Double-blinded, randomized clinical trial of Gegen Qinlian decoction pinpoints Faecalibacterium as key gut bacteria in alleviating hyperglycemia.

Background: Accumulating evidence suggests that metabolic disorders, including type 2 diabetes mellitus (T2DM), can be treated with traditional Chinese medicine formulas, such as the Gegen Qinlian decoction (GQD). This study elucidates the mechanisms by which gut microbes mediate the anti-diabetic effects of GQD. Methods: We conducted a double-blind randomized clinical trial involving 120 untreated participants with T2DM. During the 12-week intervention, anthropometric measurements and diabetic traits were recorded every 4 weeks. Fecal microbiota and serum metabolites were measured before and after the intervention using 16S rDNA sequencing, liquid chromatography-mass spectrometry, and Bio-Plex panels. Results: Anti-diabetic effects were observed in the GQD group in the human trial. Specifically, glycated hemoglobin, fasting plasma glucose, and two-hour postprandial blood glucose levels were significantly lower in the GQD group than in the placebo group. Additionally, Faecalibacterium was significantly enriched in the GQD group, and the short-chain fatty acid levels were higher and the serum inflammation-associated marker levels were lower in the GQD group compared to the placebo group. Moreover, Faecalibacterium abundance negatively correlated with the levels of serum hemoglobin, fasting plasma glucose, and pro-inflammatory cytokines. Finally, the diabetes-alleviating effect of Faecalibacterium was confirmed by oral administration of Faecalibacterium prausnitzii (DSMZ 17677) in T2DM mouse model. Conclusions: GQD improved type 2 diabetes primarily by modulating the abundance of Faecalibacterium in the gut microbiota, alleviating metabolic disorders and the inflammatory state. Trial registration: Registry No. ChiCTR-IOR-15006626.

Herbal medicine for Hashimoto's thyroiditis: A systematic review and network meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Conventional treatments for Hashimoto's thyroiditis (HT) are limited. Herbal medicines (HM) are considered a potential intervention for the treatment of HT. AIM OF THE STUDY: This study aimed to investigate the efficacy and safety of HM for HT. MATERIALS AND METHODS: A Bayesian network meta-analysis was conducted for patients with HT in randomized controlled trials identified in PubMed, Cochrane Library, Web of Science, EMBASE, Chinese Clinical Trial Registry (Chi CTR), China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (the VIP), China Chinese Biomedical Database (CBM), and Wanfang Database were searched from their inception to Oct 1, 2022. Outcomes included the primary outcome (TPOAb), secondary outcomes (TSH, TGAb, FT3, FT4, and traditional Chinese medicine symptom scores), and adverse events. This study was registered in PROSPERO (CRD42022363640). RESULTS: Sixteen trials were reviewed and 16 HM formulae were compared. Compared with non-drug therapy (NDT), all therapies, except for Tiaoqi-Qingjie Therapy, reduced the primary outcome of TPOAb with different levels of effectiveness, ranging from 0.01 (95%CI 0.00, 0.02) to 0.92 (95%CI 0.56, 1.53). Ranking probability analysis indicated that Yiqi Huayu Recipe, Liqi Xiaoying decoction, and Shugan Sanjie therapy reduced thyroid antibody levels the most, including TPOAb (100.0%, 90.9%, and 90.3%, respectively) and TGAb (98.3%, 94.4%, and 87.3%, respectively). All HMs displayed a significant effect on the TCM Symptom score and possibly benefitted the treatment of HT, ranging from 6.62 (95% CI 2.06, 21.24) to 94.50 (95% CI 15.97, 559.14). No serious adverse events were reported. CONCLUSIONS: Herbal medicines may be effective in the treatment of HT, especially in reducing thyroid antibody levels and improving clinical symptoms without affecting thyroid function. However, these results should be considered preliminary and further verified using high-quality evidence.

Clinical characteristics and prognosis of non-APAP drug-induced acute liver failure: a large multicenter cohort study.

