Proposal for the classification of sinomenine alkaloids.

The chemical structure of sinoacutine is formed by a phenanthrene nucleus and an ethylamine bridge. Because it has a similar parent structure to morphine, it is subdivided into morphinane. At present, all reports have pointed out that the basic skeleton of morphine alkaloids is salutaridine (the isomer of sinoacutine), which is generated by the phenol coupling reaction of (R)-reticuline. This study shows that the biosynthetic precursors of sinoacutine and salutaridine are different. In this paper, the sinoacutine synthetase (SinSyn) gene was cloned from Sinomenium acutum and expressed SinSyn protein. Sinoacutine was produced by SinSyn catalyzed (S)-reticuline, according to the results of enzyme-catalyzed experiments. The optical activity, nuclear magnetic resonance, and mass spectrum of sinoacutine and salutaridine were analyzed. The classification and pharmacological action of isoquinoline alkaloids were discussed. It was suggested that sinoacutine should be separated from morphinane and classified as sinomenine alkaloids.

Dietary supplementation of pyridoxine can enhance the growth performance and improve the protein, lipid utilization efficiency of mandarin fish (Siniperca chuatsi).

This study aimed to assess the effect of pyridoxine supplementation in the mandarin fish diet on growth performance, protein and lipid metabolism, and liver and intestinal histology. Mandarin fish were fed six diets with different levels of pyridoxine (2.67 mg/kg (control), 4.41 mg/kg, 6.57 mg/kg, 10.25 mg/kg, 17.93 mg/kg, 33.12 mg/kg diet) for 8 weeks, and samples were collected for analysis. The findings demonstrated that feeding mandarin fish a diet with 6.57 mg/kg pyridoxine led to a significant increase in weight gain rate (WGR), protein efficiency ratio (PER), whole-body crude protein, whole-body crude lipid, serum protein, cholesterol (CHO), triacylglycerol (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and alkaline phosphatase (ALP), as well as significantly lower serum glucose (GLU) and feed conversion ratio (FCR), compared to the control group (P < 0.05). Furthermore, we found a significant upregulation of the relative expression of genes associated with hepatic lipid oxidation and synthesis (hl, lpl, pparα, cpt1, cs, srebp1, and fas) and proteolysis (ast, alt, and gdh) in fish fed a diet containing 6.57 mg/kg pyridoxine (P < 0.05). Regarding the histological analysis, we observed a notable decrease in the quantity of intestinal mucus-secreting cells when the fish fed a diet containing 10.25 mg/kg pyridoxine (P < 0.05). These findings suggest that dietary pyridoxine supplementation promotes mandarin fish growth by improving the efficiency of protein and lipid utilization. Additionally, we used a broken-line regression analysis to estimate the optimal dietary pyridoxine requirement for mandarin fish in the range of 6.17-6.41 mg/kg based on WGR, FCR, and PER.

Feasibility study on the use of "Qi-tonifying medicine compound" as an anti-fatigue functional food ingredient based on network pharmacology and molecular docking.

Introduction: Fatigue has attracted broad attention in recent years due to its high morbidity rates. The use of functional foods to relieve fatigue-associated symptoms is becoming increasingly popular and has achieved relatively good results. In this study, network pharmacology and molecular docking strategies were used to establish the material basis and mechanisms of Chinese herbal compounds in fatigue treatment. According to traditional medicine theories and relevant guidance documents published by the Chinese Ministry of Health, four herbal medicines, including Eucommia ulmoides Oliver bark, Eucommia ulmoides Oliver male flower, Panax notoginseng, and Syzygium aromaticum (EEPS), were selected to constitute the anti-fatigue herbal compound that may be suitable as functional food ingredients. Methods: The major active ingredients in EEPS were identified via comprehensive literature search and Traditional Chinese Medicine Systems Pharmacology database search. Corresponding targets for these ingredients were predicted using SwissTargetPrediction. The network was constructed using Cytoscape 3.9.1 to obtain key ingredients. Prediction of absorption, distribution, metabolism, excretion and toxicity properties was performed using the ADMETIab 2.0 database. The anti-fatigue targets were retrieved from GeneCards v5.13, OMIM, TTD and DisGeNET 7.0 databases. Then, the potential targets of EEPS in fatigue treatment were screened through a Venn diagram. A protein-protein interaction (PPI) network of these overlapping targets was constructed, and the hub targets in the network selected through topological screening. Gene Ontology and KEGG pathway enrichment analyses were performed using the DAVID database and the bioinformatics online platform. Finally, AutoDock tools were used to verify the binding capacity between the key active ingredients and the core targets. Results and Discussion: This study identified the active ingredients and potential molecular mechanisms of EEPS in fatigue treatment, which will provide a foundation for future research on applications of herbal medicines in the functional food industry.

