Polyene phosphatidylcholine promotes tibial fracture healing in rats by stimulating angiogenesis dominated by the VEGFA/VEGFR2 signaling pathway.

One of the factors that predispose to fractures is liver damage. Interestingly, fractures are sometimes accompanied by abnormal liver function. Polyene phosphatidylcholine (PPC) is an important liver repair drug. We wondered if PPC had a role in promoting fracture healing. A rat model of tibial fracture was developed using the modified Einhorn model method. X-rays were used to detect the progression of fracture healing. Progress of ossification and angiogenesis at the fracture site were analyzed by Safranin O/fast green staining and CD31 immunohistochemistry. To investigate whether PPC has a direct angiogenesis effect, HUVECs were used. We performed MTT, wound healing, Transwell migration, and tube formation assays. Finally, RT-qPCR and Western blot analysis were used to study the underlying mechanism. The results showed that PPC significantly shortened the apparent recovery time of mobility in rats. PPC treatment significantly promoted the formation of cartilage callus, endochondral ossification, and angiogenesis at the fracture site. In vitro, PPC promoted the proliferative viability of HUVECs, their ability to heal wounds, and their ability to penetrate membranes in the Transwell apparatus and increased the tube formation of cells. The transcription of VEGFA, VEGFR2, PLCγ, RAS, ERK1/2 and MEK1/2 was significantly up regulated by PPC. Further, the protein level results demonstrated a significant increase in the expression of VEGFA, VEGFR2, MEK1/2, and ERK1/2 proteins. In conclusion, our findings suggest that PPC promotes angiogenesis by activating the VEGFA/VEGFR2 and downstream signaling pathway, thereby accelerating fracture healing.

Polyene phosphatidylcholine enhances the therapeutic response of oxaliplatin in gastric cancer through Nrf2/HMOX1 mediated ferroptosis.

Oxaliplatin (OXA)-based chemotherapy is one of the first-line treatments for advanced gastric cancer. However, the potential risk for chemotherapy-induced hepatic injury can hinder its effectiveness. Polyene phosphatidylcholine (PPC) is often used as a hepatoprotective agent to counter OXA-induced hepatic injury; however, its impact on the antitumour effectiveness of OXA remains uncertain. Our retrospective study examined 98 patients with stage IV gastric cancer to assess the impact of PPC on progression-free survival (PFS) and disease control rate (DCR). Furthermore, in vitro and in vivo assays were conducted to elucidate the combined biological effects of OXA and PPC (OXA+PPC) on gastric cancer. RNA sequencing, luciferase reporter assays, live/dead cell assays, immunofluorescence, and western blotting were used to identify the activated signalling pathways and downstream factors post OXA+PPC treatment. The findings indicated that PPC served as an independent prognostic factor, correlating with prolonged PFS and improved DCR in patients with gastric cancer. The combination of OXA and PPC significantly inhibited tumour cell growth both in vitro and in vivo. RNA sequencing revealed that OXA+PPC treatment amplified reactive oxygen species and ferroptosis signalling pathways. Mechanistically, OXA+PPC upregulated the expression of haem oxygenase-1 by promoting the nuclear migration of nuclear factor erythroid 2-related factor (Nrf2), thereby enhancing its transcriptional activity. Drug-molecule docking analysis demonstrated that PPC competitively bound to the peptide structural domains of both Nrf2 and Kelch-like ECH-associated protein 1 (KEAP1), accounting for the increased translocation of Nrf2. In conclusion, our study reveals the synergistic antitumour potential of PPC and OXA while protecting patients against hepatic injury. This suggests a promising combined treatment approach for patients with advanced gastric cancer.

