Aim To discover the potential active compounds and possible mechanisms in rheumatoid arthritis (RA) treatment with Zhi-Huang-Zhi-Tong powder (ZHZTP) by using network pharmacology and in vitro study. Methods The active ingredient targets and disease targets of Zhihuang Zhitong Powder were searched and screened by database; they intersected to get a common target; and the "drug-component-target" relationship network diagram was constructed for GO and KEGG enrichment analysis of the overlapping genes; then the core components were docked with the core targets. Finally, based on the inflammation model of HUVECs in vitro, the efficacy and mechanism of Zhihuang Zhitong powder were verified by MTT method, plate scratch test and Western blot. Results Active compounds involved in RA treatment were screened in the present study, and the top two were ursolic acid and emodin, all playing crucial roles in RA treatment with ZHZTP. Additionally, the key target was AKTA, TNF and IL-6. GO and KEGG enrichment analysis revealed that ZHZTP regulated BP, MF and CC, and also focused on regulating AKTA, TNF and IL-6 signaling pathway. Molecular docking showed that interactions between key active compounds and key targets were stable. In vitro ZHZTP significantly inhibited cell viability and migration of TNF-a-stimulated HUVECs, and the involved mechanism may be associated with PI3K/AKT/m-TOR signaling. Conclusions The present study reveals that the potential active compounds of ZHZTP are ursolic acid and emodin, and moreover, the involved mechanisms of ZHZTP for RA treatment are associated with PI3 K/AKT/m-TOR signaling.

Objective To investigate the clinical value of Yishen Gujing Kangyan Prescription(with the actions of benefiting the kidneys,consolidating essence and anti-inflammatory,mainly composed of Imperatae Rhizoma,Codonopsis Radix,Corni Fructus,Moutan Cortex,Lycii Fructus,Cuscutae Semen,Dioscoreae Rhizoma,honey-roasted Astragali Radix,Poria,Rehmanniae Radix Praeparata,etc.)in the treatment of lupus nephritis(LN)of qi and yin deficiency type.Methods A total of 116 patients with LN of qi and yin deficiency type were randomly divided into observation group and control group,58 cases in each group.The control group was given conventional western medicine treatment,and the observation group was treated with the combination of Yishen Gujing Kangyan Prescription on the basis of treatment for the control group.Both groups were treated for a period of 6 months.The changes of traditional Chinese medicine(TCM)syndrome scores,renal function parameters,immune function indicators,serum interleukin 18(IL-18),homocysteine(Hcy),transforming growth factor β1(TGF-β1),cystatin C(Cys C)levels in the two groups were observed before and after the treatment.After treatment,the clinical efficacy and the negative-conversion of anti-double-stranded DNA(ds-DNA)antibody were compared between the two groups.Results(1)After 6 months of treatment,the total effective rate of the observation group was 94.83%(55/58),and that of the control group was 75.86%(44/58).The intergroup comparison showed that the therapeutic effect of the observation group was significantly superior to that of the control group(χ2 = 5.453,P＜0.05).(2)After treatment,the scores of primary symptoms(edema,fatigue)and secondary symptoms(lumbar and knee soreness,loose stools)in the two groups were lower than those before treatment(P＜0.05),and the effect on lowering the scores in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the levels of renal function parameters of blood urea nitrogen(BUN),serum creatinine(Scr),and 24-hour urine protein quantification of the two groups were all lower than those before treatment(P＜0.05),and the effect on lowering renal function parameters in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,serum IL-18,TGF-β1,Hcy and Cys C levels of the two groups of patients were all reduced compared with those before treatment(P＜0.05),and the effect on lowering the levels of inflammatory factors and fibrosis parameters in the observation group was significantly superior to that in the control group(P＜0.01).(5)After treatment,the levels of immune function indicators of T cell subsets CD4+,CD4+/CD8+ and complement C3 in the two groups were increased compared with those before treatment(P＜0.05),and the increase in the observation group was significantly superior to that in the control group,and the differences were all statistically significant(P＜0.05 or P＜0.01).(6)The negative-conversion rate of anti-ds-DNA antibody in the observation group was 77.59%(45/58),which was significantly higher than that in the control group(55.17%,32/58),and the difference was statistically significant between the two groups(P＜0.05).Conclusion For the treatment of patients with LN of qi and yin deficiency type,Yishen Gujing Kangyan Prescription exerts synergistic effect on reducing inflammatory response,regulating immune function,promoting the recovery of renal function,and enhancing clinical efficacy.

