Simultaneous increases of filter-feeding fish and bivalves are key for controlling cyanobacterial blooms in a shallow eutrophic lake.

Eutrophication and cyanobacterial blooms have severely affected many freshwater ecosystems. We studied the effects of filter-feeding fish and bivalves on algal populations using a mesocosm experiment and long-term monitoring data from Lake Taihu (China). The mesocosm study, comprised of a two-way factorial design with the clam Corbicula fluminea and the fish Aristichthys nobilis at three biomass levels, resulted in lower chlorophyll a (Chl a) in high fish treatments, but no significant differences in the low and medium fish treatments. Chl a also decreased with an increase in clam biomass in the high fish treatments. Moreover, filter-feeding fish resulted in a decrease in algal sizes (e.g., the colony size of Microcystis aeruginosa was inversely related to fish biomass) which likely increased the filter-feeding efficiency of bivalves. Biomass of filter-feeding fish was found to be a key factor driving the synergistic effects of filter-feeding fish and bivalves in waters dominated by Microcystis colonies. Long-term monitoring revealed increasing trends in Chl a concentration, total fish catch per unit effort (TF-CPUE), and filter-feeding fish (FF-CPUE), and slightly decreasing trends in bivalve biomass and nitrogen to phosphorus ratios (N:P) from 2006 to 2016. Bivalve biomass and N:P were negatively correlated with Chl a, while FF-CPUE was not significantly related to Chl a. The current filter-feeding fish biomass in Lake Taihu is estimated to be too low to drive synergistic algal control effects together with bivalves. Furthermore, the lack of filter feeders in Lake Taihu may lead to top-down control by predators that cannot counteract the bottom-up effects of nutrients on phytoplankton. Collectively, these long-term monitoring and experimental data support the combined use filter-feeding fish and bivalves for managing cyanobacteria blooms in Lake Taihu.

Yinlai Decoction Protects Microstructure of Colon and Regulates Serum Level of D-Lactic Acid in Pneumonia Mice Fed with High-Calorie and High-Protein Diet.

OBJECTIVE: To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD). METHODS: Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice. RESULTS: The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05). CONCLUSIONS: YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.

Reveal the Patterns of Prescriptions for Recurrent Respiratory Tract Infections' Treatment Based on Multiple Illustrious Senior Traditional Chinese Medicine Practitioners.

Background: Recurrent respiratory tract infections (RRTIs) are one of the most common diseases in children and adolescents. The causes of RRTIs are various. In addition to the factors related to infection, basic diseases such as respiratory system, immune system, and digestive system are also involved. The cost of patients' frequent medical treatment and hospitalization has been deemed to be a heavy burden to the society and family. In China, traditional Chinese medicine (TCM) is commonly used to treat RRTIs. TCM treatment has been appraised to be effective, for reducing the number of hospital stays. Illustrious senior TCM practitioners of pediatrics are recognized as a group of outstanding physicians with significantly better patient outcomes. However, different illustrious senior TCM practitioners can lead to differences in treatment strategies due to factors such as region, prescription theory, and individual differences of patients. This makes it difficult for the experience of illustrious senior TCM practitioners to be popularized. However, there have been no prescription mining studies for the treatment of RRTIs based on different and multiple illustrious senior TCM practitioners. We explored the core prescriptions and drug mechanisms through data mining based on the prescriptions of illustrious senior TCM practitioners treating RRTIs from different clinical settings. This is important to promote the effective treatment of RRTIs with TCM. The objective of this study is to reveal the strategies (core prescriptions) from the prescriptions of multiple illustrious senior TCM practitioners for the treatment of RRTIs. We hope that this core prescription can help all TCM pediatricians to improve RRTIs children's outcome. Meanwhile, it could provide a new way for researchers to study the treatment of RRTIs. Methods: In this study, we prospectively collected 400 children's prescriptions with RRTIs receiving TCM treatment from four illustrious senior TCM practitioners in different hospitals. We described and analyzed the characteristics of TCM prescriptions. The prescription regularity was analyzed by hierarchical clustering and association rules. Network pharmacology methods has been used to reveal the pathway mechanism of core prescriptions which have been mined and visualized with the help of SymMap, Genecards, KEGG, Metascape databases, and R. The execution of all methods was completed in May 2022. Results: According to RRTIs multiple clinical syndromes, five new prescriptions were obtained based on illustrious senior TCM practitioners. Among them, the prescription composed of Scutellariae radix (Huangqin), Armeniacae semen amarum (Kuxingren), Peucedani radix (Qianhu), and Pheretima (Dilong) is the core strategy for the treatment of RRTIs. Cold herbs and heat herbs in the core prescription are approximately equal. Scutellariae radix (Huangqin) was dominant, and other herbs exert synergistic effects. The core prescription covered 76 pathways and 226 herb-disease genes. It promotes the differentiation of Th1, Th2, and Th17 cells and the secretion of inflammatory factors through toll-like receptor signaling pathway in the immune system, T cell receptor signaling pathway, and PPAR signaling pathway in the endocrine system, thereby exerting immune regulation and anti-inflammation. Conclusion: In this study, we revealed the prescription regularity of TCM in the treatment of RRTIs and analyzed the mechanism of core prescriptions, which provided new ideas for the treatment of RRTIs.