BACKGROUND: There is growing recognition of natural history, complications, and outcomes of patients who develop non-acetaminophen (APAP) drug-induced acute liver failure (ALF). To clarify high-risk factors and develop a nomogram model to predict transplant-free survival (TFS) in patients with non-APAP drug-induced ALF. METHODS: Patients with non-APAP drug-induced ALF from 5 participating centers were retrospectively analyzed. The primary endpoint was 21-day TFS. Total sample size was 482 patients. RESULTS: Regarding causative agents, the most common implicated drugs were herbal and dietary supplements (HDS) (57.0%). The hepatocellular type (R ≥ 5) was the main liver injury pattern (69.0%). International normalized ratio, hepatic encephalopathy grades, the use of vasopressor, N-acetylcysteine, or artificial liver support system were associated with TFS and incorporated to construct a nomogram model (drug-induced acute liver failure-5, DIALF-5). The AUROC of DIALF-5 for 7-day, 21-day, 60-day, and 90-day TFS in the internal cohort were 0.886, 0.915, 0.920, and 0.912, respectively. Moreover, the AUROC of DIALF-5 for 21-day TFS had the highest AUROC, which was significantly higher than 0.725 of MELD and 0.519 of KCC (p < 0.05), numerically higher than 0.905 of ALFSG-PI but without statistical difference (p > 0.05). These results were successfully validated in the external cohort (147 patients). CONCLUSIONS: Based on easily identifiable clinical data, the novel DIALF-5 model was developed to predict transplant-free survival in non-APAP drug-induced ALF, which was superior to KCC, MELD and had a similar prediction performance to ALFSG-PI but is more convenient, which can directly calculate TFS at multiple time points.

Kaempferol exerts antioxidant effects in age-related diminished ovarian reserve by regulating the HSP90/NRF2 pathway.

Kaempferol is the active ingredient of Er-Xian decoction (EXD), a traditional Chinese medicine formula used clinically to treat ovarian dysfunction, but the mechanism of kaempferol relieving age-related diminished ovarian reserve (AR-DOR) is still unclear. In this study, 36 volunteers and 78 DOR patients (37 patients with EXD treatment) were enrolled in the clinical research. Meanwhile, 32-week-old female mice were used to establish the AR-DOR model, and these model mice were intragastrically administered with 100 mg/kg kaempferol in the presence or absence of 200 mg/kg geranylgeranylacetone (GGA) or 1 mg/kg geldanamycin (GDA). The effects of kaempferol on serum hormone levels and oxidative stress-related indexes were detected by enzyme-linked immunosorbent assay. Antral follicle count (AFC) was determined by hematoxylin-eosin staining. The protein levels of HSP90 and nuclear factor erythroid 2-related factor 2 (NRF2) were assayed by Western blot. This study displayed that the serum anti-Mullerian hormone (AMH) level in DOR patients with EXD treatment was higher than that in DOR patients without EXD treatment. Kaempferol treatment reversed the low levels of AMH, estradiol (E2), AFC, superoxide dismutase (SOD), and catalase (CAT), as well as the high levels of follicle-stimulating hormone (FSH), reactive oxygen species (ROS), and malonaldehyde (MDA). The results showed that HSP90 was predicted to have high affinity with kaempferol, and its expression was inhibited by kaempferol, while the expression of NRF2, the target of HSP90, was up-regulated by kaempferol. However, the above effects of kaempferol were reversed by GGA. On the contrary, GDA enhanced the therapeutic effects of kaempferol on AR-DOR mice. Moreover, the treatment of kaempferol resulted in a reduction in the phosphorylation level of heat shock factor 1 (HSF1), the transcription factor associated with HSP90, and an increase in the phosphorylation level of Src, a client protein of HSP90. In summary, kaempferol exerts an antioxidant effect on AR-DOR by inhibiting HSP90 expression to up-regulate NRF2 expression. This study provides a theoretical basis for the clinical application of kaempferol in AR-DOR.

Clinical efficacy and molecular mechanism of Chinese medicine in the treatment of autoimmune thyroiditis.

ETHNOPHARMACOLOGICAL RELEVANCE: Autoimmune Thyroiditis (AIT) is a common refractory autoimmune disease of the endocrine system that may eventually lead to complete loss of thyroid function, with subsequent severe effects on the metabolism. Because of the deficiency in current clinical management of AIT, the need for alternative therapies is highlighted. With its multi-component and multi-target characteristics, Chinese medicine has good potential as an alternative therapy for AIT. AIM OF THE STUDY: The aim of this study was to systematically summarize the clinical efficacy and safety evaluation of TCM and its active ingredients in the treatment and regulation of AIT. Additionally, we provide an in-depth discussion of the relevant mechanisms and molecular targets to understand the protective effects of traditional Chinese medicine on AIT and explore new ideas for clinical treatment. MATERIALS AND METHODS: The literature related to "Hashimoto", "autoimmune thyroiditis", "traditional Chinese medicine," and "Chinese herbal medicine" was systematically summarized and reviewed from Web of Science Core Collection, PubMed, CNKI, and other databases. Domestic and international literature were analyzed, compared, and reviewed. RESULTS: An increasing number of studies have demonstrated that herbal medicines can intervene in immunomodulation, with pharmacological effects such as antibody lowering, anti-inflammatory, anti-apoptotic thyroid follicular cells, regulation of intestinal flora, and regulation of estrogen and progesterone levels. The signaling pathways and molecular targets of the immunomodulatory effects of Chinese herbal medicine for AIT may include Fas/FasL, Caspase, BCL-2, and TLRs/MyD88/NF-κB et al. CONCLUSIONS: The use of Chinese herbs in the treatment and management of AIT is clinically experienced, satisfactory, and safe. Future studies may evaluate the influence of herbal medicines on the occurrence and development of AIT by modulating the interaction between immune factors and conventional signaling pathways.

