Comparison of the components of fresh Panax notoginseng processed by different methods and their anti-anemia effects on cyclophosphamide-treated mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese herb Panax notoginseng (PN) tonifies blood, and its main active ingredient is saponin. PN is processed by different methods, resulting in different compositions and effects. AIM OF THE STUDY: To investigate changes in the microstructure and composition of fresh PN processed by different techniques and the anti-anemia effects on tumor-bearing BALB/c mice after chemotherapy with cyclophosphamide (CTX). MATERIALS AND METHODS: Fresh PN was processed by hot-air drying (raw PN, RPN), steamed at 120 °C for 5 h (steamed PN, SPN), or fried at 130 °C, 160 °C, or 200 °C for 8 min (fried PN, FPN1, FPN2, or FPN3, respectively); then, the microstructures were compared with 3D optical microscopy, quasi-targeted metabolites were detected by liquid chromatography tandem mass spectrometry (LC‒MS/MS), and saponins were detected by high-performance liquid chromatography (HPLC). An anemic mouse model was established by subcutaneous H22 cell injection and treatment with CTX. The antianemia effects of PN after processing via three methods were investigated by measuring peripheral blood parameters, performing HE staining and measuring cell proliferation via immunofluorescence. RESULTS: 3D optical profiling revealed that the surface roughness of the SPN and FPN was greater than that of the other materials. Quasi-targeted metabolomics revealed that SPN and FPN had more differentially abundant metabolites whose abundance increased, while SPN had greater amounts of terpenoids and flavones. Analysis of the composition and content of the targeted saponins revealed that the contents of rare saponins (ginsenoside Rh1, 20(S)-Rg3, 20(R)-Rg3, Rh4, Rk3, Rg5) were greater in the SPN. In animal experiments, the RBC, WBC, HGB and HCT levels in peripheral blood were increased by SPN and FPN. HE staining and immunofluorescence showed that H-SPN and M-FPN promoted bone marrow and spleen cell proliferation. CONCLUSION: The microstructure and components of fresh PN differed after processing via different methods. SPN and FPN ameliorated CTX-induced anemia in mice, but the effects of PN processed by these two methods did not differ.

Acetylcholine Analog-Modified Albumin Nanoparticles for the Enhanced and Synchronous Brain Delivery of Saponin Components of Panax Notoginseng.

BACKGROUND: Panax notoginseng saponins (PNS) are commonly used first-line drugs for treating cerebral thrombosis and stroke in China. However, the synchronized and targeted delivery of active ingredients in traditional Chinese medicine (TCM) poses a significant challenge for modern TCM formulations. METHODS: Bovine serum albumin (BSA) was modified using 2-methacryloyloxyethyl phosphorylcholine (MPC), an analog of acetylcholine, and subsequently adsorbed the major PNS onto the modified albumin to produce MPC-BSA@PNS nanoparticles (NPs). This novel delivery system facilitated efficient and synchronized transport of PNS across the blood-brain barrier (BBB) through active transport mediated by nicotinic acetylcholine receptors. RESULTS: In vitro experiments demonstrated that the transport rates of R1, Rg1, Rb1, and Rd across the BBB were relatively synchronous in MPC-BSA@PNS NPs compared to those in the PNS solution. Additionally, animal experiments revealed that the brain-targeting efficiencies of R1 + Rg1 + Rb1 in MPC-BSA@PNS NPs were 2.02 and 7.73 times higher than those in BSA@PNS NPs and the free PNS group, respectively. CONCLUSIONS: This study presents a simple and feasible approach for achieving the targeted delivery of complex active ingredient clusters in TCM.

Effects of nitrogen addition on rhizosphere priming: The role of stoichiometric imbalance.