New insights for infection mechanism and potential targets of COVID-19: Three Chinese patent medicines and three Chinese medicine formulas as promising therapeutic approaches.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high pathogenicity and infectiousness has become a sudden and lethal pandemic worldwide. Currently, there is no accepted specific drug for COVID-19 treatment. Therefore, it is extremely urgent to clarify the pathogenic mechanism and develop effective therapies for patients with COVID-19. According to several reliable reports from China, traditional Chinese medicine (TCM), especially for three Chinese patent medicines and three Chinese medicine formulas, has been demonstrated to effectively alleviate the symptoms of COVID-19 either used alone or in combination with Western medicines. In this review, we systematically summarized and analyzed the pathogenesis of COVID-19, the detailed clinical practice, active ingredients investigation, network pharmacology prediction and underlying mechanism verification of three Chinese patent medicines and three Chinese medicine formulas in the COVID-19 combat. Additionally, we summarized some promising and high-frequency drugs of these prescriptions and discussed their regulatory mechanism, which provides guidance for the development of new drugs against COVID-19. Collectively, by addressing critical challenges, for example, unclear targets and complicated active ingredients of these medicines and formulas, we believe that TCM will represent promising and efficient strategies for curing COVID-19 and related pandemics.

Exploring the Core Prescription and Underlying Mechanism of Traditional Chinese Medicine in Treating Allergic Rhinitis in Children: A Real- World Study Based on an Illustrious Senior Traditional Chinese Medicine Practitioner.

BACKGROUND: Traditional Chinese medicine (TCM) is widely used to treat allergic rhinitis (AR) in China, especially in children. However, due to the complicated composition rules and unclear underlying mechanisms, effective herbal prescriptions' popularization and application are limited. PURPOSE: This study tried to detect the core prescription of herbs in treating AR in children, reveal its mechanism based on the ingredients' network, and explore the main signaling pathways. METHODS: We screened medical records of children patients with AR who were treated by TCM in DongZhiMen Hospital from Aug 2009 to Jan 2020 and adopted a descriptive analysis method on herbal characteristics. We used association rules to mine core prescriptions and used network pharmacology to establish the ingredient-target-pathway network through online databases and TCMSP, Genecards, KEGG pathway, Excel, R-Studio, and Cytoscape software. RESULTS: The analysis of 1,092 clinical visits highlighted that the principle of formulating prescription was as follows: 'pungent and warm herbs were used more frequently while cold-natured herbs were paid equal attention as warm-natured herbs.' The core prescription was formed by FangFeng, BaiZhi, CangErzi, and ChanTui. These herbs covered 130 underlying targets and 141 signaling pathways of AR, which mainly had an effect on signal transduction and immunoregulation. CONCLUSION: The core prescription based on these real-world clinical records includes FangFeng, BaiZhi, CangErzi, and ChanTui. It principally acts on targets of signal transduction pathways and immune pathways.

On the Core Prescriptions and Their Mechanisms of Traditional Chinese Medicine in Hepatitis B, Liver Cirrhosis, and Liver Cancer Treatment.

