Network pharmacology-based prediction and verification of the active ingredients and potential targets of Huagan Decoction for reflux esophagitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Huagan Decoction (HGD), a famous traditional Chinese medicine (TCM) formula, has been widely used in the treatment of reflux esophagitis (RE). However, its effective compounds, potential targets and molecular mechanism remain unclear. AIM OF THE STUDY: To investigate effective compounds, potential targets and molecular mechanism of HGD against RE by using network pharmacology combined with in vitro validation, with the aims of observing the action of HGD and exploring new therapeutic strategies for RE treatment. MATERIALS AND METHODS: Effective compounds and potential targets of HGD, as well as related genes of RE, were collected from public databases. Pharmacological clustering and Gene Ontology (GO) enrichment analysis were applied to find targets that involving in the anti-inflammatory module. The pathways were drawn using Cytoscape 3.8.0. Important ingredients, potential targets, and signaling pathways were determined through the construction of protein-protein interaction (PPI), GO and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, cell experiments were carried out. RESULTS: A total of 54 active ingredients and 240 RE-related gene targets of HGD were identified. The active compound-target network was visualized and pharmacological clustering further sorted 53 proteins that involve in the regulation of inflammatory responses. GO analysis confirmed the classification was statistically significant. Analysis of compound-target network revealed that quercetin and geniposide may be key ingredients for the anti-inflammatory effect of HGD against RE. The potential targets regulated by HGD are IL-6, IL-1ß, PTGS2, AKT1, TNF-α, MAPK1, IL-8, IL-10, CCL2 and MAPK3. In vitro experiment showed that quercetin and geniposide could inhibit the inflammatory response of HET-1A cells through p38MAPK/NF-κB signaling pathway, which was consistent with the prediction by the network pharmacology approach. CONCLUSIONS: Geniposide and quercetin could be effective therapeutic ingredients for the HGD against RE. They play anti-inflammatory effects via down-regulating the pro-inflammatory cytokines and the conduction of p38MAPK/NF-κB signal. This research provides a comprehensive study on the active components, potential targets, and molecular mechanisms of HGD against RE. Moreover, the study supplies a feasible approach to reveal the mechanisms of TCM formula.

[Quality value transfer of substance benchmarks in Sanpian Decoction].

According to the polarity of different components in Sanpian Decoction, two fingerprints were established. Then the substance benchmark freeze-dried powder of 15 batches of Sanpian Decoction was prepared, followed by the determination of the fingerprints, index component content, and dry extract rates, the identification of attribution of characteristic peaks, and the calculation of similarities between these fingerprints and the reference(R), the content and transfer rate ranges of ferulic acid, sinapine thiocyanate, liquiritin, and glycyrrhizic acid, and the dry extract rate range. The results showed that the similarities of 15 batches of the substance benchmark fingerprints with R were all greater than 0.900.Further summarization of the characteristic peaks revealed that there were a total of 20 characteristic peaks in fingerprint 1, among which, eight were from Sinapis Semen, four from Paeoniae Radix Alba, six from Chuanxiong Rhizoma, and two from Glycyrrhizae Radix et Rhizoma. A total of 16 characteristic peaks were observed in fingerprint 2, including one from Sinapis Semen, three from Paeoniae Radix Alba, eight from Chuanxiong Rhizoma, and four from Glycyrrhizae Radix et Rhizoma. The average dry extract rate of 15 batches of substance benchmarks was 18.25%, with a dry extract rate range of 16.28%-20.76%. The index component content and transfer rate ranges were listed as follows: 0.15%-0.18% and 38.81%-58.05% for ferulic acid; 0.26%-0.42% and 36.51%-51.02% for sinapine thiocyanate; 0.09%-0.15% and 48.80%-76.61% for liquiritin; 0.13%-0.24% and 23.45%-35.61% for glycyrrhizic acid. The fingerprint, dry extract rate, and index component content determination was combined for analyzing the quality value transfer of substance benchmarks in the classic prescription Sanpian Decoction.The established quality evaluation method for the substance benchmarks was stable and feasible, which has provided a basis for the quality control of Sanpian Decoction and the follow-up development of related preparations.