Regenerative plantlets with improved agronomic characteristics caused by anther culture of tetraploid potato (Solanum tuberosum L.).

Objective: As the primary means of plant-induced haploid, anther culture is of great significance in quickly obtaining pure lines and significantly shortening the potato breeding cycle. Nevertheless, the methods of anther culture of tetraploid potato were still not well established. Methods: In this study, 16 potato cultivars (lines) were used for anther culture in vitro. The corresponding relation between the different development stages of microspores and the external morphology of buds was investigated. A highly-efficient anther culture system of tetraploid potatoes was established. Results: It was shown in the results that the combined use of 0.5 mg/L 1-Naphthylacetic acid (NAA), 1.0 mg/L 2,4-Dichlorophenoxyacetic acid (2,4-D), and 1.0 mg/L Kinetin (KT) was the ideal choice of hormone pairing for anther callus. Ten of the 16 potato cultivars examined could be induced callus with their respective anthers, and the induction rate ranged from 4.44% to 22.67% using this hormone combination. According to the outcome from the orthogonal design experiments of four kinds of appendages, we found that the medium with sucrose (40 g/L), AgNO3 (30 mg/L), activated carbon (3 g/L), potato extract (200 g/L) had a promotive induction effect on the anther callus. In contrast, adding 1 mg/L Zeatin (ZT) effectively facilitated callus differentiation. Conclusion: Finally, 201 anther culture plantlets were differentiated from 10 potato cultivars. Among these, Qingshu 168 and Ningshu 15 had higher efficiency than anther culture. After identification by flow cytometry and fluorescence in situ hybridization, 10 haploid plantlets (5%), 177 tetraploids (88%), and 14 octoploids (7%) were obtained. Some premium anther-cultured plantlets were further selected by morphological and agronomic comparison. Our findings provide important guidance for potato ploidy breeding.

Integrated Network Pharmacology and Experimental Validation Approach to Investigate the Mechanisms of Stigmasterol in the Treatment of Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints associated with systemic comorbidities. Sinomenium acutum is regarded as an effective traditional Chinese medicine (TCM) for the treatment of RA. Materials and Methods: Based on network pharmacology and Gene Expression Omnibus (GEO) database, 33 RA-related differentially-expressed genes (DEGs) targeting active compounds of Sinomenium acutum were initially screened in our investigation. Results: Gene Ontology (GO) and Kyoto encyclopaedia of genes and genome (KEGG) analyses found the important involvement of these DEGs in osteoclast differentiation, and finally 5 core DEGs, including NCF4, NFKB1, CYBA, IL-1ß and NCF1 were determined through protein-protein interaction (PPI) network. We also identified the related active component of Sinomenium acutum include Stigmasterol. Finally, in order to experimentally verify these results, a rat model of collagen-induced arthritis (CIA) was established, and subsequently treated with Stigmasterol solution. Conclusion: Similar to the healing effect of Indomethacin, Stigmasterol was observed to reduce the levels of inflammatory factors (IL-6 and IL-1ß) and osteoclast differentiation-related factors (RANKL, ACP5 and Cathepsin K), which can also reduce the arthritis index score and alleviate the degree of pathological injury of rat ankle joints. The predictions and experimental data uncover the involvement of Stigmasterol, an active component of Sinomenium acutum, in regulation of osteoclast differentiation, exerting great medicinal potential in the treatment of RA.

Gallic acid ameliorates dextran sulfate sodium-induced ulcerative colitis in mice via inhibiting NLRP3 inflammasome.

