Tripterygium wilfordii Hook.f induced kidney injury through mediating inflammation via PI3K-Akt/HIF-1/TNF signaling pathway: A study of network toxicology and molecular docking.

We intend to explore potential mechanisms of Tripterygium wilfordii Hook.f (TwHF) induced kidney injury (KI) using the methods of network toxicology and molecular docking. We determined TwHF potential compounds with its targets and KI targets, obtained the TwHF induced KI targets after intersecting targets of TwHF and KI. Then we conducted protein-protein interaction (PPI) network, gene expression analysis, gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis to explore the mechanism of TwHF-induced KI. Finally we conducted molecular docking to verify the core toxic compounds and the targets. We obtained 12 TwHF toxic compounds and 62 TwHF-induced KI targets. PPI network, gene expression analysis and GO function enrichment analysis unveiled the key biological process and suggested the mechanism of TwHF-induced KI might be associated with inflammation, immune response, hypoxia as well as oxidative stress. KEGG pathway enrichment analysis indicated PI3K-Akt signaling pathway, HIF-1 signaling pathway and TNF signaling pathway were key signaling pathways of TwHF induced KI. Molecular docking showed that the binding energy of core targets and toxic compounds was all less than -6.5 kcal/mol that verified the screening ability of network pharmacology and provided evidence for modifying TwHF toxic compounds structure. Through the study, we unveiled the mechanism of TwHF induce KI that TwHF might activate PI3K-Akt signaling pathway as well as TNF signaling pathway to progress renal inflammation, mediate hypoxia via HIF-1 signaling pathway to accelerate inflammatory processes, and also provided a theoretical basis for modifying TwHF toxic compounds structure as well as supported the follow-up research.

Enrichment efficiency of lutein in eggs and its function in improving fatty liver hemorrhagic syndrome in aged laying hens.

In this study, we evaluated the enrichment efficiency of lutein in eggs and its function in preventing fatty liver hemorrhagic syndrome (FLHS) in aged laying hens. Five groups of laying hens (65 wk old) were fed basal diets supplemented with 0, 30, 60, 90, or 120 mg/kg of lutein. The supplementation period lasted 12 wk followed by 2 wk of lutein depletion in feed. The results revealed that lutein efficiently enriched the egg yolks and improved their color with a significant increase in relative redness (P < 0.001). Lutein accumulation increased in the egg yolk until day 10, then depletion reached a minimum level after 14 d. Overall, zeaxanthin content in all the groups was similar throughout the experimental period. However, triglycerides and total cholesterol were significantly decreased in the liver (P < 0.05) but not significantly different in the serum (P > 0.05). In the serum, the lipid metabolism enzyme acetyl-CoA synthetase was significantly reduced (P < 0.05), whereas dipeptidyl-peptidase 4 was not significantly different (P > 0.05), and there was no statistical difference of either enzyme in the liver (P > 0.05). Regarding oxidation and inflammation-related indexes, malondialdehyde, tumor necrosis factors alpha, interleukin-6, and interleukin-1 beta were decreased, whereas superoxide dismutase and total antioxidant capacity increased in the liver (P < 0.001). The function of lutein for the same indexes in serum was limited. It was concluded that lutein efficiently enriched the egg yolk of old laying hens to improve their color and reached the highest level on day 10 without being subject to a significant conversion into zeaxanthin. At the same time, lutein prevented liver steatosis in aged laying hens by exerting strong antioxidant and anti-inflammatory functions, but also through the modulation of lipid metabolism, which may contribute to reducing the incidence of FLHS in poultry.

Arginine Biosynthesis Pathway Found to Play a Key Role in the Neuroprotective Effect of Liu-Wei-Luo-Bi (LWLB) Granules in Diabetic db/db Mice with Peripheral Neuropathy Using an Untargeted Metabolomics Strategy.