Nitrogen (N) input has a significant impact on the availability of carbon (C), nitrogen (N), and phosphorus (P) in the rhizosphere, leading to an imbalanced stoichiometry in microbial demands. This imbalance can result in energy or nutrient limitations, which, in turn, affect C dynamics during plant growth. However, the precise influence of N addition on the C:N:P imbalance ratio and its subsequent effects on rhizosphere priming effects (RPEs) remain unclear. To address this gap, we conducted a 75-day microcosm experiment, varying N addition rates (0, 150, 300 kg N ha-1), to examine how microbes regulate RPE by adapting to stoichiometry and maintaining homeostasis in response to N addition, using the 13C natural method. Our result showed that N input induced a stoichiometric imbalance in C:N:P, leading to P or C limitation for microbes during plant growth. Microbes responded by adjusting enzymatic stoichiometry and functional taxa to preserve homeostasis, thereby modifying the threshold element ratios (TERs) to cope with the C:N:P imbalance. Microbes adapted to the stoichiometric imbalance by reducing TER, which was attributed to a reduction in carbon use efficiency. Consequently, we observed higher RPE under P limitation, whereas the opposite trend was observed under C or N limitation. These results offer novel insights into the microbial regulation of RPE variation under different soil nutrient conditions and contribute to a better understanding of soil C dynamics.

Microwave-responsive gadolinium metal-organic frameworks nanosystem for MRI-guided cancer thermotherapy and synergistic immunotherapy.

The clinical application of cancer immunotherapy is unsatisfied due to low response rates and systemic immune-related adverse events. Microwave hyperthermia can be used as a synergistic immunotherapy to amplify the antitumor effect. Herein, we designed a Gd-based metal-organic framework (Gd-MOF) nanosystem for MRI-guided thermotherapy and synergistic immunotherapy, which featured high performance in drug loading and tumor tissue penetration. The PD-1 inhibitor (aPD-1) was initially loaded in the porous Gd-MOF (Gd/M) nanosystem. Then, the phase change material (PCM) and the cancer cell membrane were further sequentially modified on the surface of Gd/MP to obtain Gd-MOF@aPD-1@CM (Gd/MPC). When entering the tumor microenvironment (TME), Gd/MPC induces immunogenic death of tumor cells through microwave thermal responsiveness, improves tumor suppressive immune microenvironment and further enhances anti-tumor ability of T cells by releasing aPD-1. Meanwhile, Gd/MPC can be used for contrast-enhanced MRI. Transcriptomics data revealed that the downregulation of MSK2 in cancer cells leads to the downregulation of c-fos and c-jun, and ultimately leads to the apoptosis of cancer cells after treatment. In general, Gd/MPC nanosystem not only solves the problem of system side effect, but also achieves the controlled drug release via PCM, providing a promising theranostic nanoplatform for development of cancer combination immunotherapy.

Masticadienonic acid from Chios mastic gum mitigates colitis in mice via modulating inflammatory response, gut barrier integrity and microbiota.

BACKGROUND: Chios mastic gum (CMG) is a traditional Greek medicine used to treat a variety of gastrointestinal disorders, including inflammatory bowel disease (IBD). However, the bioactive compounds of CMG and the mechanisms of action for controlling of IBD remain unknown. PURPOSE: Masticadienonic acid (MDA) is one of the most abundant constituents isolated from CMG. This study aims to investigate the potential effects and underlying mechanisms of MDA in the pathogenesis of colitis. METHODS: The effects of MDA were evaluated using a dextran sulphate sodium (DSS)-induced acute colitis mouse model. The body and spleen weight and colon length and weight were measured and the clinical symptoms were analysed. Blood samples were collected to analyse the level of serum inflammatory markers. Colon tissues were processed for histopathological examination, evaluation of the epithelial barrier function, and investigation of the probable mechanisms of action. The gut microbiota composition was also studied to determine the mechanism for the beneficial effects of MDA on IBD. RESULTS: MDA could ameliorate the severity of IBD by increasing the body weight and colon length, reducing spleen weight, disease activity index, and histological score. MDA treatments reduce the release of serum inflammatory cytokines tumour necrosis factor-alpha (TNFα), interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6) via inhibiting the MAPK and NF-κB signalling pathways. MDA supplementation could also improve the intestinal barrier function by activating the NF-E2-related factor-2 (Nrf2) signalling pathway and restoring the expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin. In addition, MDA administration modulates the gut microbiota composition in DSS-induced colitis mice. CONCLUSION: The results indicate that MDA attenuated experimental colitis by restoring intestinal barrier integrity, reducing inflammation, and modulating the gut microbiota. The present study provides novel insights into CMG-mediated remission of IBD and may facilitate the development of preventive and therapeutic strategies for IBD.