Background: Ulcerative colitis (UC) is a chronic recurrent inflammatory bowel disease (IBD). The conventional drugs for UC may induce severe side effects. Herbal medicine is considered as a complementary and alternative choice for UC. Purpose: This study aims to estimate the effect of natural polyphenol gallic acid (GA) on the NLRP3 inflammasome with dextran sulfate sodium (DSS)-induced colitis in mice. Study design: The body weights and symptoms of BALB/c mice were recorded. Histological evaluation, ELISA, q-PCR, immunohistochemistry, and western blotting were carried out to observe the morphology, cytokine contents, mRNA expressions, and protein expressions, respectively. Lipopolysaccharide (LPS)-induced RAW264.7 macrophage was used to probe GA's effect on relative protein expression. Results: GA attenuated weight loss (p < 0.05), relieved symptoms, and ameliorated colonic morphological injury (p < 0.05) in mice with colitis induced by DSS. GA also lowered the contents of TNF-α, IL-1ß, IL-18, IL-33, and IFN-γ in the serum and colon of mice, which were elevated by DSS, downregulated protein, and mRNA expressions of the NLRP3 pathway in the colon tissue. Furthermore, GA downregulated the expressions of NLRP3 (p < 0.05), iNOS (p < 0.01), COX2 (p < 0.01), and P-p65 (p < 0.05), and suppressed NO release (p < 0.001) in LPS-induced RAW264.7 cells. Conclusion: GA ameliorated DSS-induced UC in mice via inhibiting the NLRP3 inflammasome. These findings furnish evidence for the anti-inflammatory effect of herbal medicines containing GA on UC.

Lian-Qu formula treats metabolic syndrome via reducing fat synthesis, insulin resistance and inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Metabolic syndrome (MetS) is a pathological condition characterized by obesity, hyperglycemia, hypertension and hyperlipidemia that increases the risk of cardiovascular disease, type 2 diabetes and non-alcoholic fatty liver disease. The traditional Chinese medicine Lian-Qu formula (LQF) is modified from Xiaoxianxiong decoction, which has been used for coronary heart disease or metabolic disease in clinical for a long time. However, the pharmacological mechanism of LQF on MetS is unclear. AIM OF THE STUDY: Here, we explored the actions of LQF on MetS via network pharmacology and validated the mechanism in the MetS mice. MATERIALS AND METHODS: The chemical components of LQF were searched in the traditional Chinese medicine systems pharmacology database and the natural product activity & species source database. The related targets of MetS disease were gathered from genes cluster with literature profiles database. The protein-protein interaction network was constructed to obtain the key target genes. The Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment of the key targets were performed to predict the potential mechanisms of LQF action on MetS. And then, the high-fat diet-induced MetS mice were used to validate its therapeutic effect and molecular targets. Insulin tolerance test and oral glucose tolerance test were used to assess insulin sensitivity. Body weight and visceral fat index were measured to assess obesity. Liver metabolism was detected by H&E section, oil red O staining and untargeted lipid metabolomics experiments. Finally, the key targets of LQF action on MetS were verified by PCR and ELISA kits. RESULTS: A total of 466 components in LQF were obtained, among which 71 were active. These components correspond to 74 targets associated with MetS. The predicted targets of LQF worked on MetS were AKT1, INSR, PPARs, FASN, LDLR, TNF, CRP, IL-6, IL-1ß and so on. Furthermore, these targets were related to pathways in cellular response to lipid, inflammatory response, glucose transmembrane transport and insulin resistance. Finally, the animal experiments validated that LQF inhibited lipids accumulation by inhibiting the gene expression of FASN and increasing ADPN, and it relieved insulin resistance by increasing GLUT-4 expression. Moreover, LQF alleviated inflammation by reducing IL-6 and CRP levels. CONCLUSION: LQF exerted anti-MetS effects through improving insulin sensitivity, ameliorating hyperlipidemia and obesity, reducing liver injury, and inhibiting inflammatory response.

Beware of the Potential Risks for Polygoni Multiflori Caulis-Induced Liver Injury.

