Comprehensive HRMS Screening and Risk Assessments of Aristolochic Acid Analogues in Asari Radix et Rhizoma and Related Commercial Health Products.

Aristolochic acid analogues (AAAs) are well-known toxins. We performed the first comprehensive screening on AAAs in Asari Radix et Rhizoma (underground part of Asarum heterotropoides Schmidt), the only Aristolochiaceae plant widely used in clinical practice. LC-HRMS revealed 70 trace AAAs using polygonal mass defect filtering and precursor ion list strategies, 38 of which were newly discovered in A. heterotropoides. UHPLC-QTrap-MS/MS was then utilized for quantitative/semiquantitative analysis of 26 abundant compounds. Seventeen AAAs were detected from 91 batches of A. heterotropoides and 20 AAAs from 166 consumable products. For 141 Asari-containing proprietary products, aristolactam I and aristolactam II-glucoside exhibited the widest distribution, present in 98% products. AA IVa was the most abundant, detected in 91%. Notably, 60% of the products contained AA I (0.03-0.79 ppm). The safety was assessed using linear extrapolation, permitted daily exposure, cumulative amount, and the margin of exposure. It is recommended that AA I content be limited to 3 ppm.

Targeting the PHF8/YY1 axis suppresses cancer cell growth through modulation of ROS.

High levels of mitochondrial reactive oxygen species (mROS) are linked to cancer development, which is tightly controlled by the electron transport chain (ETC). However, the epigenetic mechanisms governing ETC gene transcription to drive mROS production and cancer cell growth remain to be fully characterized. Here, we report that protein demethylase PHF8 is overexpressed in many types of cancers, including colon and lung cancer, and is negatively correlated with ETC gene expression. While it is well known to demethylate histones to activate transcription, PHF8 demethylates transcription factor YY1, functioning as a co-repressor for a large set of nuclear-coded ETC genes to drive mROS production and cancer development. In addition to genetically ablating PHF8, pharmacologically targeting PHF8 with a specific chemical inhibitor, iPHF8, is potent in regulating YY1 methylation, ETC gene transcription, mROS production, and cell growth in colon and lung cancer cells. iPHF8 exhibits potency and safety in suppressing tumor growth in cell-line- and patient-derived xenografts in vivo. Our data uncover a key epigenetic mechanism underlying ETC gene transcriptional regulation, demonstrating that targeting the PHF8/YY1 axis has great potential to treat cancers.

Species discrimination of multiple botanical origins of Fritillaria species based on infrared spectroscopy, thin layer chromatography-image analysis and untargeted metabolomics.

BACKGROUND: Fritillaria Bulbus (FB), a precious medicinal herb renowned for its heat-clearing, lung-moistening, cough-relieving and phlegm-eliminating effects. In pursuit of profits, unscrupulous merchants have engaged in the substitution or adulteration of valuable varieties with cheaper alternatives. It is, therefore, urgent to develop effective technical approaches to identify FBs from adulterants. METHODS: This paper employed infrared spectroscopy (IR), thin layer chromatography-image analysis (TLC-IA), and untargeted metabolomics techniques to discriminate ten species of FBs. RESULTS: Five species of FBs were successfully differentiated using mid-infrared spectroscopy. Furthermore, the power of TLC-IA technology allowed the differentiation of five species of FBs and two origins of FCBs (Fritillariae Cirrhosae Bulbus). Remarkably, through the application of untargeted metabolomics technique, the precise discrimination of five species of FBs, as well as three origins of FCBs were accomplished. Moreover, a comprehensive identification of 101 markers that reliably distinguished diverse FBs was achieved through the employment of untargeted metabolomics technique. CONCLUSION: The investigation presented powerful means of detection for assuring the quality control of Fritillaria herbs.

Ent-labdane-type diterpene glycosides obtained from Rubus chingii Hu and their inhibitory effects on PDE5A activity.