Nitidine chloride induces cardiac hypertrophy in mice by targeting autophagy-related 4B cysteine peptidase.

Nitidine chloride (NC) is a standard active component from the traditional Chinese medicine Zanthoxylum nitidum (Roxb.) DC. (ZN). NC has shown a variety of pharmacological activities including anti-tumor activity. As a number of anti-tumor drugs cause cardiotoxicity, herein we investigated whether NC exerted a cardiotoxic effect and the underlying mechanism. Aqueous extract of ZN (ZNE) was intraperitoneally injected into rats, while NC was injected into beagles and mice once daily for 4 weeks. Cardiac function was assessed using echocardiography. We showed that both ZNE administered in rats and NC administered in mice induced dose-dependent cardiac hypertrophy and dysfunction, whereas administration of NC at the middle and high dose caused death in Beagles. Consistently, we observed a reduction of cardiac autophagy levels in NC-treated mice and neonatal mouse cardiomyocytes. Furthermore, we demonstrated that autophagy-related 4B cysteine peptidase (ATG4B) may be a potential target of NC, since overexpression of ATG4B reversed the cardiac hypertrophy and reduced autophagy levels observed in NC-treated mice. We conclude that NC induces cardiac hypertrophy via ATG4B-mediated downregulation of autophagy in mice. Thus, this study provides guidance for the safe clinical application of ZN and the use of NC as an anti-tumor drug.

Resveratrol alleviates salivary gland dysfunction induced by ovariectomy in rats.

Resveratrol (Res), found abundant in many medicinal plants, exerts multiple biological functions in the body, including anti-inflammatory, antioxidant, and anti-aging properties. Xerostomia is a major symptom of salivary gland dysfunction in menopausal women, which significantly compromises the quality of life. Here, we investigated the effect of Res on estrogen deficiency-induced salivary gland dysfunction in rats. We found that Res administration could reduce body weight and water consumption, and increase salivary fluid secretion and blood flow of the submandibular gland. Furthermore, Res therapy alleviated histological lesions, increased AQP5 expression, and inhibited cell apoptosis in submandibular gland tissue. Meanwhile, the action of antioxidants was restored and the levels of inflammatory cytokines were attenuated by Res supplementation. Collectively, Res effectively improved estrogen deficiency-induced hyposalivation, which may provide a novel, safe, and practical approach to protect the salivary glands of estrogen-deficient females against xerostomia.

Nitrogen-doped carbon dots/curcumin nanocomposite for combined Photodynamic/photothermal dual-mode antibacterial therapy.

Due to their excellent photophysical properties, carbon quantum dots have great potential in biomedical and drug delivery fields. In this study, nitrogen-doped carbon quantum dots with good water solubility were prepared using citric acid and ethylenediamine as precursors, and compounded with curcumin, a photosensitive component, to produce composite nanomaterials with photodynamic therapy and synergistic photothermal therapy. The formation of nitrogen-doped carbon quantum dots and composite nanomaterials was verified using physical and optical means. In addition, the composite nanomaterials produced single-linear oxygen and exacerbated the increase of solution temperature under blue (405 nm) and near-infrared (808 nm) light irradiation, respectively. The plate counting method showed that the composite nanomaterials exhibited good photodynamic synergistic photothermal antibacterial properties against both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus under dual light source (405+808 nm) irradiation, which improved the photoinactivation of curcumin against bacteria. In addition, the composite nanomaterials exhibited low toxicity and good hemocompatibility. These experimental results suggested that the composite nanomaterials showed great potential in a multimodal photodynamic therapy synergistic photothermal treatment platform.

Myocardial Rev-erb-Mediated Diurnal Metabolic Rhythm and Obesity Paradox.

