OBJECTIVE To study the effects of enteral immune microecological nutrition combined with ω-3 fish oil fat emulsion on postoperative recovery， immune function， liver function and inflammation level in patients with hepatocellular carcinoma resection， as well as the safety of the medication. METHODS A total of 106 patients with hepatocellular carcinoma admitted to our Hospital from June 2020 to December 2023 were selected and divided into control group and study group according to the random number table method， with 53 cases in each group. After undergoing hepatocellular carcinoma resection， control group was given Intacted protein enteral nutrition solution+Enhanced enteral immune microecological nutrition， and the study group was given ω-3 fish oil fat emulsion injection based on the control group. The clinical indicators （postoperative exhaust time， defecation time， postoperative ambulation， and hospital stay）， liver function indicators [alanine transaminase （ALT）， lactate dehydrogenase （LDH）， aspartate transaminase （AST）]， immune function indexes （CD3+ ， CD4+ ， CD8+ ， CD4+/CD8+）， inflammatory factor indexes [tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， IL-6， IL-8]， and indicators of intestinal mucosal barrier [D-lactic acid， intestinal fatty acid binding protein （I-FABP）] were compared between 2 groups， and the occurrence of ADR was recorded. RESULTS Compared with the control group， the postoperative exhaust time， postoperative defecation time， and hospital stay of the study group were shortened significantly， and postoperative ambulation increased significantly （P＜0.05）. After treatment， ALT， LDH， AST， CD8+， inflammatory factors， D-lactic acid and I-FABP of 2 groups were significantly lower than before treatment， and the study group was significantly lower than the control group （P＜0.05）； CD4+， CD3+， and CD4+/CD8+ of two groups were significantly higher than before treatment， and the study group was significantly higher than the control group （P＜0.05）. There was no significant difference in the incidence of ADR between 2 groups （P＞0.05）. CONCLUSIONS Enteral immune microecological nutrition combined with ω-3 fish oil fat emulsion injection can shorten the recovery time of patients after hepatocellular carcinoma resection， improve immune function， reduce inflammatory response， and improve liver function with good safety.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective To investigate the effects of Rhodojaponin Ⅲ on cartilage injury in post-traumatic osteoarthritis rats and its mechanism.Methods SD rats were randomly divided into sham operation group,model group(based on cruciate ligamentectomy),low dose experimental group(after modeling,0.12 mg·kg-1 Rhodojaponin Ⅲ was given by intragastric administration),high dose experimental group(after modeling,0.24 mg·kg-1 Rhodojaponin Ⅲ was given by intragastric administration),positive drug group(2 mL/100 g glucosamine sulfate was given intragastric administration after modeling).Ten rats in each group were given continuous intragastric administration for 28 days,blood was collected from the heart,and cartilage tissue was taken from the rats.Mankin's score method was used to analyze the cartilage tissue of rats in each group,Western blot method was used to detecte the proteins level,enzyme-linked immunosorbent assay(ELISA)test was used to detect the expression level of serum bone formation indexes and related factors in cartilage tissue,and kit method was used to detect the expression of oxidative stress related indexes.Results The Mankin's scores of sham operation group,model group,low dose experimental group,high dose experimental group and positive drug group were 0.10±0.30,5.30±0.46,4.00±0.63,3.10±0.54 and 1.50±0.81;bone gla protein(BGP)level were(10.25±0.77),(2.39±0.34),(4.87±0.27),(7.99±0.51)and(8.55±0.71)ng·mL-1;the expression levels of cleaved cysteine aspartate proteinase-3(Cl-caspase-3)protein were 0.25±0.02,0.86±0.06,0.65±0.05,0.47±0.04 and 0.33±0.03;superoxide dismutase(SOD)activity were(109.07±7.51),(60.24±5.73),(67.99±4.73),(76.16±8.84)and(80.11±3.96)U·mg-1;the protein levels of nuclear transcription factor E2 related factors(Nrf2)were 1.03±0.08,0.33±0.04,0.43±0.05,0.75±0.10 and 0.74±0.09;heme oxygen-1(HO-1)protein expression levels were 0.88±0.08,0.27±0.04,0.39±0.04,0.56±0.10 and 0.58±0.06,respectively.Model group compared with sham operation group,low dose experimental group,high dose experimental group compared with model group;low dose experimental group compared with high dose experimental group,the differences of the above indexes were all statistically significant(all P＜0.05).Conclusion Rhodojaponin Ⅲ may inhibit oxidative stress,inflammatory response,regulate bone metabolism and improve cartilage injury in post-traumatic osteoarthritis rats by activating Nrf2/HO-1 pathway.