Background: Reynoutria multiflora (Thunb.) Moldenke (PM) is a widely-used medicinal plant in China, whose root and stem are included in the Chinese Pharmacopoeia as Polygoni Multiflori Radix (RPM), Polygoni Multiflori Radix Preparata (PMP), and Polygoni Multiflori Caulis (PMC). The hepatotoxicity of RPM and PMP is concerned by the public, while the risk of PMC is ignored. Purpose: Here, we investigate the potential risks for PMC-induced liver injury from clinical, chemical, and animal features. Study design: First, we analyzed the 12-month usage of RPM, PMP, and PMC in Longhua Hospital. Second, we determined the contents of gallic acid, cis-2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-D-glucoside (cis-SG), trans-2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-D-glucoside (trans-SG), emodin-8-O-ß-D-glucoside (EG), physcion-8-O-ß-D-glucoside (PG), emodin, and physcion in the water extracts from 15 batches of RPM, PMP, and PMC. Third, we probed the hepatotoxic effect of RPM, PMP, and PMC in mice and explored the mechanism of cis-SG and trans-SG causing the liver injury at the dosages based on our results from the first and second parts. Results: PMC had nearly five times the amount of usage in both outpatient prescriptions and inpatient orders than RPM and PMP. Overall, 68% dosage of PMC was 30 g. The contents of cis-SG, trans-SG, and emodin in PMC water extracts were significantly lower than those in RPM and PMP water extracts. PMC induced milder idiosyncratic liver injury for its lower content of cis-SG and trans-SG than its root counterparts. Conclusion: The potential risks for PMC-induced liver injury should be fully aware of.

Oreocharioside A-G, new acylated C-glycosylflavones from Oreocharis auricula (Gesneriaceae).

Seven new acylated C-glycosylflavones, oreocharioside A-G, together with two known compounds were isolated from the whole plant of Oreocharis auricula. Their structures were characterized by the comprehensive analysis of their NMR, IR, UV, CD spectra and HRESIMS data. All the new compounds were evaluated for the antioxidant and anti-inflammatory activities. The results showed that compounds 1 and 2 had significant DPPH and ABTS radical scavenging activities, with the IC50 values of 0.32-3.20 µg/mL. Compounds 2 and 3 exhibited the higher potency among all the new compounds in reducing TNF-α production.

The mechanism of Bai He Gu Jin Tang against non-small cell lung cancer revealed by network pharmacology and molecular docking.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related burden and deaths, thus effective treatment strategies with lower side effects for NSCLC are urgently needed. To systematically analyze the mechanism of Bai He Gu Jin Tang (BHGJT) against NSCLC by network pharmacology and molecular docking. METHODS: The active compounds of BHGJT were obtained by searching the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine and Encyclopaedia of Traditional Chinese Medicine. Search tool for interactions of chemicals was used for acquiring the targets of BHGJT. The component-target network was mapped by Cytoscape. NSCLC-related genes were obtained by searching Genecards, DrugBank and Therapeutic Target Database. The protein-protein interaction network of intersection targets was established based on Search Tool for Recurring Instances of Neighboring Genes (STRING), and further, the therapeutic core targets were selected by topological parameters. The hub targets were transmitted to Database for Annotation, Visualization and Integrated Discovery for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, AutoDock Vina and MglTools were employed for molecular docking validation. RESULTS: Two hundred fifty-six compounds and 237 putative targets of BHGJT-related active compounds as well as 1721potential targets of NSCLC were retrieved. Network analysis showed that 8 active compounds of BHGJT including kaempferol, quercetin, luteolin, isorhamnetin, beta-sitosterol, stigmasterol, mairin and liquiritigenin as well as 15 hub targets such as AKR1B10 and AKR1C2 contribute to the treatment of BHGJT against NSCLC. GO functional enrichment analysis shows that BHGJT could regulate many biological processes, such as apoptotic process. Three modules of the endocrine related pathways including the inflammation, hypoxia related pathways as well as the other cancer related pathways based on Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis might explain the biological mechanisms of BHGJT in treating BHGJT. The results of molecular docking verified that AKR1B10 and AKR1C2 had the strongest binding activity with the 8 key compounds of NSCLC. CONCLUSION: Our study reveals the mechanism of BHGJT in treating NSCLC involving multiple components, multiple targets and multiple pathways. The present study laid an initial foundation for the subsequent research and clinical application of BHGJT and its active compounds against NSCLC.

Fingerprinting and Determination of Hepatotoxic Constituents in Polygoni Multiflori Radix Praeparata of Different Producing Places by HPLC.