Objective To investigate the therapeutic effect and mechanism of Jianwei Xiaozhang Tablets on rats with precancerous lesions of gastric cancer(PLGC).Methods Forty male SD rats were randomly divided into the normal group,the model group,the folic acid group and the Jianwei Xiaozhang Tablets group,with 10 rats in each group.In addition to the normal group,the other three groups of rats were prepared by gavage with Ranitidine Aqueous Solution combined with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)solution drinking method for the preparation of PLGC model.After successful modeling,drugs were administered accordingly for 7 weeks.The changes in body mass of rats during modeling and drug administration were recorded,the gross view of the stomach was observed and scored pathologically,the coefficients of spleen and liver were determined,the pathological changes in gastric tissue were observed by hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA)was used to measure serum gastrin(GAS),motilin(MTL)and glucagon(GC),Alisin Blue-Periodic Acid Schiff's(AB-PAS)staining was used to observe the thickness of the mucosal layer of gastric tissues,the expressions of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),phosphorylated Akt(p-Akt),and endothelial-type nitric oxide synthase(eNOS)proteins in gastric tissues were detected by protein immunoblotting(Western Blot),and the expression of vascular endothelial growth factor A(VEGFA)protein in gastric tissues was detected by immunofluorescence staining.Results Compared with the normal group,the body mass of rats in the model group grew slowly during the experimental period,gastric macroscopic pathological scores were significantly increased(P＜0.01),splenic coefficient and hepatic coefficient were significantly decreased(P＜0.01),the gastric tissues showed cuprocyte hyperplasia and intestinal chemotaxis,gastric tissues'inflammation scores were significantly increased(P＜0.01),the serum GAS content was significantly increased(P＜0.01),and the MTL,GC contents were significantly reduced(P＜0.05),and the thickness of the mucous membrane layer of gastric tissue was significantly reduced(P＜0.05),the protein expression levels of PI3K,p-PI3K,Akt,p-Akt and eNOS were reduced(P＜0.01),and the protein expression level of VEGFA was reduced(P＜0.01);compared with the model group,the above indexes of the Jianwei Xiaozhang Tablets group and the folic acid group were all significantly improved(P＜0.05 or P＜0.01),among which,the Jianwei Xiaozhang Tablets group had a better improvement effect in the proliferation of cup cells and intestinal chemotaxis in gastric tissues,the content of serum GAS,and the thickness of the mucous layer in gastric tissues.Conclusion The mechanism of the improvement of PLGC in rats by Jianwei Xiaozhang Tablets may be related to the activation of the PI3K-Akt-eNOS pathway,which in turn promotes the angiogenesis and repair of gastric damaged tissues.

Objective To analyse the analgesic effect and possible mechanism of panax notoginseng saponin (PNS) on mouse models of chronic inflammatory pain caused by complete Freund’s adjuvant (CFA). Methods A total of 48 male C57BL/ 6J mice were divided randomly into four groups: normal saline control group (Ctrl), CFA group (CFA), CFA + PNS group (CFA+PNS), CFA + dexamethasone (DEX) group (CFA+DEX). Von Frey filaments were used to detect mechanical pain in mice. Immunohistochemistry was used to detect the number and morphological changes of glial fibrillary acidic protein (GFAP) positive astrocytes. Western blotting was used to detect the expressions of GFAP, nucleotide-binding and oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, interleukin (IL)-1β, and IL-18 in mice’s spinal cord segments in each group. Results Compared with the Ctrl group, mice in the CFA group showed a significant decrease in mechanical pain thresholds at day 1, day 3, day 5, day 7, and day 14. Additionally, there was a significant decrease in NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the spinal cord of the mice. PNS intervention could relieve mechanical pain and down-regulate the expressions of NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the spinal cord of mice, with no significant difference compared with the CFA+DEX group. CFA group mice had significantly more GFAP positive cells in their posterior horns than Ctrl group mice, as measured by immunohistochemistry; PNS intervention decreased the number of GFAP positive cells in the posterior horn of the spinal cord in model mice;DEX had no effect on the number of GFAP positive cells in the dorsal horn of spinal cord. According to Western blotting results, GFAP expression in the spinal cord of the CFA group was significantly more than that of the Ctrl group; PNS intervention significantly reduced GFAP expression in the spinal cord of CFA group mice;DEX had no effect on the expression of GFAP in the posterior horn of spinal cord. Conclusion PNS has a good alleviating effect on inflammatory pain, and its mechanism may be related to inhibition of astrocyte activation and NLRP3 inflammasome activation.

