Arachidonic acid can be transformed into a variety of metabolites that trigger an inflammatory response through cyclooxygenase, lipoxygenase, cytochrome P450 enzymes, and other metabolic pathways. Moreover, it plays a key role in the occurrence and development of inflammatory diseases. In recent years, multi-target drugs based on the arachidonic acid metabolic pathway have become an important direction of anti-inflammatory drug research. This article summarizes the opportunities and challenges of arachidonic acid metabolic pathways as well as their interference in the development of anti-inflammatory drugs, reviews the research progress of multi-target drug design, synthesis, and anti-inflammatory activity based on the arachidonic acid metabolic pathway, and discusses the difficulties and prospects of multi-target drugs based on metabolic pathways in anti-inflammatory drug development, aiming to provide some reference and inspiration for the study of multi-target anti-inflammatory drugs based on the arachidonic acid metabolic pathway.

Objective:To discuss the effect of hirudin on post-stroke depression(PSD)in the mice,and to clarify its potential mechanism.Methods:Sixty male C57BL/6 mice were randomly divided into control group,PSD group,PSD+low dose of hirudin group,PSD+medium dose of hirudin group,and PSD+high dose of hirudin group,and there were 12 mice in each group.The stroke model was established by middle cerebral artery occlusion(MCAO),and the depression model was induced by chronic unpredictable mild stress(CUMS)combined with solitary housing.The mice in PSD+low dose of hirudin,PSD+medium dose of hirudin,and PSD+high dose of hirudin groups were intravenously injected with 10,20,and 40 U·kg-1 hirudin,respectively,while the mice in control and PSD groups received equal volumes of saline.The body weights of the mice were recorded on days 0,7,14,and 21 of CUMS.The LONGA neurological function score was calculated.Sucrose preference test,tail suspension test,and forced swimming test were used to detect the sucrose preference rate,immobility time in tail suspension,and forced swimming in various groups,respectively;HE staining was used to observe the histopathological changes in the medial prefrontal cortex(mPFC);biochemical kits were used to detect the levels of malondialdehyde(MDA)and reduced glutathione(GSH)as well as superoxide dismutase(SOD)activity in mPFC tissue of the mice in various groups;2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescence probe method was used to detect the reactive oxygen species(ROS)positive rate in mPFC tissue of the mice in various groups;real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting method were used to detect the expression levels of nucleoredoxin(NXN)mRNA and protein in mPFC tissue of the mice in various groups.Results:Compared with control group,the body weight of the mice in PSD group was significantly decreased on days 0,7,14,and 21 of CUMS(P<0.05 or P<0.01).Compared with PSD group,the body weights of the mice in PSD+low dose of hirudin,PSD+medium dose of hirudin,and PSD+high dose of hirudin groups were significantly increased on days 14 and 21 of CUMS(P<0.05 or P<0.01),and the neurological function scores were significantly decreased(P<0.05 or P<0.01).The sucrose preference test,tail suspension test,and forced swimming test results showed that compared with control group,the sucrose preference rate of the mice in PSD group was significantly decreased(P<0.01),while the immobility times in tail suspension and forced swimming were significantly increased(P<0.01).Compared with PSD group,the sucrose preference rates of the mice in PSD+low dose of hirudin,PSD+medium dose of hirudin,and PSD+high dose of hirudin groups were significantly increased(P<0.05 or P<0.01),and the immobility times were significantly decreased(P<0.05 or P<0.01).The HE staining showed normal cell morphology,clear structure,and uniform size distribution in mPFC tissue in control group.In PSD and PSD+low dose of hirudin groups,the number of the cells in mPFC tissue was significantly reduced,with severe vacuolar degeneration and pyknotic nuclei.Compared with PSD group,the numbers of the cells in PSD+medium dose of hirudin and PSD+high dose of hirudin groups were significantly increased,and the vacuolar degeneration and nuclear pyknosis were alleviated.The Biochemical and DCFH-DA fluorescence probe assays results showed that compared with control group,the GSH level and SOD activity in mPFC tissue of the mice in PSD group were significantly decreased(P<0.01),while the MDA level and ROS positive rate were significantly increased(P<0.01).Compared with PSD group,the GSH levels and SOD activities of the mice in PSD+low dose of hirudin,PSD+medium dose of hirudin,and PSD+high dose of hirudin groups were significantly increased(P<0.05 or P<0.01),while the MDA levels and ROS positive rates were significantly decreased(P<0.05 or P<0.01).The RT-qPCR and Western blotting results showed that compared with control group,the expression levels of NXN mRNA and protein in mPFC tissue of the mice in PSD group were significantly decreased(P<0.01).Compared with PSD group,the expression levels of NXN mRNA and protein in mPFC tissue of the mice in PSD+low dose of hirudin,PSD+medium dose of hirudin,and PSD+high dose of hirudin groups were significantly increased(P<0.05 or P<0.01).Conclusion:Hirudin promotes redox balance in mPFC of the PSD mice,repairs neurological damage,and improves PSD.