Effect of polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine on pregnancy outcomes in intrahepatic cholestasis.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that occurs in pregnant women and can lead to a range of adverse pregnancy outcomes. The condition is typically marked by pruritus (itching) and elevated levels of liver enzymes and bile acids. The standard treatment for ICP has generally been ursodeoxycholic acid and ademetionine 1,4-butanedisulfonate, but the efficacy of this approach remains less than optimal. Recently, polyene phosphatidylcholine has emerged as a promising new therapeutic agent for ICP due to its potential hepatoprotective effects. AIM: To evaluate the effect of polyene phosphatidylcholine/ursodeoxycholic acid/ ademetionine 1,4-butanedisulfonate on bile acid levels, liver enzyme indices, and pregnancy outcomes in patients with ICP. METHODS: From June 2020 to June 2021, 600 patients with ICP who were diagnosed and treated at our hospital were recruited and assigned at a ratio of 1:1 via random-number table method to receive either ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate (control group, n = 300) or polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate (combined group, n = 300). Outcome measures included bile acids levels, liver enzyme indices, and pregnancy outcomes. RESULTS: Prior to treatment, no significant differences were observed between the two groups (P > 0.05). Post-treatment, patients in both groups had significantly lower pruritus scores, but the triple-drug combination group had lower scores than the dual-drug combination group (P < 0.05). The bile acid levels decreased significantly in both groups, but the decrease was more significant in the triple-drug group (P < 0.05). The triple-drug group also exhibited a greater reduction in the levels of certain liver enzymes and a lower incidence of adverse pregnancy outcomes compared to the dual-drug group (P < 0.05). CONCLUSION: Polyene phosphatidylcholine/ursodeoxycholic acid/ademetionine 1,4-butanedisulfonate effectively relieves pruritus and reduces bile acid levels and liver enzyme indices in patients with ICP, providing a positive impact on pregnancy outcome and a high safety profile. Further clinical trials are required prior to clinical application.

Polyene phosphatidylcholine ameliorates synovial inflammation: involvement of PTEN elevation and glycolysis suppression.

BACKGROUND: Synovial inflammation, characterized by the activation of synovial fibroblasts (SFs), is a crucial factor to drive the progression of rheumatoid arthritis (RA). Polyene phosphatidylcholine (PPC), the classic hepatoprotective drug, has been reported to ameliorate arthritis in animals. However, the molecular mechanism remains poorly understood. METHODS AND RESULTS: Using in vitro primary synovial fibroblast (SFs) culture system, we revealed that phosphatase and tension homolog deleted on chromosome 10 (PTEN), a tumor suppressor, mediates the anti-inflammatory effect of PPC in lipopolysaccharide (LPS)-stimulated primary SFs. PPC decreased the production of TNF-α and IL-6 production while elevating the level of IL-10 and TGF-ß. Furthermore, PPC up-regulated the expression of PTEN, but inhibited the expression of p-AKT (ser473) and PI3K-p85α. Moreover, pre-treatment of SF1670 (the inhibitor of PTEN) or 740Y-P (the agonist of AKT/PI3K pathways) partially abrogated the anti-inflammatory effect of PPC. In addition, PPC could inhibit the expression of GLUT4, a key transporter of glucose that fuels the glycolysis, which is accompanied by the expression downregualtion of glycolytic enzymes PFKFB3 and PKM2. Furthermore, PPC could reduce ROS production and mitochondrial membrane potential in LPS-stimulated SFs and MH7A cell line. CONCLUSION: The present study supported that PPC can alleviate synovial inflammation, which involves in the elevation of PTEN and blockage of glycolysis.

The effect of polyene phosphatidylcholine combined with Shudan decoction on the recovery of gallbladder function after fallbladder-preserving cholecystolithotomy / 中国医师进修杂志

Objective:To investigate the effect of polyene phosphatidylcholine combined with Shudan decoction on the recovery of gallbladder function after gallbladder-preserving cholecystolithotomy.Methods:Sixty patients with gallbladder stone admitted to Shenzhen Hospital (Longgang), Beijing University of Chinese Medicine from June 2018 to July 2021 were selected. All patients were received gallbladder-preserving cholecystolithotomy, and they were divided in two groups by random number table, each group with 30 patients. The control group was treated with polyene phosphatidylcholine capsule after the operation, while the observation group was treated with Shudan decoction on the basis of the control group. After 30 d of continuous treatment, the traditional Chinese medicine symptoms score, gallbladder contraction function and the levels of serum alkaline phosphatase (ALP), gamma-glutamine transferase (GGT), incidence of adverse reactions, clinical efficacy were compared between the two groups.Results:After treatment, the scores of abdominal distension, abdominal pain and anorexia in the observation group were lower than those in the control group ( P<0.05). After treatment, the thickness of the gallbladder wall in the observation group was lower than that in the control group and the the gallbladder contraction rate was higher than that in the control group: (2.62 ± 0.29) mm vs. (3.21 ± 0.32) mm, (74.17 ± 6.49)% vs. (62.03 ± 6.05)%, there were statistical differences ( P<0.05). After treatment, the levels of GGT and ALP in the observation group were lower than those in the control group: (132.32 ± 30.09) U/L vs. (150.27 ± 30.33)U/L, (56.12 ± 14.89) U/L vs. (75.07 ± 16.22) U/L, there were statistical differences ( P<0.05). The total effective rate in the observation group was higher than that in the control group: 96.67%(29/30) vs. 80.00%(24/30), there was statistical difference ( χ2 = 4.04, P<0.05). The adverse reactions in the two groups had no significant differences ( P>0.05). Conclusions:Polyene phosphatidylcholine combined with Shudan decoction has a definite efficacy for patients with cholecystolithiasis after gallbladder-preserving cholecystolithotomy, and can effectively promote the recovery of their gallbladder function and with good safety.