Aim: Liu-Wei-Luo-Bi (LWLB) granules was a Chinese compound prescription for treating diabetic peripheral neuropathy (DPN). The aim of this study was to investigate the effect of LWLB granules on diabetic mice with peripheral neuropathy and to elucidate the potential mechanism based on an untargeted metabolomics approach. Methods: One hundred forty db/db mice were randomly divided into seven groups: the Control group, DPN group, Mudan (MD) granules group, Epalrestat (Epa) group, and the LWLB low, medium, or high dose (LW-l, LW-m, or LW-h) group. After 12 weeks of treatment, body weight, blood glucose, mechanical pain threshold, motor conduction velocity (MCV), sensory conduction velocity (SCV), and Pathological Organization of the Sciatic and Caudal Nerves in mice were measured. Serum samples were collected for untargeted metabolomics analysis using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and multivariate statistics. Disease-related pathways were screened out with function enrichment analyses of candidate biomarkers. Results: LWLB granules can improve the peripheral neuropathy of type 2 diabetic mice with peripheral nerve conduction disorders, mainly through significantly improving the nerve conduction velocity (P < 0.05) and lowering the mechanical pain threshold (P < 0.05). A total of 43 metabolites were identified as potential biomarkers related to the therapeutic effect of LWLB granules. Fifty, 4, and 26; 23, 4, and 22; and 24, 1, and 16 biomarkers were discovered in the LW-l, LW-m, and LW-h groups at the 4th, 6th, and 12th weeks, respectively. Five, three, seven, five, and four metabolic pathways were found in MD, Epa, LW-l, LW-m, and LW-h groups, respectively. The arginine biosynthesis pathway is the overlapping pathway in LW-l, LW-m, and LW-h groups. Conclusion: LWLB granules have an obvious neuroprotective effect on diabetic peripheral neuropathy, and the metabolism mechanism of LWLB is mainly related to the arginine biosynthesis pathway on diabetic db/db mice with peripheral neuropathy.

[Expert consensus on core indicators for lifecycle value assessment of Chinese patent medicine].

The establishment of core indicators for assessment plays an important role in carrying out the lifecycle value assessment of Chinese patent medicine, which are developed based on the concepts such as clinical value oriented, paying attention to the human use experience, and whole process quality control. To this end, the Specialty Committee of Data Monitoring and Decision Making of the World Federation of Chinese Medicine Societies organized experts to draft the Expert Consensus on Core Indicators for Lifecycle Value Assessment of Chinese Patent Medicine based on the research including Chinese Medicine Registration Review Evidence System in Combination of Traditional Chinese Medicine Theory, Human Use Experience, and Clinical Trials(GZY-FJS-2022-206) by National Administration of Traditional Chinese Medicine. This consensus proposed 92 core indicators from four stages, including new drug R&D project approval, pre-clinical research, new drug marketing authorization, and post-marketing, combining the assessment purposes and needs of different stakeholders from different dimensions such as clinical needs, clinical positioning, human use experience, effectiveness, safety, quality control, innovation, accessibility, and suitability. This consensus also interpreted the indicators to clearly elucidate the core elements of the value assessment of Chinese patent medicine in different R&D stages and guided the stakeholders to identify, analyze, and assess the value of Chinese patent medicine in the R&D and use process based on the core indicators in a scientific, objective, and standardized approach. This consensus is expected to play an important role in the high-quality new drug development, drug pricing and compensation of Chinese patent medicine, the development of clinical pathways, and rational clinical application.

Encapsulation of Selenium Nanoparticles and Metformin in Macrophage-Derived Cell Membranes for the Treatment of Spinal Cord Injury.

Spinal cord injury is an impact-induced disabling condition. A series of pathological changes after spinal cord injury (SCI) are usually associated with oxidative stress, inflammation, and apoptosis. These pathological changes eventually lead to paralysis. The short half-life and low bioavailability of many drugs also limit the use of many drugs in SCI. In this study, we designed nanovesicles derived from macrophages encapsulating selenium nanoparticles (SeNPs) and metformin (SeNPs-Met-MVs) to be used in the treatment of SCI. These nanovesicles can cross the blood-spinal cord barrier (BSCB) and deliver SeNPs and Met to the site of injury to exert anti-inflammatory and reactive oxygen species scavenging effects. Transmission electron microscopy (TEM) images showed that the SeNPs-Met-MVs particle size was approximately 125 ± 5 nm. Drug release assays showed that Met exhibited sustained release after encapsulation by the macrophage cell membrane. The cumulative release was approximately 80% over 36 h. In vitro cellular experiments and in vivo animal experiments demonstrated that SeNPs-Met-MVs decreased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and reduced the expression of inflammatory (TNF-α, IL-1ß, and IL-6) and apoptotic (cleaved caspase-3) cytokines in spinal cord tissue after SCI. In addition, motor function in mice was significantly improved after SeNPs-Met-MVs treatment. Therefore, SeNPs-Met-MVs have a promising future in the treatment of SCI.

