Rapid Remission With Upadacitinib in a Child With Refractory Crohn's Disease and ATM Mutation: A Case Report.

Managing pediatric Crohn's disease (PCD) presents challenges due to severe complications and higher biologic therapy needs. Transitioning from anti-tumor necrosis factor agents to off-label therapies adds complexity. Although upadacitinib has demonstrated efficacy and tolerability in adult inflammatory bowel disease and pediatric atopic dermatitis, there are limited data for its application in PCD. This case report delineates successful remission with upadacitinib in a child with CD refractory to infliximab, ustekinumab, adalimumab, thalidomide, and prednisone. Notably, the patient carried an ataxia telangiectasia mutated (ATM) gene mutation. These findings provide valuable evidence for PCD management and highlight the potential benefits of upadacitinib in this population.

Assessment of the quality of online information on dietary recommendations for inflammatory bowel disease.

Objective: The internet has become a preferred source for people seeking health information, including diet recommendations which are pivotal in the management of inflammatory bowel disease (IBD). Hence, we aimed to assess the quality of online information in China regarding IBD dietary recommendations. Methods: The search engines Baidu and Bing were used to screen for their top 25 webpages using the keywords "inflammatory bowel disease diet," "ulcerative colitis diet," "Crohn's disease diet," "inflammatory bowel disease nutrition," "ulcerative colitis nutrition," and "Crohn's disease nutrition." The quality of information was assessed by two physicians according to the Journal of the American Medical Association (JAMA) benchmark, the Global Quality Score (GQS), and the DISCERN instrument. Results: One hundred and eight webpages were selected for evaluation. The mean scores for JAMA, GQS, and DISCERN were 1.48, 3.11, and 36.20, respectively. Articles from professionals and non-profit organizations demonstrated superior quality compared to those from commercial and health portal websites. Many webpages failed to provide an explicit source of information or support for shared decision-making. The information on several pages lacked comprehensive descriptions of food types for IBD, with some pages even containing inaccuracies. No statistically significant differences in scores were observed between Baidu and Bing. Conclusions: The quality of online information on IBD dietary recommendations in China is moderate to low and exhibits significant variation across different sources. This warrants joint efforts from online authors, internet platforms, and regulators, to improve the quality of popular medical information.

ASB3 expression aggravates inflammatory bowel disease by targeting TRAF6 protein stability and affecting the intestinal microbiota.

E3 ubiquitin ligase (E3) plays a vital role in regulating inflammatory responses by mediating ubiquitination. Previous studies have shown that ankyrin repeat and SOCS box-containing protein 3 (ASB3) is involved in immunomodulatory functions associated with cancer. However, the impact of ASB3 on the dynamic interplay of microbiota and inflammatory responses in inflammatory bowel disease (IBD) is unclear. Here, we systematically identify the E3 ligase ASB3 as a facilitative regulator in the development and progression of IBD. We observed that ASB3 exhibited significant upregulation in the lesions of patients with IBD. ASB3-/- mice are resistant to dextran sodium sulfate-induced colitis. IκBα phosphorylation levels and production of proinflammatory factors IL-1ß, IL-6, and TNF-α were reduced in the colonic tissues of ASB3-/- mice compared to WT mice. This colitis-resistant phenotype was suppressed after coprophagic microbial transfer and reversed after combined antibiotics removed the gut commensal microbiome. Mechanistically, ASB3 specifically catalyzes K48-linked polyubiquitination of TRAF6 in intestinal epithelial cells. In contrast, in ASB3-deficient organoids, the integrity of the TRAF6 protein is shielded, consequently decelerating the onset of intestinal inflammation. ASB3 is associated with dysregulation of the colitis microbiota and promotes proinflammatory factors' production by disrupting TRAF6 stability. Strategies to limit the protein level of ASB3 in intestinal epithelial cells may help in the treatment of colitis. IMPORTANCE: Ubiquitination is a key process that controls protein stability. We determined the ubiquitination of TRAF6 by ASB3 in intestinal epithelial cells during colonic inflammation. Inflammatory bowel disease patients exhibit upregulated ASB3 expression at focal sites, supporting the involvement of degradation of TRAF6, which promotes TLR-Myd88/TRIF-independent NF-κB aberrant activation and intestinal microbiota imbalance. Sustained inflammatory signaling in intestinal epithelial cells and dysregulated protective probiotic immune responses mediated by ASB3 collectively contribute to the exacerbation of inflammatory bowel disease. These findings provide insights into the pathogenesis of inflammatory bowel disease and suggest a novel mechanism by which ASB3 increases the risk of colitis. Our results suggest that future inhibition of ASB3 in intestinal epithelial cells may be a novel clinical strategy.