Background: As a frequent cause of death in cancer patients, liver cancer usually occurs in hepatitis B and cirrhosis. In China, Chinese people have been using traditional Chinese medicine (TCM) in treating various chronic liver diseases, which could effectively improve the symptoms and slow down the progression of liver diseases. However, due to the complexity rules of TCM prescription, their action mechanisms are still not clearly understood, which may affect the popularization of effective prescriptions. This study aims to identify the core TCM herbs in the treatment of hepatitis B, liver cirrhosis, and liver cancer so as to clarify the mechanism of action of the core herb networks. Methods: There were 1,673 prescriptions for chronic liver diseases collected in this study, of which 854 were hepatic B prescriptions, 530 were for liver cirrhosis, and 289 were for liver cancer. The basic characteristics of herbal medicine were firstly explained via descriptive analysis, then the core prescriptions of herbal medicine were analyzed through association rule, and finally, the mechanism of core prescriptions was explored with the help of systematic network pharmacology and by applying such databases as TCMIP, HERB, OMIM, GeneCards, KEGG, and software like RStudio and Cytoscape. Results: The rule of the core prescriptions in these cases was characterized by the application of herbs with both cold and warm properties, in which bitter herbs with cold property took priority. Tonifying deficiency, clearing heat, and activating blood circulations to remove stasis were common treatment principles for the three liver diseases. Turmeric Root Tuber (YuJin), White Peony Root (BaiShao), Bupleurum (ChaiHu), Salvia miltiorrhiza (DanShen), and Astragali Radix (HuangQi) were prescribed the most in hepatitis B treatment to invigorate the spleen and soothe the liver. Astragali Radix (HuangQi), Tuckahoe (FuLing), Atractylodis Macrocephalae Rhizoma (BaiZhu), Fructus Polygoni Orientalis (ShuiHongHuaZi), and Curcumae Rhizome (EZhu) were most frequently applied in liver cirrhosis treatment to replenish qi and activate blood. Oldenlandia (BaiHuaSheSheCao), Bearded Scutellaria (BanZhiLian), Curcumae Rhizome (EZhu), and Cardamom (DouKou) were most frequently prescribed to eliminate cancer toxin, invigorate the spleen, and activate blood. These core herbs mainly act through signal transduction and immune system pathways, in which the PI3K-Akt pathway plays a key role. The core prescription for liver cirrhosis regulated more endocrine system pathways than the hepatitis B prescription, and liver cancer prescription regulated more nervous system-related pathways. Conclusion: Three core prescriptions for hepatitis B, liver cirrhosis, and liver cancer treatment were identified, which acted mainly through signal transduction and immune system pathways to regulate immunity and cell growth and participate in inflammation inhibition, in which liver cancer prescription regulated more pathways, especially more nervous system-related pathways than the other two.

Efficacy of adenosylmethionine combined with Si Mo Tang in treatment of neonatal jaundice.

OBJECTIVE: To investigate the efficacy of S-adenosylmethionine (SAM-e) combined with Si Mo Tang in the treatment of neonatal jaundice and its effect on liver function, cardiac enzymes, immune function, serum transferrin (TRF) and C-reactive protein (CRP) levels. METHODS: The clinical data of 149 infants with neonatal jaundice were collected retrospectively. The infants were grouped according to the treatment methods. All neonates were treated with blue light phototherapy. Besides, group A was treated with SAM-e, group B was treated with Si Mo Tang, and group C was treated with SAM-e combined with Si Mo Tang. The treatment efficacy, serum bilirubin level, neonatal behavioral neurological assessment (NBNA) score, liver function, cardiac enzymes, immune function, serum TRF and CRP level were compared among the three groups before and after treatment. RESULTS: The total effective rate of treatment in group C was 96.00%, which was higher than group A (73.47%) and group B (78.00%) (P < 0.05), but no significant difference was observed between groups A and B (P > 0.05). Compared with groups A and B, group C had higher NBNA scores, lower serum bilirubin levels, and lower serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase-MB (CK-MB) levels (all P < 0.05); however, there was no statistical differences in NBNA scores, serum bilirubin levels, serum AST and ALT, LDH, CK and CK-MB levels between group A and group B (all P > 0.05). Compared with groups A and B, group C showed higher CD4+, CD4+/CD8+, TRF levels and lower serum CRP levels (P < 0.05), while there was no statistical differences in CD4+, CD4+/CD8+, CD8+, TRF levels and serum CRP levels between group A and group B (all P > 0.05). CONCLUSION: SAM-e combined with Si Mo Tang promoted the regression of jaundice, improved liver function, neurodevelopmental conditions and the myocardial enzyme spectrum, reduced the level of inflammation, and improved the immunity of newborns with neonatal jaundice.

Intestinal Flora: A Potential Mechanism by Which Yinlai Decoction Treats Lipopolysaccharide-Induced Pneumonia.