BACKGROUND: The nuclear receptor Rev-erbα/ß, a key component of the circadian clock, emerges as a drug target for heart diseases, but the function of cardiac Rev-erb has not been studied in vivo. Circadian disruption is implicated in heart diseases, but it is unknown whether cardiac molecular clock dysfunction is associated with the progression of any naturally occurring human heart diseases. Obesity paradox refers to the seemingly protective role of obesity for heart failure, but the mechanism is unclear. METHODS: We generated mouse lines with cardiac-specific Rev-erbα/ß knockout (KO), characterized cardiac phenotype, conducted multi-omics (RNA-sequencing, chromatin immunoprecipitation sequencing, proteomics, and metabolomics) analyses, and performed dietary and pharmacological rescue experiments to assess the time-of-the-day effects. We compared the temporal pattern of cardiac clock gene expression with the cardiac dilation severity in failing human hearts. RESULTS: KO mice display progressive dilated cardiomyopathy and lethal heart failure. Inducible ablation of Rev-erbα/ß in adult hearts causes similar phenotypes. Impaired fatty acid oxidation in the KO myocardium, in particular, in the light cycle, precedes contractile dysfunctions with a reciprocal overreliance on carbohydrate utilization, in particular, in the dark cycle. Increasing dietary lipid or sugar supply in the dark cycle does not affect cardiac dysfunctions in KO mice. However, obesity coupled with systemic insulin resistance paradoxically ameliorates cardiac dysfunctions in KO mice, associated with rescued expression of lipid oxidation genes only in the light cycle in phase with increased fatty acid availability from adipose lipolysis. Inhibition of glycolysis in the light cycle and lipid oxidation in the dark cycle, but not vice versa, ameliorate cardiac dysfunctions in KO mice. Altered temporal patterns of cardiac Rev-erb gene expression correlate with the cardiac dilation severity in human hearts with dilated cardiomyopathy. CONCLUSIONS: The study delineates temporal coordination between clock-mediated anticipation and nutrient-induced response in myocardial metabolism at multi-omics levels. The obesity paradox is attributable to increased cardiac lipid supply from adipose lipolysis in the fasting cycle due to systemic insulin resistance and adiposity. Cardiac molecular chronotypes may be involved in human dilated cardiomyopathy. Myocardial bioenergetics downstream of Rev-erb may be a chronotherapy target in treating heart failure and dilated cardiomyopathy.

Systematic investigation on the distribution of four hidden toxic Aconitum alkaloids in commonly used Aconitum herbs and their acute toxicity.

Yunaconitine (YAC), crassicauline A (CCA), 8-deacetylyunaconitine (DYA), and 8-deacetylcrassicauline A (DCA), as hidden toxic Aconitum alkaloids, are detected in some products of processed Aconitum carmichaelii lateral root and poisoning cases. The distribution and toxicity of these four components in Aconitum herbs should be further systematically studied for medication safety. This study developed a new UHPLC-QQQ-MS/MS method to determine ten Aconitum alkaloids, including aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine, benzoylhypaconine, YAC, CCA, DYA, and DCA, for Aconitum herbs simultaneously. YAC and CCA were founded in some samples of unprocessed A. carmichaelii lateral root (7.04%), A. carmichaelii root (9.43%), A. brachypodum root (6.00%), and A. ouvrardianum root (100%). Four hidden toxic Aconitum alkaloids were detected in processed A. carmichaelii lateral root (2.56%) and A. vilmorinianum root (100%). Four hidden toxic Aconitum alkaloids played significant roles in the classification of Aconitum herbs by OPLS-DA analysis. The acute toxicity test was performed by up-and-down procedure (UDP). The oral administration of the half lethal dose (LD50) of YAC, CCA, DYA, and DCA to female ICR mice was 2.37 mg/kg, 5.60 mg/kg, 60.0 mg/kg, and 753 mg/kg, respectively. The LD50 by intravenous injection was 0.200 mg/kg, 0.980 mg/kg, 7.60 mg/kg, and 34.0 mg/kg, respectively. The LD50 of unprocessed A. carmichaelii lateral root, A. vilmorinianum root, and A. brachypodum root to mice orally was 1.89 g/kg, 0.950 g/kg, and 0.380 g/kg, respectively. Symptoms of Aconitum alkaloid poisoning in mice were decreased activity, fur erect, palpebral edema, vomiting, polypnea, and convulsions. The main change of organs was flatulence. No poisoning or death occurred in mice at the maximum dosage (27.0 g/kg) of A. ouvrardianum root orally. To better control the quality and safety of Aconitum herbs, this study provides favorable support for improving the existing standards to strengthen the supervision of the four hidden toxic Aconitum alkaloids.