Combined photothermal-immunotherapy via poly-tannic acid coated PLGA nanoparticles for cancer treatment.

Photothermal therapy (PTT) is able to ablate tumors via hyperthermia, while immunotherapy could prevent tumor recurrence and metastasis by activating the host immune responses. Therefore, the combination of PTT and immunotherapy offers great advantages for the treatment of cancer. To achieve this goal, poly tannic acid (pTA) coated PLGA nanoparticles (PLGA-pTA NPs) were synthesized for combined photothermal-immunotherapy. pTA was a coordination complex formed by TA and Fe3+ and it could be easily coated on PLGA NPs within seconds with a coating rate of 5.89%. As a photothermal agent, PLGA-pTA revealed high photothermal conversion efficiency and excellent photo-stability upon 808 nm laser irradiation. It also exhibited strong photothermal cytotoxicity against 4T1 cells. Moreover, PLGA-pTA based PTT could effectively trigger DC maturation since it could induce the release of DAMPs. The result of animal experiments showed that PLGA-pTA plus laser irradiation raised the tumor temperature up to ca. 60 °C and effectively suppressed the growth of primary tumors. What's more, the progression of distant tumors as well as lung metastasis was also significantly inhibited due to the activation of anti-tumor responses by PLGA-pTA mediated PTT. When further combined with anti-PD-L1 antibody (a-PD-L1), the tumor growth and metastasis were almost completely inhibited. Our study provided a versatile platform to achieve combined photothermal-immunotherapy with enhanced therapeutic efficacy.

[Analysis on quality value transmitting of substance benchmark of Houpo Wenzhong Decoction].

By preparing 15 batches of lyophilized powder samples of substance benchmark in Houpo Wenzhong Decoction,the fingerprint,index component content and extract rate were determined,and the characteristic peaks,the range of similarity with the reference map,the content range and transfer rate range of magnolol,hesperidin,glycyrrhizic acid and pinocembrin,the extract rate range and the change range were clarified. The results showed that the similarity between the fingerprint of substance benchmark and the reference map R generated from the 15 batches of substance benchmark samples was higher than 0. 90. The assignment of the characteristic peaks in the full prescription's fingerprint of the herbs except Poria cocos was clarified. Nineteen characteristic peaks were assigned,and 12 characteristic peaks were assigned by the reference substance,of which 4 were from Magnolia ocinalis Cortex,5 from Exocarpium Citri Rubrum,2 from Radix aucklandiae,3 from Glycyrrhiza Radix et Rhizoma,4 from Semen Alpiniae Katsumadai,and one from Rhizoma Zingiberis and Zingiber officinale Roscoe. The index component content range and transfer rate range were 0. 80%-1. 14% and 20. 25%-39. 61% for hesperidin,0. 49%-0. 79% and 23. 09%-33. 87%for glycyrrhizic acid,0. 03%-0. 07% and 3. 55%-10. 09% for pinocembrin,0. 15%-0. 38% and 8. 08%-24. 35% for magnolol. The extract rate range and the change range were22. 60%-25. 57% and 12. 67%-23. 68% respectively. In this study,we introduced the concepts of index component content,fingerprint,extract rate,explored the transfer relation of quality value transmitting of substance benchmark in Houpo Wenzhong Decoction,and initially established the quality standard of Houpo Wenzhong Decoction,all of which would provide ideas for the development and research of similar prescriptions.

Poly-tannic acid coated paclitaxel nanocrystals for combinational photothermal-chemotherapy.