Manganese-doped albumin-gelatin composite nanogel loaded with berberine applied to the treatment of gouty arthritis in rats via a SPARC-dependent mechanism.

In this study, manganese-doped albumin-gelatin composite nanogels (MAGN) were prepared and used to load berberine (Ber) for the treatment of gouty arthritis (GA). The nanodrug delivery system (Ber-MAGN) can target inflammatory joints due to the intrinsic high affinity of albumin for SPARC, which is overexpressed at the inflammatory site of GA. Characterization of the pharmaceutical properties in vitro showed that Ber-MAGN had good dispersion, and the particle size was 121 ± 10.7 nm. The sustained release effect significantly improved the bioavailability of berberine. In vitro and in vivo experimental results showed that Ber-MAGN has better therapeutic effects in relieving oxidative stress and suppressing inflammation. Therefore, Ber-MAGN, as a potential pharmaceutical preparation for GA, provides a new reference for the clinical treatment plan of GA.

Amorphous selenium inhibits oxidative stress injury of neurons in vascular dementia rats by activating NMDAR pathway.

Vascular dementia (VD) is one of the most common causes of dementia, taking account for about 20% of all cases. Although studies have found that selenium supplementation can improve the cognitive ability of Alzheimer's patients, there is currently no research on the cognitive impairment caused by VD. This study aimed to investigate the role and mechanism of Amorphous selenium nanodots (A SeNDs) in the prevention of VD. The bilateral common carotid artery occlusion (BCCAO) method was used to establish a VD model. The neuroprotective effect of A SeNDs was evaluated by Morris water maze, Transcranial Doppler TCD, hematoxylin-eosin (HE) staining, Neuron-specific nuclear protein (Neu N) staining and Golgi staining. Detect the expression levels of oxidative stress and Calcium-calmodulin dependent protein kinase II (CaMK II), N-methyl-D-aspartate receptor subunit NR2A, and postsynaptic dense protein 95 (PSD95). Finally, measure the concentration of calcium ions in neuronal cells. The results showed that A SeNDs could significantly improve the learning and memory ability of VD rats, restore the posterior arterial blood flow of the brain, improve the neuronal morphology and dendritic remodeling of pyramidal cells in hippocampal CA1 area, reduce the level of oxidative stress in VD rats, increase the expression of NR2A, PSD95, CaMK II proteins and reduce intracellular calcium ion concentration, but the addition of selective NR2A antagonist NVP-AAMO77 eliminated these benefits. It suggests that A SeNDs may improve cognitive dysfunction in vascular dementia rats by regulating the NMDAR pathway.

[Post-marketing effectiveness evaluation of traditional Chinese medicine in paradigm based on "proving efficacy, conforming standard, and exploring mechanism":a case study of Danhong Injection].

At present, new concepts, new technologies, and new methods are emerging in the field of medical research, breaking through the inherent thinking patterns and research models, and promoting the transformation of the research paradigm of traditional Chinese medicine(TCM). This paper gave a case study of clinical research in Danhong Injection in the treatment of chronic stable angina, and based on the background of the study, index evaluation model, experimental design method, blind implementation of placebo, data management system, and exploration of clinical efficacy mechanism of traditional Chinese medicine compounds under the framework of modular pharmacology, the scientific idea of "proving efficacy, conforming standard, and exploring mechanism" was used as the guideline to discuss the research model of reevaluation of the effectiveness of post-marketing TCM varieties. This paper drew a target network map of Danhong Injection in the treatment of chronic stable angina for the first time, which was composed of targeted functional modules. By combining evidence-based clinical research with modular pharmacology framework, changes in the pharmacolo-gical mechanism were finally associated with changes in clinical efficacy, and the advantages of phenotypic correlation of efficacy were explored. This study is expected to provide references for the post-marketing effectiveness evaluation and new ideas for the phenotypic pharmacological mechanism study of multi-target TCM compounds and precise treatment, thereby promoting the innovative development of TCM.

