Positive benefit-risk ratio of Psoraleae Fructus: Comprehensive safety assessment and osteogenic effects in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoraleae Fructus (PF), the dried fruit of Psoralea corylifolia L., is a commonly used traditional medicine that has contributed to the treatment of orthopedic diseases for thousands of years in China. However, recent PF-related liver injury reports have drawn widespread attention regarding its potential hepatotoxicity risks. AIM OF THE STUDY: This study was aimed to evaluate the long-term efficacy and chronic toxicity of PF using a 26-week administration experiment on rats in order to simulate the clinical usage situation. MATERIALS AND METHODS: The PF aqueous extract was consecutively administrated to rats daily at dosages of 0.7, 2.0, and 5.6 g/kg (equivalent to 1-8 times the clinical doses for humans) for as long as 26 weeks. Samples were collected after 13, 26, and 32 weeks (withdrawal for 6 weeks) since the first administration. The chronic toxicity of PF was evaluated by conventional toxicological methods, and the efficacy of PF was evaluated by osteogenic effects in the natural growth process. RESULTS: In our experiments, only the H group (5.6 g/kg) for 26-week PF treatment demonstrated liver or kidney injury, which the injuries were reversible after 6 weeks of withdrawal. Notably, the PF treatment beyond 13 weeks showed significant benefits for bone growth and development in rats, with a higher benefit-risk ratio in female rats. CONCLUSIONS: PF displayed a promising benefit-risk ratio in the treatment and prevention of osteoporosis, a disease that lacks effective medicine so far. This is the first study to elucidate the benefit-risk balance associated with clinical dosage and long-term use of PF, thereby providing valuable insights for rational clinical use and risk control of PF.

Geniposide from Gardeniae Fructus exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The desiccative ripe fruits of Gardenia (Gardenia jasminoides Ellis) (called Zhizi in China) are known with cold character and the effects of reducing fire except vexed, clearing away heat evil, and cooling blood and eliminating stasis. Zhizi is often clinical formulated to treat various types of fever. Fever is a sign of inflammation and, geniposide from Zhizi has been proved with anti-inflammatory in various inflammatory models. AIM OF STUDY: The aim of this study was to investigate the antipyretic role of geniposide with three classical inflammatory fever models and explore the underlying mechanisms. MATERIALS AND METHODS: Water extract (WE), high polar part (HP), iridoid glycoside part (IG), and gardenia yellow pigment part (GYP) from Gardeniae Fructus (GF) were obtained from Zhizi. The antipyretic activities of these composes were tested with dry yeast induced fever rats. Geniposide was further purified from IG and the antipyretic activity was evaluated by gavage, intraperitoneal injection, and caudal intravenous injection to rats of fever induced by dry yeast, lipopolysaccharide (LPS), and 2, 4-dinitrophenol (DNP) in rats. Then, the mechanism of geniposide by intragastric administration was studied. The contents of thermoregulatory mediators and inflammatory factors relating to TLR4/NF-κB pathway in serum were determined by ELISA and Western blot, and the pathological changes of the hypothalamus were observed by HE staining. RESULTS: The temperature was decreased by geniposide in the three fever model rats. Geniposide can not only inhibit the increase of inflammatory factors in serum but also protect the hypothalamus from fever pathological damage in the three fever models. Western blot showed that geniposide could inhibit the TLR4/NF-κB pathway. CONCLUSION: Geniposide exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.

Exploring the mechanism and phytochemicals in Psoraleae Fructus-induced hepatotoxicity based on RNA-seq, in vitro screening and molecular docking.

