Efficacy of Qingpeng ointment (a Tibetan medicine) for acute gouty arthritis: a multi-center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: This study aims to assess the efficacy and safety of Qingpeng ointment (QPO), a Tibetan medicine for alleviating symptoms in individuals with acute gouty arthritis (AGA). METHODS: This study was a randomized, double-blind, placebo-controlled trial that involved individuals with AGA whose joint pain, as measured on a visual analog scale (VAS) from 0 to 10, was equal to or greater than 3. The participants were randomly assigned to either the QPO or the placebo group and received their respective treatments twice daily for seven consecutive days. In case of intolerable pain, the participants were allowed to use diclofenac sodium sustained-release tablets as a rescue medicine. The primary outcomes measured were joint pain and swelling, while the secondary outcomes included joint mobility, redness, serum uric acid levels, C-reactive protein levels, and the amount of remaining rescue medicine. Any adverse events that occurred during the trial were also recorded. RESULTS: A total of 203 cases were divided into two groups, with balanced baselines: 102 in the QPO group and 101 in the placebo group. For joint pain, differences between the groups were notable in the VAS scores [1.75 (0, 3.00) versus 2.00 (1.00, 3.50); P = 0.038], changes in VAS [5.00 (3.00, 6.00) versus 4.00 (2.00, 6.00); P = 0.036], and disappearance rate [26.47% compared to 15.84%; P = 0.046] after treatment. Concerning joint swelling, significant between-group differences were observed in the VAS scores [1.00 (0, 2.30) versus 2.00 (0.70, 3.00); P = 0.032] and disappearance rate [33.33% compared to 21.78%; P = 0.046] at treatment completion. The QPO group exhibited a statistically significant mobility improvement compared to the placebo group (P = 0.004). No significant differences were found in other secondary outcomes. Five patients, four from the QPO group and one from the other, encountered mild adverse events, primarily skin irritation. All of these cases were resolved after dosage reduction or discontinuation of the medication. CONCLUSIONS: Compared to the placebo, QPO exhibits positive effects on AGA by alleviating pain, reducing swelling, and enhancing joint mobility, without causing significant adverse effects. TRIAL REGISTRATION: ISRCTN34355813. Registered on 25/01/2021.

Progress of nanopreparation technology applied to volatile oil drug delivery systems.

Traditional Chinese medicine volatile oil has a long history and possesses extensive pharmacological activity. However, volatile oils have characteristics such as strong volatility, poor water solubility, low bioavailability, and poor targeting, which limit their application. The use of volatile oil nano drug delivery systems can effectively improve the drawbacks of volatile oils, enhance their bioavailability and chemical stability, and reduce their volatility and toxicity. This article first introduces the limitations of the components of traditional Chinese medicine volatile oils, discusses the main classifications and latest developments of volatile oil nano formulations, and briefly describes the preparation methods of traditional Chinese medicine volatile oil nano formulations. Secondly, the limitations of nano formulation technology are discussed, along with future challenges and prospects. A deeper understanding of the role of nanotechnology in traditional Chinese medicine volatile oils will contribute to the modernization of volatile oils and broaden their application value.

Multimodal integrated strategy for the discovery and identification of antiplatelet aggregation Q-markers in Paris polyphylla var. yunnanensis.

To enhance the quality evaluation and control of traditional Chinese medicine (TCM) and ensure the safety and efficacy of clinical medication, it is imperative to establish a comprehensive quality assessment method aligned with TCM efficacy. This study uses a representative Chinese medicine with multi-origin and multi-efficacy, Paris polyphylla var. yunnanensis (PY), as an illustrative example. Surprisingly, despite the high fingerprint similarity among the 12 batches of PY samples collected from various regions in Yunnan, a notable variation in the composition and content of components was observed. The chromatographic analysis identified seven common peaks, namely, polyphyllin I, polyphyllin II, polyphyllin V, polyphyllin VI, polyphyllin VII, polyphyllin H, and polyphyllin D. In the bioactivity evaluation, an in vitro antiplatelet aggregation model induced by adenosine diphosphate was established, showcasing excellent stability. The maximum antiplatelet aggregation inhibition rate for all PY samples consistently remained stable at 73.1%-99.1%. However, the 50% inhibitory concentration (IC50 ) values exhibited a range from 1.615 to 18.200 mg/mL. This approach not only meets high-throughput screening requirements but also demonstrates remarkable discrimination. The results of chemical and bioactivity evaluations were analyzed using hierarchical cluster analysis and canonical correlation analysis. Polyphyllin I, polyphyllin II, polyphyllin VII, polyphyllin H, and polyphyllin D were identified as the Q-markers for antiplatelet aggregation in PY samples. Validation of the bioactivity for these monomer components aligned with the previously mentioned findings. Notably, this study established a spectrum-effect model for PY samples, enhancing the scientific robustness of the quality evaluation method. Furthermore, these findings offer valuable research insights for improving the quality assessment of other TCMs.