Background: We intended to explore the mechanism of Yinlai decoction in the treatment of lipopolysaccharide (LPS)-induced pneumonia from the perspective of intestinal flora. Methods: Thirty Sprague-Dawley rats were randomly assigned to the blank control group (N), the pneumonia group (P), and the Yinlai decoction group (PT). The rat pneumonia model was established using LPS inhalation (0.5 mg/mL, 5 mL, 30 min/day, 3 days). Yinlai decoction was administered intragastrically (2 mL/100 g, 3 days). Lung tissue pathology, organ indexes, serum inflammatory factors, tumor necrosis factor-alpha (TNF-α), and intestinal flora changes were measured. Results: Lung tissue inflammation was prevented by Yinlai decoction. IL-6 levels showed a higher tendency to be higher, and IL-12 and TNF-α were significantly higher in the PT group than in the P group. The structure of the intestinal flora in the P differed from that in the N. The relative abundance of 10 out of 12 microflora was significantly higher in the P group than in the N and PT groups. In the PT group, the structure and the distribution of microbial groups were like those of the N group. Conclusions: Yinlai decoction inhibited LPS-induced lung and systemic inflammation in rats and may help the intestinal flora restore equilibrium by inhibiting the colonization of pathogenic bacteria and adjusting the ratio between probiotics and pathogenic bacteria. Intestinal flora may serve as a mediator of Yinlai decoction's effect on LPS-induced pneumonia.

The effect of Raphanus sativus L. seeds on regulation of intestinal motility in rats consuming a high-calorie diet.

PURPOSE: The purpose of this study was to explore the effects of a short-term high-calorie diet and the regulation mechanism of Raphanus sativus L. seeds (RSL seeds) on the intestinal motility of young rats. METHODS: We fed 20 Specific Pathogen Free (SPF) 4-week-old male Sprague-Dawley (SD) rats special high-calorie diet for 3 days and then randomized them to a high-calorie diet group (HCG, 10 rats) and an RSL seeds treatment group (TG, 10 rats). Ten rats of the same age served as the control group (CG). HCG and TG rats continued to be fed high-calorie feed. All of the rats were weighed every 2 days. After 3 days of treatment, the effects of RSL seeds on the regulation of intestinal motility in rats consuming a high-calorie diet were examined. RESULTS: After 3 days of consuming a high-calorie diet, body weight was significantly lower in the HCG group than in the control group, and body weight of the HCG group increased slowly with time. Serum substance P (SP) and ghrelin levels were significantly lower, while the nitric oxide (NO) level was significantly higher. There were no differences in hematoxylin-eosin (HE) staining of colon sections between the groups. The expression levels of Cx43 and BDNF protein and mRNA in colon tissue were significantly lower in the HCG group. There were no significant differences in body weight between the CG and TG groups. Serum SP and ghrelin indexes in TG group were higher than those in the HCG group, and the NO index was significantly decreased. The expression levels of Cx43 and BDNF proteins and mRNA in the colon tissue were also significantly greater. CONCLUSION: Consumption of a short-term high-calorie diet may result in intestinal motility dysfunction and reduced intestinal motility. RSL seeds may improve the intestinal motility by regulating the secretion of gastrointestinal motility hormones and the expression of intestinal motility-related proteins, such as Cx43 and BDNF.

Potential effect of Maxing Shigan decoction against coronavirus disease 2019 (COVID-19) revealed by network pharmacology and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Since the occurrence of coronavirus disease 2019 (COVID-19) in Wuhan, China in December 2019, COVID-19 has been quickly spreading out to other provinces and countries. Considering that traditional Chinese medicine (TCM) played an important role during outbreak of SARS and H1N1, finding potential alternative approaches for COVID-19 treatment is necessary before vaccines are developed. According to previous studies, Maxing Shigan decoction (MXSGD) present a prominent antivirus effect and is often used to treat pulmonary diseases. Furthermore, we collected 115 open prescriptions for COVID-19 therapy from the National Health Commission, State Administration of TCM and other organizations, MXSGD was identified as the key formula. However, the underlying molecular mechanism of MXSGD against COVID-19 is still unknown. AIM OF THE STUDY: The present study aimed to evaluate the therapeutic mechanism of MXSGD against COVID-19 by network pharmacology and in vitro experiment verification, and screen the potential components which could bind to key targets of COVID-19 via molecular docking method. MATERIALS AND METHODS: Multiple open-source databases related to TCM or compounds were employed to screen active ingredients and potential targets of MXSGD. Network pharmacology analysis methods were used to initially predict the antivirus and anti-inflammatory effects of MXSGD against COVID-19. IL-6 induced rat lung epithelial type Ⅱ cells (RLE-6TN) damage was established to explore the anti-inflammatory damage activity of MXSGD. After MXSGD intervention, the expression level of related proteins and their phosphorylation in the IL-6 mediated JAK-STAT signaling pathway were detected by Western blot. Molecular docking technique was used to further identify the potential substances which could bind to three key targets (ACE2, Mpro and RdRp) of COVID-19. RESULTS: In this study, 105 active ingredients and 1025 candidate targets were selected for MXSGD, 83 overlapping targets related to MXSGD and COVID-19 were identified, and the protein-protein interaction (PPI) network of MXSGD against COVID-19 was constructed. According to the results of biological enrichment analysis, 63 significant KEGG pathways were enriched, and most of them were related to signal transduction, immune system and virus infection. Furthermore, according the relationship between signal pathways, we confirmed MXSGD could effectively inhibit IL-6 mediated JAK-STAT signal pathway related protein expression level, decreased the protein expression levels of p-JAK2, p-STAT3, Bax and Caspase 3, and increased the protein expression level of Bcl-2, thereby inhibiting RLE-6TN cells damage. In addition, according to the LibDock scores screening results, the components with strong potential affinity (Top 10) with ACE2, Mpro and RdRp are mainly from glycyrrhiza uralensis (Chinese name: Gancao) and semen armeniacae amarum (Chinese name: Kuxingren). Among them, amygdalin was selected as the optimal candidate component bind to all three key targets, and euchrenone, glycyrrhizin, and glycyrol also exhibited superior affinity interactions with ACE2, Mpro and RdRp, respectively. CONCLUSION: This work explained the positive characteristics of multi-component, multi-target, and multi-approach intervention with MXSGD in combating COVID-19, and preliminary revealed the antiviral and anti-inflammatory pharmacodynamic substances and mechanism of MXSGD, which might provide insights into the vital role of TCM in the prevention and treatment of COVID-19.