Objective To investigate the neuroprotective effect of Tibetan medicine 70 Wei Pearl Pill(RNSP)on 6-hydroxydopamine(6-OHDA)induced Parkinson's disease model rats and its related mechanism.Methods Totally 48 male SD rats were randomly divided into control group,model group,model plus low-dose RNSP group(90 mg/kg),model plus medium-dose RNSP group(180 mg/kg),model plus high-dose RNSP group(360 mg/kg),and model plus madopar group(50 mg/kg),with 8 rats in per group.Except for the control group,the other rats were treated with 6-OHDA single injection into the striatum to establish the PD model.Each group was given intragastric administration after modeling and the control group and model group were given an equal volume of saline once a day for 4 weeks.The rats were subjected to apomorphine-induced rotation,experiments at the 2nd and 4th week after the completion of modeling,and the open field experiment was conducted the next day after the last rotation experiment to observe the animal behavior.After the behavioral experiment,the rats were stained with tyrosine hydroxylase(TH)in the substantia nigra pars compacta by immunohistochemical method and the positive neurons were counted.The protein levels of Bcl-2,BAX,Caspase-3 in substantia nigra and P38,P-P38,ERK,P-ERK,JNK,P-JNK in the striatum were detected by Western blotting.Results Compared with the control group,the rotation frequency and percentage of rotating rats in the model group increased significantly at the 2nd and 4th weeks after modeling;the open field active distance,average speed and times of crossing the grid were significantly decreased;and the rest time was significantly increased.While the number of TH positive neurons in the substantia nigra was significantly decreased,the BAX and Caspase-3 protein levels were increased significantly,Bcl-2 was decreased significantly,the ratios of P-P38/P38,P-JNK/JNK and P-ERK/ERK in the striatum were significantly increased in PD group.Compared with the model group,the rotation frequency and percentage of rotating rats in the low-,medium-and high-dose groups of RNSP had no significant changes after 2 weeks of administration,the rotation frequency in the high-dose group and percentage of rotating rats in the low-and medium-dose RNSP groups significantly decreased after 4 weeks of administration.The open field active distance,average speed,and times of crossing the grid were significantly increased;the rest time was significantly decreased.The number of TH positive neurons in the substantia nigra was significantly increased,the Bax and Caspase-3 protein levels were decreased significantly while the Bcl-2 was significantly increased.The ratios of P-P38/P38,P-JNK/JNK and P-ERK/ERK in the striatum were significantly decreased.Conclusion Tibetan medicine RNSP can improve the motor ability and reduce the loss of DA neurons in PD rats,and its mechanism may be related to inhibiting P38/JNK/ERK signaling pathway and reducing the apoptosis of midbrain neurons.

Objective:To investigate the clinical characteristics of urea cycle disorder (UCD), the efficacy and safety of glyceryl phenylbutyrate (GPB) therapy in pediatric patients with UCD.Methods:This study was a retrospective, single-arm, multicenter clinical study. The clinical data of 20 pediatric patients with UCD who received GPB treatment at 9 hospitals nationwide between December 2021 and August 2024 were collected. The clinical manifestations, laboratory results, and molecular genetic characteristics were analyzed, ammonia levels and other laboratory results were evaluated pre-post GPB therapy by paired t-tests or Wilcoxon tests. Results:Among the 20 pediatric patients with UCD, there were 8 males and 12 females, and the onset age was 2.8 (1.4, 5.7) years. The ammonia levels were 174 (125, 342) μmol/L at first onset. The symptoms included vomiting in 6 cases, drowsiness in 5 cases, epilepsy in 5 cases, developmental delay in 5 cases, psychiatric and behavioral abnormalities in 3 cases, and lethargy in 1 case, and 18 cases exhibited abnormal liver function. Twenty cases included 6 UCD subtypes, with 11 cases being ornithine transcarbamylase deficiency. A total of 27 variants were identified, 11 (41%) of which were novel. The age of patients who began GPB therapy was 4.0 (1.5, 6.6) years. Ten cases stopped GPB after 4.2 (3.4, 5.3) months, with 4 patients undergoing liver transplantation and 6 discontinuing for financial reasons. The remaining ten patients continued GPB therapy for 11.6 (8.6, 14.0) months. The duration of GPB treatment was 6.0 (4.2, 12.3) months, at the final visit, the levels of ammonia, platelets and aspartate aminotransferase were lower compared to those of pre-treatment (all P<0.05). The serum albumin level was higher than that of pre-treatment ( P=0.016). Two patients suffered only one episode of acute hyperammonaemia, with ammonia levels of 232 and 141 μmol/L, respectively. Nine cases experienced adverse effects potentially related to GPB, decreased appetite in 6 cases, vomiting in 3 cases, abnormal skin oil odor in 2 cases, somnolence, fatigue and diarrhea each in 1 case, with symptoms improved within 6 (3, 10) days. Conclusions:UCD primarily manifests with neurological and gastrointestinal symptoms, and early diagnosis of UCD could be achieved through the analysis of ammonia. GPB may effectively reduce ammonia levels in UCD pediatric patients, with favorable safety and tolerability.