Effectiveness of polyene phosphatidylcholine and its combination with other drugs in patients with liver diseases based on real-world research.

OBJECTIVES: Polyene phosphatidylcholine (PPC) is a widely used hepatoprotective drug. We aim to explore the effectiveness of PPC in patients with liver diseases based on real-world research, and compare with other hepatoprotective drugs. METHODS: This was a 'three-phase' retrospective study, including a descriptive study, a self-control case study, and a specific-disease cohort study. A total of 14,800 hospitalized patients were enrolled in phase I from 1 January 2015 to 1 January 2020, of which 793 patients using PPC alone were included for phase II and III. The major measurement of effectiveness analysis was the ALT level and its changes. Wilcoxon signed-rank test, Chi-square test, and Mann-Whitney U test were used. RESULTS: In patients without liver tumor, ALT level decreased after using PPC (p < 0.01), and the decrease in ALT level using PPC was greater than using glutathione or magnesium isoglycyrrhizinate alone (p = 0.044; p = 0.038). In patients without liver tumor but having abnormal liver function, the decrease in ALT level using PPC + glutathione was greater than using glutathione alone (p = 0.047). CONCLUSION: PPC had a beneficial effect on liver function in patients without liver tumor, and PPC could enhance the liver protective function of glutathione and magnesium isoglycyrrhizinate.

A Multicenter Real-World Study Evaluating the Hepatoprotective Effect of Polyene Phosphatidylcholine Against Chronic Hepatitis B.

Background: Polyene phosphatidylcholine (PPC) has been widely used to treat liver diseases in China. However, there is a lack of post-marketing evidence demonstrating its liver-protective efficiency among patients infected with hepatitis B virus (HBV). This study analyzed the multicenter real-world data to compare the effectiveness of PPC with those of magnesium isoglycyrrhizinate (IsoMag) and glutathione (GSH) in patients with liver injury. Methods: This study comprised the real-world data analysis of a multicenter, retrospective observational cohort. The data were retrieved from the Cooperative Registry of the Hospital Prescription in China between 1 October 2018, and 30 September 2019. A growth curve analysis was performed to compare the effects of different treatments on liver function longitudinally for up to 30 days after treatment commencement. In addition, the dose effect of the PPC treatment was investigated. Results: The final cohort included 6,052 patients with approximately 8% infected with HBV (N = 471). There were 1,649, 1,750, and 2,653 patients in the PPC, GSH, and IsoMag groups, respectively, with an average age of 53.9 years. In patients with HBV infection, the PPC treatment was associated with a significant decline in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (slopes: -3.7, 95% CI, -6.0 to -1.5 U/L/day; -2.4, 95% CI, -4.5 to -0.3 U/L/day, respectively). However, there were no significant differences in the effects among the three groups. In patients without HBV infection, the PPC treatment decreased ALT, AST, γ-glutamyl transferase (GGT), and albumin levels (-5.2, 95% CI, -5.8 to -4.5 U/L/day; -3.5, 95% CI, -4.2 to -2.7 U/L/day; -4.9, 95% CI, -6.2 to -3.7 U/L/day, -0.07, 95% CI, -0.09 to -0.04 g/L/day, respectively) and showed a stronger effect on lowering ALT levels than GSH (-2.6, 95% CI, -3.3 to -1.8 U/L/day, p < 0.05), as well as a stronger effect on lowering GGT levels than IsoMag (-1.4, 95% CI, -2.4 to -0.4 U/L/day, p < 0.05). PPC had no impact on prothrombin activity levels in patients with or without HBV infection. High-dose PPC exhibited a stronger effect on lowering ALT and AST levels than low-dose PPC. Conclusion: This was the first real-world multicenter study to demonstrate that PPC efficiently lowers ALT and AST levels in patients with liver diseases regardless of the status of HBV infection. PPC treatment showed a comparable or better effect compared with GSH and IsoMag treatments. High-dose PPC resulted in a stronger effect than low-dose PPC.

