ObjectiveTo explore the effects of Kaixuan Jiedu core prescription （KXJD） on sphingolipid metabolism in the mouse model of imiquimod-induced psoriasis-like skin lesions. MethodsThirty-seven male C57BL/6J mice were randomly assigned into five groups： healthy control （n=11）， model （n=11）， methotrexate （MTX， n=5）， low-dose （15.21 g·kg^-1） KXJD （n=5）， and high-dose （30.42 g·kg^-1） KXJD （n=5）. Psoriasis-like skin lesions were induced in mice with 62.5 mg 5% imiquimod cream applied on the back. The KXJD groups and MTX group were treated with 0.2 mL corresponding decoction and MTX， respectively， by gavage daily， while the other groups were given an equal volume of normal saline by the same way. After 5 days of treatment， back skin lesions were collected. Firstly， healthy control and model mice were selected for tandem mass tag （TMT） quantitative proteomics （control vs model=3 vs 3） and targeted lipid metabolomics （control vs model=11 vs 11）. Then， the binding degree between core components and target proteins was predicted via network pharmacology and molecular docking. Finally， an animal experiment was performed to decipher the specific regulation mechanism of KXJD on sphingolipid metabolism. Immunohistochemistry was employed to determine the expression level of sphingosine-1-phosphate （S1P）， and Western blot was employed to determine the expression levels of sphingosine kinase 2 （SPHK2） and monocyte chemotactic protein-1 （MCP-1）. ResultsTMT proteomics and targeted lipid metabolomics suggested that sphingolipid metabolism was active in the psoriatic skin， and key proteases ［serine palmitoyltransferase， long chain base subunit 2 （SPTLC2）， SPHK2， delta（4）-desaturase sphingolipid 1 （Degs1）， and ceramide synthase 4 （CerS4）］ and 8 sphingolipid metabolites （including ceramides， sphingol， sphingomyelin， and glycosphingolipid） expressed abnormally （P<0.05） compared with those in the healthy skin. The molecular docking results indicated that the binding energy between the active components （quercetin， kaempferol， and luteolin） in KXJD and key proteins involved in sphingolipid metabolism was less than-8 kal·mol^-1. Further experimental verification showed elevated expression levels of SPHK2， S1P， and MCP-1 in psoriatic skin compared with healthy skin （P<0.05）， and KXJD down-regulated the expression levels of SPHK2， S1P， and MCP-1 compared with the model group （P<0.05）. ConclusionThis study indicates that there is an imbalance in sphingolipid metabolism in psoriatic skin lesions. KXJD may reduce psoriasis-like lesions in mice by regulating sphingolipid metabolism via the SPHK2/S1P/MCP-1 pathway.

ObjectiveTo explore the effects of Kaixuan Jiedu core prescription （KXJD） on sphingolipid metabolism in the mouse model of imiquimod-induced psoriasis-like skin lesions. MethodsThirty-seven male C57BL/6J mice were randomly assigned into five groups： healthy control （n=11）， model （n=11）， methotrexate （MTX， n=5）， low-dose （15.21 g·kg^-1） KXJD （n=5）， and high-dose （30.42 g·kg^-1） KXJD （n=5）. Psoriasis-like skin lesions were induced in mice with 62.5 mg 5% imiquimod cream applied on the back. The KXJD groups and MTX group were treated with 0.2 mL corresponding decoction and MTX， respectively， by gavage daily， while the other groups were given an equal volume of normal saline by the same way. After 5 days of treatment， back skin lesions were collected. Firstly， healthy control and model mice were selected for tandem mass tag （TMT） quantitative proteomics （control vs model=3 vs 3） and targeted lipid metabolomics （control vs model=11 vs 11）. Then， the binding degree between core components and target proteins was predicted via network pharmacology and molecular docking. Finally， an animal experiment was performed to decipher the specific regulation mechanism of KXJD on sphingolipid metabolism. Immunohistochemistry was employed to determine the expression level of sphingosine-1-phosphate （S1P）， and Western blot was employed to determine the expression levels of sphingosine kinase 2 （SPHK2） and monocyte chemotactic protein-1 （MCP-1）. ResultsTMT proteomics and targeted lipid metabolomics suggested that sphingolipid metabolism was active in the psoriatic skin， and key proteases ［serine palmitoyltransferase， long chain base subunit 2 （SPTLC2）， SPHK2， delta（4）-desaturase sphingolipid 1 （Degs1）， and ceramide synthase 4 （CerS4）］ and 8 sphingolipid metabolites （including ceramides， sphingol， sphingomyelin， and glycosphingolipid） expressed abnormally （P<0.05） compared with those in the healthy skin. The molecular docking results indicated that the binding energy between the active components （quercetin， kaempferol， and luteolin） in KXJD and key proteins involved in sphingolipid metabolism was less than-8 kal·mol^-1. Further experimental verification showed elevated expression levels of SPHK2， S1P， and MCP-1 in psoriatic skin compared with healthy skin （P<0.05）， and KXJD down-regulated the expression levels of SPHK2， S1P， and MCP-1 compared with the model group （P<0.05）. ConclusionThis study indicates that there is an imbalance in sphingolipid metabolism in psoriatic skin lesions. KXJD may reduce psoriasis-like lesions in mice by regulating sphingolipid metabolism via the SPHK2/S1P/MCP-1 pathway.