In this study, 16 new ent-labdane-type diterpene glycosides, designated as goshonosides J1-J16 (1-16), along with nine previously known diterpene glycosides (17-25) were extracted from the fruits of Rubus chingii Hu. The structures of goshonosides J1-J16 were elucidated using various analytical techniques, such as nuclear magnetic resonance, electron capture detector ECD, high-resolution electrospray ionization mass spectrometry HREIMS, single-crystal X-ray diffraction, and hydrolysis. Furthermore, the isolates' efficacy in inhibiting the activity of phosphodiesterase type 5 A was evaluated. Goshonosides J1, J2, and G effectively inhibited the activity of the aforementioned enzyme (IC50 values: 6.15 ± 1.76, 3.27 ± 0.65, and 9.61 ± 2.36 µM, respectively). Our findings highlight the remarkable structural diversity of bioactive compounds in R. chingii Hu and offer insights into the use of this shrub.

[Transcriptional regulation mechanism of differential accumulation of flavonoids in leaves and roots of Sarcandra glabra based on metabonomics and transcriptomics].

This study aims to explore the molecular regulation mechanism of the differential accumulation of flavonoids in the leaves and roots of Sarcandra glabra. Liquid chromatography-mass spectrometry(LC-MS) and high-throughput transcriptome sequencing(RNA-seq) were employed to screen out the flavonoid-related differential metabolites and differentially expressed genes(DEGs) encoding key metabolic enzymes. Eight DEGs were randomly selected for qRT-PCR verification. The results showed that a total of 37 flavonoid-related differential metabolites between the leaves and roots of S. glabra were obtained, including pinocembrin, phlorizin, na-ringenin, kaempferol, leucocyanidin, and 5-O-caffeoylshikimic acid. The transcriptome analysis predicted 36 DEGs associated with flavonoids in the leaves and roots of S. glabra, including 2 genes in the PAL pathway, 3 genes in the 4CL pathway, 2 genes in the CHS pathway, 4 genes in the CHI pathway, 2 genes in the FLS pathway, 1 gene in the DFR pathway, 1 gene in the CYP73A pathway, 1 gene in the CYP75B1 pathway, 3 genes in the PGT1 pathway, 6 genes in the HCT pathway, 2 genes in the C3'H pathway, 1 gene in the CCOAOMT pathway, 1 gene in the ANR pathway, 1 gene in the LAR pathway, 2 genes in the 3AT pathway, 1 gene in the BZ1 pathway, 2 genes in the IFTM7 pathway, and 1 gene in the CYP81E9 pathway. Six transcription factors, including C2H2, bHLH, and bZIP, were involved in regulating the differential accumulation of flavonoids in the leaves and roots of S. glabra. The qRT-PCR results showed that the up-or down-regulated expression of the 8 randomly selected enzyme genes involved in flavonoid synthesis in the leaves and roots of S. glabra was consistent with the transcriptome sequencing results. This study preliminarily analyzed the transcriptional regulation mechanism of differential accumulation of flavonoids in the leaves and roots of S. glabra, laying a foundation for further elucidating the regulatory effects of key enzyme genes and corresponding transcription factors on the accumulation of flavonoids in S. glabra.

Study on Optimal Extraction and Hypoglycemic Effect of Quercetin.

Quercetin was extracted from Portulaca oleracea L. through biphasic acid hydrolysis to investigate its potential as a suppressor of dipeptidyl peptidase IV (DPP-IV) and its hypoglycemic effect in type 2 diabetic mice. The extraction procedure was optimized utilizing the response surface method (RSM) in a single-factor experimental setting. An extraction efficiency of 0.675% was achieved using the following optimized parameters: 0.064 mol/L vitriol, 1 : 109.155 solid-liquid ratio, and 21.408 min ultrasonication. Overall, findings indicate the effectiveness of quercetin extraction. A mouse model for type 2 diabetes was established to receive oral treatment with various quercetin concentrations for 8 weeks. Fasting blood glucose (FBG) and the DPP-IV activity in the serum were significantly reduced. The weight and insulin levels of the mice in the quercetin group were raised compared to those in the model group (P < 0.01). Quercetin dose-dependently inhibited postprandial blood glucose excursions, as demonstrated by the oral glucose tolerance test. These results confirmed that quercetin has hypoglycemic effects and considerably improves insulin sensitivity via DPP-IV targeting.