The effect of phytosterol supplementation on lipid profile: A critical umbrella review of interventional meta-analyses.

Despite multiple investigations assessing the impact of phytosterol supplementation on serum lipid levels, there is still a great deal of debate regarding the benefits of this intervention in the management of dyslipidemia. Therefore, we aimed at clarifying this dilemma by conducting the present umbrella review of interventional meta-analyses. Scopus, PubMed, Web of Science, and EMBASE were used to search for pertinent publications on the effect of phytosterol supplementation on the lipid profile in humans up to June 2023. To compute the overall effect size (ES) and confidence intervals (CI), the random-effects model was used. The I2 statistic and Cochrane's Q-test were applied to estimate the heterogeneity among the studies. Seventeen meta-analyses with 23 study arms were included in the umbrella meta-analysis. Data pooled from the 23 eligible arms revealed that phytosterol supplementation reduces low-density lipoprotein cholesterol (LDL-C) (ES = -11.47 mg/dL; 95% CI: -12.76, -10.17, p < 0.001), total cholesterol (TC) (ES = -13.02 mg/dL; 95% CI: -15.68, -10.37, p < 0.001), and triglyceride (TG) (ES = -3.77 mg/dL; 95% CI: -6.04, -1.51, p = 0.001). Subgroup analyses showed that phytosterol administration with dosage ≥2 g/day and duration over 8 weeks and in hypercholesterolemic subjects was more likely to decrease LDL-C, TC, and TG. Phytosterol administration did not significantly modify HDL-C (ES = 0.18 mg/dL; 95% CI: -0.13, -0.51, p = 258) levels when compared to controls. The present umbrella meta-analysis confirms that phytosterol administration significantly reduces LDL-C, TC, and TG, with a greater effect with doses of ≥2 g/day and treatment duration >8 weeks, suggesting its possible application as a complementary therapy for cardiovascular risk reduction. Further studies are needed to determine the efficacy of phytosterols in patients with specific health conditions, as well as to ascertain the adverse effects, the maximum tolerable dose, and the maximum recommended duration of phytosterol administration.

Assembly and comparative analysis of the first complete mitochondrial genome of a traditional Chinese medicine Angelica biserrata (Shan et Yuan) Yuan et Shan.

Duhuo, a member of the Angelica family, is widely used to treat ailments such as rheumatic pain. It possesses a diverse array of bioactivities, including anti-tumor, anti-inflammatory, and analgesic properties, as recent pharmacological research has revealed. Nevertheless, the mtDNA of Angelica species remains relatively unexplored. To address this gap, we sequenced and assembled the mtDNA of A. biserrata to shed light on its genetic mechanisms and evolutionary pathways. Our investigation indicated a distinctive multi-branched conformation in the A. biserrata mtDNA. A comprehensive analysis of protein-coding sequences (PCGs) across six closely related species revealed the presence of 11 shared genes in their mitochondrial genomes. Intriguingly, positive selection emerged as a significant factor in the evolution of the atp4, matR, nad3, and nad7 genes. In addition, our data highlighted a recurring trend of homologous fragment migration between chloroplast and mitochondrial organelles. We identified 13 homologous fragments spanning both chloroplast and mitochondrial genomes. The phylogenetic tree established a close relationship between A. biserrata and Saposhnikovia divaricata. To sum up, our research would contribute to the application of population genetics and evolutionary studies in the genus Acanthopanax and other genera in the Araliaceae family.