Efficacy of Qingfei Paidu Decoction on Patients with COVID-19 Pneumonia in Wuhan, China: A Propensity Score Matching Study.

BACKGROUND: In view of the global efforts to develop effective treatments for the current worldwide coronavirus 2019 (COVID-19) pandemic, Qingfei Paidu decoction (QPD), a novel traditional Chinese medicine (TCM) prescription, was formulated as an optimized combination of constituents of classic prescriptions used to treat numerous febrile and respiratory-related diseases. This prescription has been used to treat patients with COVID-19 pneumonia in Wuhan, China. Hypothesis/Purpose. We hypothesized that QPD would have beneficial effects on patients with COVID-19. We aimed to prove this hypothesis by evaluating the efficacy of QPD in patients with COVID-19 pneumonia. METHODS: In this single-center, retrospective, observational study, we identified eligible participants who received a laboratory diagnosis of COVID-19 between January 15 and March 15, 2020, in the west campus of Union Hospital in Wuhan, China. QPD was supplied as an oral liquid packaged in 200-mL containers, and patients were orally administered one package twice daily 40 minutes after a meal. The primary outcome was death, which was compared between patients who did and did not receive QPD (QPD and NoQPD groups, respectively). Propensity score matching (PSM) was used to identify cohorts. RESULTS: In total, 239 and 522 participants were enrolled in the QPD and NoQPD groups, respectively. After PSM at a 1 : 1 ratio, 446 patients meeting the criteria were included in the analysis with 223 in each arm. In the QPD and NoQPD groups, 7 (3.2%) and 29 (13.0%) patients died, and those in the QPD group had a significantly lower risk of death (hazard ratio (HR) 0.29, 95% CI: 0.13-0.67) than those in the NoQPD group (p = 0.004). Furthermore, the survival time was significantly longer in the QPD group than in the NoQPD group (p < 0.001). CONCLUSION: The use of QPD may reduce the risk of death in patients with COVID-19 pneumonia.

Flavonoids-rich extract from Bidens bipinnata L. protects pancreatic ß-cells against oxidative stress-induced apoptosis through intrinsic and extrinsic pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicinal, Bidens bipinnata L. has been used to treat many diseases with a long history in China. The anti-diabetic effects of extract from B. bipinnata have been demonstrated in the previous reports. AIM OF THE STUDY: The protective effects of flavonoids-rich extract from B. bipinnata (BBTF) on cell damage induced by H2O2 in pancreatic ß cell and its potential mechanisms were evaluated. MATERIALS AND METHODS: MTT, ROS production, nuclear staining and flow cytometry assays were adopted to determine the effects of BBTF on cell viability, production of ROS and cell apoptosis in H2O2-treated INS-1 cell. Cell apoptosis-related proteins expressions were detected by Western blot assay. RESULTS: Pre-treatment of BBTF could significantly increase INS-1 cell viability, inhibit the production of intracellular ROS and reduced the characteristic features of cell apoptosis induced by H2O2 in INS-1 cells. The studies of the underlying mechanism showed that BBTF could regulate Bax and Bcl-2 proteins expressions, suppress the phosphorylation of JNK, ERK and p38, as well as down-regulate Fas and FasL proteins expressions induced by H2O2. The expressions of caspase-8, caspase-9 and caspase-3 were therefore decreased. CONCLUSION: The results indicated that flavonoids-rich extract from B. bipinnata could be a natural agent in diabetic prevention and therapy.

Perilla frutescens Leaf Extract and Fractions: Polyphenol Composition, Antioxidant, Enzymes (α-Glucosidase, Acetylcholinesterase, and Tyrosinase) Inhibitory, Anticancer, and Antidiabetic Activities.