Psoraleae Fructus (PF) is a widely-used herb with diverse pharmacological activities, while its related hepatic injuries have aroused public concerns. In this work, a systematic approach based on RNA sequencing (RNA-seq), high-content screening (HCS) and molecular docking was developed to investigate the potential mechanism and identify major phytochemicals contributed to PF-induced hepatotoxicity. Animal experiments proved oral administration of PF water extracts disturbed lipid metabolism and promoted hepatic injuries by suppressing fatty acid and cholesterol catabolism. RNA-seq combined with KEGG enrichment analysis identified mitochondrial oxidative phosphorylation (OXPHOS) as the potential key pathway. Further experiments validated PF caused mitochondrial structure damage, mtDNA depletion and inhibited expressions of genes engaged in OXPHOS. By detecting mitochondrial membrane potential and mitochondrial superoxide, HCS identified bavachin, isobavachalcone, bakuchiol and psoralidin as most potent mitotoxic compounds in PF. Moreover, molecular docking confirmed the potential binding patterns and strong binding affinity of the critical compounds with mitochondrial respiratory complex. This study unveiled the underlying mechanism and phytochemicals in PF-induced liver injuries from the view of mitochondrial dysfunction.

Association between polymorphism and haplotype of ATP2B1 gene and skeletal fluorosis in Han population.

To evaluate the association between ATP2B1 gene polymorphisms and skeletal fluorosis, a cross-sectional study was conducted. In China, 962 individuals were recruited, including 342 cases of skeletal fluorosis. Four TP2BA1 polymorphisms (rs2070759, rs12817819, rs17249754, and rs7136259) were analysed. The results suggested that rs17249754 and rs7136259 were associated with skeletal fluorosis. After controlling confounders, the protective effect of GG genotype in rs17249754 was apparent in individuals over 45 years old, female, with urine fluoride concentration below 1.6 mg/L, serum calcium above 2.25 mmol/L or serum phosphorus between 1.1 and 1.3. Heterozygote TC in rs7136259 increased the risk of skeletal fluorosis in subjects who are elderly, female, with urinary fluoride more than 1.6 mg/L, serum calcium more than 2.25 mmol/L and blood phosphorus between 1.1 and 1.3 mmol/L. Four loci were found to be tightly related by linkage disequilibrium analysis, and the frequency of distribution of haplotype GCGT was lower in the skeletal fluorosis group.

DIA-based serum proteomics revealed the protective effect of modified siwu decoction against hypobaric hypoxia.

ETHNOPHARMACOLOGICAL RELEVANCE: Siwu decoction (SWD) is a common traditional formula for nourishing blood, and its derived formulas are also widely used in traditional Chinese medicine (TCM) clinic. However, the protective effects of SWD and its derived formulas on blood deficiency and blood stasis caused by rushing to the plateau are rarely reported, and the underlying mechanism has not been fully elucidated. AIM OF THE STUDY: This study explores the pharmacological effects and mechanisms of modified siwu decoction (MSWD) adding Persicae Semans (Prunus persica (L.) Batsch) and Carthami Flos (Carthamus tinctorius L.) against hypobaric hypoxia (HH). The acute toxicity of MSWD was also evaluated to further validate the potential of MSWD as a therapeutic candidate for HH. MATERIALS AND METHODS: Hypoxic models of C57BL/6 J and KM male mice were used to evaluate the pharmacological effect of MSWD. 2 µL serum sample of C57BL/6 J mice was digested into peptide mixtures and analyzed with DIA mode on an Orbitrap Fusion Lumos mass spectrometer after LC separation. The peptide and protein identifications were limited to a 1% FDR. Screening of differential expressed proteins, correlation analysis, hierarchical clustering analysis, principal components analysis and Mfuzz analysis were all performed by R packages. The protein-protein interaction network was analyzed using the STRING website and constructed with Cytoscape software. RESULTS: MSWD showed a protective effect against acute hypoxia exposure through increasing the number of red blood cells and improving hemodynamics indexes in mice. Meanwhile, the biochemical results showed that MSWD could reduce the inflammation and oxidative stress, reduce the content of organ injury biomarkers and significantly improve the high-intensity exercise ability of mice. Subsequently, serum DIA proteomic results revealed significant changes in proteomic characteristics after MSWD intervention. Specifically, proteins related to oxidative stress and ubiquitin-proteasome system, such as Sod1, Gstp1, Vcp and Usp14, were down-regulated after MSWD intervention, suggesting that the protective effect of MSWD involved the reduction of oxidative stress and energy expenditure. MSWD also intervened in energy metabolism and lipid metabolism processes by altering the expression levels of Eno1, Sphk1 and Apoa1 to ameliorate hypoxia-induced disorders. At the same time, MSWD acute toxicity test showed no obvious toxicity. CONCLUSIONS: MSWD has a good protective effect against HH by ameliorating hypoxia-induced disorders of energy and lipid metabolism, supporting MSWD as a safe drug candidate for the prevention and treatment of acute hypoxia fatigue.