Based on the long bud stage phenotype of a new Lonicera japonica Flos variety "Huajin 6", using "Huajin 6" and "Da Mao Hua" as materials, probing the mechanism of its phenotype formation. Detection of endogenous Jasmonic acid hormones (JAs) content; the genes related to jasmonic acid (JA) synthesis were identified by transcriptome analysis of Lonicera japonica; flower buds and flowers of "Huajin 6" and "Da Mao Hua" were collected at different periods, and the qRT-PCR (quantitative real-time PCR) technique was used to analyze the trend of the expression of synthesis-related enzyme genes in Lonicera japonica Flos during the bud stage. The study found that the content of JAs in "Huajin 6" Lonicera japonica Flos was significantly lower than that in "Da Mao Hua"; applying exogenous methyl-jasmonate (MeJA) to "Huajin 6" can restore its flowering phenotype, making it close to wild type Lonicera japonica Flos; there are significant differences in the expression of two allene oxide synthase genes (AOS), three lipoxygenase genes (LOX), and two allene oxide cyclase genes (AOC) in the flowers and buds of "Huajin 6" and "Da Mao Hua" at different periods. It is hypothesized that the low expression of JA synthesis-related enzyme genes in " Huajin 6" leads to the blockage of JA synthesis, which causes the formation of the long bud phenotype. This study laid a certain foundation for the genetic breeding of Lonicera japonica, provided a new idea for the improvement of Lonicera japonica varieties, and provided a reference for the study of JAs in plant flower organs.

A precursor ion selection (PIS) based ultra high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-Q-TOF-MS) analytical method was used to screen the chemical components in Jiawei Dingzhi pills (JWDZP) comprehensively and rapidly. To compile the components of the compound medicine, a total of 1 921 components were found utilizing online databases and literature. After verifying the sources, unifying the component names, merging the multi-flavor attributed components, and removing the weak polar molecules, 450 components were successfully retained. The Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 μm) was used, with a 0.1% formic acid water (A)-acetonitrile (B) as the mobile phase. The flow rate was 0.35 mL·min^-1, the column temperature was 35 ℃, and an electrospray ion source was used. Data was collected with the PIS strategy in both positive and negative ion modes. Compounds were screened through matching accurate molecular weight of the database, and identified according to MS/MS data (characteristic fragment ions and neutral loss), with comparison of reference. Some compounds were confirmed using standard products. A total of 176 compounds were screened out in the extract of JWDZP, among which 26 compounds were confirmed by standard products. These compounds include 96 components from the sovereign drug, and 34 coefflux components with low ion intensity. The PIS-UHPLC-Q-TOF-MS/MS method established in this study can quickly and comprehensively screen the chemical components of JWDZP, which enhanced the screening rate of components with co-elution compounds of low ion intensities and provided a basis for the study of the material foundation of JWDZP.

Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.