Multiomics analyses of two Leonurus species illuminate leonurine biosynthesis and its evolution.

The Lamiaceae family is renowned for its terpenoid-based medicinal components, but Leonurus, which has traditional medicinal uses, stands out for its alkaloid-rich composition. Leonurine, the principal active compound found in Leonurus, has demonstrated promising effects in reducing blood lipids and treating strokes. However, the biosynthetic pathway of leonurine remains largely unexplored. Here, we present the chromosome-level genome sequence assemblies of Leonurus japonicus, known for its high leonurine production, and Leonurus sibiricus, characterized by very limited leonurine production. By integrating genomics, RNA sequencing, metabolomics, and enzyme activity assay data, we constructed the leonurine biosynthesis pathway and identified the arginine decarboxylase (ADC), uridine diphosphate glucosyltransferase (UGT), and serine carboxypeptidase-like (SCPL) acyltransferase enzymes that catalyze key reactions in this pathway. Further analyses revealed that the UGT-SCPL gene cluster evolved by gene duplication in the ancestor of Leonurus and neofunctionalization of SCPL in L. japonicus, which contributed to the accumulation of leonurine specifically in L. japonicus. Collectively, our comprehensive study illuminates leonurine biosynthesis and its evolution in Leonurus.

The impact of medroxyprogesterone acetate on lipid profiles in Women: A time and dose-response meta-analysis of randomized controlled trials.

BACKGROUND: The effect of MPA on the lipid profile and CVD risk is still controversial; hence, this comprehensive dose-response meta-analysis of randomized controlled trials was conducted to assess the effect of MPA on lipid profiles in women. METHODS: A comprehensive search was conducted in the following databases: Web of Science, Scopus, PubMed/Medline, and Embase, up to October 20, 2023. A random-effects meta-analysis approach based on the DerSimonian and Laird method was used to compute the combined estimates of the intervention's impact on the lipid profile. RESULTS: 35 eligible studies with 58 arms were included in our meta-analyses analysis. Combined effect sizes suggested a significant effect of MPA on total cholesterol (TC) levels (WMD: -3.43 mg/dL, 95 % CI: -5.38 to -1.48, p < 0.001), HDL-C levels (WMD: -3.34 mg/dL, 95 % CI: -3.77 to -2.91, p < 0.001), and triglyceride (TG) levels (WMD: -9.13 mg/dL, 95 % CI: -10.92 to -7.33, p < 0.001). The subgroup meta-analysis revealed a more substantial reduction in TC in studies with dosages > 2.5 mg/day (WMD: -4.10 mg/dL), mean participant age lower than 60 years (WMD: -3.80 mg/dL), mean BMI lower than 25 kg/m2 (WMD: -5.61 mg/dL), duration of intervention of 12 months or more (WMD: -3.98 mg/dL), and when the baseline TC value was equal to or greater than 200 mg/dL (WMD: -4.13 mg/dL). CONCLUSIONS: The current meta-analysis showed a statistically significant decrease in TC, TG, and HDL-C levels and a non-significant increase in LDL-C levels after MPA administration in women.

Phyllanthi Tannin Loaded Solid Lipid Nanoparticles for Lung Cancer Therapy: Preparation, Characterization, Pharmacodynamics and Safety Evaluation.

The objective of the present study was to develop PTF-loaded solid lipid nanoparticles (PTF-SLNs) and investigate their efficacy in treating lung cancer. The PTF-SLNs were prepared by the thin film hydration method and verified by FTIR and TEM. Their physicochemical properties were characterized by particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE), drug loading (DL), etc. Then, the pharmacodynamic studies of PTF-SLNs were performed on Lewis lung cancer cells and tumor-bearing mice. Finally, the safety studies were assessed by organ index, serum biochemical indicators, and histopathological changes. The PTF-SLNs were characterized by around 50 nm sphere nanoparticles, sustained ideal stability, and controlled drug release effects. The pharmacodynamic evaluation results showed that PTF-SLNs had stronger anti-tumor efficacy than PTF. An in vitro study revealed a more obvious cytotoxicity and apoptosis effect. The IC 50 values of PTF and PTF-SLNs were 67.43 µg/mL and 20.74 µg/mL, respectively. An in vivo study showed that the tumor inhibition rates of 2 g/kg PTF and 0.4 g/kg PTF-SLNs were 59.97% and 64.55%, respectively. The safety preliminary study indicated that PTF-SLNs improve the damage of PTF to normal organs to a certain extent. This study provides a nanoparticle delivery system with phenolic herbal extract to improve anti-tumor efficacy in lung cancer.