Polyene Phosphatidylcholine Ameliorates High Fat Diet-Induced Non-alcoholic Fatty Liver Disease via Remodeling Metabolism and Inflammation.

Recent years have witnessed a rise in the morbidity of non-alcoholic fatty liver disease (NAFLD), in line with the global outbreak of obesity. However, effective intervention strategy against NAFLD is still unavailable. The present study sought to investigate the effect and mechanism of polyene phosphatidylcholine (PPC), a classic hepatoprotective drug, on NAFLD induced by high fat diet (HFD). We found that PPC intervention reduced the mass of liver, subcutaneous, epididymal, and brown fats in HFD mice. Furthermore, PPC supplementation significantly mitigated liver steatosis and improved glucose tolerance and insulin sensitivity in HFD mice, which was accompanied by declined levels of hepatic triglyceride, serum triglyceride, low density lipoprotein, aspartate aminotransferase, and alanine aminotransferase. Using transcriptome analysis, there were 1,789 differentially expressed genes (| fold change | ≥ 2, P < 0.05) including 893 upregulated genes and 896 downregulated genes in the HFD group compared to LC group. A total of 1,114 upregulated genes and 1,337 downregulated genes in HFD + PPC group were identified in comparison to HFD group. With the help of Gene Ontology (GO) analysis, these differentially expressed genes between HFD+PPC and HFD group were discovered related to "lipid metabolic process (GO: 0006629)," "lipid modification (GO: 0030258)," and "lipid homeostasis (GO: 0055088)". Though Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we found pathways associated with hepatic homeostasis of metabolism and inflammation. Notably, the pathway "Non-alcoholic fatty liver disease (mmu04932)" (P-value = 0.00698) was authenticated in the study, which may inspire the potential mechanism of PPC to ameliorate NAFLD. The study also found that lipolysis, fatty acid oxidation, and lipid export associated genes were upregulated, while the genes in uptake of lipids and cholesterol synthesis were downregulated in the liver of HFD mice after PPC supplementation. Interestingly, PPC attenuated the metabolic inflammation via inhibiting pro-inflammatory macrophage in the livers of mice fed by HFD. In summary, this study demonstrates that PPC can ameliorate HFD-induced liver steatosis via reprogramming metabolic and inflammatory processes, which inspire clues for further clarifying the intervention mechanism of PPC against NAFLD.

Polyene Phosphatidylcholine Interacting with TLR-2 Prevents the Synovial Inflammation via Inactivation of MAPK and NF-κB Pathways.

Rheumatoid arthritis (RA) is a chronic autoimmune joint disease that causes cartilage and bone damage or even disability, seriously endangering human health. Chronic synovial inflammation has been shown to play a vital role in disease sustainability. Therefore, downregulation of synovial inflammation is considered to be an effective discipline for RA therapy. Polyene phosphatidylcholine (PPC) is a hepatoprotective agent, which was observed to inhibit inflammation in macrophages and prevent collagen-induced arthritis (CIA) of rats in our previous study. However, the underlying mechanism remains unclear. The present study further reported that PPC can inhibit synovial inflammation. In lipopolysaccharide (LPS)-stimulated primary synovial fibroblasts (SFs) of mice, PPC significantly decreased pro-inflammatory cytokines production while increasing anti-inflammatory cytokines level. In this process, PPC downregulated the expression of TLR-2 and their downstream signaling molecules such as MyD88, p-ERK1/2, p-JNK1/2, and p-P38 in MAPK pathway and p-IκBα and NF-κB-p65 in NF-κB pathway. Moreover, the inhibitory effect of PPC on the above molecules and cytokines was weakened after pre-treatment with TLR-2 agonist Pam3CSK4. In addition, PPC lost its anti-inflammatory effect and its suppressing capability on MAPK and NF-κB pathways in TLR-2-/- primary SFs after exposure to LPS. Collectively, this study demonstrated that PPC can alleviate synovial inflammation through TLR-2-mediated MAPK and NF-κB pathways, which can be proposed to be a potential drug candidate for RA prevention.