Combinational photothermal-chemotherapy offers great advantages for the treatment of cancer. To achieve this goal, the poly-tannic acid (pTA) coated paclitaxel nanocrystals (PNC) were prepared, which was denoted as PNC-pTA. Herein, paclitaxel (PTX) was prepared as nanocrystals acting as chemo-agent for chemotherapy. And the tannic acid formed a pTA layer coated on PNC in the presence of Fe3+ serving as a potential agent for photothermal therapy (PTT). PNC-pTA was around 470 nm in rod shape and the pTA content was determined to be 11.50 ± 0.48 wt% by mass ratio. pTA exhibited photothermal effect upon laser irradiation of 808 nm, and this effect could be strengthened with the increased amount of Fe3+ in pTA. Moreover, pTA showed excellent photostability under repeated laser irradiation. And with the aid of pTA, the cellular uptake of PNC-pTA was greatly enhanced for different cancerous cell lines. PNC-pTA plus laser irradiation showed much stronger cytotoxicity against the 4T1 cell line compared with that without laser irradiation. And the result of animal experiments showed that PNC-pTA exhibited mild photothermal effect in vivo and the strongest tumor inhibition effect upon laser irradiation compared with single photothermal therapy or chemotherapy. These results confirmed the combinational chemo-photothermal effect of PNC-pTA. Our study provided a versatile platform to achieve combined photothermal-chemotherapy with enhanced therapeutic efficacy.

Real-world use of extracorporeal photopheresis for patients with cutaneous T-cell lymphoma in the United States: 2010-2015.

Introduction: The National Comprehensive Cancer Network and the European Organization for Research and Treatment of Cancer recommend extracorporeal photopheresis (ECP) as systemic therapy for cutaneous T-cell lymphoma (CTCL).Objective: To investigate real-world use of ECP in CTCL patients in the US.Methods: Data from the Truven MarketScan® database (2010-2015) were used to create a cohort of CTCL patients receiving systemic treatment. Multivariable regressions were performed to compare health care resource utilization between ECP and propensity score-matched non-ECP patients.Results: Of the 1106 eligible patients, 117 (10.6%) received ECP, with an average treatment duration of 13.6 months. Psoriasis, organ transplant, graft versus host disease, and scleroderma were the most common comorbidities. ECP was used as monotherapy in 76 patients (65.0%) and combination in 41 patients (35.0%), mostly with interferon and/or a retinoid. Higher Charlson Comorbidity Index (2.6 vs 2.2, p < .05), rates of organ transplant (49.6% vs 7.8%, p < .001), and graft vs host disease (41.9% vs 3.4%, p < .001) were observed in ECP versus non-ECP patients. Post-matching analyses showed that ECP patients had shorter all-cause inpatient stay (6.67 vs 11.80 days, p = .001).Conclusions: Approximately 1 out of 10 CTCL patients receiving systemic treatment were on ECP treatment in the US. Post-matching analysis showed ECP was associated with a shorter hospital stay.

Comparison between Xingnaojing Injection () and Naloxone in Treatment of Acute Alcohol Intoxication: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: To investigate the effectiveness and safety of Xingnaojing Injection (XNJ, ) compared with naloxone for the treatment of acute alcohol intoxication (AAI), and provide the latest evidence through evidence-based approach. METHODS: Seven electro-databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure Databases, Chinese Biomedical Literature Database, Chinese Science and Technology Periodical Database (VIP) and Wanfang Database were searched from the inception to January 2018. Randomized controlled trials (RCTs) comparing XNJ with naloxone for patients with AAI and reporting at least one of the below outcomes were included: patients' conscious recovery time, stay length in emergency department, disappearance time of the ataxia symptom, the severity of the symptoms, the blood alcohol content as well as the adverse events. Methodological quality of included trials was assessed using the risk of bias tool which recommended by the Cochrane Collaboration. Meta-analysis was conducted by Review Manager 5.3 software. RESULTS: Totally 141 trials with 13,901 patients were included in this review, all of them were assessed as unclear or high risk of bias. Results showed that on the basis of routine therapy, standard dose XNJ (10-20 mL) may have similar results with naloxone on the recovery time of consciousness (MD 12 min, 95% CI 7.2-17.4 min) and disappearance time of symptoms (MD 6 min, 95% CI-13.8-25.8 min) for patients with AAI. Larger dose of XNJ Injection (21-40 mL) may speed up the time (almost 1 h earlier). Combination of XNJ and naloxone seemed superior to the naloxone alone for all the relevant outcomes. The average difference of time in consciousness recovery was 2 h and the number of AAI patients whose consciousness recovery within 1 h was above 50% the combination group than in the control group (RR 1.42, 95% CI 1.29 to 1.56). No severe adverse events or adverse reactions of XNJ were reported in the included trials. CONCLUSIONS: Low quality of evidence showed XNJ may have equal effect as naloxone and may achieve better effect as add-on intervention with naloxone for patients with AAI. We failed to evaluate the safety of XNJ Injection due to the insufficient evidence in this review. Registration number. in PROSPERO (No. CRD42018087804).