Application of Nursing Outcome-Oriented Integrated Zero-Defect Nursing Combined with Respiratory Function Training in Long-Term Bedridden Patients Undergoing Stroke.

Objective: To explore the application effect of nursing outcome-oriented integrated zero-defect nursing combined with respiratory function training in long-term bedridden patients with stroke. Methods: A total of 120 long-term bedridden patients with stroke were randomly divided into three groups: groups A, B, and C. Group A was given nursing outcome-oriented integrated zero-defect nursing combined with respiratory function training, group B was given nursing outcome-oriented integrated zero-defect nursing, and group C was given routine nursing. Rosenbek aspiration degree classification criteria were used to evaluate the incidence of aspiration; blood oxygen saturation, arterial oxygen partial pressure, and respiratory pressure were compared before and after the intervention. The swallowing function was evaluated by a water swallowing test (WST). The quality of life was assessed using the Generic Quality of Life Inventory-74 (GQOLI-74). Results: After treatment, the Rosenbek aspiration degree of groups A and B were better than those of group C (P < 0.05); the improvement degree of respiratory function indexes in group A was better than those in B and C, and the blood oxygen saturation and arterial blood oxygen partial pressure in group B were better than those in C (P < 0.05). The incidence of complications in groups A and B was lower than that in C, and complications in group A were lower than that in B (P < 0.05). After treatment, the scores of psychological function, social function, and material life status of the three groups were increased, and each score of groups A and B was higher than that of C, and each score of group A was higher than that of B (P < 0.05). Conclusion: Nursing outcome-oriented integrated zero-defect nursing combined with respiratory function training can effectively improve aspiration, respiratory function, swallowing function, complication rate, and quality of life in long-term bedridden patients with stroke.

Amorphous selenium nanodots alleviate non-alcoholic fatty liver disease via activating VEGF receptor 1 to further inhibit phosphorylation of JNK/p38 MAPK pathways.

In clinic, there is still no unified standard for the treatment of non-alcoholic fatty liver disease (NAFLD), and the development of effective novel drugs to alleviate NAFLD remains a challenge. This study aimed to explore the effect and mechanism of amorphous selenium nanodots (A SeNDs) in alleviating NAFLD. Model rats with NAFLD were induced by the high-fat diet (HFD). Histomorphology was used to observe liver tissue, automatic biochemical analyzer was used to analyze liver function indicators, and ELISA kit was used to detect the effect of A SeNDs on oxidative stress and inflammatory factors in NAFLD rats. The results exhibited that A SeNDs could reduce hepatocyte steatosis, liver index, blood lipid level, and transaminase level in NAFLD rats. Furthermore, A SeNDs could relieve the oxidative stress and inflammatory reaction and maintain liver tissue structure in NAFLD rats. Mechanistically, A SeNDs (0.3 mg/kg/day) inhibit the phosphorylation of JNK/p38 MAPK pathways after activating vascular endothelial growth factor receptor 1 (VEGFR1) in the liver of rats with NAFLD to allay oxidative stress and inflammatory response and improves hepatic structure and liver function. Therefore, it should be an important method to mitigate NAFLD by supplementing A SeNDs to normalize hepatic structure and liver function.

Astaxanthin improved the storage stability of docosahexaenoic acid-enriched eggs by inhibiting oxidation of non-esterified poly-unsaturated fatty acids.