Yamogenin Exhibits Antidepressant-like Effects via Inhibition of ER Stress and Microglial Activation in LPS-Induced Mice.

Depression is a multifaceted psychiatric disorder that affects a significant number of individuals worldwide, and its pathophysiology encompasses a variety of mechanisms, including the induction of endoplasmic reticulum (ER) stress, which has been correlated with depressive-like behaviors in animal models. Yamogenin, a bioactive compound derived from traditional Chinese medicine Dioscorea species, possesses diverse pharmacological properties. This investigation aimed to explore the antidepressant-like effects of yamogenin and the underlying mechanisms involved. By utilizing a murine model of lipopolysaccharide (LPS)-induced depressive-like behavior, we demonstrated that yamogenin enhanced sucrose preference and reduced immobility time in the forced swimming test. These effects were observed alongside the attenuation of ER stress through modulation of the PERK/eIF2α/ATF4/CHOP signaling pathway in the prefrontal cortex. Moreover, yamogenin augmented the expression of the antiapoptotic protein Bcl-2 while diminishing the expression of the proapoptotic protein caspase-3. Additionally, yamogenin exhibited inhibitory effects on microglial activation but did not elicit the promotion of brain-derived neurotrophic factor (BDNF) signaling. Collectively, our findings propose that yamogenin exerts antidepressant-like effects in LPS-induced mice by inhibiting ER stress and microglial activation. This study contributes novel insights into the potential utilization of yamogenin as a natural antidepressant agent.

Downregulation of BDNF-TrkB signaling may contribute to the colonic motility disorders in mice with streptozocin-induced diabetes.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) acts as a neuromodulator to regulate gut motility, but the role of BDNF in diabetes-related dysmotility is uncertain. The aim of this study was to investigate the possible involvement of BDNF and its receptor TrkB in the colonic hypomotility of mice with streptozotocin (STZ)-induced diabetes. METHODS: A single intraperitoneal injection of STZ was used to establish a type 1 diabetes model. An organ bath system was applied to observe the contractile activities of colonic muscle strips. Immunofluorescence and western blotting were performed to evaluate the expression of BDNF and TrkB in the colon. ELISA was used to detect BDNF and SP levels in the serum and colon. The patch-clamp technique was applied to record the currents of L-type calcium channels and large conductance Ca2+ -activated K+ channels on smooth muscle cells. KEY RESULTS: Compared with healthy controls, diabetic mice showed attenuated colonic muscle contraction (p < 0.001), which was partly reversed by BDNF supplementation. TrkB protein expression was significantly reduced in diabetic mice (p < 0.05). In addition, both BDNF and substance P (SP) levels were decreased, and exogenous administration of BDNF increased SP levels in diabetic mice (p < 0.05). Both the TrkB antagonist and the TrkB antibody inhibited the spontaneous contraction of colonic muscle strips (p < 0.01). Moreover, the BDNF-TrkB signaling system enhanced SP-induced muscle contraction. CONCLUSIONS: Downregulation of BDNF/TrkB signaling and reduced SP release from the colon may contribute to the colonic hypomotility associated with type 1 diabetes. Brain-derived neurotrophic factor supplementation may have therapeutic potential for diabetes-related constipation.

Plant growth-promoting rhizobacteria are important contributors to rice yield in karst soils.

The difficulty of releasing nutrients from soils in karst areas limits the yield of local crops and leads to poverty. In this study, two strains of plant growth-promoting rhizobacteria (PGPR) were isolated from the rhizosphere soil of typical plants in karst areas, which were both identified as Bacillus sp. and named GS1 and N1. And two isolates were used to construct a composite PGPR named MC1. These three strains of PGPR were used for soil inoculation in the pot experiment and field trial and their capacity to promote rice development was assessed. The results showed that MC1 inoculation exhibited notable rice growth-promoting ability in pot experiments, and, respectively, had an increment of 16.96, 18.74, and 11.50% in shoot biomass, total biomass, and rice height compared with control. This is largely attributed to PGPR's capacity to secrete phytohormones and soil enzymes, particularly urease (UE) in GS1, whose secreted UE content was significantly higher by 12.18% compared to the control. When applied to the field, MC1 inoculation not only increased rice yield by 8.52% and the available nutrient content in rice rhizosphere soil, such as available phosphorus (AP) and exchangeable magnesium (EMg); but also improved the abundance of beneficial rhizobacteria and the diversity of microbial communities in rice rhizosphere soil. Results in this study revealed that inoculated PGPR played a major role in promoting rice growth and development, and a new strategy for facilitating the growth of rice crops in agriculture was elucidated. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03593-0.