Two new pregnane alkaloids from Pachysandra terminalis Sieb. et Zucc. and their cytotoxic activities.

Pactermines E and F (1 and 2), two new pregnane alkaloids were isolated from the whole plant of Pachysandra terminalis Sieb. et Zucc. Their structures were determined by physicochemical properties and spectroscopic methods including 1D, 2D NMR, IR, HR-ESI-MS data. Cytotoxic activities against three human cancer A549, HCT116 and SW620 cell lines of the isolated compounds were evaluated by CCK8 method. However, all compounds showed no significant activity against the three cancer cells (IC50>100 µM) except for compound 1, which showed inhibitory effects against HCT116 cells with IC50 values of 84.6 µM.

The Sources, Structures and Cytotoxicity of Animal-Derived Bisindole Compounds.

Bisindole compounds constitute a significant class of natural compounds distinguished by their characteristic bisindole structure and renowned for their anticancer properties. Over the past four decades, researchers have isolated 229 animal-derived bisindole compounds (ADBCs) from various animals. These compounds demonstrate a wide range of pharmacological properties, including cytotoxicity, antibacterial, antifungal, antiviral, and other activities. Notably, among these activities, cytotoxicity emerges as the most prominent characteristic of ADBCs. This review also summarizes the structureactivity relationship (SAR) studies associated with the cytotoxicity of these compounds and explores the druggability of these compounds. In summary, our objective is to provide an overview of the research progress concerning ADBCs, with the aim of fostering their continued development and utilization.

High cadmium-accumulating Salix ecotype shapes rhizosphere microbiome to facilitate cadmium extraction.

Cadmium (Cd) contamination poses a significant threat to agricultural soils and food safety, necessitating effective remediation strategies. Salix species, with their high coverage and Cd accumulating capacity, hold promise for remediation efforts. The rhizosphere microbiome is crucial for enhancing Cd accumulating capacity for Salix. However, the mechanisms by how Salix interacts with its rhizosphere microbiome to enhance Cd extraction remains poorly understood. In this study, we compared the remediation performance of two Salix ecotypes: 51-3 (High Cd-accumulating Ecotype, HAE) and P646 (Low Cd-accumulating Ecotype, LAE). HAE exhibited notable advantages over LAE, with 10.80 % higher plant height, 43.80 % higher biomass, 20.26 % higher Cd accumulation in aboveground tissues (93.09 µg on average), and a superior Cd translocation factor (1.97 on average). Analysis of the rhizosphere bacterial community via 16S rRNA amplicon sequencing revealed that HAE harbored a more diverse bacterial community with a distinct composition compared to LAE. Indicator analysis identified 84 genera specifically enriched in HAE, predominantly belonging to Proteobacteria, Actinobacteria, and Firmicutes, including beneficial microbes such as Streptomyces, Bacillus, and Pseudomonas. Network analysis further elucidated three taxa groups specifically recruited by HAE, which were highly correlated with functional genes that associated with biosynthesis of secondary metabolites, glycan biosynthesis and metabolism, and metabolism of cofactors and vitamins. These functions contribute to enhancing plant growth, Cd uptake, and resistance to Cd in Salix. Overall, our findings highlight the importance of the rhizosphere microbiome in facilitating Cd extraction and provide insights into microbiome-based strategies for sustainable agricultural practices.

Improved calculation method for dry modal analysis of four-stage centrifugal-pump rotor system based on concentrated-mass method.