Objective:To investigate and evaluate the clinical efficacy and safety of a modified anterior approach for transpupillary silicone oil removal combined with phacoemulsification and intraocular lens (IOL) implantation.Methods:A retrospective case-control study. A total of 148 patients (148 eyes) who underwent silicone oil removal combined with cataract surgery at the Department of Ophthalmology, Guangdong Provincial People's Hospital between January 2020 and November 2024 were included in the study. All affected eyes underwent preoperative examinations including best-corrected visual acuity (BCVA), intraocular pressure, corneal topography, and optical coherence tomography (OCT). Based on the method of silicone oil removal, the eyes were divided into two groups: group A (modified anterior approach transpupillary silicone oil removal combined with phacoemulsification and IOL implantation, 99 eyes) and group B (standard pars plana vitrectomy for silicone oil removal combined with phacoemulsification and IOL implantation, 49 eyes). The surgical duration, changes in BCVA and intraocular pressure at 1 day, 7 days, and 1 month postoperatively, as well as the incidence of complications such as corneal edema and its resolution, conjunctival congestion, iris prolapse, posterior capsule rupture, nucleus drop, IOL position, residual silicone oil in the vitreous cavity or anterior chamber, vitreous hemorrhage, recurrent retinal detachment (RD), and choroidal detachment or hemorrhage, were compared between the two groups. The independent sample t-test was used for the comparison of measurement data between the two groups, and the χ2 test was used for the comparison of count data. Results:The operation time of group A and group B was (17.01±1.28) min and (31.62±2.32) min, respectively. The operation time of group A was significantly shorter than that of group B, and the difference was statistically significant ( t=?41.002, P<0.001). The comparison of BCVA ( t =?0.561, ?0.833, ?1.386) and IOP ( t=?0.055, 1.375, ?0.507) between the two groups of affected eyes before surgery and at 1 day and 7 days after surgery showed no statistically significant differences ( P>0.05). There was no silicone oil residual in group A, while 3 eyes in group B were observed with silicone oil residual (6.1%, 3/49). Neovascular glaucoma was observed in one eye. Compared to group A, group B exhibited a statistically significant increase in the incidence of postoperative conjunctival congestion, silicone oil retention, and posterior capsular opacification ( χ2=10.600, 6.187, 92.617; P<0.05). In contrast, no statistically significant differences were observed between the groups in the incidence of corneal edema or recurrent retinal detachment (RD) ( χ2=0.272, 1.557; P>0.05). No intraoperative complications, such as iris prolapse, posterior capsular rupture, nucleus drop, zonular dehiscence, choroidal detachment, or hemorrhage, occurred in any of the operated eyes. Furthermore, no postoperative complications, including corneal endothelial decompensation, IOL displacement, or endophthalmitis, were observed during the follow-up period. Conclusion:Compared to the conventional pars plana approach for silicone oil removal combined with cataract surgery, the modified anterior perfusion transpupillary approach demonstrated significantly shorter surgical duration and a reduced incidence of postoperative complications.