Objective To compare the efficacy and safety of empagliflozin and linagliptin in the treatment of patients with type 2 diabetes mellitus(T2DM)with heart failure(HF).Methods Patients with T2DM and HF were randomly into control group and treatment group.Both groups were treated with individualized anti-HF and metformin-based hypoglycemic therapy.On this basis,the control group was given linagliptin orally(5 mg each time,once a day),while the treatment group was given oral administration of empagliflozin 10 mg every day.Patients in both groups were treated continuously for 6 months.The clinical efficacy and blood glucose indicators[fasting blood glucose(FBG),2 h postprandial blood glucose(2 h PBG),hemoglobin A1c(HbA1c)],cardiac molecular markers[N-terminal pro-brain natriuretic peptide(NT-proBNP),fibroblast growth factor 23(FGF23),copeptin(CPP)]and caridac function indicators[left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),left ventricular remodeling index(LVRI)]before and after treatment were compared,and the adverse drug reactions were recorded.Results There were 40 cases in treatment group and 40 cases in control group.After treatment,the total effective rates in treatment group and control group were 97.50％(39 cases/40 cases)and 80.00％(32 cases/40 cases),with no significant difference(P＜0.05).The FBG levels in treatment group and control group were(7.64±1.18)and(7.83±1.24)mmol·L-1;2 h PBG levels were(8.97±1.46)and(9.04±1.35)mmol·L-1;HbA1c levels were(7.58±1.27)％and(7.65±1.42)％,all with no significant difference(all P＞0.05).The NT-proBNP levels in treatment group and control group were(612.53±204.62)and(1 045.24±316.75)pg·mL-1;FGF23 levels were(362.74±62.61)and(493.27±74.64)μg·L-1;CPP levels were(12.58±3.43)and(16.87±4.36)pmol·L-1;LVEDD values were(51.19±2.36)and(53.35±2.24)mm;LVEF values were(52.69±3.38)％and(50.28±3.75)％;LVRI values were(2.62±0.29)and(2.96±0.33)kg·L-1,all with significant difference(all P＜0.05).The incidence rates of adverse reactions in treatment group and control group were 5.00％(2 cases/40 cases)and 10.00％(4 cases/40 cases),with no significant difference(P＞0.05).Conclusion Both empagliflozin and linagliptin can effectively reduce the blood glucose in patients with T2DM complicated with HF.Empagliflozin can better promote the improvement of cardiac function in patients without significantly increase the incidence of adverse drug reactions.

Objective To investigate the effects of trigonelline combined with aerobic exercise on hyperlipidemia rats and its mechanism.Methods SD rats were randomly divided into control group(normal diet),model group(hyperlipidemia rat model was established by feeding high fat diet),experimental-L,-H groups(high fat diet+15,45 mg·kg-1 trigonelline)and combine group(high fat diet+45 mg·kg-1 trigonelline+aerobic exercise).Each group had 11 rats.Serum lipid metabolism related indexes were detected by automatic biochemical analyzer.Serum levels of 6 ketone prostaglandin F1a(6-keto-PGF1a);the levels of glutamic oxaloacetic transaminase(GOT)in liver tissue were detected by enzyme-linked immunosorbent assay;the mRNA levels of interleukin-1β(IL-1β)in liver tissue were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR);Western blot assay was used to detect the expression of proprotein convertase subtilin/kexin 9 type(PCSK9)and low density lipoprotein receptor(LDLR)protein in liver tissue.Results The serum TC levels in control group,model group,experimental-L group,experimental-H group and combine group were(1.81±0.10),(6.68±0.77),(5.10±0.44),(3.57±0.47)and(2.40±0.35)mmol·L-1;the levels of 6-keto-PGF1a were(841.47±86.74),(536.03±36.50),(664.06±52.44),(759.19±52.30)and(824.45±67.62)pg·mL-1;GOT levels were(11.95±0.88),(18.20±1.81),(15.05±1.10),(13.32±0.98)and(12.47±0.83)U·L-1;IL-1β mRNA expression levels were 1.00±0.09,2.21±0.17,1.57±0.10,1.26±0.16 and 1.14±0.09;the expression of PCSK9 protein were 0.39±0.07,0.88±0.08,0.71±0.08,0.60±0.04 and 0.52±0.07;LDLR protein levels were 1.12±0.13,0.52±0.07,0.74±0.11,0.84±0.08 and 0.96±0.11,respectively.Model group was compared with the control group,experimental-L group and experimental-H group were compared with model group respectively,combine group was compared with the experimental-H group,the differences of the above indexes were statistically significant(all P＜0.05).Conclusion Trigonelline combined with aerobic exercise may inhibit the expression of PCSK9 and up-regulate the expression of LDLR to improve lipid metabolism,so as to play a lipid-lowering role in hyperlipidemia rats.