Lipidomic-based investigation into the therapeutic effects of polyene phosphatidylcholine and Babao Dan on rats with non-alcoholic fatty liver disease.

In recent years, with the improvement of people's living standards, non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in the world. In this paper, the metabolic disorders in Sprague Dawley (SD) rats were induced by a choline-deficient, l-amino acid-defined (CDAA) diet. The therapeutic effects of polyene phosphatidylcholine (PPC) and Babao Dan (BBD) on NAFLD were observed. Lipidomic analysis was performed using ultra-high-performance liquid chromatography-Orbitrap MS, and data analysis and lipid identification were performed using the software LipidSearch. Both PPC and BBD can reduce lipid accumulation in the liver and improve abnormal biochemical indicators in rats, including reduction of triglycerides, total cholesterol, alanine transaminase and aspartate transaminase in serum. In addition, lipids in rat serum were systematically analyzed by lipidomics. The lipidomic results showed that the most obvious lipids with abnormal metabolism in CDAA diet-induced rats were glycerides (triglycerides and diacylglycerols), phospholipids and cholesterol esters. Both BBD and PPC partly reversed the disturbance to lipids induced by the CDAA diet. PPC may be more effective than BBD in alleviating NAFLD because it has a better effect on inhibiting the abnormal accumulation of lipids and reducing the inflammatory reaction in the body.

Treatment of Drug-Induced Liver Injury.

Current pharmacotherapy options of drug-induced liver injury (DILI) remain under discussion and are now evaluated in this analysis. Needless to say, the use of the offending drug must be stopped as soon as DILI is suspected. Normal dosed drugs may cause idiosyncratic DILI, and drugs taken in overdose commonly lead to intrinsic DILI. Empirically used but not substantiated regarding efficiency by randomized controlled trials (RCTs) is the intravenous antidote treatment with N-acetylcysteine (NAC) in patients with intrinsic DILI by N-acetyl-p-aminophenol (APAP) overdose. Good data recommending pharmacotherapy in idiosyncratic DILI caused by hundreds of different drugs are lacking. Indeed, a recent analysis revealed that just eight RCTs have been published, and in only two out of eight trials were DILI cases evaluated for causality by the worldwide used Roussel Uclaf Causality Assessment Method (RUCAM), representing overall a significant methodology flaw, as results of DILI RCTs lacking RUCAM are misleading since many DILI cases are known to be attributable erroneously to nondrug alternative causes. In line with these major shortcomings and mostly based on anecdotal reports, glucocorticoids (GCs) and other immuno-suppressants may be given empirically in carefully selected patients with idiosyncratic DILI exhibiting autoimmune features or caused by immune checkpoint inhibitors (ICIs), while some patients with cholestatic DILI may benefit from ursodeoxycholic acid use; in other patients with drug-induced hepatic sinusoidal obstruction syndrome (HSOS) and coagulopathy risks, the indication for anticoagulants should be considered. In view of many other mechanistic factors such as the hepatic microsomal cytochrome P450 with a generation of reactive oxygen species (ROS), ferroptosis with toxicity of intracellular iron, and modification of the gut microbiome, additional therapy options may be available in the future. In summation, stopping the offending drug is still the first line of therapy for most instances of acute DILI, while various therapies are applied empirically and not based on good data from RCTs awaiting further trials using the updated RUCAM that asks for strict exclusion and inclusion details like liver injury criteria and provides valid causality rankings of probable and highly probable grades.

Exploring the efficacy and safety of polyene phosphatidylcholine for treatment of drug-induced liver injury using the Roussel Uclaf causality assessment method: a propensity score matching comparison.

Objective In China, polyene phosphatidylcholine (PPC) is widely used to treat alanine aminotransferase (ALT) elevation associated with various liver diseases. Here, we assessed the efficacy and safety of PPC in treating drug-induced liver injury (DILI).Methods Data from a multicenter retrospective cohort study (DILI-R) were analyzed to compare PPC and magnesium isoglycyrrhizinate (MgIG) for treatment of DILI. We used the Roussel Uclaf causality assessment method (RUCAM) to evaluate patients with DILI. Patients with RUCAM scores ≥6 were included in the study, while those with RUCAM scores <6 were further evaluated by a panel of hepatologists. The primary outcome was the proportion of patients with ALT normalization at discharge. Propensity score matching was used to identify 183 matched pairs of patients (366 patients in total) from 25,927 patients with DILI.Results Among the DILI patients, 64 of 183 (34.97%) achieved normal ALT levels after treatment in both the PPC and the MgIG groups.Conclusion There were no significant differences in safety biomarkers including serum creatinine, blood urea nitrogen, white blood cells, platelets, hemoglobin, and albumin between patients treated with PPC or MgIG. The safety and efficacy of these two agents for treatment of DILI were comparable.