To improve the accuracy of modal analysis for a four-stage centrifugal-pump rotor system with a balancing disc based on the concentrated-mass analytical method, a simplified concentrated mass mathematical model and an ANSYS simulation model are established. The results from these two models are compared to determine factors that cause significant differences in the mode shapes. Subsequently, an optimized mathematical model based on the corrected mass moment of an inertia matrix and stiffness correction coefficients is proposed, and the effectiveness of this optimized mathematical model is validated using a four-stage centrifugal pump with back blades. The results show that the natural frequencies obtained from the ANSYS simulations are consistently higher than those obtained using the analytical method. The simplification of the moment of inertia at the impeller and balancing disc contributes primarily to the calculated errors. The optimized mathematical model reduces the errors in the natural frequencies from 12.96%, 12.13%, 9.96%, 5.85%, and 8.74% to 2.45%, 1.56%, 0.65%, 5.34%, and 2.28%, respectively. The optimization of natural frequencies offers better performance at lower-order modes, whereas its effects on higher-order modes are less significant. The optimization method is applicable to centrifugal pumps with back blades and reduces the error in theoretical calculations, based on reductions in the concentrated mass from 13.11%, 12.85%, 9.91%, and 7.2% to 3.7%, 3.86%, 0.57%, and 2.87%, respectively, thus further confirming the feasibility of the optimized model design.

Comparison of accelerated and standard infliximab induction regimens in acute severe ulcerative colitis using propensity score analysis: a retrospective multicenter study in China.

Background: The optimal regimen of infliximab salvage in acute severe ulcerative colitis (ASUC) patients remains controversial. This study aimed to compare accelerated and standard infliximab induction in Chinese ASUC patients, and to explore risk factors and concrete accelerated regimens for them. Methods: Data were retrospectively collected from steroid-refractory ASUC patients receiving infliximab as rescue therapy at seven tertiary centers across China. Outcomes including colectomy and clinical remission (Mayo score ≤ 2 and every subscore ≤ 1 at Day 14) rates were compared between patients receiving accelerated and standard infliximab induction using propensity score adjustment for potential confounders. The dose-response relationship was explored by plotting restricted cubic splines. Logistic regression and Cox proportional hazards regression analyses were performed to determine risk factors for adverse outcomes. A systematic review and meta-analysis was also performed. Results: A total of 76 patients were analysed: 29 received standard and 47 received accelerated induction. The accelerated group had a higher 90-day colectomy rate (17.8% vs 0%, P = 0.019) and lower clinical remission rate (27.7% vs 65.5%, P = 0.001). After adjusting for propensity score and institution, there was no significant difference in colectomy or clinical remission rates (both P > 0.05). Dose-effect curves showed decreased colectomy hazard with higher cumulative infliximab dosage within 5 days, with no improvement observed for increasing cumulative infliximab dosage within 28 days. Multivariate logistic regression analyses revealed C-reactive protein of >10 mg/L at infliximab initiation (odds ratio = 5.00, 95% confidence interval: 1.27-24.34) as an independent risk factor for no clinical remission. Meta-analysis also revealed no significant difference in colectomy rates at 3 months (P = 0.54). Conclusions: After adjusting for confounders, there were no significant differences in colectomy or clinical remission rates between accelerated and standard infliximab induction among ASUC patients. Early administration of an intensified dosage within 5 days may be beneficial. Elevated C-reactive protein at infliximab initiation indicated need for intensive treatment.

Sesquilignans: Current research and potential prospective.

Lignans are widely distributed in nature, primarily found in the xylem and resins of plants, with the constituent units C6-C3, and their dimers are the most common in plants. In recent years, the trimeric sesquilignans have also received increasing attention from scholars. More than 200 derivatives have been isolated and identified from nearly 50 families, most of which are different types (monoepoxy lignans, bisepoxy lignans, benzofuran lignans) connected with simple phenylpropanoids through ether bonds, C-C bonds, and oxygen-containing rings to constitute sesquilignans. Some of them also possess pharmacological properties, including antioxidants, hepatoprotectives, antitumors, anti-inflammatory properties, and other properties. In addition, the chemical structure of sesquilignans is closely related to the pharmacological activity, and chemical modification of methoxylation enhances the pharmacological activity. In contrast, phenolic hydroxyl and hydroxyl glycosides reduce the pharmacological activity. Therefore, the present review aims to summarize the chemical diversity, bioactivities, and constitutive relationships to provide a theoretical basis for the more profound development and utilization of sesquilignans.

