ObjectiveTo investigate the mechanism of ferroptosis mediated by long-chain acyl-CoA synthetase 4 （ACSL4） signalling pathway in rats with coronary heart disease with blood stasis syndrome and the intervention effect of Xuefu Zhuyutang. MethodsSPF male SD rats were randomly divided into normal group， sham-operation group， model group， trimetazidine group （5.4 mg·kg^-1）， low-， medium-， and high-dose group （3.51， 7.02，14.04 g·kg^-1） of Xuefu Zhuyutang. The coronary artery left anterior descending ligation method was used to prepare a model of coronary heart disease with blood stasis syndrome， and continuous treatment for 7 d was conducted， while the sham-operation group was only threaded and not ligated. The general macroscopic symptoms of the rats were observed， and indicators such as electrocardiogram， echocardiography， and blood rheology were detected. The pathological morphology of myocardial tissue was observed by hematoxylin-eosin （HE） staining， and the changes in mitochondria in myocardial tissue were observed by transmission electron microscopy. The level of iron deposition in myocardial tissue was observed by Prussian blue staining. The levels of 12-hydroxyeicosatetraenoic acid （12-HETE） and 15-HETE were detected in serum by enzyme-linked immunosorbent assay. A biochemical colourimetric assay was used to detect the levels of Fe²⁺， lipid peroxidation （LPO）， glutathione （GSH）， and T-GSH/glutathione disulfide （GSSG） in myocardial tissue. DCFH-DA fluorescence quantitative assay was employed to detect the levels of reactive oxygen species （ROS）. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was adopted to detect the protein and mRNA expressions of glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， ACSL4， and ly-sophosphatidylcholine acyltransferase3 （LPCAT3） in myocardial tissue. ResultsCompared with those in the normal group， the rats in the model group were poor in general macroscopic symptoms. The electrocardiogram showed widened QRS wave amplitude and increased voltage， bow-back elevation of the ST segments， elevated T waves， J-point elevation， and accelerated heart rate. Echocardiography showed a significant reduction in left ventricular ejection fraction （LVEF） and left ventricular fraction shortening （LVFS） （P<0.01）. Blood rheology showed that the viscosity of the whole blood （low， medium， and high rate of shear） was significantly increased （P<0.01）. HE staining showed an abnormal structure of myocardial tissue. There was a large area of myocardial necrosis and inflammatory cell infiltration and a large number of connective tissue between myocardial fibers. Transmission electron microscopy showed that the mitochondria were severely atrophy or swelling. The cristae were reduced or even broken， and the matrix was flocculent or even vacuolated. Prussian blue staining showed that there were a large number of iron-containing particles， and the iron deposition was obvious. The content of 12-HETE and 15-HETE in the serum was significantly increased （P<0.01）. The content of Fe²⁺， LPO， and ROS in myocardial tissue was significantly increased （P<0.01）. The content of GSH was significantly decreased （P<0.01）， and T-GSH/GSSG was decreased （P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 in myocardial tissue were both significantly decreased （P<0.05， P<0.01）， while those of ACSL4 and LPCAT3 increased significantly （P<0.01）. Compared with the model group， the general macroscopic symptoms and electrocardiogram results of rats in low-， medium- and high-dose groups of Xuefu Zhuyutang were alleviated， and the differences in LVEF/LVFS ratios were all significantly increased （P<0.05， P<0.01）. The differences in whole-blood viscosity （low， medium， and high rate of shear） were all significantly decreased （P<0.01）. The results of HE staining and transmission electron microscopy showed that the morphology， structure， and mitochondria of cardiomyocytes were improved. The content of 12-HETE and 15-HETE in serum was reduced to different degrees in low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. The content of Fe²⁺， LPO， and ROS was significantly reduced in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and the content of GSH and T-GSH/GSSG was significantly increased （P<0.05， P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 were significantly increased to varying degrees in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and ACSL4 and LPCAT3 were decreased to different degrees in the low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. ConclusionXuefu Zhuyutang can regulate iron metabolism and anti-lipid oxidation reaction to mediate ferroptosis through the ACSL4 signalling pathway， thus exerting a protective effect on rats with coronary heart disease with blood stasis syndrome.