Efficacy and safety of tart cherry supplementary citrate mixture on gout patients: a prospective, randomized, controlled study.

BACKGROUND: Low urine pH, which may be mediated by metabolic syndrome (MetS), is common in gout. Tart cherries are shown to improve MetS symptoms and possess anti-inflammatory properties. However, the efficacy of tart cherry supplements on urine pH has yet to be studied. OBJECTIVES: This study aimed to investigate the efficacy and safety of tart cherry supplementary citrate (TaCCi) mixture on urine pH, serum urate (sUA), C-reactive protein (CRP), and gout flares in gout patients initiating urate-lowering therapy (ULT), in comparison to citrate mixture and sodium bicarbonate. METHODS: A prospective, randomized (1:1:1), open-label, parallel-controlled trial was conducted among 282 men with gout and fasting urine pH ≤ 6, who were initiating ULT with febuxostat (initially 20 mg daily, escalating to 40 mg daily if serum urate ≥ 360 µmol/L). Participants were randomized to groups taking either sodium bicarbonate, citrate mixture, or TaCCi mixture. All participants were followed every 4 weeks until week 12. Urine pH and sUA were co-primary outcomes, with various biochemical and clinical secondary endpoints. RESULTS: Urine pH increased to a similar extent in all three groups. SUA levels declined in all three groups as well, with no significant differences observed between the groups. At week 12, the TaCCi mixture group exhibited a greater reduction in the urine albumin/creatinine ratio (UACR) compared to the other two groups (p < 0.05). Participants taking TaCCi mixture or citrate mixture experienced fewer gout flares than those in the sodium bicarbonate group over the study period (p < 0.05). Additionally, the TaCCi mixture group had a lower CRP level at week 12 relative to the other two groups (p < 0.01). Adverse events were similar across all three groups. CONCLUSION: The TaCCi mixture had similar efficacy and safety on urine alkalization and sUA-lowering as the citrate mixture and sodium bicarbonate in patients with gout. However, the TaCCi mixture resulted in greater improvements in UACR and CRP, which suggests that tart cherry supplements may provide additional benefits for renal protection and reduce inflammation in gout, particularly when starting ULT. TRIAL REGISTRATION: This project was registered in ChiCTR ( www.chictr.org.cn ), with the registration number: ChiCTR2100050749.

Triterpene acids from Rosa roxburghii Tratt fruits exert anti-hepatocellular carcinoma activity via ROS/JNK signaling pathway-mediated cell cycle arrest and mitochondrial apoptosis.

BACKGROUND: Rosa roxburghii Tratt (RRT) is a famous healthy and medicinal edible fruit in southwest China and has been shown to have some hepatoprotective properties. However, whether the active components, such as the triterpene acids from Rosa roxburghii Tratt fruits (TAR), have anti-hepatocellular carcinoma (HCC) effects and the potential molecular mechanisms are still unclear. PURPOSE: This study aimed to investigate the anti-HCC effects and potential action mechanisms of triterpene components in RRT fruits. METHODS: The triterpene acids in TAR were analyzed by using UPLC-Q-Exactive Orbitrap/MS, and the main components were virtual screening for targets based on pharmacophore and then performed enrichment analysis. HepG2 cells were used for in vitro experiments, including MTT assay, wound healing assay, and flow cytometry to detect cell cycle, reactive oxygen species (ROS) level, caspase-3 activity, and mitochondrial membrane potential (MMP) changes. Moreover, the western blot was used to detect mitochondrial apoptosis and ROS/ c-Jun N-terminal kinase (JNK) signaling pathway-related proteins. RESULTS: The main components in TAR are pentacyclic triterpene acids (mainly euscaphic acid and roxburic acid). TAR could inhibit cell viability, cell migration ability and suppress the proliferation of HepG2 cells through G2/M cell cycle arrest. On the other hand, TAR could induce HepG2 cells apoptosis, which was achieved by causing the accumulation of ROS and activation of the JNK signaling pathway, and our research showed that this apoptosis was mediated through the mitochondrial pathway. In addition, the free radical scavenger N-acetyl cysteine (NAC) could attenuate TAR-induced ROS accumulation and JNK signaling pathway activation, which ultimately reversed mitochondrial apoptosis. CONCLUSION: TAR could activate the ROS/JNK signaling pathway, which could inhibit the proliferation through G2/M cell cycle arrest and promote apoptosis through the mitochondrial pathway in HCC cells. This supports the anti-tumor potential in RRT fruits.