TLR-2-mediated metabolic reprogramming participates in polyene phosphatidylcholine-mediated inhibition of M1 macrophage polarization.

This study aimed to investigate whether the classic hepatoprotective drug polyene phosphatidylcholine (PPC) regulates macrophage polarization and explores the potential role of TLR-2 in this process. In RAW264.7 macrophages and murine bone marrow-derived macrophages (BMDMs) stimulated by lipopolysaccharide (LPS), PPC significantly inhibited the production of IL-6, TNF-α, and the mRNA expression of M1-type macrophage markers. Consistently, PPC reduced the mRNA expression of several key enzymes in the pathways of glycolysis and lipid synthesis while increasing the expression of key enzymes associated with lipid oxidation. Moreover, blocking the glycolytic pathway using 2-deoxy-D-glucose (2-DG) significantly enhanced the anti-inflammatory effect of PPC. However, inhibition of lipid oxidation using GW9662 (an inhibitor of PPAR-γ) and GW6471 (an inhibitor of PPAR-α) abolished the anti-inflammatory effect of PPC. Interestingly, TLR-2 expression in macrophages was significantly downregulated after exposure to PPC. Moreover, pre-activation of TLR-2 hampered the anti-inflammatory effect of PPC. In addition, PPC did not inhibit the secretion of IL-6 and TNF-α in TLR-2-/- BMDMs that were activated by LPS. This was consistent with the increased expression of M1 markers and glycolytic and lipid synthesis enzymes but decreased lipid oxidation-related enzymes. These results showed that PPC inhibits the differentiation of M1-type macrophages, which was most likely related to TLR-2-mediated metabolic reprogramming.

Gut microbiota signatures and lipids metabolism profiles by exposure to polyene phosphatidylcholine.

The aim of the study was to address the causality links and identify specific features of the gut microbiota signatures contributing to host lipids metabolism in the presence or absence of polyene phosphatidylcholine (PPC) administration, and evaluate potential risk of PPC consumption. About 20 C57BL/6J mice were randomly allocated into two groups, normal diet group (CK) and PPC administration group (205.2 mg/kg). Compared with CK group, the contents of unsaturated fatty acids were increased and the saturated fatty acids were decreased in PPC group. The content of free fatty acids (FFA) and lipopolysaccharides (LPS) were significantly decreased (P < 0.05), and expression of carnitine palmitoyltransferase 1A (CPT1A), cluster of differentiation 36 (CD36), liver fatty acid binding protein (L-FABP), fatty acid transport protein 5 (FATP5), and fatty acid synthase (FASN) were significantly decreased in the mRNA and protein levels after treated by PPC (P < 0.05, P < 0.01). Also, we found that acetic acid in feces was significantly increased after consumption of PPC (P < 0.05). After PPC administration the relative abundances of Firmicutes and Clostridia were increased within the phylum level and the class level, respectively. Microbial abundances in genus level were dominated by Lachnospiraceae and Lachnospiraceae_NK4A136_group, whereas the proportion of sequences assigned to Bacteroidetes within the phylum level, class Bacteroidias and Mollicutes, order Anaeroplasmatalesl, genus Bacteroidales_S24-7_group were decreased in metagenomes of treated group with PPC and did not significantly influence on the accumulation of trimethylamine-N-oxide (TMAO). This study revealed that intake of PPC could regulate the gut microbiota signatures and lipids metabolism in mice without TMAO accumulations. © 2019 BioFactors, 45(3):439-449, 2019.

