity, respiratory chain complex Ⅲ level, and thioredoxin peroxidase(TPX) activity.The vascular aging was detected via the biomarker senescence-associated beta-galactosidase(SA-ß-Gal).The expression levels of MFN2 and aging marker proteins silent information regulator 1(SIRT1), Klotho, p21, and p53 in thoracic aorta were detected by immunohistochemistry/fluorescence, qRT-PCR, and Western blot.Compared with the young group and the normal group, the aging group had risen blood pressure, lumen stenosis caused by thickened intima of blood vessels, decreased SOD and TPX activities, increased MDA and mitochondrial respiratory chain complex Ⅲ levels, down-regulated expression of MFN2, SIRT1, and Klotho, and up-regulated expression of p21 and p53(P<0.01 or P<0.05).The treatment with Tianma Gouteng Decoction significantly lowered blood pressure, mitigated vascular intimal thickening, increased SOD and TPX activities, and decreased MDA and mitochondrial respiratory chain complex Ⅲ levels, thus alleviating vascular aging.At the same time, the decoction up-regulated the expression of MFN2, SIRT1, and Klotho, while down-regulated that of p21 and p53(P<0.01 or P<0.05).In summary, Tianma Gouteng Decoction can significantly delay the vascular aging in hypertension.Specifically, it may up-regulate the expression of MFN2 and regulate the expression of aging-related proteins to alleviate oxidative stress.

A Functional Screening Identifies a New Organic Selenium Compound Targeting Cancer Stem Cells: Role of c-Myc Transcription Activity Inhibition in Liver Cancer.

Cancer stem cells (CSCs) are reported to play essential roles in chemoresistance and metastasis. Pathways regulating CSC self-renewal and proliferation, such as Hedgehog, Notch, Wnt/ß-catenin, TGF-ß, and Myc, may be potential therapeutic targets. Here, a functional screening from the focused library with 365 compounds is performed by a step-by-step strategy. Among these candidate molecules, phenyl-2-pyrimidinyl ketone 4-allyl-3-amino selenourea (CU27) is chosen for further identification because it proves to be the most effective compound over others on CSC inhibition. Through ingenuity pathway analysis, it is shown CU27 may inhibit CSC through a well-known stemness-related transcription factor c-Myc. Gene set enrichment analysis, dual-luciferase reporter assays, expression levels of typical c-Myc targets, molecular docking, surface plasmon resonance, immunoprecipitation, and chromatin immunoprecipitation are conducted. These results together suggest CU27 binds c-Myc bHLH/LZ domains, inhibits c-Myc-Max complex formation, and prevents its occupancy on target gene promoters. In mouse models, CU27 significantly sensitizes sorafenib-resistant tumor to sorafenib, reduces the primary tumor size, and inhibits CSC generation, showing a dramatic anti-metastasis potential. Taken together, CU27 exerts inhibitory effects on CSC and CSC-associated traits in hepatocellular carcinoma (HCC) via c-Myc transcription activity inhibition. CU27 may be a promising therapeutic to treat sorafenib-resistant HCC.

The natural product berberine synergizes with osimertinib preferentially against MET-amplified osimertinib-resistant lung cancer via direct MET inhibition.

Berberine is a natural product that has long been used in traditional Chinese medicine due to its antimicrobial, anti-inflammatory and metabolism-regulatory properties. Osimertinib is the first third-generation EGFR-tyrosine kinase inhibitor (TKI) approved for the treatment of non-small cell lung cancer (NSCLC) with activating EGFR mutations and those resistant to earlier generation EGFR-TKIs due to a T790M mutation. However, emergence of acquired resistance to osimertinib limits its long-term efficacy in the clinic. One known mechanism of acquired resistance to osimertinib and other EGFR-TKIs is MET (c-MET) gene amplification. Here, we report that berberine, when combined with osimertinib, synergistically and selectively decreased the survival of several MET-amplified osimertinib-resistant EGFR mutant NSCLC cell lines with enhanced induction of apoptosis likely through Bim elevation and Mcl-1 reduction. Importantly, this combination effectively enhanced suppressive effect on the growth of MET-amplified osimertinib-resistant xenografts in nude mice and was well tolerated. Molecular modeling showed that berberine was able to bind to the kinase domain of non-phosphorylated MET, occupy the front of the binding pocket, and interact with the activation loop, in a similar way as other known MET inhibitors do. MET kinase assay showed clear concentration-dependent inhibitory effects of berberine against MET activity, confirming its kinase inhibitory activity. These findings collectively suggest that berberine can act as a naturally-existing MET inhibitor to synergize with osimertinib in overcoming osimertinib acquired resistance caused by MET amplification.