The gut-brain axis involved in polystyrene nanoplastics-induced neurotoxicity via reprogramming the circadian rhythm-related pathways.

The production of plastic is still increasing globally, which has led to an increasing number of plastic particles in the environment. Nanoplastics (NPs) can penetrate the blood-brain barrier and induce neurotoxicity, but in-depth mechanism and effective protection strategies are lacking. Here, C57BL/6 J mice were treated with 60 µg polystyrene NPs (PS-NPs, 80 nm) by intragastric administration for 42 days to establish NPs exposure model. We found that 80 nm PS-NPs could reach and cause neuronal damage in the hippocampus, and alter the expression of neuroplasticity-related molecules (5-HT, AChE, GABA, BDNF and CREB), and even affect the learning and memory ability of mice. Mechanistically, combined with the results of hippocampus transcriptome, gut microbiota 16 s ribosomal RNA and plasma metabolomics, we found that the gut-brain axis mediated circadian rhythm related pathways were involved in the neurotoxicity of NPs, especially Camk2g, Adcyap1 and Per1 may be the key genes. Both melatonin and probiotic can significantly reduce intestinal injury and restore the expression of circadian rhythm-related genes and neuroplasticity molecules, and the intervention effect of melatonin is more effective. Collectively, the results strongly suggest the gut-brain axis mediated hippocampal circadian rhythm changes involved in the neurotoxicity of PS-NPs. Melatonin or probiotics supplementation may have the application value in the prevention of neurotoxicity of PS-NPs.

Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway.

OBJECTIVE: This work explores the impact of electroacupuncture (EA) on acute postoperative pain (APP) and the role of stimulator of interferon genes/type-1 interferon (STING/IFN-1) signaling pathway modulation in the analgesic effect of EA in APP rats. METHODS: The APP rat model was initiated through abdominal surgery and the animals received two 30 min sessions of EA at bilateral ST36 (Zusanli) and SP6 (Sanyinjiao) acupoints. Mechanical, thermal and cold sensitivity tests were performed to measure the pain threshold, and electroencephalograms were recorded in the primary somatosensory cortex to identify the effects of EA treatment on APP. Western blotting and immunofluorescence were used to examine the expression and distribution of proteins in the STING/IFN-1 pathway as well as neuroinflammation. A STING inhibitor (C-176) was administered intrathecally to verify its role in EA. RESULTS: APP rats displayed mechanical and thermal hypersensitivities compared to the control group (P < 0.05). APP significantly reduced the amplitude of θ, α and γ oscillations compared to their baseline values (P < 0.05). Interestingly, expression levels of proteins in the STING/IFN-1 pathway were downregulated after inducing APP (P < 0.05). Further, APP increased pro-inflammatory factors, including interleukin-6, tumor necrosis factor-α and inducible nitric oxide synthase, and downregulated anti-inflammatory factors, including interleukin-10 and arginase-1 (P < 0.05). EA effectively attenuated APP-induced painful hypersensitivities (P < 0.05) and restored the θ, α and γ power in APP rats (P < 0.05). Meanwhile, EA distinctly activated the STING/IFN-1 pathway and mitigated the neuroinflammatory response (P < 0.05). Furthermore, STING/IFN-1 was predominantly expressed in isolectin-B4- or calcitonin-gene-related-peptide-labeled dorsal root ganglion neurons and superficial laminae of the spinal dorsal horn. Inhibition of the STING/IFN-1 pathway by intrathecal injection of C-176 weakened the analgesic and anti-inflammatory effects of EA on APP (P < 0.05). CONCLUSION: EA can generate robust analgesic and anti-inflammatory effects on APP, and these effects may be linked to activating the STING/IFN-1 pathway, suggesting that STING/IFN-1 may be a target for relieving APP. Please cite this article as: Ding YY, Xu F, Wang YF, Han LL, Huang SQ, Zhao S, Ma LL, Zhang TH, Zhao WJ, Chen XD. Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway. J Integr Med. 2023; 21(5): 496-508.

Probiotic Fermentation of Herbal Medicine: Progress, Challenges, and Opportunities.