Objective To study the role of sphingosine-1-phosphate(S1P)signal on the proliferation of breast cancer BT549 cells.Methods Cells were divided into control group and experimental group,experimental group were treated with 0.1,1.0,10.0 μmol·L-1 S1P receptor agonist SEW2871 for 72 h.Control group was cultured with 0.1％fetal bovine serum.Cell proliferation was detected by methyl thiazolyl tetrazolium(MTT)assay.Cell models of overexpressing S1P receptors in BT549 were divided into three groups:blank plasmid group(LUC),wild type S1P receptor overexpression group(WT),S1P receptor phosphorylation site mutation overexpression group(MUT);the proliferation ratio was detected by MTT,the number of cell clones was counted by colony formation experiment.S1P antagonist W146(10 μmol·L-1)and protein kinase(AKT)signaling inhibitor MK2206(90 nmol·L-1)were used to detect the role of S1P signaling in the proliferation of breast cancer cells.The expression of phosphorylate signal transducer and activator of transcription 3(p-STAT3),c-Myc proteins were detected by Western blot.Results The growth ratio of BT549 cells in control group and 0.1,1.0,10.0 μmol·L-1experimental groups were 1.00±0.03,1.13±0.06,1.06±0.10 and 1.07±0.03,0.1 μmol·L-1 SEW2871 promot the cell proliferation(P＜0.05).Compared between WT group,MUT group and LUC group,the growth rate and the number of clonal colonies were increased after overexpression of S1P receptor(all P＜0.05).The growth ratio of BT549 cells after treatment with W146 and MK2206 in the LUC group,WT group and MUT group were 1.25±0.12,1.31±0.03,1.43±0.14 and 0.87±0.15,0.77±0.03,0.88±0.02.Compared between MUT group,WT group and corresponding DMSO group,the differences were statistically significant(all P＜0.01).The number of cell clony formation number after treatment with W146 were 65.65±5.12,141.48±5.63 and 93.64±5.14;compared between MUT,WT group and corresponding DMSO group,the differences were statistically significant(all P＜0.05).The relative protein expression levels of p-STAT3 in LUC group,WT group and MUT group were 0.67±0.04,0.69±0.08 and 0.81±0.06,the relative protein expression levels of proto-oncogene c-Myc were 1.69±0.03,0.70±0.10 and 0.67±0.07,compared between WT group,MUT group and corresponding DMSO group,the difference was statistically significant(P＜0.05).Conclusion S1P signaling can promote proliferation in breast cancer BT549 cells,and the mechanism could be related to AKT and STAT3 signaling pathway.

Adequate inflammation can effectively eliminate harmful substances and prevent disease as a self-protective measure to prevent further damage to the body,while abnormally activated inflammation is detrimental to the body.Nucleotide binding and oligomerization domain-like receptor protein 3(NLRP3)inflammasome that participates in inflammatory responses are closely related to many physiological and pathological processes and play an important role in the occurrence and development of pulmonary diseases.This article mainly reviewed the activation mechanism and hypothesis of NLRP3 inflammasome,as well as the research on treating respiratory diseases by interfering with NLRP3 inflammasome.