Application of multiattribute utility theory in pharmacoeconomic evaluation of anti - inflammatory and hepatoprotective therapy for chronic hepatitis B / 中国基层医药

Objective To evaluate the application of multiattribute utility theory(MAUT) in pharmacoeco-nomic evaluation of anti - inflammatory and hepatoprotective therapy for chronic hepatitis B ( CHB). Methods During year 2014 - 2016,214 patients with mild to moderate CHB were selected. The patients were divided into three groups: A,B and C according to the therapeutic regimen,and they were given compound glycyrrhizin,tiopronin and polyene phosphatidylcholine to prevent inflammation and protect liver. MAUT model was constructed,the evaluation factors were determined and appropriate weight was given to each element parameter,the specific utility values for each factor were calculated,and by calculating the total utility value of final results quantitatively demonstrated the three regimens in the treatment of chronic hepatitis B. Results The total effective rates of A,B,C three groups were 78. 38％ ,69. 44％ ,79. 41％ ,respectively,the difference was statistically significant( χ2 = 5. 559,P < 0. 05). The incidence rates of adverse reaction of A,B,C three groups were 16. 22％ ,8. 33％ ,5. 88％ ,respectively. As to direct cost,group B(1430. 45 yuan) was better than group C(1494. 04 yuan) and group A (1515. 92 yuan). The hospital days of A,B,C three groups were (11. 3 ± 4. 8) d,(10. 9 ± 10. 6) d,(12. 5 ± 6. 4) d,respectively. The results of MAUT comprehensive evaluation showed that the total score value in polyene phosphatidylcholine group was the highest,and was the optimal treatment in the study. Conclusion Application of MAUT in the study of pharmacoeco-nomics is comprehensive,intuitive and flexible.

Polyene Phosphatidylcholine inhibited the inflammatory response in LPS-stimulated macrophages and ameliorated the adjuvant-induced rat arthritis.

This study sought to investigate the anti-inflammatory effect of Polyene Phosphatidylcholine (PPC), a clinical drug that is used to treat hepatopathy, on lipopolysaccharide (LPS)-stimulated macrophages and on bovine collagen II-induced arthritis (CIA) rats. In stimulated primary and Raw264.7 macrophages by LPS, PPC significantly down-regulated the relative expression of mRNA such as IL-6, TNF-α, TLR-2, TLR-4, MyD88, and NF-κB while up-regulated IL-10 and TGF-ß expression. Moreover, the concentration of IL-6, TNF-α, IL-10, and TGF-ß in the cultured supernatants showed the similar tendency with their mRNA alterations. In addition, PPC could significantly inhibit the LPS-induced expression of MyD88 and NF-κB p65 in both mRNA and protein levels. These results suggest that PPC could down-regulate the LPS-stimulated inflammation in macrophages through TLR-2/TLR-4/MyD88/NF-κB pathway in vitro. Furthermore, to explore its effects in vivo, PPC was administrated to CIA rats. In comparison to CIA group, PPC-treated rats showed decreased arthritis score and osteopenia. Besides, PPC exhibited its ability to alleviate the degree of synovial hyperplasia, inflammatory cell infiltration, and destruction of cartilage and bone, thus remarkably improving the condition of CIA rats. In short, this study demonstrated that PPC had the potential to be an anti-inflammatory drug to treat inflammatory disorders such as rheumatoid arthritis.

Improved pipe-washing prevents blockage of PICC for polyenephosphatidy lcholine infusion / 现代临床护理

Objective To discuss the impact of improved pipe-washing on blockage of PICC for infusion of polyene phosphatidylcholine injection (PPI). Methods A total of 15 patients treated with infusion of PPI from April 2014 to March 2015 were chosen as the control group by convenience sampling method, while another 18 patients treated with PPI from April 2015 to March 2016 were selected as the experimental group. In the control group the pipes were washed with 0.9%10 mL sodium chloride injection before PPI infusion, while in the experimental group improved pipe washing method was applied. We compared the two groups in terms of the maximum number of transfusion drops and rate of unplanned extubation caused by pipe blockage. Results The maximum number of transfusion drops for pipe biockage test in the experimental group was significantly greater than that in the control group (P<0.01). The incidence of pipe blockage was smaller than that in the control group (P<0.01). Conclusion Improved pipe washing method caneffectively reduce rate of tube blockage.

Improved pipe-washing prevents blockage of PICC for polyenephosphatidy lcholine infusion / 现代临床护理

Objective To discuss the impact of improved pipe-washing on blockage of PICC for infusion of polyene phosphatidylcholine injection (PPI). Methods A total of 15 patients treated with infusion of PPI from April 2014 to March 2015 were chosen as the control group by convenience sampling method, while another 18 patients treated with PPI from April 2015 to March 2016 were selected as the experimental group. In the control group the pipes were washed with 0.9%10 mL sodium chloride injection before PPI infusion, while in the experimental group improved pipe washing method was applied. We compared the two groups in terms of the maximum number of transfusion drops and rate of unplanned extubation caused by pipe blockage. Results The maximum number of transfusion drops for pipe biockage test in the experimental group was significantly greater than that in the control group (P<0.01). The incidence of pipe blockage was smaller than that in the control group (P<0.01). Conclusion Improved pipe washing method caneffectively reduce rate of tube blockage.