Effects of traditional Chinese culture-based bibliotherapy on the spiritual health of patients with liver cancer.

BACKGROUND: Liver cancer is a serious global health problem and is associated with poor spiritual health. Bibliotherapy is beneficial in improving health outcomes in cancer patients, yet there is a lack of empirical evidence of its effect on the spiritual health of liver cancer patients in China. The study aimed to investigate the effects of bibliotherapy based on Chinese traditional culture on the spiritual health of patients with liver cancer in China. This study was approved by the Ethics Committee of Hunan Normal University School of Medicine and registered with the Chinese Clinical Trial Registry with the registration (No: 2021260), which registration in June 30th 2021. METHODS: A total of 60 patients with liver cancer were divided into the intervention group (n = 30) and the control group (n = 30) through WeChat. The intervention group received bibliotherapy therapy based on traditional Chinese culture, while the control group received routine care. Spiritual health was assessed using the Spiritual Attitude and Involvement List (SAIL) and compared before and after the intervention between the two groups. The chi-square test and t-test were used to analyze the intervention effects. RESULTS: The two groups were comparable in all baseline characteristics including the SAIL score. After 5 weeks of intervention, the score of SAIL increased significantly from 96.76 ± 15.08 to 106.93 ± 13.82 in the intervention group (t = - 29.380, p < 0.001), while no significant difference in SAIL score was observed in the control group (from 95.27 ± 16.40 to 95.31 ± 16.24, t = - 0.189, p = 0.852). Similar patterns were also observed in its three dimensions of connecting with oneself, connecting with the environment, and connecting with transcendence. CONCLUSIONS: Our study showed that bibliotherapy based on traditional Chinese culture using the WeChat platform can greatly improve the spiritual health of patients with liver cancer and has the potential to be widely applied to cancer patients to improve their well-being.

Tauroursodeoxycholic Acid Inhibited Apoptosis and Oxidative Stress in H2O2-Induced BMSC Death via Modulating the Nrf-2 Signaling Pathway: the Therapeutic Implications in a Rat Model of Spinal Cord Injury.

Spinal cord injury (SCI) is a prevalent and significant injury to the central nervous system, resulting in severe consequences. This injury is characterized by motor, sensory, and excretory dysfunctions below the affected spinal segment. Transplantation of bone marrow mesenchymal stem cells (BMSCs) has emerged as a potential treatment for SCI. However, the low survival as well as the differentiation rates of BMSCs within the spinal cord microenvironment significantly limit their therapeutic efficiency. Tauroursodeoxycholic acid (TUDCA), an active ingredient found in bear bile, has demonstrated its neuroprotective, antioxidant, and antiapoptotic effects on SCI. Thus, the present study was aimed to study the possible benefits of combining TUDCA with BMSC transplantation using an animal model of SCI. The results showed that TUDCA significantly enhanced BMSC viability and reduced apoptosis (assessed by Annexin V-FITC, TUNEL, Bax, Bcl-2, and Caspase-3) as well as oxidative stress (assessed by ROS, GSH, SOD, and MDA) both in vitro and in vivo. Additionally, TUDCA accelerated tissue regeneration (assessed by HE, Nissl, MAP2, MBP, TUJ1, and GFAP) and improved functional recovery (assessed by BBB score) following BMSC transplantation in SCI. These effects were mediated via the Nrf-2 signaling pathway, as evidenced by the upregulation of Nrf-2, NQO-1, and HO-1 expression levels. Overall, these results indicate that TUDCA could serve as a valuable adjunct to BMSC transplantation therapy for SCI, potentially enhancing its therapeutic efficacy.