FangNet: Mining herb hidden knowledge from TCM clinical effective formulas using structure network algorithm.

The use of herbs to treat various human diseases has been recorded for thousands of years. In Asia's current medical system, numerous herbal formulas have been repeatedly verified to confirm their effectiveness in different periods, which is a great resource for drug innovation and discovery. Through the mining of these clinical effective formulas by network pharmacology and bioinformatics analysis, important biologically active ingredients derived from these natural products might be discovered. As modern medicine requires a combination of multiple drugs for the treatment of complex diseases, previously clinical formulas are also combinations of various herbs according to the main causes and accompanying symptoms. However, the herbs that play a major role in the treatment of diseases are always unclear. Therefore, how to rank each herb's relative importance and determine the core herbs, is the first step to assisting herb selection for active ingredients discovery. To solve this problem, we built the platform FangNet, which ranks all herbs on their relative topological importance using the PageRank algorithm, based on the constructed symptom-herb network from a collection of clinical empirical prescriptions. Three types of herb hidden knowledge, including herb importance rank, herb-herb co-occurrence, and associations to symptoms, were provided in an interactive visualization. Moreover, FangNet has designed role-based permission for teams to store, analyze, and jointly interpret their clinical formulas, in an easy and secure collaboration environment, aiming at creating a central hub for massive symptom-herb connections. FangNet can be accessed at http://fangnet.org or http://fangnet.herb.ac.cn.

Deciphering the Pharmacological Mechanisms of Ma Xing Shi Gan Decoction against COVID-19 through Integrating Network Pharmacology and Experimental Exploration.

The outbreak of new infectious pneumonia caused by SARS-CoV-2 has posed a significant threat to public health, but specific medicines and vaccines are still being developed. Traditional Chinese medicine (TCM) has thousands of years of experience in facing the epidemic disease, such as influenza and viral pneumonia. In this study, we revealed the efficacy and pharmacological mechanism of Ma Xing Shi Gan (MXSG) Decoction against COVID-19. First, we used liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) to analyze the chemical components in MXSG and identified a total of 97 components from MXSG. Then, the intervention pathway of MXSG based on these components was analyzed with network pharmacology, and it was found that the pathways related to the virus infection process were enriched in some of MXSG component targets. Simultaneously, through literature research, it was preliminarily determined that MXSG, which is an essential prescription for treating COVID-19, shared the feature of antiviral, improving clinical symptoms, regulating immune inflammation, and inhibiting lung injury. The regulatory mechanisms associated with its treatment of COVID-19 were proposed. That MXSG might directly inhibit the adsorption and replication of SARS-CoV-2 at the viral entry step. Besides, MXSG might play a critical role in inflammation and immune regulatory, that is, to prevent cytokine storm and relieve lung injury through toll-like receptors signaling pathway. Next, in this study, the regulatory effect of MXSG on inflammatory lung injury was validated through transcriptome results. In summary, MXSG is a relatively active and safe treatment for influenza and viral pneumonia, and its therapeutic effect may be attributed to its antiviral and anti-inflammatory effects.