Clinical Observation and Economic Evaluation of 3 Kinds of Drugs Preventing Chemotherapy-induced Liv-er Damage in Patients with Gastrointestinal Tumors / 中国药房

OBJECTIVE:To observe the preventive effects and safety of 3 kinds of drugs on chemotherapy-induced liver dam-age in patients with gastrointestinal tumors,and to evaluate economics. METHODS:A total of 128 patients with gastrointestinal malignant tumor and systemic chemotherapy indication selected from our hospital during 2014-2015 were divided into group A(42 cases),B(46 cases)and C(40 cases)according to random number table. Since the first day of chemotherapy,group A,B and C were given Reduced glutathione for injection(1.2 g),Magnesium isoglycyrrhizinate injection(100 mg)and Polyene phosphati-dylcholine injection(465 mg)for preventing chemotherapy-induced liver damage respectively,for 7 d. The preventive effects and ADR occurrence were observed in 3 groups,and the economic analysis was conducted. RESULTS:Total response rates of group A,B and C were 90.48%,97.83% and 87.50%,and that of group B was significantly higher than other 2 groups,with statistical significance(P<0.05). But there was no statistical significance between group A and C(P>0.05). The costs of group A,B and C were 1 465.86,1 518.94,1 554.04 yuan,and cost-minimization analysis was adopted to evaluate the plans of group A and C. The plan of group A was more economical. Cost-effectiveness analysis was used to evaluate the plans of group A and B,cost-effectiveness ratio of group A and B were 1 620.09 and 1 552.63;incremental cost-effectiveness ratio was 722.18, and the plan of group B was more economical. The above conclusion was supported by the results of sensitivity analysis. Three patients in group B suffered from transient elevated blood pressure and then recovered 2-3 d after drug withdrawal. CONCLU-SIONS:The preventive effects and economics of Magnesium isoglycyrrhizinate injection is better than Reduced glutathione for injection and Polyene phosphatidylcholine injection for chemotherapy-induced liver damage in patients with gastrointestinal tu-mors. The blood pressure of patients should be monitored closely during application. Reduced glutathione for injection is more suitable for patients with primary hypertensive disease.

Effects of Polyene Phosphatidylcholine on Hepatic Injury of Tumor?bearing Nude Mice Induced by Oxaliplatin and 5?fluorouracil Chemotherapy / 中国医科大学学报

Objective To study the protective effect of polyene phosphatidylcholine on hepatic injury induced by oxaliplatin and 5?fluorouracil. Methods A subcutaneous tumor model was established by transplanting colocarcinoma HCT116 cells into 30 nude mice,which were random?ized into three groups. The polyene phosphatidylcholine group was injected with polyene phosphatidylcholine(85 mg · kg-1 · d-1)and 5?fluorouracil (20 mg·kg-1·d-1)for 7 days,and then injected with oxaliplatin(6 mg·kg-1·d-1)for 1 day. The hepatic injury group was injected with 5?fluoroura?cil(20 mg·kg-1·d-1)for 7 days and oxaliplatin(6 mg·kg-1·d-1)for 1 day. The tumor?bearing blank group was injected with normal saline. Hepat?ic injury was observed with ultrathin pathological sections. Liver homogenates were prepared to detect superoxide dismutase(SOD)and catalase (CAT)activity. Results In the hepatic injury group,pathological sections revealed dissolved cellular cytoplasm,mitochondrial membrane dam?age,cell membrane edema,and fuzzy,sinusoidal cell expansion . There were no obvious hepatic injuries observed in the polyene phosphatidylcho?line group. The expression of SOD and CAT were lower in the hepatic injury and polyene phosphatidylcholine groups compared to the tumor?bear?ing blank group(P<0.05). The expression of SOD and CAT were higher in the polyene phosphatidylcholine group compared to the hepatic injury group(P<0.05). Conclusion Polyene phosphatidylcholine has a protective effect on hepatic injury induced by oxaliplatin and 5?fluorouracil, which may be related to its effect on membrane repair and inhibition of oxidative stress.