This study aims to evaluate the bioactive components, in vitro bioactivities, and in vivo hypoglycemic effect of P. frutescens leaf, which is a traditional medicine-food homology plant. P. frutescens methanol crude extract and its fractions (petroleum ether, chloroform, ethyl acetate, n-butanol fractions, and aqueous phase residue) were prepared by ultrasound-enzyme assisted extraction and liquid-liquid extraction. Among the samples, the ethyl acetate fraction possessed the high total phenolic (440.48 µg GAE/mg DE) and flavonoid content (455.22 µg RE/mg DE), the best antioxidant activity (the DPPH radical, ABTS radical, and superoxide anion scavenging activity, and ferric reducing antioxidant power were 1.71, 1.14, 2.40, 1.29, and 2.4 times higher than that of control Vc, respectively), the most powerful α-glucosidase inhibitory ability with the IC50 value of 190.03 µg/mL which was 2.2-folds higher than control acarbose, the strongest proliferative inhibitory ability against MCF-7 and HepG2 cell with the IC50 values of 37.92 and 13.43 µg/mL, which were considerable with control cisplatin, as well as certain inhibition abilities on acetylcholinesterase and tyrosinase. HPLC analysis showed that the luteolin, rosmarinic acid, rutin, and catechin were the dominant components of the ethyl acetate fraction. Animal experiments further demonstrated that the ethyl acetate fraction could significantly decrease the serum glucose level, food, and water intake of streptozotocin-induced diabetic SD rats, increase the body weight, modulate their serum levels of TC, TG, HDL-C, and LDL-C, improve the histopathology and glycogen accumulation in liver and intestinal tissue. Taken together, P. frutescens leaf exhibits excellent hypoglycemic activity in vitro and in vivo, and could be exploited as a source of natural antidiabetic agent.

Effect of ethanolic extract from Morus alba L. leaves on the quality and sensory aspects of chilled pork under retail conditions.

The aim of this study was to investigate the performance of ethanolic extract from Morus alba L. leaves (MLEE) in preserving chilled pork under retail conditions. The four treatments were 5 mg/mL sodium benzoate solution (SB), 1 mg/mL MLEE solution (high-concentration MLEE; HM), 0.5 mg/mL MLEE solution (low-concentration MLEE; LM), and 0 mg/mL MLEE solution (C). The quality characteristics, pH, thiobarbituric acid reactive substances values, metmyoglobin, total volatile basic nitrogen, and number of microbes of MLEE-treated chilled pork stored at 4 °C for 9 days were consistent with those obtained by the SB treatment and lower than those obtained by the C treatment. Sensory analyses showed that treatment of pork with MLEE did not have a negative impact on its sensory characteristics. MLEE can extend the shelf life of chilled pork from 3 days to 6 days (9 days) in first-class (second-class) fresh meat. Results suggest that MLEE could be a candidate resource in the preservation of chilled pork.

Novel SNP markers on ginsenosides biosynthesis functional gene for authentication of ginseng herbs and commercial products.

Panax ginseng and Panax quinquefolius have similar bioactive components and morphological characteristics, but they are known to have different medicinal values, high-sensitive and accurate method is expected to identify the sources of ginseng products and evaluate the quality, but with a huge challenge. Our established UHPLC-TOF/MS method coupled with orthogonal partial least squares discriminant analysis (OPLS-DA) model based on 18 ginsenosides was applied to discriminate the sources of raw medicinal materials in ginseng products, and nested PCR strategy was used to discover 6 novel single nucleotide polymorphism (SNP) sites in functional dammarenediol synthase (DS) gene for genetic authentication of P. ginseng and P. quinquefolius for the first time. OPLS-DA model could identify the sources of raw ginseng materials are real or not. SNP markers were applied to identify ginseng fresh samples as well as commercial products, and proved to be successful. This established molecular method can tell exact source information of adulterants, and it was highly sensitive and specific even when total DNA amount was only 0.1 ng and the adulteration was as low as 1%. Therefore, this study made an attempt at the exploration of new type SNP marker for variety authentication and function regulation at the same time, and the combination of chemical and molecular discrimination methods provided the comprehensive evaluation and authentication for the sources of ginseng herbs and products.

Deep learning radiomics of ultrasonography: Identifying the risk of axillary non-sentinel lymph node involvement in primary breast cancer.