This study assessed the potential and mechanism of action of astaxanthin, to improve the stability of docosahexaenoic acid (22:6(n-3); DHA) enriched egg products, during storage at 4 °C. The reduction in DHA content after 42 days of storage in astaxanthin-DHA eggs (from hens fed supplemental astaxanthin and DHA) was <3%, whereas the reduction in regular-DHA eggs (hens fed DHA only) was over 17%. Astaxanthin also decreased production of oxidation products including 4-hydroxy-2-hexenal, 4-hydroxy-2-nonenal and malondialdehyde in eggs during storage, thus markedly improving the oxidative stability of DHA-enriched eggs. The yolk lipidomic profile showed higher intensities for most DHA-containing lipids, especially DHA-phosphatidylcholine, DHA-phosphatidylethanolamine and DHA-non-esterified fatty acid, compared with regular-DHA eggs. Astaxanthin acts primarily by suppressing oxidation of DHA-non-esterified fatty acid, which minimizes the degradation of DHA and appears to be the primary protection mode of yolk DHA during storage.

Efficacy of add-on Danhong injection in patients with unstable angina pectoris: A double-blind, randomized, placebo-controlled, multicenter clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Danhong injection (DHI)，which is extracted from Salviae miltiorrhizae and Flos carthami，has been widely prescribed to patients with unstable angina pectoris (UAP) in China. However, a high quality clinical trial is needed. AIM OF THE STUDY: To determine whether DHI can relieve symptoms of transient myocardial ischemia in patients with unstable angina pectoris. MATERIALS AND METHODS: A double-blind, placebo-controlled, randomized clinical trial was conducted in nine hospitals in China. Inpatients with UAP with blood stasis syndrome (BSS) were randomized 1:1 to receive DHI or placebo. The primary outcome was improvement rate in the quantification score of angina pectoris. Secondary outcomes included blood stasis syndrome scale, nitrates use, electrocardiogram recordings, PCI procedures, Seattle Angina Questionnaire (SAQ) and biochemical indexes. RESULTS: 160 participants were enrolled and 159 were analyzed. There was no significant difference in primary outcome as compared with control group at the end of 7-day treatment, but significant difference at 28-day follow up (70.53% [95% CI, 59.97-81.09%] and 54.34% [95% CI, 42.68-65.99%]; P = 0.0423). The BSS score was significantly lower in the DHI group than that in the control group at day 28 (6.49 [6.96] vs 10.53 [9.07], P = 0.0034). In addition, DHI was significantly superior to placebo in the angina stability score of SAQ (91.10 [17.37] versus 78.21 [22.08], P < 0.001). There were no significant differences in other secondary outcome measures. CONCLUSIONS: A small decrease in the total effective rate and an increase in the angina stability score were observed 28 days after implementation of DHI in UAP with a total blood stasis syndrome score decrease, but the efficacy was not observed at day 7. The findings support that DHI may potentially relieve clinical symptoms and can benefit angina stability. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02007187.

A naphthimide fluorescent probe for the detection of selenols in selenium-enriched Tan sheep.

An "off-on" fluorescent probe, Nap-DNB, which is based on naphthimide, was designed and developed for the detection of biological selenols in vitro. We have adopted a combination of a low-pH detection environment and reaction sites that are more difficult to destroy to avoid the interference of a large number of biological thiols in biological samples. Nap-DNB can completely respond to selenocysteine within 15 mins, with a detection limit of 92 nM. Nap-DNB was successfully used for the detection of selenols in the serum, liver, and longissimus dorsi of selenium-enriched Tan sheep. Through comparison, we found that the detection of selenols by the Nap-DNB is similar to that by thioredoxin reductase and glutathione peroxidase in a commercial kit method. Nap-DNB can be used for the detection of selenols in selenium-enriched Tan sheep.

Effect of Replacing in-Feed Antibiotic Growth Promoters with a Combination of Egg Immunoglobulins and Phytomolecules on the Performance, Serum Immunity, and Intestinal Health of Weaned Pigs Challenged with Escherichia coli K88.