Bavachin induces liver injury and cell apoptosis by targeting Wnt/ß-catenin/DRP1 signaling pathway mediated mitochondrial dysfunction.

Psraleae Fructus (PF) is a well-known traditional Chinese medicine in China. While numerous liver injury reports caused by PF limits its clinical application. Bavachin, a flavonoid compound isolated from the fruits of Psoralea corylifolia L., has been validated to induce direct apoptosis in hepatocytes and liver tissues in our previous studies. However, the subcellular mechanisms of bavachin induced liver injury is still elusive. Here, utilizing 6-week-old C57BL/6 J mice and human embryonic hepatocytes (L02 cells), we report that bavachin activates dynamic-related protein 1 (DRP1) mediated excess mitochondrial fission and endoplasmic reticulum (ER) stress related apoptosis via Wnt/ß-catenin signaling pathway. Notably, DRP1 knockdown or XAV-939 induced Wnt/ß-catenin inhibition decreased bavachin-induced ER stress and cell apoptosis in L02 cells. In addition, bavachin impaired mitochondrial structural and function in the mice liver tissues. Mdivi-1, a mitochondrial fission inhibitor targeting DRP1, prevented bavachin-induced mitochondrial and ER structural damage, ER stress, and liver injury. Our results demonstrated that bavachin induced mitochondrial fission plays a crucial role in bavachin induced ER stress related liver injury, via the mechanism that involved activation of Wnt/ß-catenin signaling pathway.

Dissection of scientific compatibility of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia from the perspective of toxicology.

ETHNOPHARMACOLOGICAL RELEVANCE: Realgar-Indigo naturalis formula (RIF), a first-line drug for the treatment of acute promyelocytic leukemia (APL),is also a TCM formula entirely designed based on TCM theories. There have been studies that explain the scientific connotation of the compatibility of RIF from the perspective of pharmacodynamics. However, as one of the arsenic-containing preparations, the safety of realgar is widely concerned, and there has not been systematic studies to explain the scientific connotation of RIF from the perspective of toxicology. AIM OF THIS STUDY: Dissection of scientific compatibility of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia from the perspective of toxicology. MATERIALS AND METHODS: We used normal mice and an APL model to explore (i) the effects of different components on intestinal permeability, (ii) the changes in intestinal flora, and (iii) toxic effects. At the same time, a bionic extraction method was used to study the effects of different components on the dissolution of soluble arsenic in realgar under the acidic environment in the stomach and the alkaline environment in the intestinal tract. RESULTS: Salvia miltiorrhiza Bunge can repair the intestinal mucosal barrier, maintain the homeostasis of intestinal flora, intervene in the dissolution process of realgar, reverse the increase in intestinal permeability and the disturbance of intestinal flora caused by realgar, and reduce toxicity. CONCLUSION: From the perspective of toxicology, we propose new insights into the definition of the roles of each component in the RIF formula, namely realgar is the monarch, Indigo naturalis is the minister, Salvia miltiorrhiza Bungeis the assistant.

[Molecular mechanism of ginsenoside Rg_1 against radiation enteritis: based on network pharmacology and in vitro experiment].