Systematical characterization of gypenosides in Gynostemma pentaphyllum and the chemical composition variation of different origins.

Gynostemma pentaphyllum (Thunb.) Makino is an herbaceous plant of Cucurbitaceae family, which has been widely used as an herbal tea and traditional Chinese medicine. Since its saponins are similar to ginsenosides and have a wide range of activities, it has attracted wide interest. However, there are still a large number of unknown saponins that have not been isolated, especially some trace gypenosides. In the present study, a HILIC × RP offline two-dimensional liquid separation combined with a multimode data acquisition was developed for the systematical characterization of gypenosides. On top of the negative mode information, considering that saponins are prone to in-source fragmentations in positive ion mode, a precursor ion list data acquisition method was used for the targeted acquisition of multistage positive data. Reference herbal drug was taken as a golden sample to probe the chemical composition of G. pentaphyllum. The mixed sample of commercially available samples were also analyzed in parallel. Furthermore, the chemical compositions of commercially available samples from different sources were compared. In total, 1108 saponins were characterized, among which 588 were accurately characterized, with 574 identified in the reference herbal drug and 700 in the mixed commercially available samples. The commercially available samples showed great composition variation. These findings clarified the material basis and provided clues for quality control of G. pentaphyllum.

Magnetic Ti3C2 MXene Nanosheets Prepared for Enrichment of Phosphopeptides.

MXenes have received lots of attention since discovered and have been applied in various fields. In this work, Ti3C2-Fe3O4 composites with exposed non-modified Ti3C2 MXene nanosheets were designed and prepared by an in situ growth strategy and then applied in the enrichment of phosphopeptides. The two-dimensional composites could interact with the phosphopeptides through a metal oxide affinity chromatography mechanism provided by Ti-O and Fe-O bonds and a hydrophilic interaction chromatography mechanism by surface hydroxyl groups. This magnetic nanomaterial with a specific surface area of 66.1 m2·g-1 had high sensitivity to phosphopeptides (0.5 nmol·L-1) and high selectivity (1:1000 of the molar ratio of ß-casein to bovine serum albumin). Non-fat milk was adopted as a real sample to preliminarily examine the applicability of the Ti3C2-Fe3O4-based protocol. Subsequently, Qingkailing injection, a kind of traditional Chinese medicine injection, was introduced to further explore the suitability of the nanocomposites for phosphopeptide enrichment from more complex matrices and satisfactory results were obtained.

Mindfulness exercises reduce death anxiety and burnout in intensive care nurses.

Intensive care units (ICUs) nurses experience a high level of death anxiety. Interventions that reduce death anxiety are needed. We conducted a nonrandomized study with 66 ICU nurses. The 34 in the intervention group received an 8-week tailored mindfulness-based intervention and the 32 in the control group received no intervention. Both groups completed pre and post-tests of death anxiety and burnout. At post-test, the levels of death anxiety and job burnout in the intervention group were significantly lower than the control group. Mindfulness-based intervention can reduce the death anxiety level and burnout of ICU nurses.

Swelling of Multilayered Calcium Alginate Microspheres for Drug-Loaded Dressing Induced Rapid Lidocaine Release for Better Pain Control.