The study was conducted to investigate the effects of replacing antibiotic growth promoters (AGPs) with an egg immunoglobulin (IgY) combined with phytomolecules (PM) on the growth rate, serum immunity, and intestinal health of weaned pigs challenged with Escherichia coli K88 (E. coli K88). A total of 192 piglets were weaned at 28 days old with an average weight of 7.29 (± 0.04) kg. They were randomly divided into four treatments containing eight replicates with six piglets per replicate. The treatment groups were NC and PC fed a basal diet, AGP fed a basal diet supplemented with 75 mg/kg chlortetracycline, 50 mg/kg oxytetracycline calcium, and 40 mg/kg zinc bacitracin, IPM fed a basal diet supplemented with IgY at dose of 2.5 g/kg and 1.0 g/kg and PM at dose of 300 mg/kg and 150 mg/kg during days 1 to 17 and 18 to 42, respectively. On days 7 to 9 of the experiment, piglets in the PC, AGP, and IPM groups were orally challenged with 20 mL E. coli K88 (109 CFU/mL), while piglets in the NC group were challenged with 20 mL medium without E. coli K88. The E. coli K88 challenge model was successful as the incidence of post-weaning diarrhea (PWD) of piglets challenged with E. coli K88 was significantly higher than that of those unchallenged piglets during the challenge time (days 7 to 9) and days 1 to 7 of post-challenge (p < 0.05). A diet with combinations of IgY and PM and AGPs significantly decreased the incidence of PWD during the challenge time and days 1 to 7 of post-challenge (p < 0.05) compared to the PC group and significantly improved the ratio of feed to weight gain (F:G) during days 1 to 17 of the experiment compared to the NC and PC groups (p < 0.05). In comparison with the PC group, piglets in the IPM group had significantly higher serum levels of IgA, IgG, and IgM (p < 0.05), but lower serum IL-1ß on day 17 of experiement (p < 0.05). Besides, diet supplementation with AGP significantly decreased serum IL-1ß, IL-6, and TNF-α on days 17 and 42 (p < 0.05) with comparison to the PC group. Piglets in the IPM group showed a significantly lower level of fecal coliforms (p < 0.05), but a higher villus height of jejunum and ileum and higher ratio of villus height to crypt depth of duodenum and jejunum (p < 0.05) than those piglets in the PC group. In summary, diet supplementation with a mixture of IgY and PM decreased the incidence of PWD and coliforms, increased feed conversion ratio, and improved intestinal histology and immune function.

Effect of Qizhitongluo capsule on lower limb rehabilitation after stroke: A randomized clinical trial.

BACKGROUND: An individual's level of lower limb motor function is associated with his or her disability level after stroke, and motor improvement may lead to a better prognosis and quality of life. Data from animal models show that Qizhitongluo (QZTL) capsule facilitates recovery after focal brain injury. We aimed to validate the efficacy and safety of the QZTL capsule for promoting lower limb motor recovery in poststroke patients. METHODS: In this randomized, multicenter, double-blind, placebo- and active-controlled trial from 13 sites in China, participants with ischemic stroke and Fugl-Meyer motor scale (FMMS) scores of <95 were eligible for inclusion. Patients were randomly assigned in a 2:1:1 ratio to the QZTL group, Naoxintong (NXT) group or placebo group for 12 weeks at 15-28 days after the onset of stroke. The primary outcome was the change in the Lower Limb FMMS (FMMS-LL) score from baseline over the 12-week intervention period. RESULTS: 622 participants were randomly assigned to the QZTL group (309), NXT group (159), or placebo group (154). The FMMS-LL score increased by 4.81 points (95 % CI, 4.27-5.35) in the QZTL group, by 3.77 points (95 % CI, 3.03-4.51) in the NXT group and by 3.00 points (95 % CI, 3.03-4.51) in the placebo group at week 12. The QZTL group showed significantly larger improvements compared with the placebo group at each interview from weeks 4-12 (difference, 0.89 [0.30,1.49] at week 4, P = 0.0032; difference, 1.83[1.01,2.66] at 90 days poststroke, P < 0.0001; difference, 1.81[0.88,2.74] at week 12, P = 0.0001). CONCLUSION: The QZTL capsule is an effective treatment for lower limb motor impairment. The finding indicates that the QZTL capsule may be used as a potential new strategy for stroke rehabilitation.

Comparative Analysis of the Efficacy and Safety of Different Traditional Chinese Medicine Injections in the Treatment of Cancer-Related Pain: A Bayesian Network Meta-Analysis.