BACKGROUND: Completion axillary lymph node dissection is overtreatment for patients with sentinel lymph node (SLN) metastasis in whom the metastatic risk of residual non-SLN (NSLN) is low. However, the National Comprehensive Cancer Network panel posits that none of the previous studies has successfully identified such subset patients. Here, we develop a multicentre deep learning radiomics of ultrasonography model (DLRU) to predict the risk of SLN and NSLN metastasis. METHODS: In total, 937 eligible breast cancer patients with ultrasound images were enrolled from two hospitals as the training set (n = 542) and independent test set (n = 395) respectively. Using the images, we developed and validated a prediction model combined with deep learning radiomics and axillary ultrasound to sequentially identify the metastatic risk of SLN and NSLN, thereby, classifying patients to relevant axillary management groups. FINDINGS: In the test set, the DLRU yields the best performance in identifying patients with metastatic disease in SLNs (sensitivity=98.4%, 95% CI 96.6-100) and NSLNs (sensitivity=98.4%, 95% CI 95.6-99.9). The DLRU also accurately stratifies patients without metastasis in SLN or NSLN into the corresponding low-risk (LR)-SLN and high-risk (HR)-SLN&LR-NSLN category with the negative predictive value of 97% (95% CI 94.2-100) and 91.7% (95% CI 88.8-97.9), respectively. Moreover, compared with the current clinical management, DLRU appropriately assigned 51% (39.6%/77.4%) of overtreated patients in the entire study cohort into the LR group, perhaps avoiding overtreatment. INTERPRETATION: The performance of the DLRU indicates that it may offer a simple preoperative tool to promote personalized axillary management of breast cancer. FUNDING: The National Nature Science Foundation of China; The National Outstanding Youth Science Fund Project of National Natural Science Foundation of China; The Scientific research project of Heilongjiang Health Committee; The Postgraduate Research &Practice Innovation Program of Harbin Medical University.

[Study on chemical constituents from Mastic (Pistacia lentiscus)].

Phytochemical investigation on the methanolic extract of Mastic by using various chromatographic techniques led to the isolation of 9 compounds. Based on the analysis of spectroscopic data(NMR and MS) and/or comparisons with the data reported in the literature, their structures were elucidated as 3ß,8α,13-trihydroxypolypoda-14-methoxy-14-methyl-17,21-diene(1), 4-hydroxymyrtenal(2),3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1, 2-diol(3), 2-oxo-Δ~3-4,5,5-trimethylcyclopentynyl acidic acid(4),(1S,2R,3R,5R)-6,6-dimethyl-4-methylidenebicyclo[3.1.1]-heptane-2,3-diol(5),(4R)-1-methyl-4-(1-hydroxyisopropyl)cyclohexene-6-one(6), 6,6-dimethyl-4-hydroxy[3.1.1]hept-2-ene-2-carboxylic acid(7), 6,6-dimethyl[3.1.1]hept-2-ene-2-carboxylic acid(8), 6,6-dimethyl-4-oxobicyclo[3.1.1]hept-2-ene-2-carboxylic acid(9). Compound 1 is a new compound and 2-9 were isolated from this species for the first time. In vitro cytotoxicity assay results indicated that compounds 1, 6 and 7 showed significant inhibitory effects against human lung cancer cell line A549 with IC_(50) values of 20.4, 25.1 and 22.5 µmoL·L~(-1).

Enrichment of flavonoid-rich extract from Bidens bipinnata L. by macroporous resin using response surface methodology, UHPLC-Q-TOF MS/MS-assisted characterization and comprehensive evaluation of its bioactivities by analytical hierarchy process.

The extract of Bidens bipinnata L. exhibited wide spectrum of bioactivities owing to the presence of flavonoids. In this study, a purification process was developed to enrich the flavonoid-rich extract from B. bipinnata L. (BBTF). AB-8 resin was selected for the purification of total flavonoids. Response surface methodology coupled with Box-Behnken design was employed to optimize the purification condition; it was optimized as pH 5.1, volume of ethanol 80 ml, flow rate of ethanol 1.8 bed volume per hour (BV/h) and concentration of ethanol 76.0%. The total flavonoid content of BBTF was 56.48% under the optimal conditions. The identification of flavonoids in BBTF was conducted using UHPLC-ESI-Q-TOF MS. A total of 14 compounds, including 12 flavonoids, were identified in BBTF. Finally, the in vitro antioxidant activities, α-glucosidase and α-amylase inhibitory activities of BBTF were comprehensively analyzed by an analytical hierarchy process. The results indicated that it exhibited higher bioactivities than the crude extract. These findings suggested that the optimized process could significantly enhance the purity of flavonoids and their bioactivities. This study showed a comprehensive analysis of a total flavonoid extract of B. bipinnata L. for the first time, which could provide a useful approach for its purification process and quality control as well as bioactivities.