Via network pharmacology, molecular docking, and cellular experiment, this study explored and validated the potential molecular mechanism of ginsenoside Rg_1(Rg_1) against radiation enteritis. Targets of Rg_1 and radiation enteritis were retrieved from BATMAN-TCM, SwissTargetPrediction, and GeneCards. Cytoscape 3.7.2 and STRING were employed for the construction of protein-protein interaction(PPI) network for the common targets, and screening of core targets. DAVID was used for Gene Ontology(GO) term and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict the possible mechanism, followed by molecular docking of Rg_1 with core targets and cellular experiment. For the cellular experiment, ~(60)Co-γ irradiation was performed for mo-deling of IEC-6 cells, which were then treated with Rg_1, protein kinase B(AKT) inhibitor LY294002, and other drugs to verify the effect and mechanism of Rg_1. The results showed that 29 potential targets of Rg_1, 4 941 disease targets, and 25 common targets were screened out. According to the PPI network, the core targets were AKT1, vascular endothelial growth factor A(VEGFA), heat shock protein 90 alpha family class A member 1(HSP90AA1), Bcl-2-like protein 1(BCL2L1), estrogen receptor 1(ESR1), etc. The common targets were mainly involved in the GO terms such as positive regulation of RNA polymerase Ⅱ promoter transcription, signal transduction, positive regulation of cell proliferation, and other biological processes. The top 10 KEGG pathways included phosphoinositide 3-kinase(PI3K)/AKT pathway, RAS pathway, mitogen-activated protein kinase(MAPK) pathway, Ras-proximate-1(RAP1) pathway, and calcium pathway, etc. Molecular docking showed that Rg_1 had high binding affinity to AKT1, VEGFA, HSP90AA1, and other core targets. Cellular experiment indicated that Rg_1 can effectively improve cell viability and survival, decrease apoptosis after irradiation, promote the expression of AKT1 and B-cell lymphoma-extra large(BCL-XL), and inhibit the expression of the pro-apoptotic protein Bcl-2-associated X protein(BAX). In conclusion, through network pharmacology, molecular docking, and cellular experiment, this study verified the ability of Rg_1 to reduce radiation enteritis injury. The mechanism was that it regulated PI3K/AKT pathway, thereby suppressing apoptosis.

An Intelligent Vascular Disrupting Dendritic Nanodevice Incorporating Copper Sulfide Nanoparticles for Immune Modulation-Mediated Combination Tumor Therapy.

Development of intelligent nanoplatforms that can simultaneously target multiple factors associated with tumor growth and metastasis remains an extreme challenge. Here, an intelligent dendritic nanodevice incorporating both copper sulfide nanoparticles (CuS NPs) and 5,6-dimethylxanthenone-4-acetic acid (DMXAA, a vascular disrupting agent) within the dendrimer internal cavities and surface modified with a targeting agent LyP-1 peptide is reported. The resulting generation 5 (G5) dendrimer-based nanodevice, known as G5-PEG-LyP-1-CuS-DMXAA NPs (GLCD NPs), possess good colloidal stability, pH-sensitive drug release kinetics, and high photothermal conversion efficiency (59.3%). These functional GLCD NPs exert a LyP-1-targeted killing effect on breast tumors by combining CuS-mediated photothermal therapy (PTT) and DMXAA-induced vascular disruption, while also triggering antitumor immune responses through PTT-induced immunogenic cell death and DMXAA-mediated immune regulation via M1 polarization of tumor-associated macrophages and dendritic cell maturation. In addition, with the LyP-1-mediated proapoptotic activity, the GLCD NPs can specifically kill tumor lymphatic endothelial cells. The simultaneous disruption of tumor blood vessels and lymphatic vessels cuts off the two main pathways of tumor metastasis, which plays a two-pronged role in inhibiting lung metastasis of the breast cancer model. Thus, the developed GLCD NPs represent an advanced intelligent nanoformulation for immune modulation-mediated combination tumor therapy with potential for clinical translations.

Photothermal-triggered dendrimer nanovaccines boost systemic antitumor immunity.