Data Mining and Systematic Pharmacology to Reveal the Mechanisms of Traditional Chinese Medicine in Recurrent Respiratory Tract Infections' Treatment.

Traditional Chinese medicine (TCM) was widely used in the treatment of recurrent respiratory tract infections (RRTIs) in East Asia, but its mechanism was not clear because of its complex prescription rules. This research prospectively collected 100 prescriptions of RRTI children treated with TCM. The characteristics of TCM in prescriptions were described and analyzed, and the rules of prescriptions were analyzed by hierarchical clustering and association rules. The results showed that the principle of RRTI was to pay equal attention to cold and mild, and six new meaningful prescriptions were obtained. Among them, the new prescription composed of Astragali Radix (Huangqi), Atractylodis Macrocephalae Rhizoma (Baizhu), Saposhnikoviae Radix (Fangfeng), Angelicae Sinensis Radix (Danggui), and Paeoniae Radix Rubra (Chishao) was an important method to treat RRTI. In order to explore the mechanism of the new prescription, the research obtained the action target of each herb of the core prescription on Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine, TCMIP v2.0. The target genes were enriched by Metascape, and 93 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were obtained. According to the classification and statistics of KEGG type, it was found that the new prescription mainly intervened in the metabolic pathway dominated by amino acid metabolism. In addition, there were also many interventions in the nervous system-, endocrine system-, and digestive system-related pathways. This study summarized the prescription rule of TCM in the treatment of RRTI, analyzed the mechanism of supplementing deficiency, and provided a new idea for the treatment of RRTI.

Network pharmacology to dissect the mechanisms of Yinlai Decoction for pneumonia.

BACKGROUND: Pneumonia is a common respiratory disorder, which brings an enormous financial burden to the medical system. However, the current treatment options for pneumonia are limited because of drug resistance and side effects. Our previous study preliminarily confirmed that Yinlai Decoction (YD), a common prescription for pneumonia in clinical practice, can regulate the expression of inflammatory factors, but the mechanisms are unknown yet. METHODS: In our work, a method named network pharmacology was applied, which investigated the underlying mechanisms of herbs based on a variety of databases. We obtained bioactive ingredients of YD on TCMSP database and collected potential targets of these ingredients by target fishing. Then the pneumonia-related targets database was built by TTD, Drugbank, HPO, OMIM, and CTD. Based on the matching targets between YD and pneumonia, the PPI network was built by STRING to analyze the interactions among these targets and then input into Cytoscape for further topological analysis. DAVID and KEGG were utilized for GO and pathway enrichment analysis. Then rat model based on LPS stimulated pneumonia was used to verify the possible mechanism of YD in treating pneumonia. RESULTS: Sixty-eight active ingredients, 103 potential targets and 8 related pathways, which likely exert a number of effects, were identified. Three networks were constructed using Cytoscape, which were herb-component-network, YD-pneumonia target network, and herb-component-YD target-pneumonia network. YD was verified to treat LPS-induced pneumonia by regulating the inflammatory factor IL-6, which was a predicted target. CONCLUSION: Network analysis indicated that YD could alleviate the symptoms and signs of pneumonia through regulating host immune inflammatory response, angiogenesis and vascular permeability, the barrier function of the airway epithelial cells, hormone releasing and cell growth, proliferation, and apoptosis.

Study on the mechanisms of "Xiaoerhuashi Pill, XP" in intervening the health status of high-calorie diet animals.