Objective To prepare nifedipine nanocrystals(NDP-NCs)and evaluate their in vivo pharmacokinetics in rats.Methods The NDP-NCs was prepared by medium grinding method,and the formulation and preparation technology of NDP-NCs were determined by single factor experiment.The microstructure of NDP-NCs and its solid powder was observed under scanning electron microscope.The particle size distribution and Zeta potential of NDP-NCs before and after spray drying were compared.The stability of the spray drying granules of NDP-NCS was investigated.The dissolution rates of the NDP raw material and NDP-NCs granules were compared.The in vivo pharmacokinetics of NDP suspension and NDP-NCs granules were evaluated after oral administration in rats.Results Using hydroxypropyl cellulose(HPC-SL)and sodium dodecyl sulfate(SDS)as stabilizers,the ratio of drug to stabilizer was 5∶1,the size of grinding medium was 0.2 mm,the ratio of grinding medium to liquid volume was 1∶1,the grinding speed was 2 000 r/min,and the grinding time was 3 h.The NDP-NCs showed an irregular granular distribution,and the NDP-NCs granules were porous and spherical.The average particle size and polydispersity index had no change before and after spray drying.The NDP-NCs granules had good stability after 6 months under the condition of accelerated testing.The solubility of NDP-NCs in different pH media was obviously improved.The dissolution rate of NDP-NCs granules increased significantly,and the drug could dissolve more than 90％within 15 min.The oral bioavailability of NDP was significantly improved after it was prepared into nanocrystals.Conclusion In this study,the nifedipine is prepared into nanocrystals with reasonable formulation design and feasible preparation technology,which can significantly improve the oral bioavailability of nifedipine.

Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomod-ulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various im-mune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils'chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.

Humans ; Pregnancy ; Female ; Umbilical Cord/diagnostic imaging* ; Pregnancy Outcome ; Ultrasonography ; Ultrasonography, Prenatal

Diabetic gastroparesis (DGP) is characterized by delayed gastric emptying caused by reduction of gastrointestinal motility. Its clinical manifestations include vomiting, nausea, belching, early satiety, postprandial fullness, and abdominal distention, etc. The mechanism of DGP is still not clear. Depletion of interstitial cells of Cajal, myopathy and neuropathy are considered to be the main pathogenic factors. Gastric prokinetics, gastric electric stimulation and endoscopic therapy are the main treatment options, but the long-term efficacy of these symptomatic treatment is not very satisfactory, which seriously affects patients' quality of life. This article reviewed the advances in study on pathogenesis and treatment of DGP.

Objective To explore the clinical characteristics of interrupted of the inferior vena cava with azygous continuation and the prognosis.Methods Retrospective analysis of 21 fetuses diagnosed with interrupted inferior vena cava with azygous continuation among 28 567 pregnant women who underwent routine ultrasound scan.The clinical data,ultrasonographic features,genetic information and prognosis were collected. Results Interrupted of the inferior vena cava with azygous continuation occurred in 21(0.07%, 21/28 567)of 28 567 patients.Three fetuses(14%,3/21)complicated with heart and extracardiac malformations, including endocardiac cushion defect,single atrium and single ventricle,double superior vena cava,dextrocardia, asplenia syndrome,visceral heterotaxy,duodenal atresia;six fetuses(29%,6/21)were associated with cardiac anomalies, such as hypoplastic left heart syndrome, double outlet right ventricle, pulmonary stenosis, ventricular septal defect,persistent left superior vena cava,endocardiac cushion defect and transposition of the great arteries;six cases(29%,6/21)were only combined with extracardiac malformations,includingasplenia syndrome, visceral heterotaxy, duodenal atresia. Three fetuses (14%,3/21) were nonorganic abnormalities included thickening of the right ventricle wall, fetal bradycardia, pericardial effusion, hydrops abdominis, increased peak systolic velocity/end diastolic velocity and single umbilical artery.Three fetuses(14%,3/21) were isolated interrupted inferior vena cava with azygous continuation,but without other anomalies and 2 of them had normal fetal karyotype.Five cases(24%,5/21)were successfully vaginal delivery,1 case(5%,1/21) had cesarean section. After 12-40 months follow-up, we didn′t obeserve obviously abnormality, nor any chromosomal abnormality.Ten patients(48%,10/21)opted for termination of the pregnancy and the autopsies were not done.Five cases(24%,5/21)were lost to follow up.Conclusions Interrupted inferior vena cava with azygous continuation are associated with cardiovascular and extracardiac anomalies, cardiac malformation and visceral heterotaxy are the most common anomalies. Visceral heterotaxy should be considered and fetal karyotype should be suggested. In the cases of isolated interrupted inferior vena cava with azygous continuation and normal karyotype,the outcome is favorable.

Objective To investigate the effects of different concentrations and adsorption methods of aluminum hydroxide adjuvant produced by different manufacturers on the immunogenicity of the diphtheria-tetanus-acellular pertussis and inactivated poliovirus combined vaccine ( DTaP-sIPV) . Methods Five anti-gens of DTaP were adsorbed onto different concentrations (0. 42 mg/ml, 0. 47 mg/ml and 0. 52 mg/ml) of aluminum hydroxide from different manufacturers through sequential and separate adsorption. Adsorbability, anti-pertussis toxin ( PT)/filamentous hemagglutinin ( FHA)/pertactin ( PRN)/diphtheria toxoid ( DT)/tet-anus toxoid ( TT) antibodies and the potency of vaccines were detected. Results The adsorbability of alu-minum hydroxide adjuvant slightly decreased with the reduction of concentration. No significant difference in potency and antibody level was observed between sequential and separate adsorption. Moreover, no signifi-cant difference in antibody level was observed between vaccines prepared with aluminum hydroxide adjuvant produced by General Chemical Corp and our institute. Conclusion Aluminum hydroxide adjuvant produced by our institute at the concentration of 0. 52 mg/ml and separate adsorption method are suitable for prepara-tion of DTaP-sIPV.