Tumor vaccine that can effectively activate or strengthen the body's antitumor immune response to kill and eliminate tumor cells has attracted widespread attention. Currently developed tumor vaccines have severe shortcomings such as low bioavailability and lack of dual or multiple functions, resulting in poor antitumor efficacy. Herein, we report the development of an advanced nanosystem integrated with phenylboronic acid (PBA)-functionalized poly(amidoamine) dendrimers of generation 5 (G5), copper sulfide nanoparticles, and cyclic GMP-AMP (cGAMP), an immune adjuvant (for short, G5-PBA@CuS/cGAMP) to act as a photothermal-triggered nanovaccine. We show that the prepared functional nanosystem possesses an average CuS core size of 3.6 nm, prominent near-infrared absorption feature to have an excellent photothermal conversion efficiency of 44.0%, and good protein adsorption characteristics due to the PBA modification. With these features, the developed nanosystem can be adopted for photothermal therapy of primary melanoma tumors and simultaneously absorb the whole tumor cell antigens, thus creating photothermal-triggered dendrimeric nanovaccine of G5-PBA@CuS/cGAMP/antigen in situ to induce antitumor immune response to inhibit the distal tumors as well. Meanwhile, melanoma cells treated with the G5-PBA@CuS in vitro under laser irradiation allowed the creation of G5-PBA@CuS/antigen complexes that could be further integrated with cGAMP to form preformed nanovaccine for effective primary tumor inhibition and tumor occurrence prevention. The designed photothermal-triggered dendrimeric nanovaccine may represent an advanced nanomedicine formulation to effectively inhibit the growth of primary and distal tumors, and prevent tumor occurrence through the stimulated systemic antitumor immunity.

Carnosol inhibits KGN cells oxidative stress and apoptosis and attenuates polycystic ovary syndrome phenotypes in mice through Keap1-mediated Nrf2/HO-1 activation.

Excessive oxidative stress and apoptosis of ovarian granulosa cells lead to abnormal follicular development and ovulation disorders in polycystic ovary syndrome (PCOS). Carnosol is a plant-derived polyphenol that has been proven to exhibit several cell protective effects. In this study, we established hyperandrogenic PCOS models both in vitro and in vivo. In the human ovarian granulosa cell line, KGN cells, decreased viability and mitochondrial membrane potential, and upregulated reactive oxygen species (ROS) level and apoptosis induced by DHT were partly reversed by carnosol. Western blotting results showed that carnosol treatment inhibited the DHT-activated mitochondrial apoptotic pathway by activating nuclear factor-erythroid 2-related factor (Nrf2)/heme oxygenase 1 (HO-1). Knockdown of Nrf2 by transfecting with siRNA or inhibiting HO-1 by zinc protoporphyrin (ZnPP) blocked the protective effects of carnosol. Computational modeling and pull-down assay results confirmed the direct binding of carnosol to kelch-like ECH-associated protein 1 (Keap1). In vivo results showed that the intraperitoneal administration of carnosol (50 and 100 mg/kg) improved estrous cycle disorders, polycystic ovary, and decreased elevated androgen in the PCOS mice. In summary, Carnosol has an effective role in inhibiting oxidative stress and apoptosis in DHT-treated KGN cells and protecting against mouse PCOS phenotypes through the Keap1-mediated activation of Nrf2/HO-1 signaling.

The Mechanism of Houttuynia cordata Embryotoxicity Was Explored in Combination with an Experimental Model and Network Pharmacology.

Houttuynia cordata (H. cordata) is the most common herb as a food and traditional Chinese medicine. Currently, studies on its toxicity have mainly focused on hepatotoxicity. However, its potential embryotoxicity by long-term exposure is often overlooked. Objective: To investigate the effects of H. cordata on embryonic development and its toxicity mechanism by combining network pharmacology, molecular docking, and in vitro experimental methods. Methods: The effects of H. cordata on embryos were evaluated. Zebrafish embryos and embryoid bodies were administered to observe the effects of H. cordata on embryonic development. Based on network pharmacological analysis, it was found that the main active agents producing toxicity in H. cordata were oleanolic acid, lignan, and aristolactam AII. H. cordata can affect PI3K-Akt, MAPK, and Ras signaling pathways by regulating targets, such as AKT1, EGFR, CASP3, and IGF-1. RT-PCR and immunohistochemistry results showed that the expression of AKT1 and PI3K in the embryoid body was significantly reduced after drug administration (p < 0.05). Conclusions: The results of network pharmacology and in vitro experiments suggest that H. cordata may affect embryonic development by influencing the PI3K-Akt signaling pathway.

Yin-chen Wu-ling powder alleviate cholestatic liver disease: Network pharmacological analysis and experimental validation.