ETHNOPHARMACOLOGICAL RELEVANCE: "Xiaoerhuashi Pill, XP", with a history of 30 years in China, was included in the first part of the 2015 edition of the Chinese Pharmacopoeia and is widely used in the treatment for pediatric diseases in clinical application. Its main indications include the accumulation of heat caused by food stagnation in children, which has the effect of digestive stagnation and purge heat to relax the bowels. AIM OF THE STUDY: High-calorie diet, closely related to the occurrence and development of multiple diseases, is an unhealthy status of life. However, there is no effective intervention in clinic. Thus, based on animal experiments and bioinformatics, this study aims to explore the potential mechanisms of action of Chinese patent medicine- "Xiaoerhuashi Pill, XP" in the intervention of high-calorie diet. MATERIALS AND METHODS: A high-calorie diet model was prepared by 3-week-old rats. The defecation and intestinal mucosal morphology were observed after intragastric administration of "Xiaoerhuashi Pill, XP". The components of "Xiaoerhuashi Pill, XP" were obtained by chromatography-mass spectrometry, with the corresponding targets obtained by database and target fishing. The key effects substances were obtained by molecular docking, with the obtaining of the ore pathway of "Xiaoerhuashi Pill, XP" in intervention of high-calorie diet based on the enrichment analysis. RESULTS: "Xiaoerhuashi Pill, XP" can actively interfere with defecation and intestinal mucosal structures in high-calorie diet animals. A total of 37 substances were identified in the pediatric digestion solution, and 356 target proteins were mapped, 25 of which were associated with a high-calorie diet. Overall, the analysis shows that the highest degree of integration was quercetin and PON1 protein, with the highest enrichment of insulin resistance pathway. CONCLUSION: "Xiaoerhuashi Pill, XP" can intervene in the health status of high-calorie diet animals. Integration of quercetin and PON1 protein can regulate lipid levels, which may be the key mechanisms of action in "Xiaoerhuashi Pill, XP". The mechanisms, more specifically, may be related to the regulation of pancreas islet function, thus providing a reference for the clinical application of "Xiaoerhuashi Pill, XP", clinical intervention of high-calorie diet and new drug development.

Inhibition of Triple-Negative Breast Cancer Tumor Growth by Electroacupuncture with Encircled Needling and Its Mechanisms in a Mice Xenograft Model.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer without effective targeted drugs. While breast cancer patients often use acupuncture for the relief of cancer-induced pain or the side effects of chemo- or radiation therapy, little information is known regarding the direct effects of electroacupuncture on TNBC tumor and its potential mechanisms. Here, we created a mice model of TNBC and electroacupuncture with encircled needling around the tumors was given to the animals daily for 3 weeks at 15-20 Hz (3 min, each time). For sham electroacupuncture control, the skin was punctured to a depth of 5 mm and then the needle was quickly withdrawn without electrical stimulation or manual needle manipulation. We found that electroacupuncture significantly inhibited TNBC tumor growth and the inhibitory rate increased gradually overtime. Mechanistic analysis showed that electroacupuncture inhibited tumor angiogenesis by reducing the expression of vascular endothelial growth factor A (VEGF-A), its receptor VEGF-R and neuropilin 1 (NRP-1). Electroacupuncture also led to a significant decrease of matrix metalloproteinase-2 (MMP-2) expression and an increase of tissue inhibitor of MMP (TIMP-2) expression. Additionally, the expression of semaphorin 3A (Sema3A) and nerve growth factor receptor (NGFR) p75 in TNBC tissue was significantly upregulated in response to electroacupuncture. Furthermore, tumor necrosis factor (TNF)-alpha level in the serum was dramatically reduced after electroacupuncture. These results showed that electroacupuncture could directly inhibit TNBC tumor growth through the inhibition of proteins related to tumor angiogenesis and extracellular matrix, the suppression of TNBC-induced inflammation and the upregulation of nerve growth factor receptors.

Traditional Chinese herb for low endometrial receptivity and its effect on pregnancy: Protocol for a systematic review and meta-analysis.

BACKGROUND: Low endometrial receptivity is associated with infertility in women through multiple and complex mechanisms. Existing treatments are not always effective. Symptomatic drugs such as estradiol valerate and/or aspirin do not completely solve the problem. Traditional Chinese herbs have been widely used in infertility and uterine disease including low endometrial receptivity. However, their effectiveness and safety are still obscure and deserve further investigation. OBJECTIVE: To assess the effect and safety of traditional Chinese herbs in treating low endometrial receptivity. METHODS: We will summarize and meta-analyze randomized controlled trials (RCTs) of traditional Chinese herbs for the treatment of low endometrial receptivity. RCTs comparing traditional Chinese herbs with blank control, placebo, or conventional therapies will be included. RCTs comparing traditional Chinese herbs plus conventional therapies with conventional therapies alone will also be included. The following electronic databases will be searched: PubMed, Cochrane Library, EMBASE, CNKI, CBM, VIP, and WANFANG DATA. The methodological quality of RCTs will be assessed using the Cochrane risk assessment tool. All trials included will be analyzed according to the criteria of the Cochrane Handbook. Review Manager 5.3, R-3.5.1 software will be used for publication bias analysis. GRADE pro GDT web solution will be used for evidence evaluation. RESULTS: This review will evaluate the effects of traditional Chinese herbs on estradiol, progesterone, thickness, volume, and perfusion index(PI) of the endometrium, pregnancy rate, and symptoms. CONCLUSIONS: This review will provide clear evidence to assess the effectiveness and safety of traditional Chinese herbs for low endometrial receptivity. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/M85VT.