Background: Given the limitations of three-step analgesic therapy and the extensive use of traditional Chinese medicine injections (TCMIs) for cancer-related pain (CRP), this network meta-analysis (NMA) aims to compare the efficacy and safety of different regimens of TCMIs for CRP. Methods: A literature search was conducted in seven electronic databases for all related articles published before 12 April 2021. Randomized controlled trials (RCTs) were screened by a prior eligible criteria. The quality of literature was evaluated by the Cochrane risk of bias tool. We used Stata 16.0 software to analyze data including total pain relief rate, quality of life, and the incidence of adverse reactions. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the interventions. Radar map was used to exhibit the most outstanding regimen for a certain outcome. Synthetic sorting bubble diagram was performed to show the relatively better regimen by integrating two or three outcomes. Results: A total of 84 RCTs involving 8,044 patients were included. The results indicated that YDZYR + AN (Yadanziyouru injection plus analgesic) ranked first for pain relief rate, closely followed by KLT + AN (Kanglaite injection plus analgesic). AD + AN (Aidi injection plus analgesic) ranked first for quality of life, KLT + AN following closely. The total adverse reaction rate of FFKS + AN (Fufangkushen injection plus analgesic) was the lowest, and the constipation rate of FFKS was the lowest. In terms of the incidence of nausea and vomiting, KLT + AN was the best choice. In the plots analysis, the results of integrated total incidence of adverse reactions and pain relief rate analysis indicated that FFKS + AN was the most appropriate regimen. Meanwhile, it had the lowest incidence of integrated constipation, nausea and vomiting, and total adverse reactions. KLT + AN was the best in alleviating pain and improving quality of life integrated outcomes. Conclusion: In conclusion, FFKS + AN was the best treatment regimen for the pain relief rate and total adverse reaction rate, and it was also the safest regimen for CRP treatment. KLT + AN was the most effective choice. Further, compared with analgesic treatment alone for patients with CRP, TCMIs + AN combination treatment strategies are significantly more effective. However, more high-quality RCTs are required to support these conclusions. Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/#recordDetails, https://www.crd.york.ac.uk/prospero/export_details_pdf.php), identifier (ChiCTR-ONC-CRD42021267829).

Met-Controlled Allosteric Module of Neural Generation as A New Therapeutic Target in Rodent Brain Ischemia.

OBJECTIVE: To investigate a Met-controlled allosteric module (AM) of neural generation as a potential therapeutic target for brain ischemia. METHODS: We selected Markov clustering algorithm (MCL) to mine functional modules in the related target networks. According to the topological similarity, one functional module was predicted in the modules of baicalin (BA), jasminoidin (JA), cholic acid (CA), compared with I/R model modules. This functional module included three genes: Inppl1, Met and Dapk3 (IMD). By gene ontology enrichment analysis, biological process related to this functional module was obtained. This functional module participated in generation of neurons. Western blotting was applied to present the compound-dependent regulation of IMD. Co-immunoprecipitation was used to reveal the relationship among the three members. We used IF to determine the number of newborn neurons between compound treatment group and ischemia/reperfusion group. The expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) were supposed to show the changing circumstances for neural generation under cerebral ischemia. RESULTS: Significant reduction in infarction volume and pathological changes were shown in the compound treatment groups compared with the I/R model group (P<0.05). Three nodes in one novel module of IMD were found to exert diverse compound-dependent ischemic-specific excitatory regulatory activities. An anti-ischemic excitatory allosteric module (AME) of generation of neurons (AME-GN) was validated successfully in vivo. Newborn neurons increased in BJC treatment group (P<0.05). The expression of VEGF and MMP-9 decreased in the compound treatment groups compared with the I/R model group (P<0.05). CONCLUSIONS: AME demonstrates effectiveness of our pioneering approach to the discovery of therapeutic target. The novel approach for AM discovery in an effort to identify therapeutic targets holds the promise of accelerating elucidation of underlying pharmacological mechanisms in cerebral ischemia.

Standard Operating Procedures for Chinese Medicine Data Monitoring Committees of Clinical Studies.