Integrating serum metabolomics and network analysis to explore the antidepressant activity of crocin in rats with chronic unexpected mild stress-induced depression.

CONTEXT: Crocin exhibits anti-depressant properties. However, its underlying mechanisms and its relationship with metabolomics remain unclear. OBJECTIVE: This study elucidates the mechanism of action and potential targets of crocin in treating chronic unexpected mild stress (CUMS)-induced depression in rats. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats underwent 4 weeks of CUMS to establish the depression model. The normal control (distilled water), crocin (25 mg/kg), and fluoxetine (5.4 mg/kg) groups were orally administered for 4-weeks. Behavioural tests evaluated the effects of crocin, while liquid chromatography-mass spectrometry metabolomics identified differential metabolites and their associated metabolic pathways. Subsequently, network pharmacology was utilized to predict the targets of crocin. RESULTS: Crocin significantly increased body weight (from 319.16 ± 4.84 g to 325.67 ± 2.84 g), sucrose preference (from 0.46 ± 0.09 to 0.70 ± 0.09), vertical activity (from 2.83 ± 1.94 to 8 ± 2.36), horizontal activity (from 1 ± 0.63 to 4.5 ± 3.08) and decreased immobilization time (from 13.16 ± 2.69 to 3.97 ± 3.00). Metabolomics analysis identified 7 metabolites and 5 associated metabolic pathways. From the combined analysis of network pharmacology and metabolomics, three targets (PRMT1, CYP3A4, and GLB1) are the overlapping targets and the two most important metabolic pathways are tryptophan metabolism and glycerolipid metabolism. DISCUSSION AND CONCLUSIONS: This study provides insights into the antidepressant therapeutic effect of crocin and its underlying mechanisms. The findings contribute to a better understanding of the metabolic mechanism involved in the anti-depressant effect of crocin, establishing a strong foundation for future research in this area.

Comparative and phylogenetic analysis of Asparagus meioclados Levl. and Asparagus munitus Wang et S. C. Chen plastomes and utility of plastomes mutational hotspots.

Tiandong is a vital traditional Chinese herbal medicine. It is derived from the tuber root of the Asparagus cochinchinensis according to the Pharmacopoeia of the people's republic of China (2020 Edition). On account of the similar morphology, Asparagus meioclados and Asparagus munitus were used as Tian-Dong in southwest China. Chloroplast (cp) genomes are highly active genetic components of plants and play an extremely important role in improving the efficiency of the identification of plant species. To differentiate the medicinal plants belonging to the genus Asparagus, we sequenced and analyzed the complete plastomes (plastid genomes) of A. meioclados and A. munitus and obtained two plastomes whose length changed to 156,515 bp and 156,381 bp, respectively. A total of 111 unique genes have been detected in plastome, which included 78 protein-coding genes, 29 tRNA genes and 4 rRNA genes. In plastomes of A. meioclados and A. munitus, 14,685 and 14,987 codons were detected, among which 9942 and 10,207 had the relative synonymous codon usage (RSCU) values higher than 1, respectively. A. meioclados and A. munitus have 26 SSRs patterns, among which A. meioclados was 25 and A. munitus 21. The average Ka/Ks value was 0.36, and positive selection was detected in genes of the photosynthetic system (ndhF and rbcL) in Asparagus species. To perform the comparative analysis of plastomes, the two newly sequenced plastomes of the A. meioclados and A. munitus species were compared with that of A. cochinchinensis, and 12 hotspots, including 5 coding regions and 7 inter-genomic regions, were identified. Based on the whole plastome of Asparagus, 2 divergent hotspots (accD and rpl32-trnL-UAG) and 1 international barcode fragment (rbcL) were screened, which may be used as particular molecular markers for the identification of Asparagus species. In addition, we determined the phylogenetic relationship between A. meioclados and A. munitus in the genus Asparagus. This study enriches our knowledge of the molecular evolutionary relationships of the Asparagus genus and provides treasured data records for species identification, molecular breeding, and evolutionary analysis of this genus.

Combination of bioaffinity ultrafiltration-UFLC-ESI-Q/TOF-MS/MS, in silico docking and multiple complex networks to explore antitumor mechanism of topoisomerase I inhibitors from Artemisiae Scopariae Herba.