Fermentation is a processing method used in traditional Chinese medicine (TCM). However, traditional fermentation methods suffer from poor production control. In contrast, probiotic fermented herbal medicine (PFHM) offers advantages such as the use of pure strains, a controllable process, and the ability to produce a variety of active enzymes during fermentation. As a result, PFHM has become a research hotspot. This review focuses on the progress, challenges, and opportunities in the research of PFHM. The use of probiotic enzymes during fermentation alters the active ingredients of TCM, resulting in positive pharmacological effects such as increased active ingredients, reduced toxicity, new pharmacological effects, and the reuse of herbal residues. PFHM has the potential to transfer the metabolic transformation of the effective components of TCM by intestinal flora outside the body during production and preparation, which has a broad application prospect. However, due to the complexity of the chemical composition of TCM, the mechanism of PFHM requires further investigation. Finally, we discuss the prospects of industrializing PFHM, which is essential for promoting the innovation and modernization of TCM.

Purification and identification of xanthine oxidase inhibitory peptides from enzymatic hydrolysate of α-lactalbumin and bovine colostrum casein.

The development of food-derived Xanthine Oxidase (XO) inhibitors is critical to the treatment of hyperuricemia and oxidative stress-related disease. Few studies report on milk protein hydrolysates' XO inhibitory activity, with the mechanism of their interaction remaining elusive. Here, different commercial enzymes were used to hydrolyze α-lactalbumin and bovine colostrum casein. The two proteins hydrolyzed by alkaline protease exhibited the most potent XO inhibitory activity (bovine casein: IC50 = 0.13 mg mL-1; α-lactalbumin: IC50 = 0.28 mg mL-1). Eight potential XO inhibitory peptides including VYPFPGPI, GPVRGPFPIIV, VYPFPGPIPN, VYPFPGPIHN, QLKRFSFRSFIWR, LVYPFPGPIHN, AVFPSIVGR, and GFININSLR (IC50 of 4.67-8.02 mM) were purified and identified from alkaline protease hydrolysates by using gel filtration, LC-MS/MS and PeptideRanker. The most important role of inhibiting activity of peptides is linked to hydrophobic interactions and hydrogen bonding based on the results of molecular docking and molecular dynamics simulation. The enzymatic hydrolysate of α-lactalbumin and bovine colostrum casein could be a competitive candidates for hyperuricemia-resisting functional food.

Inhibition mechanism of α-glucosidase inhibitors screened from Tartary buckwheat and synergistic effect with acarbose.

Tartary buckwheat has been shown to provide a good antihyperglycemic effect. However, it is unclear which active compounds play a key role in attenuating postprandial hyperglycemia. Presently, acetone extract from the hull of Tartary buckwheat had the best effect for α-glucosidase inhibition (IC50 = 0.02 mg/mL). Twelve potential α-glucosidase inhibitors from Tartary buckwheat were screened and identified by the combination of ultrafiltration and high-performance liquid chromatography coupled with mass spectrometry. Myricetin and quercetin exhibited the highest anti-α-glucosidase activity with IC50 values of 0.02 and 0.06 mg/mL, respectively. These inhibitors manifested different types of inhibition manners against α-glucosidase via direct interaction with the amino acid residues. The results of structure-activity relationships indicated that an increase in the number of -OH on the B-ring greatly strengthened α-glucosidase inhibitory activity, but glucoside and rutinoside replacement on the C-ring obviously weakened this influence. Furthermore, a synergistic effect was observed between inhibitors with different inhibition manners.

Electroacupuncture reverses endothelial cell death and promotes angiogenesis through the VEGF/Notch signaling pathway after focal cerebral ischemia-reperfusion injury.

BACKGROUND: Angiogenesis is an important mechanism of recovery from ischemic stroke. Recent studies have found that there is a close relationship between the VEGF/Notch pathway and angiogenesis. It is unknown whether EA can exert a brain protection effect and promote angiogenesis by acting on the VEGF/Notch signaling pathway after focal cerebral ischemia-reperfusion injury (CIRI). METHODS: The Middle Cerebral Artery occlusion/Reperfusion (MCAo/R) model was established, in which rats were subjected to occlusion with ischemic intervention for 30 min, followed by reperfusion for 8 h, 1 day, 3 days, and 7 days. The first EA treatment was performed 90 min after the animal model was successfully established, and then EA treatments were performed once a day for 7 days. The 2,3,5-triphenyltetrazolium chloride staining and neurological deficit examination were performed to assess the level of CIRI and neuroprotection by EA. Expression levels of VEGFA, Notch1, and Hes1 proteins were measured via western blotting, while the morphological changes of ECs and microvasculature in the cortex were determined using an ultrastructural observation method. RESULTS: EA treatment of PC6, GV26, and SP6 can significantly improve the neurological function of MCAO/R rats, reduce the volume of cerebral infarction, and modulate the ultrastructure of ECs and microvessels in pathological states. Western blotting revealed that EA increased VEGFA protein expression at 8 h and 3 days after CIRI, as well as Notch1 protein expression at 1 and 7 days. Subsequently, EA activated the VEGF/Notch pathway, increasing the expression of the downstream target protein Hes1, reversing EC death, and promoting angiogenesis. CONCLUSION: Our findings showed that EA plays a role in promoting angiogenesis following focal CIRI, and we hypothesized that this was due to the regulation of ECs by the EA-activated VEGF/Notch signaling pathway.