Objective To investigate the effect and mechanism of rosuvastatin on liver injury induced by high fat diet in hyperlipidemia rats.Methods All rats were randomly divided into control group,model group and experimental group,with 10 rats in each group.Except the control group,hyperlipidiosis model rats were fed with high-fat diet combined with alcohol to construct hyperlipidiosis model rats.The experimental group was given 10 mg·kg-1 rosuvastatin by gavage,control group and model group were given gavage with 10 mL·kg-1 distilled water,once a day for 4 weeks.Serum lipids and liver function were measured by enzyme-linked immunosorbent assay(ELISA).Quantitative real-time polymerase chain reaction(qRT-PCR)was used to analyze the expression of microRNA(miR)-185-3p and mastermind like transcription coactivator 1(MAML1);the expression levels of MAML1 and inducible nitric oxide synthase(iNOS)were detected by Western blot.Results The liver tissue injury scores of control group,model group and experimental group were 0.32±0.15,4.03±1.62 and 2.36±1.14;the TG levels were(4.95±0.86),(6.75±1.42)and(5.51±0.91)mmol·L-1;the TC were(2.36±0.48),(5.11±2.05)and(3.24±1.39)mmol·L-1;the LDL-C were(0.67±0.16),(1.73±0.42)and(1.03±0.25)mmol·L-1;the HDL-C were(0.72±0.23),(0.51±0.14)and(0.64±0.11)mmol·L-1;the GOT were(158.31±32.46),(253.19±49.27)and(187.52±53.46)U·L-1;the GPT values were(53.17±6.81),(79.64±13.92)and(55.63±9.11)U·L-1.Compared with the control group,the expression of miR-185-3p in the model group was significantly down-regulated,the expression of MAML1 and iNOS was significantly increased.Compared with the model group,the expression of miR-185-3p in the liver tissue of experimental group was significantly up-regulated,while the expression of MAML1 and iNOS was significantly decreased(all P＜0.05).There were statistically significant differences in the above indexes between the control group and the model group(P＜0.05);the above data in the model group were statistically significant compared with the experimental group(P＜0.05).Conclusion Rosuvastatin inhibits the expression of MAML1 and iNOS by regulating miR-185-3p,thereby improving the liver injury induced by hyperlipidemia in rats.