Objective:To explore the correlation between the oxygenation index and the monitored parameters of lung injury view in ventilator,so as to provide a basis for monitoring the change of oxygenation index by the parameters of lung injury view.Methods:A total of 28 patients who received mechanical ventilation treatment and admitted to respiratory department of the First Affiliated Hospital with Nanjing Medical University from May 14 to September 30,2024 were selected.The monitored parameters of lung injury views of them during mechanical ventilation treatment with invasive ventilators were collected,including platform pressure(Pplat),driving pressure(ΔP),mechanical energy(Emech),ratio of tidal volume to ideal body weight(TVe/IBW),etc..Then,the data of oxygenation index were obtained.Finally,135 valid data were screened out.The 84 pieces of data with oxygenation index≤300mmHg were included in low oxygen group,and 51 data with oxygenation index>300mmHg were included in normal group.The correlations between oxygenation index and Pplat,ΔP,Emech,TVe/IBW were conducted by pairwise analysis.Results:In the low oxygen group,the oxygenation index was[(196.302±74.522)mmHg]significantly negative correlation with Emech[(12.686±5.401)J/min](ρ=-0.425,P<0.05),but not was significant correlation with Pplat,ΔP,and TVe/IBW(P>0.05).In the normal group,there were not significant correlations between the oxygenation index and Pplat,ΔP,Emech and TVe/IBW(P>0.05).There was a significant negative correlation between Emech and rank of oxygenation index(β=-0.389,P<0.05)in the low oxygen group.Conclusion:The visualization function of the Emech of the monitored parameters in lung injury view of ventilator can provide help for monitoring the changes of oxygenation index of patients in the low oxygen group,and can improve the oxygenation of patients by optimizing mechanical energy.However,it is necessary to balance the contradiction between ventilation intensity and protection for lung.

Objective To investigate the diagnostic value of combined clinical imaging model in deep infiltrating endometriosis of uterosacral ligaments(USL-DIE).Methods The preoperative clinical symptoms,signs,transvaginal ultrasound(TVS)and MRI diagno-ses of 102 DIE patients were reviewed and subjected to univariate analysis,and the significant variables were screened and included in the multivariable logistic regression analysis to construct a combined clinical imaging model.The diagnostic value of statistically signifi-cant factors and combined model was assessed and compared using receiver operating characteristic(ROC)curve.Results The inci-dence of USL nodule with tenderness,the detection rates of TVS and MRI for USL-DIE were higher than those of other patients with DIE,and the differences were statistically significant.TVS(P=0.021)and MRI(P<0.001)were independent factors in the diag-nosis of USL-DIE.The combined clinical imaging model had the highest area under the curve(AUC)(0.909)and specificity(0.929)for the diagnosis of USL-DIE.Conclusion The combined clinical imaging model has a higher value for the comprehensive diagnosis of USL-DIE compared with clinical or imaging diagnosis alone.

Objective To explore the effects of physical activity(PA)on carotid intima-media thickness(CIMT)thickening in patients with type 2 diabetes mellitus(T2DM)with poor HbA1c control.Methods A total of 2505 T2DM inpatients with poor HbA1c control who visited the Endocrinology Department of the Integrated Traditional Chinese and Western Medicine Hospital Affiliated with Nanjing University of Traditional Chinese Medicine and Changzhou Second People's Hospital Affiliated with Nanjing Medical University from January 2019 to February 2022 were enrolled in this study.The patients were categorized into the mild-intensity PA(1～599 MET-min/w,n=795),moderate-intensity PA(600～1499 MET-min/w,n=1107)and high-intensity PA(≥1500 MET-min/w,n=603)based on the metabolic equivalence level(MET).Logistic regression was performed to analyze the relationship between PA and CIMT thickening.Statified analysis was used to investigate the effects of blood pressure(BP)and low-density lipoprotein cholesterol(LDL-C)target status on CIMT thickness in different PA groups.Results Restricted cubic spline plots showed a nonlinear relationship between PA levels and the risk of CIMT thickening(P<0.05).Logistic regression showed that with moderate-intensity PA as the control,while high-intensity PA was the influence factor of CIMT thickening(OR 1.581,95%CI 1.244～2.010,P<0.05).Statified analyses showed that under mild-intensity PA,using neither BP nor LDL-C on target as reference,achievement of either index and both were the influence factor of CIMT thickening.Using BP on target as reference,achievements of both indexes,achievements of neither of both indexes,and achievement of LDL-C only were the influence factor of CIMT thickening.Using LDL-C on target as reference,achievement of neither of them and achievement of BP only were the influence factor of CIMT thickening.Under high-intensity PA,achievement of both indexes was negatively associated with CIMT thickening.Conclusions Moderate-intensity PA is the recommended scheme to prevent CIMT thickening in T2DM patients whose HbA1c is not up to standard.Mild-intensity PA is not related to the risk of CIMT thickening,while high-intensity PA is positively related to the risk of CIMT thickening,and focusing on LDL-C compliance is particularly important to avoid CIMT thickening.