Apigenin ameliorates non-eosinophilic inflammation, dysregulated immune homeostasis and mitochondria-mediated airway epithelial cell apoptosis in chronic obese asthma via the ROS-ASK1-MAPK pathway.

BACKGROUND: Obese asthma is one of the important asthma phenotypes that have received wide attention in recent years. Excessive oxidative stress and different inflammatory endotypes may be important reasons for the complex symptoms, frequent aggravation, and resistance to traditional treatments of obese asthma. Apigenin (API), is a flavonoid natural small molecule compound with good anti-inflammatory and antioxidant activity in various diseases and proved to have the potential efficacy to combat obese asthma. METHODS: In vivo, this study fed C57BL/6 J mice with high-fat diets(HFD)for 12 weeks and then stimulated them with OVA for 6 weeks to establish a model of chronic obese asthma, while different doses of oral API or dexamethasone were used for therapeutic interventions. In vitro, this study used HDM to stimulate human bronchial cells (HBEs) to establish the model and intervened with API or Selonsertib (SEL). RESULTS: This study clarified that OVAinduced a type of mixed granulocytic asthma with elevated neutrophils and eosinophils in obese male mice fed with long-term HFD, which also exhibited mixed TH17/TH1/TH2 inflammation. Apigenin effectively suppressed this complex inflammation and acted as a regulator of immune homeostasis. Meanwhile, apigenin reduced AHR, inflammatory cell infiltration, airway epithelial cell apoptosis, airway collagen deposition, and lung oxidative stress via the ROS-ASK1-MAPK pathway in an obese asthma mouse model. In vitro, this study found that apigenin altered the binding status of TRAF6 to ASK1, inhibited ASK1 phosphorylation, and protected against ubiquitin-dependent degradation of ASK1, suggesting that ROS-activated ASK1 may be an important target for apigenin to exert anti-inflammatory and anti-apoptotic effects. To further verify the intervention mechanism, this study clarified that apigenin improved cell viability and mitochondrial function and inhibited apoptosis by interfering with the ROS-ASK1-MAPK pathway. CONCLUSIONS: This study demonstrates for the first time the therapeutic effect of apigenin in chronic obese asthma and further clarifies its potential therapeutic targets. In addition, this study clarifies the specificity of chronic obese asthma and provides new options for its treatment.

The relationships between clinical teaching behaviour and transition shock in newly graduated nurses.

AIM: To explore the relationships between clinical teaching behaviour and transition shock in newly graduated nurses and significant differences in the northwest and northeast China. DESIGN: A cross-sectional design. METHODS: A total of 211 (nurses) and 925 (preceptors) were recruited in six Third-class different hospitals from July to August 2019. RESULTS: The transition shock is negatively correlated with the clinical teaching behaviour in northwest and northeast China, while the transition shock in the northwest is higher than that in the northeast for the behindhand economy and natural limit. CONCLUSION: The transition process of newly graduated nurses in northeast China with ethnic minorities and the behindhand economy is more difficult. For newly graduated nurses, personal health and a supportive environment need further improvement. Teaching strategies for preceptors need to be enhanced. Two-way feedback is more useful for both the newly graduated nurses and preceptors to improve quality care, and holistic care.

New furofuran and tetrahydrofuran lignans from the flower buds of Magnolia biondii Pamp and their antiallergic effects.

The dried flower buds of Magnolia biondii Pamp (herbal name, Xin-Yi) are a traditional Chinese medicine with a long history of clinical use in the treatment of allergic rhinitis and sinusitis. However, the constituents responsible for its antiallergic effects remain clearly unidentified. In the present study, totally 33 lignans were obtained from M. biondii. Among them, two novel furofuran lignans (1 and 2), two novel tetrahydrofuran lignans (3 and 4), and other 16 known lignans were isolated first time from M. biondii. The antiallergic effects of compounds 1-33 on mouse bone marrow-derived mast cells (BMMCs) degrunaliton were evaluated and results showed that compounds 7, 8, 13, 15 and 18 could significantly inhibited ß-hex release on BMMCs. The results proved that furofuran and tetrahydrofuran lignans were the main constituents in M. biondii and their antiallergic effects were related with suppressing mast cell activation.