Objective To investigate the effect of naringin on hyperlipidemia in mice and to elucidate its mechanism.Methods C57BL/6 mice were randomly divided into control group,hyperlipidemia group and naringin group.Mice in hyperlipidemia group and naringin group were fed high-fat diet for 4 weeks,and hyperlipidemia model was established.The control group was fed normal diet.After successful modeling,naringin group mice were intragastric with 200 mg·kg-1 naringin per day,and mice in control group and hyperlipemia group were intragastric with 0.9％NaCl per day for 5 weeks.The blood of mice was collected for lipid detection.The activities of superoxide dismutase(SOD)and catalase(CAT)and the contents of malondialdehyde(MDA)and glutathione(GSH)were detected by biochemical method.Western blot was used to detect the protein expression.Results The activity of SOD in liver tissue of mice in control group,hyperlipidemia group and naringin group were(58.43±6.27),(37.16±4.10)and(51.23±4.81)U·mg prot-1,respectively;CAT activities were(176.11±13.59),(112.65±10.02)and(158.46±14.37)U·mg prot-1,respectively;the contents of MDA were(3.15±0.74),(12.62±2.07)and(5.76±1.83)U·mg prot-1;the contents of GSH were(91.52±11.47),(34.16±4.62)and(71.64±8.79)U·mg prot-1,respectively;the relative protein expression levels of induced nitric oxide synthase(iNOS)were 0.28±0.05,4.26±1.13 and 0.94±0.19;the relative protein expression levels of adenosine 5'-monophosphate activated protein kinase(AMPK)were 1.32±0.18,0.84±0.11 and 1.49±0.16,respectively;the relative protein expression levels of cholesterol regulatory element binding protein(SREBP)were 1.76±0.24,5.78±1.21 and 2.93±0.42;the relative protein expression levels of 3-hydroxy-3-methyl glutaryl coenzyme A reductase(HMGCR)were 1.69±0.18,6.13±1.38 and 3.26±0.43,respectively.The above indexes in the control group and the naringin group were significantly different from those in the hyperlipidemia group(P＜0.05,P＜0.01,P＜0.001).Conclusion Naringin can effectively regulate the level of blood lipids,inhibit oxidative stress and apoptosis in hyperlipidemia mice,and its mechanism may be related to the regulation of AMPK/HMGCR/SREBP signaling pathway.

Objective To explore the impact of contrast agent concentration on the excimer laser's effect on plaque ablation.Methods Using a laser catheter with a diameter of 0.9 mm,we conducted plaque model ablation experiments employing a 308-nanometer xenon chloride excimer laser.During the excimer laser ablation process,five groups were formed based on the injected contrast agent concentrations:a saline group,25%concentration group,50%concentration group,75%concentration group,and 100%concentration group.Optical coherence tomography was utilized to assess the changes in plaque lumen area after excimer laser ablation,evaluating the impact of contrast agent concentration on the excimer laser's ablation efficacy.Simultaneously,a water manometer was used to measure the shockwave pressure generated by the excimer laser in liquids with different contrast agent concentrations,aiming to explore the correlation between the shockwave pressure of the excimer laser and its ablative effect.Results The ablation areas in the 75%concentration group and the 100%concentration group were similar(P＞0.05),both exceeding those in the 50%concentration contrast agent group,25%concentration group,and saline group(all P＜0.001).Specifically,the ablation area in the 50%concentration group was significantly larger than that in the 25%concentration group and saline group(both P＜0.001),while the 25%concentration group was larger than the saline group(P＜0.001).The influence of contrast agent concentration on the shockwave pressure of the excimer laser exhibited a similar trend.Additionally,there was a significant positive correlation between the shockwave pressure generated by the excimer laser and its ablation area(r=0.9987,P＜0.001).Conclusions The intensity of excimer laser ablation on plaque tissue can be modulated by altering the contrast agent concentration.These findings offer guidance for the application of excimer laser in conjunction with contrast agent injection techniques in the treatment of coronary artery disease.

In recent years, nucleic acid therapy, as a revolutionary therapeutic tool, has shown great potential in the treatment of genetic diseases, infectious diseases and cancer. Lipid nanoparticles (LNPs) are currently the most advanced mRNA delivery carriers, and their emergence is an important reason for the rapid approval and use of COVID-19 mRNA vaccines and the development of mRNA therapy. Currently, mRNA therapeutics using LNP as a carrier have been widely used in protein replacement therapy, vaccines and gene editing. Conventional LNP is composed of four components: ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, which can effectively load mRNA to improve the stability of mRNA and promote the delivery of mRNA to the cytoplasm. However, in the face of the complexity and diversity of clinical diseases, the structure, properties and functions of existing LNPs are too homogeneous, and the lack of targeted delivery capability may result in the risk of off-targeting. LNPs are flexibly designed and structurally stable vectors, and the adjustment of the types or proportions of their components can give them additional functions without affecting the ability of LNPs to deliver mRNAs. For example, by replacing and optimizing the basic components of LNP, introducing a fifth component, and modifying its surface, LNP can be made to have more precise targeting ability to reduce the side effects caused by treatment, or be given additional functions to synergistically enhance the efficacy of mRNA therapy to respond to the clinical demand for nucleic acid therapy. It is also possible to further improve the efficiency of LNP delivery of mRNA through machine learning-assisted LNP iteration. This review can provide a reference method for the rational design of engineered lipid nanoparticles delivering mRNA to treat diseases.