BACKGROUND: Yin-chen Wu-ling Powder (YWP) has potential therapeutic effects on cholestatic liver disease (CLD), however, its active compounds and conceivable mechanism are as yet indistinct. METHODS: The network pharmacology and gene function annotation examined the multiple active ingredients, potential targets, and possible mechanisms of YWP in CLD treatment. Then the molecular docking reassured the reliability of the core compounds including the key genes and farnesoid X receptor (FXR). Finally, The Mdr2-/- mice were used to test the effect and mechanism of YWP against CLD. RESULTS: The network analysis identified nine main active ingredients, including quercetin, capillarisin, eupalitin, isorhamnetin, skrofulein, genkwanin, cerevisterol, gederagenin, and sitosterol. The PPI network predicted the ten hub genes involved were AKT1, MAPK1, MAPK14, IL6, RXRA, ESR1, IL10, NCOA1, CAV1, and EGFR. The KEGG and GO analysis showed that YWP might contribute to CLD treatment through the PI3K/Akt and MAKP signalings to manage pathological reactions, for instance, inflammatory responses. The molecular docking displayed a functional similarity among the core compounds with ursodeoxycholic acid (UDCA) and Obeticholic acid (OCA) on the effects on AKT1, MAPK1, MAPK14, RXRA, and ESR, and the affinity to FXR. In addition, the YWP could significantly attenuate hepatic injury and improve inflammatory response in Mdr2-/- mice. The mechanism exploration showed that YWP mainly decreased inflammatory response by inhibiting AKT/P38MAPK signaling. CONCLUSION: This study firstly revealed the multiple active ingredients, potential targets, and possible mechanism of YWP to treat CLD based on network pharmacology Analysis and molecular docking. YWP could alleviate cholestasis in Mdr2-/- mice by impairing inflammation via inhibiting AKT/P38MAPK Signaling.

A global bibliometric and visualized analysis of the links between the autophagy and acute myeloid leukemia.

Background and objectives: Autophagy is a cellular process where damaged organelles or unwanted proteins are packaged into a double-membrane structure and transported to lysosomes for degradation. Autophagy plays a regulatory role in various hematologic malignancies, including acute myeloid leukemia (AML). However, there are few bibliometric studies on the role of autophagy in AML. The purpose of this study is to clarify the role of autophagy in acute myeloid leukemia through bibliometric analysis. Methods: The literature on autophagy and AML research from 2003 to 2023 was searched in Web of Science Core Collection, and bibliometric tools such as VOSviewer 1.6.18, Cite Space (6.1.R3), RStudio (R package bibliometrix), and Scimago Graphica were used to understand the current status and hotspots of autophagy and AML research. The study conducted an analysis of various dimensions including the quantity of publications, countries, institutions, journals, authors, co-references, keywords, and to predict future development trends in this field by drawing relevant visualization maps. Results: A total of 343 articles were obtained, published in 169 journals, written by 2,323 authors from 295 institutions in 43 countries. The journals with the most publications were Blood and Oncotarget. China had the most publications, and Chongqing Medical University and Sun Yat-sen University had the most publications. The author with the highest number of publications was Tschan, Mario P. The main types of research included clinical research, in vitro experiments, in vivo experiments, public database information, and reviews, and the forms of therapeutic effects mainly focused on genetic regulation, traditional Chinese medicine combination, autophagy inhibitors, and drug targets. The research hotspots of autophagy and AML in the past 17 years have focused on genetic regulation, autophagy inhibition, and targeted drugs. Chemotherapy resistance and mitochondrial autophagy will be the forefront of research. Conclusion: The gradual increase in the literature on autophagy and AML research and the decline after 2022 could be a result of authors focusing more on the type of research and the quality of the literature. The current research hotspots are mainly genetic regulation, autophagy inhibition, and autophagy-related targeted drugs. In future, autophagy will remain the focus of the AML field, with research trends likely to focus more on AML chemotherapy resistance and mitochondrial autophagy.

Medication rule of traditional Chinese medicine in the treatment of plateau hypoxia based on data mining. / 基于数据挖掘中药治疗高原性缺氧的组方规律.