Reminiscence music intervention on cognitive, depressive, and behavioral symptoms in older adults with dementia.

This study aimed to examine the efficacy and feasibility of a reminiscence music therapy program on improving cognition and decreasing depressive and behavioral symptoms in older adults with dementia. Participants in the reminiscence music therapy group participated in 60-minute reminiscence music therapy twice a week over a period of 4 weeks. Control group received usual care. Results showed that the intervention group exhibited a significant decrease in depressive symptoms compared to the control group (B=-5.30, p=.003). The reminiscence music therapy program exerted non-significant effects on cognition and behavioral symptoms in patients with dementia (p>.05). High adherence (96%) and positive participation data indicated that this reminiscence music program is feasible for people with dementia. Healthcare professionals in community or geriatric care units can create supportive environments and conduct regular reminiscence music activities that are related to festival features and reminiscence music for older adults with dementia to reduce depressive symptoms.

Meranzin Hydrate Improves Depression-Like Behaviors and Hypomotility via Ghrelin and Neurocircuitry.

OBJECTIVE: To investigate whether meranzin hydrate (MH) can alleviate depression-like behavior and hypomotility similar to Chaihu Shugan Powder (CSP), and further explore the potential common mechanisms. METHODS: Totally 120 Spraque-Dawley rats were randomly divided into 5-8 groups including sham, vehicle, fluoxetine (20 mg/kg), mosapride (10 mg/kg), CSP (30 g/kg), MH (9.18 mg/kg), [D-Lys3]-GHRP-6 (Dlys, 0.5 mg/kg), and MH+Dlys groups by a random number table, 8 rats in each group. And 32 mice were randomly divided into wild-type, MH (18 mg/kg), growth hormone secretagogue receptor-knockout (GHSR-KO), and GHSR+MH groups, 8 mice in each group. The forced swimming test (FST), open field test (OFT), tail suspension test (TST), gastric emptying (GE) test, and intestinal transit (IT) test were used to assess antidepressant and prokinetic (AP) effects after drug single administration for 30 min with absorbable identification in rats and mice, respectively. The protein expression levels of brain-derived neurotrophic factor (BDNF) and phosphorylated mammalian target of rapamycin (p-mTOR) in the hippocampus of rats were evaluated by Western blot. The differences in functional brain changes were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent (fMRI-BOLD). RESULTS: MH treatment improved depression-like behavior (FST, OFT) and hypomotility (GE, IT) in the acute forced swimming (FS) rats (all P<0.05), and the effects are similar to the parent formula CSP. The ghrelin antagonist [D-Lys3]-GHRP-6 inhibited the effect of MH on FST and GE (P<0.05). Similarly, MH treatment also alleviated depression-like behavior (FST, TST) in the wild-type mice, however, no effects were found in the GHSR KO mice. Additionally, administration of MH significantly stimulated BDNF and p-mTOR protein expressions in the hippocampus (both P<0.01), which were also prevented by [D-Lys3]-GHRP-6 (P<0.01). Besides, 3 main BOLD foci following acute FS rats implicated activity in hippocampus-thalamus-basal ganglia (HTB) circuits. The [D-Lys3]-GHRP-6 synchronously inhibited BOLD HTB foci. As expected, prokinetic mosapride only had effects on the thalamus and basal ganglia, but not on the hippocampus. Within the HTB, the hippocampus is implicated in depression and FD. CONCLUSIONS: MH accounts for part of AP effects of parent formula CSP in acute FS rats, mainly via ghrelin-related shared regulation coupled to BOLD signals in brain areas. This novel functionally connection of HTB following acute stress, treatment, and regulation highlights anti-depression unified theory.