The development of effective drug-loaded dressings has been considered a hot research topic for biomedical therapeutics, including the use of botanical compounds. For wound healing, adequate dressings can provide a good microenvironment for drug release, such as lidocaine. Biological macromolecular materials such as alginate show excellent properties in wound management. This study involves the preparation and evaluation of biocompatible multilayered-structure microspheres composed of chitosan, porous gelatin, and calcium alginate microspheres. The multilayered structure microspheres were named chitosan@ porous gelatin@ calcium alginate microspheres (CPAMs) and the drugs were rapidly released by the volume expansion of the calcium alginate microspheres. The in vitro release curve revealed that the peak release of lidocaine from CPAMs was reached within 18[Formula: see text]min. After 21[Formula: see text]min, the remaining lidocaine was then slowly released, and the active drug release was converted to a passive drug release phase. The initial release effect of lidocaine was much better than that reported in the published studies. Additionally, blood coagulation experiments showed that CPAMs coagulated blood in 60[Formula: see text]s, and the blood liquidity of the CPAMs group was worse than that of the woundplast group. Therefore, the coagulation characteristics of CPAMs were superior to the commonly used woundplast containing lidocaine healing gel. These study outcomes indicated that the CPAMs acted as fast-release dressings for faster pain control and better coagulation properties.

Guben Tongluo Formula Protects LPS-induced Damage in Lamina Propria B Lymphocytes Through TLR4/MyD88/NF-κB Pathway.

OBJECTIVE: The main pathological feature of immunoglobulin A nephropathy (IgAN), an autoimmune kidney disease, is the deposition of IgA immune complexes, accompanied by mesangial cell proliferation and elevated urine protein. The Guben Tongluo formula (GTF) is a traditional Chinese medicine prescription, which has predominant protective effects on IgAN. However, the therapeutic mechanism of the GTF in IgAN remains elusive. The present study aimed to determine the effects of GTF in treating IgAN via regulating the TLR4/MyD88/NF-κB pathway. METHODS: In the present study, lamina propria B lymphocytes were treated with different concentrations of lipopolysaccharide (LPS) (0, 1, 5, 10 and 20 ng/mL). Flow cytometry was used to define positive CD86+CD19+ cells. CCK-8 assay was used to examine cell proliferation. RNAi was used to induce TLR4 silencing. qRT-PCR and Western blotting were used to determine gene expression. RESULTS: It was found that the LPS dose-dependently increased the content of IgA and galactose-deficient IgA1 (Gd-IgA), the levels of TLR4, Cosmc, MyD88 and phosphorylated (p)-NF-κB, and the ratio of CD86+CD19+ and IgA-producing B cells. However, the TLR4 knockdown reversed the role of LPS. This suggests that TLR4 mediates the effects of LPS on lamina propria B lymphocytes. Furthermore, the GTF could dose-dependently counteract the effects of LPS and TLR4 overexpression on lamina propria B lymphocytes through the TLR4/MyD88/NF-κB pathway. CONCLUSION: Collectively, these results demonstrate that the GTF can regulate the TLR4/MyD88/NF-κB pathway to treat IgAN model lamina propria B lymphocytes stimulated by LPS.

Emotion Management for College Students: Effectiveness of a Mindfulness-Based Emotion Management Intervention on Emotional Regulation and Resilience of College Students.

ABSTRACT: The discovery of psychological healing methods that are easy to master and can be developed by the individual as a means of improving students' self-psychological adjustment ability is of great practical value. This study is a randomized control trial intended to investigate the effectiveness of mindfulness-based emotion management interventions and to test their effects on the mood state and resilience of college students. A total of 72 students were recruited and randomly divided into an intervention group and a control group. Thirty-six students in the intervention group received a modified mindfulness-based emotion management intervention once per week for 4 weeks, with each intervention having a duration of 80 minutes. Participants were assessed by questionnaires to measure mindfulness level, emotion, and resilience before and after intervention. There were significant interaction effects on mindfulness level (F = 97.76, p < 0.00), mood state (F = 353.52, p < 0.00), and resilience (F = 178.99, p < 0.00) scores. A modified 4-week mindfulness-based emotion management intervention can improve the mindfulness level and resilience of college students and is an innovative and feasible strategy for enhancing mental health in college students.

[Identification of Bacterial Flora and Metabolic Function of Sediments in Different Channels of Duliujian River Basin, Tianjin].