Efficacy and safety of acupuncture combined Chinese herbal medicine for diabetic peripheral neuropathy: A protocol for systematic review and meta-analysis.

BACKGROUND: Acupuncture combined with Chinese herbal medicine has been widely utilized for pain management in patients with diabetic peripheral neuropathy (DPN). However, its results are still inconsistent, and no systematic review has specifically addressed this issue. Thus, this systematic review will comprehensively and systematically investigate the effectiveness and safety of acupuncture combined with Chinese herbal medicine for pain relief in DPN. METHODS: Randomized controlled trials on acupuncture combined with Chinese herbal medicine treatment of DPN published before September of 2021 will be searched in 9 databases including Medline, Web of Science, PubMed, Cochrane Library, Excerpta Medica Database, Sinomed, China National Knowledge Infrastructure, WanFang, and China Science and Technology Journal Database. The methodological assessment performed using the risk of bias assessment tool of Cochrane, and the level of evidence quality for the main results will be evaluated by a recommended grading, evaluation, formulation, and evaluation system approach. Bayesian network meta-analysis will be conducted using STATA V.14.0 and WinBUGS V.1.4.3. RESULTS: This study will provide a high-quality comprehensive evaluation of the safety of acupuncture combined with Chinese herbal medicine for treating DPN. CONCLUSION: This systematic review will evaluate the efficacy and safety of Chinese herbal medicine combined with acupuncture in the treatment of DPN, and provide the latest evidence for clinical application. ETHICS AND DISSEMINATION: The protocol of the systematic review does not require ethical approval because it does not involve humans. This article will be published in peer-reviewed journals and presented at relevant conferences.Registration number: INPLASY2021100004.

Traditional chinese medicine syndromes classification associates with tumor cell and microenvironment heterogeneity in colorectal cancer: a single cell RNA sequencing analysis.

BACKGROUND: Colorectal cancer (CRC) is one of the common gastrointestinal malignancies, tumor heterogeneity is the main cause of refractory CRC. Syndrome differentiation is the premise of individualized treatment of traditional Chinese medicine (TCM), but TCM syndrome lacks objective identification in CRC. This study is to investigate the correlation and significance of tumor heterogeneity and TCM syndromes classification in CRC. METHODS: In this study, we using scRNA-seq technology, investigate the significance of tumor heterogeneity in TCM syndromes classification on CRC. RESULTS: The results showed that 662 cells isolated from 11 primary CRC tumors are divided into 14 different cell clusters, and each cell subtype and its genes have different functions and signal transduction pathways, indicating significant heterogeneity. CRC tumor cell clusters have different proportions in Excess, Deficiency and Deficiency-Excess syndromes, and have their own characteristic genes, gene co-expression networks, gene functional interpretations as well as monocle functional evolution. Moreover, there were significant differences between the high expressions of MUC2, REG4, COL1A2, POSTN, SDPR, GPX1, ELF3, KRT8, KRT18, KRT19, FN1, SERPINE1, TCF4 and ZEB1 genes in Excess and Deficiency syndrome classification in CRC (P < 0.01). CONCLUSIONS: The Excess and Deficiency syndromes classification may be related to tumor heterogeneity and its microenvironment in CRC.

[Effects of natural organic soil amendments on quality of Panax notoginseng].