Objective To compare the clinical efficacies between warm needling and Ibuprofen sustained release capsules (a nonsteroidal anti-inflammatory drug, NSAID) in treating patients with dysmenorrhea in adenomyosis. MethodSixty-five patients with dysmenorrhea induced by adenomyosis were randomized into a treatment group of 33 cases and a control group of 32 cases. The control group was intervened by oral administration of Ibuprofen sustained release capsules, while the treatment group was intervened by warm needling.The intervention lasted 3 menstrual cycles and a 3-month follow-up was studied. The Visual Analogue Scale (VAS), dysmenorrhea symptoms scores and clinical efficacy were compared between the two groups.ResultThe VAS scores after the intervention and inthe first and second months of the follow-up study were significantly different from the pre-treatment score in the two groups (P<0.01); the VAS score of the 3-month follow-up was significantly different from the score before the intervention in the treatment group (P<0.01). There were significant differences in comparing the VAS score after the intervention and in the follow-up study between the two groups (P<0.01), and the treatment group was superior to the control group. The dysmenorrhea symptoms scoresdeclined significantly after the intervention and in the first and second months of the follow-up study in both groups (P<0.01); the dysmenorrhea symptoms score of the 3-month follow-up study decreased in the treatment group and was significantly different from the pre-treatment score (P<0.01). There were significant differences in comparing the dysmenorrhea symptoms scores in the second and third months of the follow-up study between the two groups (P<0.01). The total effective rate was 93.9% in the treatment group, significantly better than 62.5% in the control group (P<0.01).ConclusionWarm needling is effective in easing pain and improving the symptoms of dysmenorrhea in adenomyosis, and can produce a consistent efficacy after the termination of thetreatment; it's superior to NSAIDs in comparing both short-term and long-term treatment efficacies.

OBJECTIVE: To establish the cell model using human leukemia cell line HL-60 for exposure of coke oven emissions( COE) in vitro and to explore the mechanism of COE-induced acute toxicity in HL-60 cells. METHODS: HL-60 cells were collected in their logarithmic growth phase and cultured in medium that had final concentrations of COE in 2. 5,5. 0,10. 0 and 20. 0 mg / L for 24 hours. Cell survival rate was examined by CCK-8 assay. The cytotoxicity was evaluated using lactate dehydrogenase release assay. Reactive oxygen species( ROS) production was determined by the 2',7'-dichlorofluorescein diacetate and nitroblue tetrazolium method. The activation of nuclear factor-κB( NF-κB) pathway was evaluated by western blot. RESULTS: With the increasing exposure concentrations of COE,the cytotoxicity of HL-60 cells increased( P < 0. 01),the cell survival rate decreased( P < 0. 01),intracellular ROS decreased( P < 0. 01),whereas extracellular ROS increased( P < 0. 01). These changes had a dose-effect relationship. The levels of phospho-nuclear factor-kappa B p65 and phospho-inhibitor of kappa Bα were higher in all the COE-treated cells compared with untreated cells( P < 0. 05),with no dose-effect relationship. CONCLUSION: COE could cause acute toxicity in HL-60 cells in a doseeffect relationship. The mechanism may be related to the COE-induced in-balanced ROS release and removal,leading to the activation of NF-κB pathway. HL-60 cells can be used as a common cell line for COE hematotoxicity analysis.

Objective:To prepare celecoxib nanostructured lipid carriers and investigate the characteristics of tissue distribution in rats. Methods:Celecoxib nanostructured lipid carriers were prepared by a melt-emulsion ultrasonication and low temperature-solidifi-cation method. The physicochemical properties of nanostructured lipid carriers were studied, such as particle size distribution, zeta po-tential and morphology. The concentration of celecoxib in different tissues was determined after tail vein injection of celecoxib nano-structured lipid carriers in rats. Results:The obtained celecoxib nanostructured lipid carriers were spherical with the average particle size of (103. 5 ± 32. 6) nm and zeta potential of ( -37. 3 ± 5. 1) mV. The re of celecoxib nanostructured lipid carriers in liver, spleen, brain and muscle respectively was 3. 43, 2. 99, 2. 38 and 2. 93 times higher than that of celecoxib injection. Conclusion:The biodistribution of celecoxib is changed by the nanostructured lipid carriers. Celecoxib nanostructured lipid carriers have the characteris-tics of liver, spleen and muscle targeting, which is benefit to improving the efficacy.