Objective To investigate whether the pyroptosis-related Toll-like receptor 4(TLR4)signaling pathway influences the malignant transformation of actinic keratosis(AK)into cutaneous squamous cell carcinoma(SCC).Methods A total of 6 lesion tissue samples each from patients with AK and SCC,as well as 5 normal skin tissue samples from healthy subjects as controls,were collected from the First Affiliated Hospital of Kunming Medical University between August 2020 and August 2021.Quantitative PCR(qPCR)and Western blot analysis were performed to determine the mRNA and protein expression levels of TLR4 pathway-related factors,including TLR4,CPB1,NLRP3,IL-1β,and IL-18.TLR4/TUNEL double immunofluorescence staining was used to evaluate TLR4 expression and the level of cellular pyroptosis in tissue samples.In addition,Western blotting was performed to analyze the expression differences of pyroptosis-related core proteins(pro-caspase-1,cleaved caspase-1/p20,GSDMD,and cleaved N-terminal GSDMD)and TLR4 among the normal keratinocyte cell line HaCaT and SCC cell lines A431 and SCL-1.Results Quantitative PCR and Western blot results showed that the mRNA and protein expression levels of TLR4,CPB1,NLRP3,IL-1β,and IL-18 were significantly higher in SCC tissues than in AK and normal skin tissues(P<0.05).TLR4/TUNEL double immunofluorescence results revealed a progressive increasing trend in TLR4 expression and pyroptosis levels from normal skin to AK and further to SCC(P<0.05).Furthermore,in SCL-1 cells,the expression levels of pro-caspase-1,cleaved caspase-1/p20,cleaved N-terminal GSDMD,and TLR4 were significantly upregulated(P<0.05),whereas in A431 cells,only TLR4 expression was increased(P<0.05),and the levels of other pyroptosis-related proteins were downregulated compared to HaCaT cells(P<0.05).Conclusion The expression of the TLR4 signaling pathway gradually increased from AK to SCC,and its activation status varied among different cutaneous squamous cell carcinoma cell lines.

Objective To explore the change of serum chloride ion(Cl-)level and its relationship with prognosis in patients with acute heart failure(AHF).Methods A total of 289 patients with AHF admitted to the hospital from September 2020 to March 2023 were included in the study.Clinical and laboratory data of patients were collected,serum Cl-levels were detected at admission and discharge,and the difference of Cl-levels was calculated(△Cl-).Patients with AHF were divided into poor prognosis group and good prognosis group according to the incidence of adverse cardiovascular events during follow-up.Clinical and laboratory data of the two groups were compared.Logistic regression analysis was used to analyze the relationship between se-rum △Cl-level and poor prognosis of AHF by using restricted cubic spline(RCS)curve drawn by the func-tions in the rms package.Receiver operating characteristic(ROC)curve was plotted to analyze the value of△Cl-levels in predicting the risk of adverse cardiovascular events within 1 year of discharge from hospital in patients with AHF.Results The age and the proportion of patients with atrial fibrillation in the poor progno-sis group were higher than those in the good prognosis group,and the difference was statistically significant(P＜0.05).The levels of left ventricular ejection fraction(LVEF)and Cl-at discharge in the poor prognosis group were lower than those in the good prognosis group,and the levels of brain natriuretic peptide(BNP)and △Cl-in the poor prognosis group were higher than those in the good prognosis group,with statistical sig-nificance(P＜0.05).Logistic regression analysis showed that LVEF was an independent protective factor for poor prognosis of AHF,and age,BNP and △Cl-levels were independent risk factors for poor prognosis of AHF(P＜0.05).RCS curve analysis showed a significant linear association between △Cl-levels and the risk of adverse cardiovascular events in patients with AHF within 1 year of discharge.ROC curve analysis showed that the area under the curve of △Cl-level in predicting the risk of adverse cardiovascular events in AHF pa-tients within 1 year after discharge was 0.857,the sensitivity was 88.37％,and the specificity was 69.46％.Conclusion The change of serum Cl-level of patients with AHF is related to the prognosis of patients with AHF,and monitoring the serum Cl-level of patients with AHF can guide the early clinical intervention.