Objective Cervical disc herniation(CDH)is one of the common orthopaedic diseases.With the in-depth study of it and the development of cervical implants,the establishment of cervical fusion animal models has become an indispensable part.Notably however,studies of the establishment and evaluation of cervical fusion animal models in China are currently lacking.This study aimed to provide a suitable animal model and evaluation scheme for implants for cervical spine-related research.Methods Small-tailed Han sheep were chosen for anterior cervical discectomy fusion(ACDF)after modified surgery,and a polyetheretherketone(PEEK)interbody fusion cage(Cage)(control group),3D-printed Ti6Al4V Cage(group 1),and new method Ti6Al4V Cage(group 2)were implanted in different cervical segments(C2/3～C4/5)in each sheep,respectively.Hematology and histopathological analyses were carried out after surgery to evaluate recovery of sheep and the biosafety of the materials.Bone in-growth and bone fusion were assessed by X-ray,computed tomography(CT),Micro-CT and quantitative analysis,hard tissue section staining,and biomechanical tests.Results The modified ACDF ovine model was established successfully.There were no significant differences in important hematology indexes(P＞0.05)and histopathological analysis showed no pathological changes,such as inflammatory cell infiltration.The implants had good biosafety.Furthermore,X-ray and CT examinations showed that the position of internal fixation and the interbody fusion were good.Micro-CT and quantitative analysis at 3 and 6 months after operation showed that compared with PEEK Cage group,the bone volume/total volume and trabecular number were significantly increased(P＜0.01)while the trabecular spacing was significantly decreased in the new method Ti6Al4V and 3D-printed Ti6Al4V groups compared with the PEEK Cage group(P＜0.01).Moreover,the new method new method Ti6Al4V Cage group had more bone growth(P＜0.01).Hard tissue section staining demonstrated that the pores of the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cage had obvious bone growth and relatively dense pores in the new method Ti6Al4V and 3D-printed Ti6Al4V groups,and the combination was slightly better than that of PEEK Cage.Biomechanical evaluation indicated that the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cage reduced the range of cervical flexion-extension,lateral bending,and axial rotation(P＜0.05)compared with the PEEK cage,as well as enhancing the stability of the cervical vertebra,and the new method Ti6Al4 V Cage was more advantageous(P＜0.05).Conclusions After the establishment of the modified ACDF ovine model,reasonable and effective assessment method were used to demonstrate the suitability and effectiveness of the model and the good biosecurity of all three Cage materials.Compared with the PEEK Cage,the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cages showed better performances in terms of bone growth and bone fusion,which could enhance the stability of the cervical vertebrae.The new method Ti6Al4V Cage was particularly advantageous.

Objective To study the trend of stroke mortality in Minhang District,Shanghai from 2012 to 2022 and to predict stroke mortality from 2023 to 2027.Methods Annual percentage change(APC)of stroke deaths in Minhang District,Shanghai from 2012 to 2022 was calculated,and then Joinpoint linear regression model was used to analyze the time trend of stroke deaths.A grey GM(1,1)model was constructed based on the stroke mortality rate in Minhang District,Shanghai from 2012 to 2022.The model was used to predict and analyze the stroke mortality rate in Minhang District,Shanghai from 2023 to 2027.The fitting effect of the model was evaluated using relative error and grade deviation.Results From 2012 to 2022,the overall mortality rate of stroke in Minhang District,Shanghai was on the rise for both males and females(total population:APC=2.50%,P<0.001;male:APC=3.41%,P<0.001;female:APC=1.46%,P=0.008).The grey GM(1,1)model was used to predict the increasing trend of stroke mortality rate in Minhang District from 2023 to 2027.The crude mortality rate of stroke in the entire population in 2027 would be 97.55/100000,with 112.31/100000 for males and 83.33/100000 for females.The fitting effect of the model was tested and evaluated to meet high requirements.Conclusion In the past decade,the mortality rate of stroke in Minhang District,Shanghai has shown a significant upward trend.The 5-year prediction results showed that the mortality rate will still on the rise year by year.