Although there is guidance from different regulatory agencies, there are opportunities to bring greater consistency and stronger applicability to address the practical issues of establishing and operating a data monitoring committee (DMC) for clinical studies of Chinese medicine. We names it as a Chinese Medicine Data Monitoring Committee (CMDMC). A panel composed of clinical and statistical experts shared their experience and thoughts on the important aspects of CMDMCs. Subsequently, a community standard on CMDMCs (T/CACM 1323-2019) was issued by the China Association of Chinese Medicine on September 12, 2019. This paper summarizes the key content of this standard to help the sponsors of clinical studies establish and operate CMDMCs, which will further develop the scientific integrity and quality of clinical studies.

Inulin supplementation ameliorates hyperuricemia and modulates gut microbiota in Uox-knockout mice.

PURPOSE: Inulin is a type of fermentable dietary fiber, which is non-digestible, and can improve metabolic function by modulating intestinal microbiota. This study aimed to evaluate the role of inulin in hyperuricemia and microbial composition of the gut microbiota in a mouse model of hyperuricemia established through knockout of Uox (urate oxidase) gene. METHODS: KO (Uox-knockout) and WT (wild-type) mice were given inulin or saline by gavage for 7 weeks. The effect of inulin to combat hyperuricemia was determined by assessing the changes in serum UA (uric acid) levels, inflammatory parameters, epithelial barrier integrity, fecal microbiota alterations, and SCFA (short-chain fatty acid) concentrations in KO mice. RESULTS: Inulin supplementation can effectively alleviate hyperuricemia, increase the expressions of ABCG2 in intestine, and downregulate expression and activity of hepatic XOD (xanthine oxidase) in KO mice. It was revealed that the levels of inflammatory cytokines and the LPS (lipopolysaccharide) were remarkably higher in the KO group than those in the WT group, indicating systemic inflammation of hyperuricemic mice, but inulin treatment ameliorated inflammation in KO mice. Besides, inulin treatment repaired the intestinal epithelial barrier as evidenced by increased levels of intestinal TJ (tight junction) proteins [ZO-1 (zonula occludens-1) and occluding] in KO mice. Moreover, serum levels of uremic toxins, including IS (indoxyl sulfate) and PCS (p-cresol sulfate), were reduced in inulin-treated KO mice. Further investigation unveiled that inulin supplementation enhanced microbial diversity and raised the relative abundance of beneficial bacteria, involving SCFAs-producing bacteria (e.g., Akkermansia and Ruminococcus). Additionally, inulin treatment increased the production of gut microbiota-derived SCFAs (acetate, propionate and butyrate concentrations) in KO mice, which was positively correlated with the effectiveness of hyperuricemia relief. CONCLUSIONS: Our findings showed that inulin may be a promising therapeutic candidate for the treatment of hyperuricemia. Moreover, alleviation of hyperuricemia by inulin supplementation was, at least, partially conciliated by modulation of gut microbiota and its metabolites.

A comparative pharmacogenomic analysis of three classic TCM prescriptions for coronary heart disease based on molecular network modeling.

Traditional Chinese medicine (TCM) has evolved over several thousands of years, which has been shown to be efficacious in the treatment of ischemic heart disease. Three classical TCM prescriptions, namely Xuefu Zhuyu Decoction, Zhishi Xiebai Guizhi Decoction, and Gualou Xiebai Banxia Decoction, have been extensively used in the treatment of coronary heart disease (CHD). Based on molecular network modeling, we performed a comparative pharmacogenomic analysis to systematically determine the drug-targeting spectrum of the three prescriptions at molecular level. Wide-area target molecules of CHD were covered, which was a common feature of the three decoctions, demonstrating their therapeutic functions. Meanwhile, collective signaling involved metabolic/pro-metabolic pathways, driving and transferring pathways, neuropsychiatric pathways, and exocrine or endocrine pathways. These organized pharmacological disturbance was mainly focused on almost all stages of CHD intervention, such as anti-atherosclerosis, lipid metabolism, inflammation, vascular wall function, foam cells formation, platelets aggregation, thrombosis, arrhythmia, and ischemia-reperfusion injury. In addition, heterogeneity analysis of the global pharmacological molecular spectrum revealed that signaling crosstalk, cascade convergence, and key targets were tendentious among the three decoctions. After all, it is unadvisable to rank the findings on targeting advantages of the three decoctions. Comparative pharmacological evidence may provide an appropriate decoction scheme for individualized intervention of CHD.