Utilization of domestic wastewater as a water source of Tetradesmusobliquus PF3 for the biological removal of nitric oxide.

The reduction of nitrogen oxide (DeNOx) from flue gas by microalgae is a promising technology that has attracted increasing attention. Because the water source is a major limitation of microalgae application in the DeNOx from flue gas, we investigated the feasibility of using domestic wastewater (WW) as a water source. As a result, a biomass accumulation rate of 0.27 ± 0.01 mg L-1 d-1 was achieved by Tetradesmusobliquus PF3 cultivated in WW for 8 d, and 30 mg L-1 of nitrate nitrogen was added to the WW to fulfill the nutrient requirements of the microalgae cells. The ammonium (NH4+) nitrogen present in WW exerted inhibitory effects on the removal of nitric oxide (NO), thereby leading to 8% decrease removal efficiency in comparison with that using clean water and nutrients (BG11 medium). However, these inhibitory effects disappeared following the exhaustion of NH4+ by T. obliquus PF3 after 1 d. To overcome the inhibition of NH4+ and to achieve a high NO removal efficiency, a strategy of connecting two reactors in series was presented. The removal efficiency of NO by the two series reactors reached up to 71.2 ± 2.9%, which was significantly higher than that obtained by a single reactor (43.1 ± 3.6%). In addition, 70.9 ± 4.8% of the supplied NO was fixed into microalgae cells in the two reactors, which was 1.75 times higher than that in the single reactor (40.6 ± 5.1%), thereby suggesting that connecting two reactors in series rendered effective recovery of NO from flue gas using WW as a water source. In this study, we provided an economically viable water source for the application of microalgae in the biological DeNOx from flue gases.

Effect of Shenfu Injection on Porcine Renal Function after Cardiopulmonary Resuscitation.

OBJECTIVE: To comprehensively evaluate the protective effect of Shenfu injection (SFI) on renal ischaemia/reperfusion injury (IRI) after cardiopulmonary resuscitation (CPR) through neutrophil gelatinase-associated lipocalin (NGAL) and to explore effective monitoring of early renal injuries after CPR. METHODS: Thirty healthy minipigs were randomly divided into 3 groups: sham operation (SO) (n = 6), control (n = 12), and SFI (n = 12). The SO group underwent only catheterization, whereas the control and SFI groups were subjected to program-controlled electrical stimulation to establish a cardiac arrest (CA) model due to ventricular fibrillation. After CPR, the return of spontaneous circulation was achieved. Each animal in the SFI group was intravenously injected with SFI after resuscitation. Haemodynamic parameters were monitored at baseline and 2, 6, 12, and 24 hr after CPR. At each time point, venous blood samples were collected for NGAL, creatinine, and ATPase screening. RESULTS: After CA, the MAP, CPP, and CO of the animals in the control and SFI groups decreased significantly. However, at 6 hr after CPR, the MAP, CPP, and CO of the animals in the SFI group began to recover gradually; the differences between the control and SFI groups were significant (P < 0.005). The renal damage immediately after CPR appeared to be significant in the pathological examinations. However, the degree of renal injury in the SFI group improved significantly, and the apoptosis index was also notably reduced. The blood and urine NGAL levels were clearly elevated after CPR. The greatest increase in NGAL was found in the control group, which was significantly different from that of the SFI group (P < 0.001). SFI can significantly increase the ATPase activity of kidney tissues after CPR and improve abnormal caspase-3 protein expression. CONCLUSION: SFI can effectively prevent acute kidney injuries caused by CPR through improving energy metabolism and inhibiting apoptosis.