OBJECTIVES: The development of traditional Chinese medicine (TCM) in the plateau area is relatively backward. There is a lack of system to analyze the effects of the special environment of plateau low pressure and hypoxia on human meridians qi and blood, as well as the etiology and pathogenesis of plateau hypoxic diseases. To analyze the composition rules of anti-hypoxia TCM formulation with data mining methods. METHODS: The experimental literatures related to high altitude hypoxia were searched in China National Knowledge Infrastructure (CNKI), Wanfang Med Online, VIP, China Biology Medicine disc and other databases, a standardized prescription database was established after screening and standardization of prescription data in the literature. The composition rules of these prescription including drug frequency, drug attributes, drug efficacy, drug combination, and core prescription were analyzed and displayed with visual charts. RESULTS: A total of 135 TCM prescriptions were included, and 229 flavored drugs were included. Among these prescriptions, the TCM with high frequency of use were Astragalus, Danshen, Ginseng, and Angelica, etc. Four natures of the TCM were mostly warm and calm. Five flavours of the TCM were mostly sweet, bitter, and pungent. And channel tropism of the TCM mostly entered the heart, lung, and liver meridians. The frequency combination of TCM was Astragalus-Danshen and Astragalus-Angelica. The core medicines of these prescriptions were Astragalus, Danshen, Angelica, Rhodiola, Goji, and Ginseng. TCM could alleviate symptoms such as chest tightness, chest pain, coughing and wheezing, coughing, vomiting, fatigue, and loss of appetite caused by hypoxia at high altitude. CONCLUSIONS: Through data mining, it is concluded that the prevention or treatment of plateau hypoxic diseases mostly utilized products can nourish blood, replenish qi and dispel stasis, and help yang and dispel qi, most of them are compatible with qi tonic drugs and blood circulation and stasis dissolving drugs, and pay attention to the combination of virtual and real, yin and yang.

[Clinical efficacy of Manlyman Spray combined with biofeedback therapy on premature ejaculation].

Objective： To observe the clinical effect of Manlyman Spray combined with biofeedback therapy in the treatment of premature ejaculation (PE)．Methods： A total of 60 primary premature ejaculation patients with stable sexual partners and regular sexual activity (≥１ times per week) from April 2021 to October 2022 were involved in the clinical observation, The patients' age is (34.3 ± 4.9) years old, and the course of the disease is (112.5 ± 65.5) months, and Manlyman Spray combined with biofeedback therapy was used to treat patients for 8 weeks. Manlyman Spray was sprayed 3 times on the surface of the penisqd for 4 weeks, and Biofeedback therapy is treated twice a week according to the AI setting module, for a total of 8 weeks. Before and 8 weeks after medication and at 4 weeks after drug withdrawal, the Intravaginal Ejaculation Latency Time (IELT), Premature Ejaculation Diagnostic Tool (PEDT) scores and Clinical Global Impression of Change (CGIC) scores were Obtained and compared. Results： After 8 weeks of treatment, the IELT of the patients was significantly prolonged (ï¼»351.4 ± 76.7ï¼½ vs ï¼»87 ± 16.8ï¼½,P<0.05) and at 4 weeks after drug withdrawal, the therapeutic effect still existed (ï¼»345.9 ± 80.3ï¼½ vs ï¼»87 ± 16.8ï¼½,P<0.05), the PEDT scores were significantly improved after treatment (ï¼»18.2 ± 1.1ï¼½ vs ï¼»9.0 ± 1.4ï¼½,P<0.05)and at 4 weeks after drug withdrawal(ï¼»18.0 ± 1.2ï¼½ vs ï¼»9.0 ± 1.4ï¼½,P<0.05), and so were the CGIC scores (ï¼»13.4 ± 1.3ï¼½ vs ï¼»3.3 ± 1.4ï¼½,P<0.05, and ï¼»12.6 ± 1.6ï¼½ vs ï¼»3.3 ± 1.4ï¼½,P<0.05). Conclusion： The combination of Manlyman Spray and biofeedback therapy can effectively treat primary premature ejaculation, with a long duration of treatment and good safety, and the specific mechanism needs further study.

A systematic review on the safety of Psoraleae Fructus: potential risks, toxic characteristics, underlying mechanisms and detoxification methods.