Petroleum ether extract of Schisandra sphenanthera prevents hyperglycemia and insulin resistance in association with modulation of sweet taste receptors and gut microbiota in T2DM rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra sphenanthera (Schisandra sphenanthera Rehd. et Wils.) is the dried mature fruit of Schisandra sphenanthera, a plant in the Magnoliaceae family. It was used in the treatment of diabetes mellitus in the Jade Fluid Decoction and the Xiaoke pills, which were recorded in ancient books. However, its mechanism of action in the treatment of type 2 diabetes mellitus (T2DM) was unclear and needs further study. AIM OF THE STUDY: This research aimed to investigate the chemical composition and lignan content of Schisandra sphenanthera petroleum ether parts (SPEP) and to evaluate the effects of SPEP on sweet taste receptors (STRs) and intestinal flora in rats on a high-fat diet (HFD). Additionally, the relationships between SPEP and hyperglycemia and insulin resistance were examined. MATERIALS AND METHODS: GC-MS was used to determine the chemical composition of SPEP, and HPLC was used to determine the lignin content. A combination of the HFD and the administration of streptozotocin (STZ) was employed to generate a rat model of T2DM. Petroleum ether extracts from Schisandra sphenanthera were used as the focus of the research to evaluate the effects of these extracts on the glucolipid metabolism of T2DM rats, as well as the underlying mechanisms. RESULTS: Analysis of the GC-MS spectrum of SESP revealed a total of 58 compounds. HPLC analysis revealed that SPEP had the highest concentration of Schisandrin A and the lowest concentration of Schisandrol A. The drug administration intervention resulted in a significant decrease in body weight and pancreatic weight of diabetic rats compared to the Normal group. When compared to the Model group, the body weight of rats in the drug administration group and the Metformin group had a more moderate decrease, while the pancreatic weight and pancreatic-to-body ratio increased. The Model group shown significant increases in FBG, OGTT, GHb, TC, TG, LDL-C, ALT, AST, MDA, FINS, and NEFA, as well as significant decreases in HDL-C and SOD, when compared to the Normal group (P < 0.05). The administration of each group was found to be significantly effective in decreasing FBG, OGTT, GHb, TC, TG, LDL-C, ALT, AST, MDA, FINS, NEFA, while increasing HDL-C and SOD when compared to the Model group. The application of SPEP had a positive impact on hepatocyte swelling, hepatocyte degeneration, and necrosis, as well as the morphological structure of pancreatic islet cells. Furthermore, the protein expression levels of T1R2, TRPM5 and GLP-1 in the small intestine of the Model group were reduced. After a period of six weeks, the protein expression levels began to align more closely with those of the Normal group of rats. Analysis of 16S rRNA sequencing revealed that the intestinal microbiota of diabetic rats was significantly disrupted, with a decrease in the abundance of the Firmicutes phylum and an increase in the abundance of the Bacteroidetes phylum. Furthermore, the composition of the dominant genus was distinct from that of the control group. After the drug intervention, the microbiota of diabetic rats was significantly altered, exhibiting a higher abundance and diversity, as well as a significant enrichment of the community. The SPEP treatment resulted in a significant increase in acetic acid, propionic acid, and butyric acid. CONCLUSIONS: The findings of this research indicated that SPEP could be effective in treating T2DM through the regulation of STRs, the adjustment of disturbed metabolite levels, and the alteration of intestinal flora.

Schisandrol A, the Major Active Constitute in Schisandra chinensis: A Review of Its Preparation, Biological Activities, and Pharmacokinetics Analysis.