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We analyzed the particle size distribution of soil aggregates in 0-20 and 20-40 cm soil layers of rice-wheat rotation field based on a field plot test with two treatments, conventional straw returning (CK) and straw returning with the addition of straw decomposition promoting microbial inoculants (IT). We evaluated the water stability indices of soil aggregates (the number of soil water stable large aggregates R0.25, the average weight diameter MWD, and the geometric average diameter GMD), and measured the contents of soil organic carbon (SOC), total nitrogen (TN), and total phosphorus (TP) in the soil aggregates of ＜0.053, 0.053-0.25, 0.25-1, ＞1 mm. The results showed that: 1) The number of aggregates ＜0.053, 0.053-0.25, ＞0.25 mm in the 0-20 and 20-40 cm soil layers under IT decreased by 10.0% and 6.8%, increased by 3.0% and 5.7%, and 17.9% and 26.1% compared with CK, respectively. IT effectively increased R0.25, MWD, and GMD by 26.4%, 20.0%, 18.2% and 18.2%, 10.5%, 10.0% in 0-20 and 20-40 cm soil, respectively. 2) Compared to CK, the TP content of 0.25-1 mm aggregates in 0-20 and 20-40 cm soil under IT was significantly increased by 40.3% and 37.5%, respectively, without difference in TN and SOC contents. There was no significant difference in nutrient contents of the other aggregates between the treatments. The contents of SOC and TN in large aggregates (>0.25 mm) were higher than those in silty aggregates (<0.053 mm). Compared to CK, the cumulative contribution rates of SOC, TN and TP of <0.053 mm aggregates under IT were decreased in two soil layers. There was no significant difference in the nutrient cumulative contribution rates of 0.053-0.25 mm aggregates between treatments. The cumulative contribution rates of SOC, TN, and TP of large aggregates (>0.25 mm) under IT were 32.1%, 19.6%, 52.8% and 22.8%, 11.8%, 42.9% higher than those under CK in 0-20 and 20-40 cm soils, respectively. 3) The number of <0.053 mm aggregates was significantly negatively correlated with SOC and TP contents, while that of 0.053-0.25 mm aggregates was negatively correlated with nutrient content. The number of large aggregates (>0.25 mm) were significantly positively correlated with SOC, TN, and TP contents. In conclusion, straw returning with microbial-inoculant addition could promote the formation of soil macroaggregates (>0.25 mm), and improve the water stability of soil aggregates, increasing nutrient contents in soil macroaggregates, with the nutrients transferring from silty aggregates to macroaggregates.

Effectiveness and safety analysis of SanHanHuaShi granules for the treatment of coronavirus disease 2019: Study protocol and statistical analysis plan for a randomized, parallel-controlled, open-label clinical trial.

Background: Coronavirus disease 2019 (COVID-19) was declared a global pandemic in March 2020 by the World Health Organization (WHO). As of July 2, 2022, COVID-19 has caused more than 545 million infections and 6.3 million deaths worldwide, posing a significant threat to human health. Currently, there is still a lack of effective prevention and control strategies for the variation and transmission of SARS-CoV-2. Traditional Chinese medicine (TCM), which has a unique theoretical system, has treated various conditions for thousands of years. Importantly, recent studies have revealed that TCM contributed significantly to COVID-19. SanHanHuaShi (SHHS) granules, a Chinese herbal medicine, which has been included in Protocol for the Diagnosis and Treatment of Novel Coronavirus Disease 2019 (6th to 9th editions) issued by the National Health Commission of China and used to prevent and treat COVID-19 disease. A previous retrospective cohort study showed that SHHS could significantly reduce the severity of mild and moderate COVID-19. However, there is an absence of high-quality randomized controlled clinical studies to confirm the clinical effectiveness of SHHS. Therefore, a clinical study protocol and a statistical analysis plan were designed to investigate the efficacy and safety of SHHS for the prevention and treatment of COVID-19. This study will increase the integrity and data transparency of the clinical research process, which is of great significance for improving the practical application of SHHS granules in the future. Methods and analysis: The study was designed as a 7-day, randomized, parallel controlled, open-label, noninferiority clinical trial of positive drugs. A total of 240 patients with mild and moderate COVID-19 will be enrolled and randomly assigned to receive SanHanHuaShi granules or LianHuaQingWen granules treatment in a 1:1 ratio. Disease classification, vital signs, SARS-CoV-2 nucleic acid testing, symptoms, medications, adverse events, and safety evaluations will be recorded at each visit. The primary outcome will be the clinical symptom recovery rate. Secondary outcomes will include the recovery time of clinical symptoms, negative conversion time of SARS-CoV-2 nucleic acid test negative conversion rate, hospitalization time, antipyretic time, rate of conversion to severe patients, and time and rate of single symptom recovery. Adverse incidents and safety assessments will be documented. All data will be analyzed using a predetermined statistical analysis plan, including our method for imputation of missing data, primary and secondary outcome analyses, and safety outcomes. Discussion: The results of this study will provide robust evidence to confirm the effectiveness and safety of SHHS in the treatment of COVID-19. Clinical Trial Registration: http://www.chictr.org.cn. Trial number: ChiCTR2200058080. Registered on 29 March 2022.