Comparative efficacy of Chinese herbal injections for the treatment of community-acquired pneumonia: A Bayesian network meta-analysis of randomized controlled trials.

BACKGROUND: Considering the limitations of conventional western treatment for community-acquired pneumonia (CAP) and the extensive exploration of Chinese herbal injections (CHIs), systematically and critically evaluating the efficacy of CHIs in the treatment of CAP is necessary. PURPOSE: This study constructed a network meta-analysis (NMA) to investigate the efficacy of CHIs (including the Reduning injection (RDN), Yanhuning injection (YHN), Xiyanping injection (XYP), and Tanreqing injection (TRQ)) combined with Western medicine (WM) and WM alone in CAP. METHODS: A literature review was conducted in several databases from inception to June 2018. The quality of the included studies was assessed by the Cochrane risk of bias tool and modified Jadad scale. Data were analyzed by STATA 13.0 and WinBUGS 14.0 software. Surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. Clustering analysis was utilized to compare the effect of CHIs between two different outcomes. RESULTS: A total of 47 eligible randomized controlled trials involving 4713 patients and 4 CHIs were included. The results of the NMA showed that RDN, YHN, XYP and TRQ combined with WM significantly improved treatment performance compared to WM alone. YHN+WM had obvious superiorities in the clinical effective rate, time for the disappearance of cough and the level of C-reactive protein. TRQ+WM was the most advantageous in shortening the time for defervescence and the average hospitalization time. XYP+WM was shown to reduce the time for the disappearance of lung rales best. Sixteen articles reported adverse drug reactions/adverse drug events (ADRs/ADEs) in detail, and 17 articles reported that there were no obvious ADRs/ADEs. CONCLUSION: This NMA showed that using CHIs in combination with WM improved treatment performance and could be beneficial for patients with CAP compared to using WM alone. Thereinto, YHN+WM showed a preferable improvement on patients with CAP when unified considering the clinical effective rate and other outcomes. As for safety, more evidence is needed to support this hypothesis.

Shengmai injection as an adjunctive therapy for the treatment of chronic obstructive pulmonary disease: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the clinical efficacy of Shengmai injection for the treatment of chronic obstructive pulmonary disease (COPD) through an evidence-based approach. METHODS: Randomized controlled trials (RCTs) investigating the effect of Shengmai injection on COPD were included in this study. Seven electronic databases were searched to obtain eligible studies. The quality of the included RCTs was evaluated according to the Cochrane Risk of Bias Assessment Tool. When appropriate, meta-analysis of the data was conducted by RevMan 5.3 software and Stata 13.0 software. The relative risk (RR) or mean difference (MD) and 95% confidence interval (CIs) were reported for dichotomous or continuous outcomes, respectively. Sensitivity analysis was performed to verify the independence of the results. Funnel plots and the Begg and Egger tests were implemented to determine the potential publication bias. RESULTS: Ultimately, 23 RCTs were included, involving 1804 participants. Meta-analysis showed that the combination of Shengmai injection and western medicine (WM) could achieve a better effect than WM alone in terms of improving the clinical total effective rate (RR = 1.20, 95% CIs: 1.15-1.24), pulmonary function (FEV1(L): MD = 0.41, 95% CIs 0.32 to 0.49; FEV1(%): MD = 6.21, 95% CIs: 2.72-9.71), blood gas index (PaO2: MD = 6.13, 95% CIs: 2.93-9.32; PaCO2: MD=-6.2, 95% CIs: -11.63 to -0.77), immunoglobulin levels (IgG: MD = 3.55, 95% CIs: 3.10-3.99; IgA: MD = 0.34, 95% CIs: 0.31to 0.38; IgM: MD = 0.35, 95% CIs: 0.27 to 0.42), C-reactive protein levels (MD = -8.05, 95% CIs: -10.11 to -6.00) and the lung rale disappearance time (MD = -2.57, 95% CIs: -3.19 to -1.95). Additionally, the CAT score, mMRC and average hospitalization time were also reduced significantly by Shengmai injection plus WM. Among 11 RCTs that mentioned safety issues, 6 RCTs found no adverse events, and the other 5 RCTs reported the details of adverse events. CONCLUSION: Shengmai injection may positively influence COPD in combination with WM. However, firm conclusions could not be draw due to the low quality of the evidence. Further high-quality studies are still required to test the efficacy of Shengmai injection for this condition.