Schisandra chinensis (S. chinensis) has a long history as a traditional Chinese medicine that is astringent, beneficial to vital energy, tonifies the kidney, tranquilizes the heart, etc. Significantly, Schisandrol A (SA) is extracted from S. chinensis and shows surprising and satisfactory biological activity, including anti-inflammatory, hepatoprotective, cardiovascular protection, and antitumor properties, among others. SA has a more pronounced protective effect on central damaged nerves among its numerous pharmacological effects, improving neurodegenerative diseases such as Alzheimer's and Parkinson's through the protection of damaged nerve cells and the enhancement of anti-oxidant capacity. Pharmacokinetic studies have shown that SA has a pharmacokinetic profile with a rapid absorption, wide distribution, maximal concentration in the liver, and primarily renal excretion. However, hepatic and intestinal first-pass metabolism can affect SA's bioavailability. In addition, the content of SA, as an index component of S. chinensis Pharmacopoeia, should not be less than 0.40%, and the content of SA in S. chinensis compound formula was determined with the help of high-performance liquid chromatography (HPLC), which is a stable and reliable method, and it can lay a foundation for the subsequent quality control. Therefore, this paper systematically reviews the preparation, pharmacological effects, pharmacokinetic properties, and content determination of SA with the goal of updating and deepening the understanding of SA, as well as providing a theoretical basis for the study of SA at a later stage.

Epimedium Linn: A Comprehensive Review of Phytochemistry, Pharmacology, Clinical Applications and Quality Control.

Epimedium genus is a traditional Chinese medicine, which has functions of tonifying kidney and yang, strengthening tendons and bones, dispelling wind and emoving dampness. It is mainly used for the treatment of impotence and spermatorrhea, osteoporosis, Parkinson's, Alzheimer's, and cardiovascular diseases. The aim of this review is to provide a systematic summary of the phytochemistry, pharmacology, and clinical applications of the Epimedium Linn. In this paper, the relevant literature on Epimedium Linn. was collected from 1987 to the present day, and more than 274 chemical constituents, including flavonoids, phenylpropanoids, lignans, phenanthrenes, and others, were isolated from this genus. Modern pharmacological studies have shown that Epimedium Linn. has osteoprotective, neuroprotective, cardiovascular protective, and immune enhancing pharmacological effects. In addition, Epimedium Linn. has been commonly used to treat osteoporosis, erectile dysfunction, hypertension and cardiovascular disease. In this paper, the distribution of resources, chemical compositions, pharmacological effects, clinical applications and quality control of Epimedium Linn. are progressed to provide a reference for further research and development of the resources of this genus.

Therapeutic mechanism of Cornus Officinalis Fruit Coreon on ALI by AKT/Nrf2 pathway and gut microbiota.

BACKGROUND: Acute liver injury (ALI) often precipitates severe liver function impairment and is associated with high mortality rates. Traditional Chinese Medicine (TCM) has demonstrated efficacy in mitigating hepatic damage by exhibiting anti-inflammatory effects, enhancing antioxidant activity, and modulating gut microbiota (GM). Numerous studies have identified similar or identical bioactive compounds within the Cornus Officinalis Fruit Coreon(COFO) and its flesh. Notably, Cornus Officinalis has been shown to possess potent hepatoprotective properties. However, studies on the pharmacological effects and mechanism of action of COFO for hepatoprotection have received little attention. PURPOSE: To elucidate the mechanisms underlying the COFO effect in ALI by integrating GM gene sequencing, quantifying Short-Chain Fatty Acids (SCFAs), and examining relevant signaling pathways. MATERIALS AND METHODS: A rat model for carbon tetrachloride (CCl4)-induced ALI was established, and the best liver protective components of COFO were selected by pathological observation and biochemical determination. The therapeutic efficacy of COFO in mitigating liver injury was elucidated through an integrated approach that included network pharmacology, biochemical indexes, 16S rDNA sequencing analyses, short-chain fatty acids, Western blotting analysis of protein levels, and immunohistochemical evaluations. RESULTS: Pharmacological evaluation established that the n-butanol fraction (CNBP) provided optimal hepatoprotective effects. Firstly, the chemical constituents of CNBP were characterized, and its principal anti-ALI targets, such as ALI, AKT1, TNF, and IL-6, were identified through network pharmacology analysis. Secondly, experimental validation revealed that CNBP may enhance the genetic diversity of the GM, augmenting the diversity of the microbial community, increasing the levels of three SCFAs, and activating key proteins in the AKT/Nrf2 signaling pathway (AKT1, TNF-α, IL-6, NF-κB p65, Nrf2, and HO-1). Consequently, CNBP exhibited hepatoprotective effects, with antioxidative and anti-inflammatory properties. CONCLUSION: CNBP may mitigate GM-induced disturbances, augment the levels of three SCFAs, activate the AKT/Nrf2 signaling pathway, and exhibit antioxidant and anti-inflammatory effects, thereby conferring hepatoprotective benefits.