Objective To investigate the role and mechanism of acyl-CoA syntbetase long chain family member 4(ACSL4)in Sevoflurane(Sev)induced neuronal cell damage.Methods Human neuroblastoma SH-SY5Y cells were used as the research object,and control group(dimethyl sulfoxide,10 μmol/L),Sev group and Sev+iron death inhibitor Ferrostatin-1(Fer-1,10 μmol/L)group were set up.CCK-8 method was used to detect cell activity in each group.4.1%Sev exposed postoperative cognitive dysfunction model was constructed in vitro and divided into Ctrol group,Sev group,Sev+si-NC group,Sev+si-ACSL4 group,and Sev+si-ACSL4+compound C group according to the transfection category.The contents of Malonaldehyde(MDA),4-hydroxynonenal(4-HNE),Glutathione(GSH)and Fe2+in each group were detected by colorimetry.The level of reactive oxygen species was detected using a 2',7'-dichlorofluorescein diacetate(DCFH-DA)fluorescent probe.Real time fluorescence quantitative PCR(qRT-PCR)was used to detect the mRNA expression of ACSL4,glutathione peroxidase 4(GPX4),and solute carrier family 7 member 11(SLC7A11).Protein immunoblotting was used to detect the expression of ACSL4,GPX4,adenosine 5'-monophosphate activated protein kinase(AMPK),phosphorylated(p)-AMPK,mammalian target of rapamycin(mTOR)and p-mTOR proteins.Results CCK-8 results showed that the cell viability of Sev group(0.41±0.11)was significantly lower than that of control group(0.98±0.07),and the cell viability of Sev+Fer-1 group(0.83±0.09)was significantly higher than that of Sev group(0.41±0.11),and the differences were statistically significant(t=7.572,5.118,all P<0.01).The levels of Fe2+,MDA,4-HNE,ROS and p-AMPK/AMPK ratios,as well as the mRNA and protein expression of ACSL4 in the Sev group cells,were higher than those in the Ctrol group(t=5.900,7.421,4.795,13.517,10.825,9.945,11.334),the GSH conten,p-mTOR/mTOR ratio,and mRNA and protein expression of SLC7A11 and GPX4 were lower than those in the Ctrol group(t=20.438,3.551,11.460,12.211,6.845,8.287),and the differences were statistically significant(all P<0.05)repectively.The levels of Fe2+,MDA,4-HNE,ROS,and p-AMPK/AMPK ratios,as well as the mRNA and protein expression of ACSL4 in the Sev+si-ACSL4 group,were lower than those in the Sev+si-NC group(t=3.818,3.164,3.054,4.465,13.088,7.918,9.737),the cell viability,GSH content,p-mTOR/mTOR ratio,and protein expression of SLC7A11 and GPX4 were higher than those in the Sev+si-NC group(t=2.912,7.248,7.574,20.092,5.915),and the differences were statistically significant(all P<0.05),respectively.The cell viability,GSH content,SLC7A11,and GPX4 protein expression in the Sev+si-ACSL4+compound C group were lower than those in the Sev+si-ACSL4 group(t=4.435,8.521,4.522,8.767),while the levels of Fe2+,MDA,4-HNE,and ROS were higher than those in the Sev+si-ACSL4 group(t=10.046,4.004,2.957,3.752),and the differences were statistically significant(all P<0.05).Conclusion Inhibiting ACSL4 expression attenuates Sev-induced iron death in SH-SY5Y cells by activating the AMPK/mTOR signaling pathway.

Objective:To prepare hydroxyapatite(HA)coating on polyether ether ketone(PEEK)surface by magnetron sputtering technique and to study its biosafety.Methods:Sulfonated PEEK was used to increase the binding area and HA coating was constructed on it using magnetron sputtering technology.SEM and energy dispersive spectroscopy(EDAX)were used to detect the construction effect.Cell adhesion assay,cytoskeletal fluorescence staining and SEM validation were used to assess cytologrcal safety.In vivo safety tests were conducted in SD rats and golden hamsters.Results:HA coating with gradient morphology was successfully constructed on the PEEK surface using above technique.The coating promoted cell adhesion,extension and proliferation.No systemic toxicity and no sig-nificant influence in HE staining of the main infernal organs samples were observed.The coating alleviated the oral mucosal irritation caused by simple sulfonation to a certain extent.Conclusion:HA coating can be prepared stably with magnetron sputtering technology and can meet the biosafety needs for clinical applications.

Objective:Employing the cascade care model, this qualitative study explores determinants influencing the cascading care stages of hypertension and diabetes by interviewing various stakeholders.Methods:In July 2023, purposive sampling was employed to recruit participants from Gongyi and Wugang cities in Henan Province, and Linqu County in Weifang City, Shandong Province. Semi-structured in-depth interviews were conducted with representatives of policymakers, healthcare institution managers, providers, and patients with hypertension and diabetes.And thematic analysis was performed using both inductive and deductive approaches.Results:A total of 82 individuals were interviewed, with an age range of (53.8±12.0) years, among which 48 (58.5%) were male; including 5 policymakers, 10 institutional managers, 20 healthcare providers, and 47 patients with hypertension and diabetes. The study identified both barriers and facilitating factors at the patient, healthcare provider, and system levels across various stages: awareness, screening, diagnosis, treatment, long-term management, and control of hypertension and diabetes.Conclusion:By delineating and analyzing the barriers and facilitators at each stage of hypertension and diabetes care, this study lays the groundwork for the development of effective, feasible, and sustainable implementation pathways, with significant implications for the enhanced management of hypertension and diabetes in China.