Polygoni Multiflori Radix Praeparata (PMRP) is used as Chinese herbal medicine with long history. However, reports about PMRP hepatotoxicity have increased recently, and producing area might be one reason. This article aims to figure out the relationship between producing area and hepatotoxic ingredients in PMRP. HPLC fingerprint for PMRP was established and the contents of gallic acid, trans-stilbene glycoside (TSG), emodin-8-O-ß-D-glucoside (EG), emodin and physcion were determined. Clustering heatmap was implemented by TCMNPAS software，and principal component analysis was implemented by SPSS and SIMCA-P software. Hepatotoxic constituents' contents of PMRP from separate producing area were different. PMRP from Guangxi had the highest content of gallic acid, TSG, EG, emodin and physcion, followed by Hubei, Guangdong, Guizhou, Yunnan. PMRP from Henan had the lowest contents of hepatotoxic components. Hepatotoxic components' contents of PMRP in southern were higher than central China. This study carried out a preliminary qualitative and quantitative investigation on the PMRP from different producing places, which provided a basis for safe medication of PMRP.

Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa.

Retinitis Pigmentosa (RP) is a mostly incurable inherited retinal degeneration affecting approximately 1 in 4000 individuals globally. The goal of this work was to identify drugs that can help patients suffering from the disease. To accomplish this, we screened drugs on a zebrafish autosomal dominant RP model. This model expresses a truncated human rhodopsin transgene (Q344X) causing significant rod degeneration by 7 days post-fertilization (dpf). Consequently, the larvae displayed a deficit in visual motor response (VMR) under scotopic condition. The diminished VMR was leveraged to screen an ENZO SCREEN-WELL REDOX library since oxidative stress is postulated to play a role in RP progression. Our screening identified a beta-blocker, carvedilol, that ameliorated the deficient VMR of the RP larvae and increased their rod number. Carvedilol may directly on rods as it affected the adrenergic pathway in the photoreceptor-like human Y79 cell line. Since carvedilol is an FDA-approved drug, our findings suggest that carvedilol can potentially be repurposed to treat autosomal dominant RP patients.

Effects of Qing Chang Suppository Powder and its Ingredients on IL-17 Signal Pathway in HT-29 Cells and DSS-induced Mice.

BACKGROUND: Qingchang Suppository, a formula used for more than 30 years in Longhua Hospital, has shown satisfactory clinical effects on Ulcerative Colitis (UC). However, its therapeutic mechanism has not been fully elucidated. PURPOSE: The study aims to investigate the effects of Qingchang Suppository powder (QCSP) and its ingredients by regulating the IL-17A signaling pathway which plays an important role in the development of UC. METHODS: HPLC was used to analyze the main ingredients (Gallic acid, Indigo, Indirubin) in QCSP. HT-29 cells were induced by rhIL-17A and TNF-α, and IL-17A related protein expressions were determined by western blot. BALB/C mice were induced by 4% Dextran Sodium sulfate (DSS). The effects of QCSP and its ingredients were evaluated by measuring weight loss, disease activity index (DAI), colon length, histological analysis. Western blot was used for analysis of IL-17A and MAPK related proteins p-ERK, p-JNK, p-P38. Quantitative reverse transcription polymerase chain reaction (q-PCR) was used to detect the expression of IL-17A, HSP90 and ACT1 in colon tissue. Cytokines such as IL-17A, IL-1ß, IFN-γ and TNF-α were determinated by enzyme-linked immunosorbent assay (ELISA). RESULTS: QCSP had good therapeutic effect on DSS-induced colitis in mice. QCSP significantly relieved weight loss, restored colon length, repaired colon lesions, reduced histological scores and DAI, decreased TNF-α, IL-1ß, IL-17 and IFN-γ contents, significantly suppressed the gene expressions of IL-17A, ACT1 and HSP90, and up-regulated the expressions of tight junction proteins like ZO-1 and Occludin. IL-17A pathway related proteins such as IL-17A, IL-17RA, HSP90, MAPKs, P-iκbα and iNOS were significantly increased in vitro and in vivo. CONCLUSIONS: This paper reveals that QCSP inhibited the IL-17A signaling pathway in HT-29 cells and DSS induced mice, presenting a new mechanism of QCS on treating UC.