[Pharmacological mechanism of Shenghua Decoction in treatment of abdominal pain based on network pharmacology].

The Shenghua Decoction recorded in Fu Qing Zhu's Gynaecology,is a commonly used postpartum prescription,widely used in treating postpartum and gynecological diseases. However,its mechanism of action in treating lower abdominal pain remains unclear. In this paper,network pharmacology was used to explore the mechanism of Shenghua Decoction in the treatment of lower abdomen pain,so as to provide data support for better clinical application of Shenghua Decoction. The drug targets of lower abdominal pain and Shenghua Decoction were retrieved in SymMap. String and Cytoscape were adopted for enrichment analysis to construct the disease-drug-target biological network. Relevant gene search results showed that there were 400 targets in Shenghua Decoction,11 of which coincided with the disease genes of lower abdomen pain. In String analysis,18 gene interactions were obtained. Gene modularizationbased analysis results indicated that one module containing six genes was obtained after modularization processing. Furthermore,there were 170 enrichment results of biological process,2 enrichment results of molecular function and 30 enrichment results of KEGG pathways in String enrichment analysis. Shenghua Decoction may play a role in treating lower abdomen pain through neuro-endocrine-immune,metabolism and other means. Its mechanism may be achieved by accelerating the repair and growth of endometrial tissue cells,improving microcirculation,promoting endometrial cell renewal and inflammation subsidence,and accelerating uterine involution; at the same time,it can regulate the autoimmunity,regulate and control the function of some natural immune cells in the process of antiinfection by using signaling pathway,supplement the vital energy,and induce elimination of pathogens from the body,thereby achieving the effect of treating lower abdomen pain.

Study of the Gastrointestinal Heat Retention Syndrome in Children: From Diagnostic Model to Biological Basis.

Gastrointestinal heat retention syndrome (GHRS) refers to a condition that is associated with increased gastrointestinal heat caused by a metabolic block in energy. It is common in children and is closely related to the occurrence and development of recurrent respiratory tract infection, pneumonia, recurrent functional abdominal pain, etc. However, there are no standardized diagnostic criteria to differentiate the GHRS. Therefore, this study is aimed to establish a diagnostic model for children's GHRS and explore the possible biological basis by using systems biology to achieve. Furthermore, Delphi method and the clinical data of Lasso analysis were used to screen out the core symptoms. Nineteen core symptoms of GHRS in children were screened including digestive symptoms such as dry stool, poor appetite, vomiting, and some nervous system symptoms such as night restlessness and irritability. Based on the core symptoms, a GHRS diagnosis model was established using the eXtreme Gradient Boosting (XGBoost) method, and the accuracy of internal verification reached 93.03%. Relevant targets of the core symptoms in the Human Phenotype Ontology (HPO) were retrieved, and target interactions were linked through the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and core targets were selected after topological analysis using Cytoscape. Relevant biological processes and pathways were analyzed by applying the DAVID and KEGG databases. The enriched biological processes focused on the cell proliferation, differentiation, apoptosis, and mitochondrial metabolism, which were mainly associated with PI3K-AKT, MAPK network pathways, and the Wnt signaling pathway. In conclusion, we established a diagnosis model of GHRS in children based on the core symptoms and provided an objective standard for its clinical diagnosis. And, the Wnt signaling pathway and the estrogen receptor-activated PI3K-AKT and MAPK network pathways may play important roles in the GHRS processing.

Phosphine production in anaerobic wastewater treatment under tetracycline antibiotic pressure.

The influence of tetracycline (TC) antibiotics on phosphine (PH3) production in the anaerobic wastewater treatment was studied. A lab-scale anaerobic baffled reactor with three compartments was employed to simulate this process. The reactor was operated in a TC-absence wastewater and 250µg/L TC-presence wastewater for three months after a start-up period, respectively. The responses of pH, oxidation-reduction potential (ORP), chemical oxygen demand (COD), total phosphorus (TP), enzymes activity (dehydrogenase and acid phosphatase), and microbial community were investigated to reveal the effect of TC on PH3 production. Results suggested that the dehydrogenase (DH) activity, acid phosphatase (ACP) activity and COD have positive relationship with PH3 production, while pH, ORP level and the TP in liquid phase have negative relationship with PH3 production. With prolonged TC exposure, decrease in pH and increase in DH activity are beneficial to PH3 production, while decrease in COD and ACP activity are not the limiting factors for PH3 production.