Beyond Collaborative Learning: a Comparison of Small Groups in Face-to-Face and Online Settings.

Small group-based instructional approaches such as case-based learning (CBL) and team-based learning (TBL) are widely used in medical education to promote collaboration and team learning. During the pandemic, many medical schools shifted from face-to-face instruction to online settings. While CBL/TBL are intended to foster collaborative skills, it is unclear how its use evolves in an online setting and whether the online setting impacts students' perceptions and behaviors in collaboration. This study examined how the change from in-person to online CBL/TBL impacted students' collaboration. We used a mixed-methods sequential design, first collecting and analyzing retrospective cohort quantitative data with the Class of 2023 through peer evaluation surveys followed by six focus groups. Students' assessment of their peers was generally positive. Nonparametric testing showed significant differences for two questions with less positive perceptions in the virtual setting compared to when students had in-person CBL/TBL. The focus group results identified several themes related to collaboration and learning communities. In the virtual setting, students not only lost collaboration opportunities with their group members in CBL/TBL, but also learning opportunities and social connections with other groups and the community as a whole. Virtual learning environments may have presented challenges for collaborative learning and the establishment of a sense of community.

AAV9:PKP2 improves heart function and survival in a Pkp2-deficient mouse model of arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial cardiac disease associated with ventricular arrhythmias and an increased risk of sudden cardiac death. Currently, there are no approved treatments that address the underlying genetic cause of this disease, representing a significant unmet need. Mutations in Plakophilin-2 (PKP2), encoding a desmosomal protein, account for approximately 40% of ARVC cases and result in reduced gene expression. METHODS: Our goal is to examine the feasibility and the efficacy of adeno-associated virus 9 (AAV9)-mediated restoration of PKP2 expression in a cardiac specific knock-out mouse model of Pkp2. RESULTS: We show that a single dose of AAV9:PKP2 gene delivery prevents disease development before the onset of cardiomyopathy and attenuates disease progression after overt cardiomyopathy. Restoration of PKP2 expression leads to a significant extension of lifespan by restoring cellular structures of desmosomes and gap junctions, preventing or halting decline in left ventricular ejection fraction, preventing or reversing dilation of the right ventricle, ameliorating ventricular arrhythmia event frequency and severity, and preventing adverse fibrotic remodeling. RNA sequencing analyses show that restoration of PKP2 expression leads to highly coordinated and durable correction of PKP2-associated transcriptional networks beyond desmosomes, revealing a broad spectrum of biological perturbances behind ARVC disease etiology. CONCLUSIONS: We identify fundamental mechanisms of PKP2-associated ARVC beyond disruption of desmosome function. The observed PKP2 dose-function relationship indicates that cardiac-selective AAV9:PKP2 gene therapy may be a promising therapeutic approach to treat ARVC patients with PKP2 mutations.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart disease that leads to abnormal heartbeats and a higher risk of sudden cardiac death. ARVC is often caused by changes in a gene called PKP2, that then makes less PKP2 protein. PKP2 protein is important for the normal structure and function of the heart. Human ARVC characteristics can be mimicked in a mouse model missing this gene. Given no therapeutic option, our goal was to test if adding a working copy of PKP2 gene in the heart of this mouse model, using a technique called gene therapy that can deliver genes to cells, could improve heart function. Here, we show that a single dose of PKP2 gene therapy can improve heart function and heartbeats as well as extend lifespan in mice. PKP2 gene therapy may be a promising approach to treat ARVC patients with PKP2 mutations.

Astragali Radix: comprehensive review of its botany, phytochemistry, pharmacology and clinical application.