Bacterial communities are highly sensitive to environmental changes, but their metabolic functions may be convergent under similar ecological conditions. In order to test this environmental attribute of the bacterial community and verify the feasibility in using the bacterial metabolic data to divide functional units at the river basin scale, the surface sediments in three continuous spatial units of the main stream (MS), left tributary (LT), and right tributary (RT) of the Duliujian River basin were selected as the research objects. Therefore, 16S rDNA high-throughput sequencing and the PICRUSt platform were used to analyze the bacterial diversity and metabolic function of sediments in different units. The results showed that there were no significant differences for the Shannon and Simpson indices between the different river channels (P>0.05); however, the bacterial diversity indices of Chao1, ACE, Observed_species, and PD_whole_tree of LT and RT were significantly higher than those of the MS (P<0.05). Moreover, the dominant bacterial phyla were not significantly different among the different river channels. In the present study, a total of 41 metabolic pathways were predicted based on the KEGG database, among which 34 metabolic pathways such as membrane transport, amino acid metabolism, and carbohydrate metabolism were significantly different. The functional metabolic abundance was higher in MS than that in RT and LT (P<0.05); however, there was no significant difference between those of RT and LT (P>0.05). Except for exchangeable phosphorus and nitrate nitrogen, there were no significant differences in other physicochemical properties among the different river channels (P>0.05). Furthermore, pH and iron/aluminum-phosphorus were found to significantly affect the bacterial structure, and SOM and TN were found to significantly affect the bacterial metabolic function. Overall, the sediments of MS and tributaries (LT and RT) of the river were clearly divided into level-1 and level-2 groups, indicating that the metabolic abundance of the bacterial community can be used as the key indicator in the division of functional units at the river basin scale. This study provided a theoretical basis and technical support for ecological functional division and management in coastal river basins.

Deep chemical identification of phytoecdysteroids in Achyranthes bidentata Blume by UHPLC coupled with linear ion trap-Orbitrap mass spectrometry and targeted isolation.

Achyranthes bidentata Blume is widely used as a traditional Chinese medicine with the effects of nourishing the liver and kidneys and strengthening muscles and bones. In this work, a rapid and simple strategy was developed for characterizing phytoecdysteroids by ultra-high-performance liquid chromatography coupled with liner ion trap-Orbitrap mass spectrometry using electrospray ionization in the negative mode. As a result, 47 phytoecdysteroids were unambiguously or tentatively characterized. Among them, seven known compounds were identified according to the reference standards along with molecular formula, retention time and fragmentation patterns, while others were mostly potential new compounds. Through targeted isolation, the structures of three new compounds were determined by NMR spectra, which were consistent with LC-MS characterization. The present study provides an efficient method to deeply characterize phytoecdysteroids.

An effective titanium salt dosing strategy for phosphorus removal from wastewater: Synergistic enhancement of chemical and biological treatment.

Titanium salt coagulant, as a new type of water treatment agent, has been widely studied, but most researches do not consider its effect on the biological treatment. In this study, different doses of TiCl4 were added to the biological phosphorus removal (BPR) system to investigate the impact of TiCl4 on BPR. The results showed that the addition of TiCl4 not only significantly reduced the phosphorus concentration in effluent (below 0.5 mg/L), but also kept it stable. Moreover, the sedimentation performance of activated sludge was improved, which was superior to the control group. According to the results of flow cytometry (FCM), a small amount of TiCl4 significantly improved the bioactivities, but excessive dosage caused inhibition. When the dosage of TiCl4 below 20 mg/L, polyphosphate accumulating metabolism (PAM) was strengthened. In addition, the richness of microbial community and the relative abundance of Candidatus Accumulibacter clades also increased. However, when the dosage reached 60 mg/L, the relative abundance of Candidatus Competibacter increased and the BPR system was deteriorated. This study suggests that the addition of appropriate concentration of TiCl4 can realize the synergistic enhancement of biological and chemical phosphorus removal in sewage treatment.

[Analysis of chemical constituents in classical prescription Danggui Buxue Decoction based on RP-Q-TOF-MS and HILIC-Q-TOF-MS].