BACKGROUND: Artemisiae Scopariae Herba (ASH) has been widely used as plant medicine in East Asia with remarkable antitumor activity. However, the underlying mechanisms have not been fully elucidated. METHODS: This study aimed to construct a multi-disciplinary approach to screen topoisomerase I (topo I) inhibitors from ASH extract, and explore the antitumor mechanisms. Bioaffinity ultrafiltration-UFLC-ESI-Q/TOF-MS/MS was used to identify chemical constitution of ASH extract as well as the topo I inhibitors, and in silico docking coupled with multiple complex networks was applied to interpret the molecular mechanisms. RESULTS: Crude ASH extract exhibited toxicogenetic and antiproliferative activities on A549 cells. A series of 34 ingredients were identified from the extract, and 6 compounds were screened as potential topo I inhibitors. Docking results showed that the formation of hydrogen bond and π-π stacking contributed most to their binding with topo I. Interrelationships among the 6 compounds, related targets and pathways were analyzed by multiple complex networks model. These networks displayed power-law degree distribution and small-world property. Statistical analysis indicated that isorhamnetin and quercetin were main active ingredients, and that chemical carcinogenesis-reactive oxygen species was the critical pathway. Electrophoretic results showed a therapeutic effect of ASH extract on the conversion of supercoiled DNA to relaxed forms, as well as potential synergistic effect of isorhamnetin and quercetin. CONCLUSIONS: The results improved current understanding of Artemisiae Scopariae Herba on the treatment of tumor. Moreover, the combination of multi-disciplinary methods provided a new strategy for the study of bioactive constituents in medicinal plants.

Deficit irrigation combined with nitrogen application in the early growth stage of sugar beet increases the production capacity of canopy and avoids yield loss.

BACKGROUND: Properly reduced irrigation combined with nitrogen (N) application can be used to improve crop water use efficiency (WUE) in arid regions, but its effect on sugar beet is unknown at present. A two-year field experiment was conducted to evaluate the effects of N application (N0, 0; N1, 150; N2, 225 kg N ha-1 ) on the canopy production capacity (CPC), yield and WUE of sugar beet under normal irrigation (W1, 70% of field capacity (FC)) and deficit irrigation (DI) (W2, 50% FC) in the early growth stage (EGS). RESULTS: The results showed that the W2 treatment reduced the CPC by reducing gas exchange, leaf area index (LAI) and chlorophyll content (SPAD value) of sugar beet leaves compared to the W1 treatment. However, DI combined with N application increased these parameters. Specifically, N application increased the net photosynthetic rate by 40.7% by increased gas exchange, SPAD and LAI compared to the N0 treatment. In addition, N application increased WUE by 12.5% by increasing thickness of upper surface, stomatal aperture and cross-sectional area of petiole. This ultimately led to a significant increase in taproot yield (TY; 19.7%) and sugar yield (SY; 57.6%). Although the TY of the N2 treatment was higher than that of the N1 treatment, the SY and WUE did not increase significantly and the harvest index decreased significantly by 9.3%. CONCLUSION: DI combined with 150 kg N ha-1 in the EGS of sugar beet increases the WUE in arid areas while avoiding yield loss by improving the CPC. © 2023 Society of Chemical Industry.

Qi-Dong-Huo-Xue-Yin balances the immune microenvironment to protect against LPS induced acute lung injury.

COVID-19 induces acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and leads to severe immunological changes that threatens the lives of COVID-19 victims. Studies have shown that both the regulatory T cells and macrophages were deranged in COVID-19-induced ALI. Herbal drugs have long been utilized to adjust the immune microenvironment in ALI. However, the underlying mechanisms of herbal drug mediated ALI protection are largely unknown. This study aims to understand the cellular mechanism of a traditional Chinese medicine, Qi-Dong-Huo-Xue-Yin (QD), in protecting against LPS induced acute lung injury in mouse models. Our data showed that QD intrinsically promotes Foxp3 transcription via promoting acetylation of the Foxp3 promoter in CD4+ T cells and consequently facilitates CD4+CD25+Foxp3+ Tregs development. Extrinsically, QD stabilized ß-catenin in macrophages to expedite CD4+CD25+Foxp3+ Tregs development and modulated peripheral blood cytokines. Taken together, our results illustrate that QD promotes CD4+CD25+Foxp3+ Tregs development via intrinsic and extrinsic pathways and balanced cytokines within the lungs to protect against LPS induced ALI. This study suggests a potential application of QD in ALI related diseases.