Astragali Radix (A. Radix) is the dried root of Astragalus membranaceus var. mongholicus (Bge) Hsiao or Astragalus membranaceus (Fisch.) Bge., belonging to the family Leguminosae, which is mainly distributed in China. A. Radix has been consumed as a tonic in China for more than 2000 years because of its medicinal effects of invigorating the spleen and replenishing qi. Currently, more than 400 natural compounds have been isolated and identified from A. Radix, mainly including saponins, flavonoids, phenylpropanoids, alkaloids, and others. Modern pharmacological studies have shown that A. Radix has anti-tumor, anti-inflammatory, immunomodulatory, anti-atherosclerotic, cardioprotective, anti-hypertensive, and anti-aging effects. It has been clinically used in the treatment of tumors, cardiovascular diseases, and cerebrovascular complications associated with diabetes with few side effects and high safety. This paper reviewed the progress of research on its chemical constituents, pharmacological effects, clinical applications, developing applications, and toxicology, which provides a basis for the better development and utilization of A. Radix.

Curcumae Radix: A Review of Traditional Use, Phytochemistry, Pharmacology, Toxicology and Quality Control.

Curcumae Radix (CuR) is a traditional Chinese medicine that has been used in China for more than 1,000 years. It has the traditional efficacy of activating blood and relieving pain, promoting qi and relieving depression, clearing heart and cooling blood, and promoting gallbladder and removing jaundice. Based on this, many domestic and foreign scholars have conducted systematic studies on its chemical composition, pharmacological effects, toxicity and quality control. Currently, 250 compounds, mainly including terpenoids and curcuminoids, have been isolated and identified from CuR, which has pharmacological activities, including antitumor, anti-inflammatory and analgesic, antidepressant, hepatoprotective, hemostatic, hematopoietic, and treatment of diabetes mellitus. In modern clinical practice, CuR is widely used in the treatment of tumors, breast hyperplasia, hepatitis, and stroke. However, the generation of toxicity and clinical application of CuR and Caryophylli Flos, the determination of the concoction process of artifacts, the determination of specific Quality Marker, and the establishment of the quality control system of CuR, are problems that need to be solved urgently at present.

Research progress of the detection and analysis methods of heavy metals in plants.

Heavy metal (HM)-induced stress can lead to the enrichment of HMs in plants thereby threatening people's lives and health via the food chain. For this reason, there is an urgent need for some reliable and practical techniques to detect and analyze the absorption, distribution, accumulation, chemical form, and transport of HMs in plants for reducing or regulating HM content. Not only does it help to explore the mechanism of plant HM response, but it also holds significant importance for cultivating plants with low levels of HMs. Even though this field has garnered significant attention recently, only minority researchers have systematically summarized the different methods of analysis. This paper outlines the detection and analysis techniques applied in recent years for determining HM concentration in plants, such as inductively coupled plasma mass spectrometry (ICP-MS), atomic absorption spectrometry (AAS), atomic fluorescence spectrometry (AFS), X-ray absorption spectroscopy (XAS), X-ray fluorescence spectrometry (XRF), laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), non-invasive micro-test technology (NMT) and omics and molecular biology approaches. They can detect the chemical forms, spatial distribution, uptake and transport of HMs in plants. For this paper, the principles behind these techniques are clarified, their advantages and disadvantages are highlighted, their applications are explored, and guidance for selecting the appropriate methods to study HMs in plants is provided for later research. It is also expected to promote the innovation and development of HM-detection technologies and offer ideas for future research concerning HM accumulation in plants.

Genus Helleborus: a comprehensive review of phytochemistry, pharmacology and clinical applications.

The genus Helleborus belongs to the Ranunculaceae family, distributed in southeastern Europe and western Asia. In folk medicine, it is commonly used as an anti-inflammatory and analgesic medicine for rheumatoid arthritis and bruises. Through reviewing recent articles, it was found that two hundred and twenty-six compounds have been isolated and identified from the genus Helleborus. These compounds include steroids, flavonoids, phenylpropanoids, lignans, anthraquinones, phenolics and others. Among them, the main chemical constituents are steroids. Pharmacological studies show Helleborus has anti-cancer, immunomodulatory, anti-inflammatory, analgesic, anti-hyperglycaemic, antioxidant and antibacterial properties. This article reviews the botany, phytochemistry, pharmacological effects and clinical applications of the genus Helleborus. Hopefully, it will provide a reference for in-depth research and exploitation of the genus Helleborus.