The effects of four natural organic soil amendments on the quality and pesticide residues of Panax notoginseng were investigated through field experiments and the suitable dosage ratio of each soil amendment was selected to provide a new idea for the pollution-free cultivation of P. notoginseng. The four natural organic soil amendments used in this study were Jishibao, Jihuo, Fudujing, and omnipotent nutrients, which were produced by mixed fermentation of aboveground parts of different plants, biological waste residue, and biochar. During the experiments, only four soil amendments were applied to P. notoginseng instead of any pesticides and fertilizers. The experiment was designed as four factors and three levels. There were three dosage gradients(low, medium, and high) for Jishibao(A), Jihuo(B), Fudujing(C), and omnipotent nutrients(D). When the dosage of one soil amendment changed, the do-sage of the other soil amendments remained medium. There were 10 groups in addition to the soil amendment-free group as control(CK). The results showed that the four soil amendments could significantly improve the growth environment of P. notoginseng and increase the seedling survival rate and saponin content of P. notoginseng. The seedling survival rates of the treatment groups increased by 8.24%-30.05% as compared with the control group. Furthermore, the content of pesticide residues in P. notoginseng was too low to be detected, and that of heavy metals in P. notoginseng was far lower than the specified content in the Chinese Pharmacopoeia(2020). The optimal effect was achieved at medium dosage for all the soil amendments with the highest content of saponins, high seedling survival rate, and significantly reduced heavy metals, such as lead, cadmium, arsenic, and mercury.

The Protective Effect of Taurine on Oxidized Fish-Oil-Induced Liver Oxidative Stress and Intestinal Barrier-Function Impairment in Juvenile Ictalurus punctatus.

Dietary lipids provide energy for growth and development and provide fatty acids necessary for normal structure and biological function. However, oxidized lipids cause oxidative stress and intestinal damage. An 8-week feeding trial with fresh fish oil (FFO, control group), oxidized fish oil (OFO), and taurine-supplemented diets (OFOT, OFO + 0.2% of taurine) was conducted to evaluate the protective effect of taurine on oxidized fish-oil-induced liver oxidative stress and intestine impairment in juvenile Ictaluruspunctatus. The results showed that (1) Growth performance was significantly lower in fish fed OFO than in those fed other diets, whereas the opposite occurred in the hepatosomatic index. (2) OFO-feeding significantly increased lipid deposition compared with the FFO group. The addition of taurine ameliorated the OFO-induced increase in lipid vacuolization in the liver, significantly upregulated lpl mRNA expression, and downregulated fas and srebp1 mRNA expression. (3) OFO-feeding significantly reduced oxidative damage of liver. Compared with the OFO group, the OFOT group remarkably upregulated antioxidant enzyme mRNA expression through the Nrf2-Keap1 signaling pathway based on the transcriptional expression. (4) OFO diets induced intestinal physical and immune barrier damage. Compared with the OFO group, OFOT diets remarkably downregulated il-1ß, il-6, tnf-α, and il-8 mRNA expression and upregulated tgf-ß mRNA expression through the NF-κB signaling pathway. Besides, the addition of taurine to OFO diets significantly upregulated zo-2 and zo-1 mRNA expression, and downregulated claudin-15 and claudin-12 mRNA expression. In conclusion, oxidized-fish-oil diets can cause negative physiological health effects in Ictaluruspunctatus, while adding taurine can increase growth and antioxidant ability, reduce lipid deposition, and improve intestinal health.

Antibiotics prescription for targeted therapy of pediatric invasive pneumococcal diseases in China: a multicenter retrospective study.