Bufothionine induces autophagy in H22 hepatoma-bearing mice by inhibiting JAK2/STAT3 pathway, a possible anti-cancer mechanism of cinobufacini.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinobufacini is extracted from the skins and parotid venom glands of the toad for treating symptoms like swelling and pain in ancient times. Nowadays, cinobifucini injection has also achieved satisfactory therapeutic effects on hepatocellular carcinoma (HCC) in China. AIM OF THE STUDY: Our previous work found that bufothionine, an alkaloid abundant in cinobufacini injection, induced mitochondria-mediated apoptosis. In this work, the underlying effects of bufothionine on autophagy in HCC and its possible dependent pathway were investigated. METHODS: CCK-8 and Hoechst staining assays were performed to verify effects of drugs on proliferation and apoptosis of SMMC7721 cell. H22-tumor-bearing mice model was established by inoculating ascites fluid. HE staining was used to observe pathological changes in liver and tumor tissues. ELISA and Western blot experiments were conducted to investigate IL-6/JAK2/STAT3 signaling pathway. The effects of drugs on expressions of autophagic relative proteins were investigated by Western blot in vitro and in vivo. RESULTS: In vitro, CCK-8 and Hoechst staining assays showed that bufothionine inhibited SMMC7721 cell proliferation and promoted apoptosis at 100 µM. In vivo, bufothionine relieved symptoms of H22-tumor-bearing mice and exerted anti-inflammation activity. ELISA and Western blot demonstrated that bufothionine significantly reduced serum IL-6 concentration, suppressed p-Stat3tyr705, p-Stat3ser727 and Jak2 expressions in tumor tissues and upregulated Atg5, Atg7 and LC3Ⅱ expressions in SMMC7721 cell and H22 tumor. CONCLUSION: This is the first report showing that bufothionine might induce autophagy in HCC by inhibiting JAK2/STAT3 pathway, presenting a possible anti-cancer mechanism of bufothionine in cinobufacini injection.

Low-dose PPI to prevent bleeding after ESD: A multicenter randomized controlled study.

BACKGROUND: Although proton pump inhibitors (PPIs) are widely used in the prevention of gastric bleeding caused by endoscopic submucosal dissection (ESD), there is no consensus on the optimal regimen for these patients. Therefore, we aim to investigate whether intermittent use of low-dose PPI is sufficient to prevent post-ESD bleeding. METHODS: This multicenter, non-inferiority, randomized controlled trial was conducted at 9 hospitals in China. Consecutive eligible patients with a diagnosis of gastric mucosal lesions after ESD treatment were randomly assigned (1:1) to receive either intermittent low-dose or continuous high-dose PPIs treatment. After three days, all patients administered orally esomeprazole 40 mg once a day for 8 weeks. The primary endpoint was post-ESD bleeding within 7 days. Analysis was done according to the intention-to-treat principle with the non-inferiority margin (Δ) of 5%. RESULTS: 526 consecutive patients were assessed for eligibility from 30 September 2017 to 30 July 2019, of whom 414 were randomly assigned to low-dose (n = 209) or high-dose (n = 205) esomeprazole treatment group without dropouts within7 days. The total post-ESD bleeding is occurred in 13 (6.2 %, 95 % CI 3.3-9.6) of 209 within 7 days in the intermittent low-dose group, and 12 (5.9 %, 95 % CI 2.9-9.3) of 205 in the continuous high-dose group. The absolute risk reduction (ARR) was 0.4 % (-4.2, 4.9). One month after ESD, There are 44 patients (21.1 %, 95 % CI 15.8, 26.8) and 39 patients (19.0 % 95 % CI 13.7, 24.4) in scar stage respectively in low-dose group and high-dose group (P = 0.875).The hospital costs in the low-dose PPI group was lower than high -dose group (P = 0.005). CONCLUSION: The intermittent use of low-dose PPIs is sufficient to prevent post-ESD bleeding. It might be applied in clinical practice to prevent post-ESD bleeding and reduce the costs related to PPIs.

GPC3-targeted and curcumin-loaded phospholipid microbubbles for sono-photodynamic therapy in liver cancer cells.