Psoraleae Fructus (PF) is an important traditional herbal medicine with a long history of clinical application. It is widely used to treat various diseases, such as osteoporosis, leucoderma and diarrhea. As a traditional nontoxic herb, it has aroused worldwide concern about the potential risks due to increasing adverse reaction events. This article reviews the botany, ancient records of medical uses, adverse reactions, toxicological research advance and detoxification methods of PF. According to clinical studies, liver injury is the most predominant in PF-related adverse reactions. The underlying mechanisms include bile acid metabolism and transport disorders, oxidative stress, mitochondrial damage, inhibition of liver cell regeneration and inflammatory reactions. Furthermore, the potential toxins of PF are summarized. Traditional methods of processing and compatibility will provide reference for reducing the toxicity of PF, which requires further research. In sum, this work systematically summarizes the reserach progress on the safety of PF, which will provide comprehensive insights into the toxicity of PF and facilitate its safe use and future development.

The Taste-Masking Mechanism of Chitosan at the Molecular Level on Bitter Drugs of Alkaloids and Flavonoid Glycosides from Traditional Chinese Medicine.

Taste masking of traditional Chinese medicines (TCMs) containing multiple bitter components remains an important challenge. In this study, berberine (BER) in alkaloids and phillyrin (PHI) in flavonoid glycosides, which are common bitter components in traditional Chinese medicines, were selected as model drugs. Chitosan (CS) was used to mask their unfriendly taste. Firstly, from the molecular level, we explained the taste-masking mechanism of CS on those two bitter components in detail. Based on those taste-masking mechanisms, the bitter taste of a mixture of BER and PHI was easily masked by CS in this work. The physicochemical characterization results showed the taste-masking compounds formed by CS with BER (named as BER/CS) and PHI (named as PHI/CS) were uneven in appearance. The drug binding efficiency of BER/CS and PHI/CS was 50.15 ± 2.63% and 67.10 ± 2.52%, respectively. The results of DSC, XRD, FTIR and molecular simulation further indicated that CS mainly masks the bitter taste by disturbing the binding site of bitter drugs and bitter receptors in the oral cavity via forming hydrogen bonds between its hydroxyl or amine groups and the nucleophilic groups of BER and PHI. The taste-masking evaluation results by the electronic tongue test confirmed the excellent taste-masking effects on alkaloids, flavonoid glycosides or a mixture of the two kinds of bitter components. The in vitro release as well as in vivo pharmacokinetic results suggested that the taste-masked compounds in this work could achieve rapid drug release in the gastric acid environment and did not influence the in vivo pharmacokinetic results of the drug. The taste-masking method in this work may have potential for the taste masking of traditional Chinese medicine compounds containing multiple bitter components.

Associations between dietary magnesium intake and handgrip strength were modified by serum vitamin D level among the US elderly.

Objective: The present study aimed to evaluate the associations between dietary magnesium intake and handgrip strength, and whether these associations were affected by serum vitamin D status. Methods: A total of 2,127 participants aged 60 and above from the National Health and Nutrition Examination Survey (NHANES) of the 2011-2014 cycles were included in the analyses. Magnesium intake was obtained by 24-h dietary recalls and 30-day dietary supplement. Participants in the lowest sex-specific tertile of magnesium intake were defined as having low magnesium intake. Serum 25-hydroxyvitamin D [25(OH)D)] concentrations were examined by using ultra-high performance liquid chromatography tandem mass spectrometry and categorized into three levels: deficient, suboptimal, and sufficient. Handgrip strength was determined by using a dynamometer. Multivariable linear regression models were used to investigate the associations between dietary magnesium intake and handgrip strength. Results: Low magnesium intake was not associated with handgrip strength, but interactions between low magnesium intake and serum 25(OH)D level existed on handgrip strength. The stratified analyses found that only in participants with deficient serum 25(OH)D, low magnesium intake was associated with reduced handgrip strength. The combined analyses shown that participants with both low magnesium intake and deficient serum 25(OH)D had highest decrease of handgrip strength. Conclusion: Findings suggested that low magnesium intake was associated with reduced handgrip strength only in participants with deficient serum 25(OH)D. Increased magnesium intake was recommended for participants with deficient serum 25(OH)D in maintaining muscle strength.