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) is a major cause of bacterial meningitis, septicemia and pneumonia in children. Inappropriate choice of antibiotic can have important adverse consequences for both the individual and the community. Here, we focused on penicillin/cefotaxime non-susceptibility of S. pneumoniae and evaluated appropriateness of targeted antibiotic therapy for children with IPD (invasive pneumococcal diseases) in China. METHODS: A multicenter retrospective study was conducted in 14 hospitals from 13 provinces in China. Antibiotics prescription, clinical features and resistance patterns of IPD cases from January 2012 to December 2017 were collected. Appropriateness of targeted antibiotics therapy was assessed. RESULTS: 806 IPD cases were collected. The non-susceptibility rates of S. pneumoniae to penicillin and cefotaxime were 40.9% and 20.7% respectively in 492 non-meningitis cases, whereas those were 73.2% and 43.0% respectively in 314 meningitis cases. Carbapenems were used in 21.3% of non-meningitis cases and 42.0% of meningitis cases for targeted therapy. For 390 non-meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were used in 17.9% and 8.7% of cases respectively for targeted therapy. For 179 meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were prescribed in 55.3% and 15.6% of cases respectively. Overall, inappropriate targeted therapies were identified in 361 (44.8%) of 806 IPD cases, including 232 (28.8%) cases with inappropriate use of carbapenems, 169 (21.0%) cases with inappropriate use of vancomycin and 62 (7.7%) cases with inappropriate use of linezolid. CONCLUSIONS: Antibiotic regimens for IPD definite therapy were often excessive with extensive prescription of carbapenems, vancomycin or linezolid in China. Antimicrobial stewardship programs should be implemented to improve antimicrobial use.

[Intradermal needling combined with heat-sensitive moxibustion for moderate to severe cancer pain].

OBJECTIVE: To observe the effect of intradermal needling combined with heat-sensitive moxibustion for moderate to severe cancer pain. METHODS: A total of 60 patients with moderate to severe cancer pain were randomly divided into an observation group and a control group，30 cases in each one. In the control group，opioids were taken to relief pain according to the three-step analgesic method of World Health Organization. On the base of the treatment as the control group, intradermal needling combined with heat-sensitive moxibustion were applied at Neiguan (PC 6), Hegu (LI 4), Zusanli (ST 36), Taichong (LR 3), etc. in the observation group, 14 days of treatment were required. The equivalent morphine consumption at the first day and whole course, the scores of cancer quality of life questionnaire-C30 (QLQ-C30) and Hamilton anxiety scale before and after treatment, and the adverse reaction rate were compared in the two groups. The total analgesic effective rate was evaluated. RESULTS: The total analgesic effective rate was 93.3% (28/30) in the observation group, higher than 73.3% (22/30) in the control group (P<0.05). The total equivalent morphine consumption in the observation group was less than the control group (P<0.05). After treatment, the QLQ-C30 scores were increased (P<0.001) and the HAMA scores were decreased (P<0.001) in the both groups, and those in the observation group were superior to the control group (P<0.001). The adverse reaction rates of fatigue, dizziness, nausea and vomiting, constipation in the observation group were lower than the control group (P<0.05). CONCLUSION: Intradermal needling combined with heat-sensitive moxibustion can reduce the dose of opioids, improve the quality of life, relief the anxiety in patients with moderate to severe cancer pain, and reduce the incidence of common adverse reaction of opioids.

Lycopene attenuates di(2-ethylhexyl) phthalate-induced mitophagy in spleen by regulating the sirtuin3-mediated pathway.

Lycopene (Lyc) has been discussed as a potential effector in the prevention and therapy of various diseases. Di(2-ethylhexyl) phthalate (DEHP) is regarded as a universal environmental pollutant. To clarify the potential protective effect of Lyc on DEHP-induced splenic injury, 140 male mice were randomized into seven groups: control (distilled water), vehicle control (corn oil per day), Lyc (5 mg per kg BW per day), DEHP (500 or 1000 mg per kg BW per day), and DEHP combined Lyc group, respectively. All experimental animals were treated by oral gavage for 28 days. The results that showed DEHP exposure significantly up-regulated the mRNA and protein expression of the sirtuin family (except SIRT4-5), PGC-1α, OPA1, Drp1, MFN1/2, NRF1, TFAM, Parkin and PINK in DEHP-treated alone groups and the SOD2 and LC3-II protein expression were also in accordance with the above changes. These were accompanied with an increase of the number of inflammatory cells and rate of mitochondrial damage, and autophagosome formation in the spleen. Notably, Lyc supplementation facilitated all these changes to effectively return to the normal level, indicating that Lyc exerts protective effects against DEHP-induced splenic toxicity. Altogether, the protective effects of Lyc may be a strategy to ameliorate DEHP-induced spleen damage.