Integrated analysis of topoisomerase I inhibitors from flavonoids of Scutellaria baicalensis Georgi using bioaffinity ultrafiltration UPLC-TripleTOF MS/MS, molecular docking and target-based multiple complex networks.

Scutellaria baicalensis Georgi (SBG) has been widely used as medical plant in East Asia with remarkable anti-cancer activity. However, the underlying mechanisms are still confused. In this study, an integrated analysis was conducted to screen topoisomerase I (topo I) inhibitors from flavonoids of SBG and investigate the anti-cancer mechanisms, containing bioaffinity ultrafiltration UPLC-ESI-TripleTOF-MS/MS, molecular docking, and multiple complex networks. The SBG extract exhibited notable cytotoxic activity on Hela cells. Five flavonoids were identified as potential topo I inhibitors, including skullcapflavone II, wogonin, chrysin, oroxylin A, and tenaxin I. Their ESI-MS/MS spectra showed that RDA reaction and neutral molecule loss were the main fragment patterns. Docking results demonstrated that π-π interaction and the formation of hydrogen bond contributed most to their binding with topo I. The selected compounds, related target proteins and pathways were integrated into target-based multiple complex networks, which consisted of three subnetworks. Statistical and topological analysis of these networks revealed a series of characteristics, including scale-free property with power-law degree distribution, Poisson degree distribution, and small-world property. Chrysin, wogonin, and oroxylin A exhibited as main active components with much higher degree values. Chemical carcinogenesis-receptor activation (hsa05207) was considered as critical pathway due to remarkable centrality indexes. Additionally, potential synergistic effect of wogonin and chrysin was observed on the conversion of supercoiled DNA to relaxed forms. These results improved current understanding of flavonoid-rich plants on the treatment of cancer. Moreover, the multi-disciplinary approach provided a new strategy for the research of natural products from medical plants.

Discussion on the necessity of bilateral inguinal lymphatic area irradiation for cervical cancer with invasion of the lower one-third of the vagina.

Context: According to the National Comprehensive Cancer Network guidelines for cervical cancer, patients with cervical cancer invading the lower one-third of the vagina require bilateral inguinal lymphatic area preventive irradiation. However, it is not clear whether they need preventive inguinal area irradiation. Aims: The aim of this study is to evaluate the necessity of bilateral inguinal lymphatic area irradiation for patients with cervical cancer with invasion of the lower one-third of the vagina. Settings and Design: Patients without inguinal lymph node metastasis were divided into preventive radiotherapy and nonpreventive radiotherapy groups. The occurrence of inguinal skin damage, lower extremity edema, and femoral head necrosis was observed during and after treatment. Methods and Material: In total, 184 patients with cervical cancer with invasion of the lower one-third of the vagina were selected. A trial and control method was used to select 180 patients without inguinal lymph node metastasis. Statistical Analysis: Comparison between groups was performed using a t test. Data were enumerated using frequency (percentage), and comparison between groups was performed using a Chi-square test. Results: Imaging examination revealed inguinal lymph node enlargement in 7.07% of patients, and only four cases (2.17%) were further confirmed by pathology. The inguinal lymph node metastasis rate in these patients was very low. The prophylactic irradiation group showed a high occurrence rate of side injury. In the follow-up of both groups, no recurrence was detected in the inguinal lymph nodes. Conclusions: Prophylactic irradiation of inguinal lymph nodes is not essential for patients without pathological metastasis.

Integrated Metabolomics and Network Pharmacology Investigation of Cardioprotective Effects of Myricetin after 1-Week High-Intensity Exercise.