More effective strategies are needed to improve the treatment of liver cancer. Sono-photodynamic therapy (SPDT) has a more obvious antitumor effect than sonodynamic therapy (SDT) or photodynamic therapy (PDT). We aimed to investigate Glypican-3-targeted, curcumin-loaded microbubbles (GPC3-CUR-MBs)-mediated SPDT in liver cancer cells in vitro and in vivo. GPC3-CUR-MBs were prepared by streptavidin-biotin interactions and the immune ligation method. The characterization and toxicity of GPC3-CUR-MBs and the anti-liver cancer effects of GPC3-CUR-MB-mediated SPDT in vitro and in vivo were studied. We synthetized GPC3-CUR-MBs and found that GPC3-CUR-MBs had no significant toxicity to HepG2 liver cancer cells. In terms of the anti-liver cancer effects in vitro and in vivo, when we used CUR, CUR-MBs or GPC3-CUR-MBs as the sono/photosensitizers, the outcome of SPDT was superior to that of SDT or PDT alone. The outcomes with GPC3-CUR-MBs were better than those with CUR or CUR-MBs in the SDT, PDT or SPDT groups. During the treatment period, the weight of the HepG2 tumor-bearing mice did not decrease significantly, and no significant evidence of lung, heart, liver, spleen and kidney damage was found with H&E staining. Our results indicated that the anti-liver tumor effect of SPDT was better than that of SDT and PDT and that GPC3-CUR-MBs were promising sono/photosensitizers.

Microfluidic Fabrication of Structure-Controlled Chitosan Microcapsules via Interfacial Cross-Linking of Droplet Templates.

In this work, a simple and flexible method for the fabrication of chitosan microcapsules with controllable structures and functions via the interfacial cross-linking reaction of the water-in-oil (W/O) emulsion templates is developed. The interfacial cross-linking reactions of chitosan and terephthalaldehyde (TPA) in W/O emulsion templates are comprehensively studied. The interfacial cross-linking reactions of the droplet templates in both batchwise and continuous conditions are studied. A poly(dimethylsiloxane) (PDMS) droplet-capture microfluidic chip is fabricated to investigate the interfacial reaction in continuous conditions online. In this study, the size and shell thickness of the microcapsules are affected by the preparation condition, such as the template size, emulsifier concentration, TPA concentration, and cross-linking time. Moreover, the size and shell thickness changes of chitosan microcapsules prepared in continuous conditions are much faster than those prepared in batchwise conditions. By regulating the preparation parameters, the microcapsules with controllable structures are fabricated in both batchwise and continuous conditions. The drug release behaviors of the microcapsules with controllable structures are studied. Furthermore, by adding magnetic nanoparticles to the aqueous solution, magnetic-responsive microcapsules are fabricated easily. This work provides valuable guidance for the controllable fabrication of chitosan microcapsules with designed structures and functions via single emulsion templates.

[Effect of acupoint application therapy at different timing points on gastrointestinal function recovery and heart rate variability after laparoscopic resection of colorectal cancer].

OBJECTIVE: To observe the effect of acupoint application therapy at different timing points on the gastrointestinal function recovery and heart rate variability (HRV) after laparoscopic resection of colorectal cancer under the instruction of enhanced recovery after surgery (ERAS). METHODS: A total of 105 patients for the selective laparoscopic resection of colorectal cancer were selected and randomized into a preoperative acupoint application group (35 cases, 3 cases dropped off), a postoperative acupoint application group (35 cases, 1 case dropped out) and a control group (35 cases, 2 cases dropped off). In the control group, ERAS interventions were provided, such as health education, fluid supplementation and multi-mode analgesia. On the base of the treatment as the control group, in the preoperative acupoint application group and the postoperative acupoint application group, 3 days before operation and 6 h after operation, the acupoint application therapy was given respectively. The acupoints were Zusanli (ST 36), Shangjuxu (ST 37), Sanyinjiao (SP 6), Neiguan (PC 6) and Xiajuxu (ST 39). The acupoint application was exerted for 6 h each time, once daily till the first postoperative exhaust and defecation presented. It was to observe the time of the first postoperative exhaust, defecation and food intake, the score of visual analogue scale (VAS) 1 to 3 days after operation, the total score of gastrointestinal symptom rating scale (GSRS) before and 1 week after operation, as well as the related indicators of HRV [standard deviation of NN intervals (SDNN) and the ratio of low-frequency power and high frequency power (LF/HF)] in the three groups successively. Besides, the adverse reactions were recorded during intervention in the three groups. RESULTS: Compared with the control group, the time of the first postoperative exhaust and the time of the first postoperative defecation were all earlier in the preoperative acupoint application group and the postoperative acupoint application group respectively (P<0.05), and VAS scores 1 to 3 days after operation and total GSRS scores 1 week after operation were all reduced (P<0.05); the time of first food intake was earlier after operation (P<0.05), and SDNN and LF/LF were increased 1 day and 3 days after operation in the preoperative acupoint application group (P<0.05). Compared with the postoperative acupoint application group, in the preoperative acupoint application group, the time of the first postoperative exhaust and the time of the first postoperative defecation were all earlier (P<0.05), VAS scores were reduced in 1 to 3 days after operation (P<0.05), and SDNN 1 day and 3 days after operation and LF/HF 1 day after operation were all increased (P<0.05). No adverse reaction was detected in patients of the three groups. CONCLUSION: Under the instruction of ERAS, the preoperative acupoint application effectively promotes the postoperative gastrointestinal function recovery, improves HRV and autonomous nerve function in the patients after laparoscopic resection of colorectal cancer. The therapeutic effect of this therapy is better than the postoperative acupoint application.