Objective To evaluate the characteristics of the mass balance and pharmacokinetics of[14 C]birociclib in Chinese male healthy volunteers after a single oral administration.Methods This study used a 14 C labeled method to investigate the mass balance and biological transformation of birociclib in human.Subjects were given a single oral dose of 360 mg/50 pCi of[14 C]birociclib suspension after meals.The blood,urine,and fecal samples were collected at specified time points/intervals after administration.The radiation levels of 14 C labeled birociclib-related compounds in the blood,plasma,urine,and feces were analyzed using liquid scintillation counting.In addition,a combination of high-performance liquid chromatography and on-line/off-line isotope detectors was used to obtain radioactive isotope metabolite spectra of plasma,urine,and fecal samples,and high-resolution mass spectrometry was used to identify the main metabolites.Results A total of 6 healthy male subjects were enrolled in this study.The median peak time of radioactive components in plasma was 5.00 h and the average terminal elimination half-life was 43.70 h after administration.The radioactive components were basically excreted and cleared from the body within 288.00 hours after administration,and average cumulative recovery rate of radioactive drugs was(94.10±8.19)％.The radioactive drugs were mainly excreted through feces,accounting for(84.60±7.10)％of the dose of radioactive drugs administered.Urine was the secondary excretory pathway,accounting for 9.41％of the dose of radioactive drugs administered.Metabolic analysis indicated that the prototype drug was the main radioactive components in plasma samples.The main metabolites in plasma were RM4(XZP-5286),RM6(XZP-3584),and RM7(XZP-5736).The drugs were mainly cleared from the body in the form of prototype drugs and metabolites.In addition to prototype drugs,a total of 9 metabolites were identified and analyzed in plasma,urine,and fecal samples,all of which were phase 1 metabolites.The main metabolic and clearance pathways of drugs in the body were deethylation,diisopropylat ion,oxidation,etc.Conclusion After a single oral administration of[14C]birociclib suspension to healthy subjects,it was mainly cleared from the body in the form of prototype drugs and metabolites,with feces as the main excretory pathway and urine as the secondary excretory pathway.Drugs mainly undergo metabolic reactions in the body,such as deethylation,diisopropylation,and oxidation.The subjects were well tolerance after administration.

BACKGROUND:CXC motif chemokine 5(CXCL5)is a neutrophil activating peptide derived from epithelial cells,which may be involved in arterial diseases.However,there is yet no report on the effect of CXCL5 in vascular calcification. OBJECTIVE:To explore the role of CXCL5 in the vascular calcification of carotid atherosclerosis(CAS). METHODS:(1)Cytological experiment:Mouse vascular smooth muscle cells(VSMCs)were divided into five groups:osteogenic medium group,Vector group(vector,blank plasmid transfected into VSMCs),CXCL5 group(CXCL5 plasmid transfected into VSMCs),si-NC group(CXCL5 negative control siRNA transfected into VSMCs),si-CXCL5 group(CXCL5 siRNA transfected into VSMCs),Vector+LY2157299 group and CXCL5+LY2157299 group(LY2157299 transferred into the cells 24 hours after cell transfection).Alizarin red staining,alkaline phosphatase staining,and calcium content determination were performed to evaluate the osteogenic differentiation level of VSMCs.(2)Animal experiment:Forty-eight ApoE-/-mice were randomly divided into four groups(n=12 per group):Con+si-NC group,Con+si-CXCL5 group,CAS+si-NC group and CAS+si-CXCL5 group.Animal models were not prepared in the first two groups,in which si-NC or si-CXCL5 lentivirus was injected into the tail vein;carotid atherosclerosis models were made in the latter two groups,in which si-NC or si-CXCL5 lentivirus was injected into the tail vein.Von Kossa staining and immunohistochemical staining were used to evaluate carotid vascular calcification and the expression of CXCL5 and transforming growth factor-β receptor 1(TGFBR1)in mice. RESULTS AND CONCLUSION:In the CXCL5 group,the protein level of runt-related transcription factor 2(RUNX2)was up-regulated and the level of α-smooth muscle actin was down-regulated,in contrary to the findings in the si-CXCL5 group.In addition,CXCL5 overexpression upregulated the level of TGFBR1,while CXCL5 knockdown inhibited the level of TGFBR1.Compared with the Vector group,the intensity of alizarin red staining,alkaline phosphatase activity and calcium content in the CXCL5 group increased significantly(P<0.05).Compared with the si-NC group,the intensity of alizarin red staining,alkaline phosphatase activity and calcium content in the si-CXCL5 group decreased significantly(P<0.05).When LY2157299 inhibited TGFBR1 expression,the osteogenic differentiation of VSMCs induced by CXCL5 was reduced.Compared with the Con+si-NC group,the expression of CXCL5 protein in the carotid artery and calcification area in the CAS+si-NC group increased significantly(P<0.05).Compared with the CAS+si-NC group,the expression of CXCL5 protein in the carotid artery and vascular calcification area in the CAS+si-CXCL5 group decreased significantly(P<0.05).In addition,compared with the Con+si-NC group,the expression of RUNX2 protein in the carotid artery in the CAS+si-NC group increased significantly(P<0.05),while the expression of α-smooth muscle actin protein decreased significantly(P<0.05).Compared with the CAS+si-NC group,the expression of RUNX2 protein in the carotid artery in CAS+si-CXCL5 group decreased significantly(P<0.05),while the expression of α-smooth muscle actin protein increased significantly(P<0.05).In conclusion,CXCL5 can induce osteogenic transformation of VSMCs by activating the TGFBR1 pathway,and inhibition of CXCL5 expression is effective in improving carotid arterial calcification in CAS mice.