The chemical constituents of classical prescription Danggui Buxue Decoction were analyzed by reversed-phase(RP) chromatography and hydrophilic interaction chromatography(HILIC) coupled with quadrupole time-of-flight mass spectrometry. RP separation of Danggui Buxue Decoction was performed on ACQUITY UPLC HSS T3(2.1 mm×100 mm, 1.8 µm), while HILIC separation was on Waters BEH Amide(2.1 mm×100 mm, 1.7 µm). Mass spectrometry(MS) data were acquired in both negative and positive ion modes. Chemical constituents of Astragali Radix and Angelicae Sinensis Radix were searched from Reaxys and thus the in-house library was established. MS data were further analyzed by MassLynx 4.1 combined with in-house library, HMDB, Reaxys, and comparison with reference substances. In conclusion, a total of 154 compounds were identified and characterized: 16 saponins, 44 flavonoids, 10 phthalides, 7 phenylpropanoids, 15 bases and the corresponding nucleosides, 30 oligosaccharides, and 32 other compounds. Among them, 65 compounds were detected by HILIC-MS/MS. This study provides experimental evidences for the material basis research, quality control, and preparation development of Danggui Buxue Decoction and a reference method for comprehensive characterization of Chinese medicine decoctions typified by classical prescriptions.

Effects of Jie Yu Wan on Generalized Anxiety Disorder: A Randomized Clinical Trial.

Objective: To systematically assess the clinical efficacy of the Jie Yu Wan (JYW) formula in treating generalized anxiety disorder (GAD). Methods: A multicenter, prospective, double-blind, double-dummy, randomized controlled trial (RCT) was conducted at four hospitals in China. A total of one hundred thirty-three patients with GAD were enrolled from 2017 to 2019. This study aimed to evaluate the effects of a Traditional Chinese Medicine (TCM) JYW formula on GAD at eight weeks, with the use of Buspirone as the comparator. A stepwise dosing protocol was used (JYW: high dose 24 g/day, low dose 12 g/day; Buspirone: high dose 30 mg/day, low dose 15 mg/day) and the dose was adjusted depending on whether the treatment response of Hamilton Anxiety Scale (HAMA) score was less than or equal to 25% after one week. The primary outcome was a change in total score on the HAMA. The secondary outcomes included the Hamilton Depression Scale (HAMD), Clinical Global Impression (CGI) scale, and TCM Syndrome Scale. Adverse events were recorded using the Treatment Emergent Symptom Scale (TESS). Assessments were conducted at the baseline and 1, 2, 4, and 8 weeks. Results: A total of one hundred thirty-three participants were randomly assigned to the JYW group (n = 66) and the Buspirone group (n = 67). One hundred twenty-one patients (91%) completed at least one follow-up session. There were no significant differences between the two groups in terms of gender, age, disease course, HAMA, HAMD, CGI, and TCM Syndrome Scale scores at baseline (all P > 0.05). Repeated-measures analysis of variance revealed statistically significant time effects for the HAMA (P=0.002), HAMD (P = 0.018), and CGI (P=0.001) in both groups. Sensitivity analyses supported the credibility of the main results (P > 0.05). The group effect was not significant for the HAMA (P=0.43), HAMD (P=0.27), CGI (P=0.37), and TCM Syndrome Scale (P=0.86). Furthermore, there were no significant interaction effects between time and group in terms of the HAMA (P=0.47), HAMD (P=0.79), CGI (P=0.67), and TCM Syndrome Scale (P=0.69). After one week, 53 patients (80%) of the JYW group and 52 patients (78%) of the Buspirone group were adjusted to high doses. The interaction effect between time, group, and the dose was determined by repeated measures ANOVA test, and the HAMA score served as the outcome measure. The interaction effect between time and dose was statistically significant (P=0.04), which shows that high-dose JYW (24 g/day) was more effective in decreasing patients' HAMA scores than low-dose JYW (12 g/day), and Buspirone had the same effect, which means that high-dose Buspirone (30 mg/day) was more effective than low dose. (15 mg/day). Conclusions: The conclusion of this study supports that JYW and Buspirone can effectively alleviate the anxiety symptoms of GAD patients, which are both effective and safe for treatment of mild to moderate GAD. Besides, high-dose JYW or Buspirone are more effective than low-dose, which is of great importance in assisting clinical medication choice.