Evidence for acupotomology in the management of cervical radiculopathy: A protocol for systematic review and meta-analysis.

BACKGROUND: Cervical radiculopathy (CR) describes compression or stimulation secondary to the cervical nerve root, 1 or 2 types of upper limb pain, and/or with neck. In clinical practice, both acupotomology and acupuncture are very widely and popular for the management of CR. So, we conducted a systematic review and meta-analysis to explore the efficacy, safety of acupotomology in the treatment of CR. METHODS: We will search the following databases from inception to the September 2019 : MEDLINE(PubMed), Web of Science(Thomson Reuters), Cochrane Library, Embase (Ovid, Elsevier), SinoMed, Clinical Trials. gov, the China National Knowledge Infrastructure, Wanfang database, and VIP database. We will apply no language restrictions. We will not use a randomized controlled trial filter in EMBASE, as the set of intervention terms will limit the results sufficiently. The randomised controlled trials of acupotomology versus acupuncture for CR; two independent researchers will use the bias risk tool provided by the Cochrane Collaboration to evaluate the quality of the literature using RevMan 5.3 software (Copenhagen, The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). RESULTS: This systematic review and meta-analysis will provide a synthesis of existing evidence-based medical evidence for acupotomology/ acupotomy/needle knife in the treatment of CR. CONCLUSION: The conclusions of this systematic review and meta-analysis will provide evidence to evaluate the effectiveness of acupotomology/ acupotomy/needle knife for CR and further guide clinical decision-making. ETHICS AND DISSEMINATION: This study is based on literature and therefore does not require ethical approval or patient consent. The study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020172274.

Acupotomy combined with massage for cervical spondylotic radiculopathy: A protocol for systematic review and meta-analysis.

BACKGROUND: Cervical spondylotic radiculopathy (CSR) is a clinical syndrome of radial neck and shoulder pain. Both Massage and Acupotomy have been widely used in the treatment of CSR, in China and achieved satisfied efficacy. Therefore, the aim of this study is to systematically evaluate the clinical efficacy of acupotomy combined with massage in the treatment of CSR. METHODS: The following electronic databases will be searched: PubMed, Web of Science, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library, Embase, SinoMed, Clinical Trials. gov, the China National Knowledge Infrastructure (CNKI), Wanfang database, and VIP database. Two review authors independently search databases from their respective inception dates to September 2019 to identify potentially eligible studies. Cochrane Handbook 5.1 risk of bias assessment tool will be used to evaluate the methodological quality of the included studies. The Review Manager 5.3 will be used for all statistical analysis of the final included study. RESULTS: The results of this systematic review and meta-analysis will provide a synthesis of existing evidences for the treatment of acupotomy combined with massage on CSR, especially in improving visual analog scale and symptom score. CONCLUSION: This study will summarize the current evidence of acupotomy combined with massage for the treatment of CSR. This study can further guide the promotion and clinical decisions. ETHICS AND DISSEMINATION: Ethical approval and patient consent are not required because this study is a literature-based study. This systematic review and meta-analysis will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020171825.