OBJECTIVE: To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments. METHODS: A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed. RESULTS: FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05). CONCLUSION FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.
Mice ; Animals ; Mitogen-Activated Protein Kinase 14/metabolism* ; Wolfiporia ; Lipopolysaccharides/pharmacology* ; Sepsis/complications* ; Signal Transduction ; Inflammation/drug therapy* ; Oxygen Radioisotopes

Eighteen compounds were isolated from the methanol extract of the fruits of Litsea cubeba by silica gel, ODS, Sephadex LH-20 column chromatography, semi-preparative RP-HPLC, chiral HPLC and recrystallization. Their structures were elucidated by spectroscopic analyses and by comparison with reported spectroscopic data and physicochemical properties, and the absolute configurations of the enantiomers were established by experimental and calculated electronic circular dichroism spectra. These compounds were identified as (+)-(R)-4-hydroxypiperitenone (1a), (-)-(S)-4-hydroxypiperitenone (1b), (3S,4S,6R)-3,6-dihydroxy-1-menthene (2), (4S,5R)-4-hydroxy-5-isopropyl-2-methylcyclohex-2-en-1-one (3), (R)-6-hydroxy-3-(2-hydroxypropan-2-yl)-6-methylcyclohex-2-enone (4), (4S,6R)-4-hydroxy-6-isopropyl-3-methylcyclohex-2-enone (5), (1R,3S,4R)-3-hydroxy isopulegol (6), subamone (7), (6S)-3,7-dimethyl-7-hydroxy-2(Z)-octen-6-olide (8), (6S)-6,7-dihydroxy-3,7-dimethyloct-2(Z)-enoate (9), holostylactone (10), sesamin (11), dimethylmatairesinol (12), p-hydroxybenzoylcarbinol (13), syringaldehyde (14), p-hydroxybenzaldehyde (15), 4-hydroxy-3-methoxybenzaldehyde (16), 5,4ʹ-dihydroxy-7-methoxyflavone (17). Among them, compounds 1a and 1b were a pair of new monoterpenoid enantiomers, 8 and 9 were new natural products, 2-7, 10, 11 and 17 were isolated from Litsea genus for the first time. The in vitro anti-inflammatory effects of compounds 1-17 were evaluated using lipopolysaccharide-stimulated RAW264.7 cells, the results showed that compound 14 exhibited significant anti-inflammatory activity with NO inhibitory rate of 66.27% at a concentration of 40 μmol·L^-1.

Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.