Comparative Efficacy of Chinese Herbal Injections for Treating Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) imposes a huge economic burden on healthcare systems worldwide. Chinese herbal injections (CHIs) are widely used to treat AECOPD. In this study, we examined the efficacy of CHIs in the treatment of AECOPD using a network meta-analysis (NMA). METHODS: Literature search was conducted from electronic databases of randomized controlled trials (RCTs) on CHIs plus Western medicine (WM) versus WM. WinBUGS 1.4.3 and STATA 12.0 were adopted to compute calculations and prepare graphs, respectively. RESULTS: We included 155 RCTs with 13,218 patients. The results revealed that Danhong injection (DH) + WM had the greatest therapeutic potential in terms of rate of clinical efficacy (RCE). In addition, in comprehensively improving RCE and FEV1%, and RCE and C-reactive protein, Huangqi injection (HQ) +WM was associated with preferable effects. Similarly, Xixinnao injection + WM, Reduning injection (RDN) +WM, and HQ+WM had a favorable effect on RCE and PaO2. The effect of RDN+WM was favorable in all outcomes except RCE. The safety of CHIs needs to be further assessed. CONCLUSIONS: Based on this NMA, DH+WM, HQ+WM, and RDN+WM were potential optimal therapies in AECOPD and their safety should be strictly monitored.

Description of anti-diabetic drug utilization pre- and post-formulary restriction of sitagliptin: findings from a national health plan.

OBJECTIVE: Multi-tiered formularies are commonly used for controlling costs of prescription medications. Focused on type 2 diabetes mellitus (T2DM), this database study assessed drug utilization before and after a formulary restriction (2nd-3rd tier), and compared demographic and clinical characteristics of patients affected vs not by the restriction. METHODS: Formulary restriction of sitagliptin (SITA) occurred July 1, 2012. The 'pre-period' was defined from January 1-June 30, 2012, the 'grace period' from July 1-September 30, 2012, and the 'post-period' from October 1, 2012-March 31, 2013. Patients from the OptumInsight database were included if diagnosed with T2DM, ≥18 years, had continuous enrollment, and had ≥2 prescriptions of SITA in the pre-period. Those who died or were aged ≥65 years in the post-period were excluded. Patients were grouped into SITA continuer and discontinuer cohorts based on SITA use in the post-period. Descriptive analyses assessed baseline patient characteristics and anti-hyperglycemic drug utilization in the pre- and post-periods. RESULTS: In total, 23,477 patients met inclusion criteria. In the post-period, 36.1% (n = 8480) of patients discontinued SITA. Among SITA discontinuers, 44.1% switched to a preferred DPP-4 inhibitor, 9.2% switched to glucagon-like peptides-1 (GLP-1) or insulin, and 2.4% switched to metformin or sulfonylurea. Of the SITA discontinuers, 21.6% dropped SITA without replacement and 8.4% discontinued all diabetes medications. In the post-period, a greater proportion of SITA discontinuers used GLP-1 (12.6% vs 5.8%) and insulin (29.1% vs 20.9%) than continuers, or had some change in anti-hyperglycemic treatment (67.5% vs 22.1%). Baseline demographic and clinical characteristics were similar between SITA continuers and discontinuers, indicating a lack of an association with SITA discontinuation. LIMITATIONS: This descriptive study used a non-controlled observational approach. CONCLUSIONS: Following formulary change, 1/3 of patients discontinued SITA and 30% of discontinuers received less intensive anti-hyperglycemic treatment in the post-restriction period. Meanwhile, 44% of discontinuers switched to a new preferred DPP-4 inhibitor.