Cardiovascular adverse effects caused by high-intensity exercise (HIE) have become a public health problem of widespread concern. The therapeutic effect and metabolic regulation mechanism of myricetin, a phytochemical with potential therapeutic effects, have rarely been studied. In this study, we established mice models of different doses of myricetin intervention with 1 week of HIE after intervention. Cardiac function tests, serology, and pathological examinations were used to evaluate the protective effect of myricetin on the myocardium. The possible therapeutic targets of myricetin were obtained using an integrated analysis of metabolomics and network pharmacology and verified using molecular docking and RT-qPCR experiments. Different concentrations of myricetin improved cardiac function, significantly reduced the levels of myocardial injury markers, alleviated myocardial ultrastructural damage, reduced the area of ischemia/hypoxia, and increased the content of CX43. We obtained the potential targets and regulated metabolic network of myricetin by combined network pharmacology and metabolomics analysis and validated them by molecular docking and RT-qPCR. In conclusion, our findings suggest that myricetin exerts anti-cardiac injury effects of HIE through the downregulation of PTGS2 and MAOB and the upregulation of MAP2K1 and EGFR while regulating the complicated myocardial metabolic network.

Effects of online mindfulness-based interventions on the mental health of university students: A systematic review and meta-analysis.

Objectives: Mental health problems among university students are a cause of widespread concern. Mindfulness-based interventions (MBIs) delivered online have considerable potential to help university students manage mental health challenges. However, there is no consensus regarding the efficacy of online MBIs. This meta-analysis aims to determine whether MBIs are feasible and effective for improving university students' mental health. Methods: Randomised controlled trials (RCTs) in Web of Science, PubMed, Cochrane Library, Embase and the US National Library of Medicine (Clinical Trial Registry) published through August 31, 2022, were searched. Two reviewers selected the trials, conducted a critical appraisal, and extracted the data. Nine RCTs met our inclusion criteria. Results: This analysis showed that online MBIs were effective in improving depression (standardised mean difference [SMD] = -0.27; 95% confidence interval [CI], -0.48 to -0.07; P = 0.008), anxiety (SMD = -0.47; 95% CI, -080 to -0.14; P = 0.006), stress (SMD = -0.58; 95% CI, -0.79 to -0.37; P < 0.00001), and mindfulness (SMD = 0.71; 95% CI, 0.17 to 1.25; p = 0.009) in university students. No significant effect was found on wellbeing (SMD = 0.30; 95% CI, -0.00 to 0.60; P = 0.05). Conclusion: The findings indicated that online MBIs could effectively improve the mental health of university students. Nevertheless, additional rigorously designed RCTs are required. Systematic review registration: https://inplasy.com/inplasy-2022-9-0099/, identifier INPLASY202290099.

Manipulation and elimination of circulating tumor cells using multi-responsive nanosheet for malignant tumor therapy.

Tumor recurrence caused by metastasis is a major cause of death for patients. Thus, a strategy to manipulate the circulating tumor cells (CTCs, initiators of tumor metastasis ) and eliminate them along with the primary tumor has significant clinical significance for malignant tumor therapy. In this study, a magnet-NIR-pH multi-responsive nanosheet (Fe3O4@SiO2-GO-PEG-FA/AMP-DOX, FGPFAD) was fabricated to capture CTCs in circulation, then magnetically transport them to the primary tumor, and finally perform NIR-dependent photothermal therapy as well as acidic-environment-triggered chemotherapy to destroy both the CTCs and the primary tumor. The FGPFAD nanosheet consists of silica-coated ferroferric oxide nanoparticles (Fe3O4@SiO2, magnetic targeting agent), graphene oxide (GO, photothermal therapy agent), polyethylene glycol (PEG, antifouling agent for sustained circulation), folic acid (FA, capturer of CTCs) and antimicrobial-peptide-conjugated doxorubicin (AMP-DOX, agent for chemotherapy), in which the AMP-DOX was bound to the FGPFAD nanosheet via a cleavable Schiff base to achieve acidic-environment-triggered drug release for tumor-specific chemotherapy. Both in vitro and in vivo results indicated that the effective capture and magnetically guided transfer of CTCs to the primary tumor, as well as the multimodal tumor extermination performed by our FGPFAD nanosheet, significantly inhibited the primary tumor and its metastasis.