ObjectiveTo study the effect of Taikong Yangxin Pills on the metabolism of simulated weightless rats based on metabolomics and discuss the metabolism mechanism. MethodsIn the simulated space capsule environment on the ground， the rat model of simulated weightlessness was established by the tail suspension method. Rats were randomly grouped as follows： out-of-capsule control， in-capsule control， model， and high （3.0 g·kg^-1） and low （1.5 g·kg^-1） doses of Taikong Yangxin Pills， and they were administrated with corresponding drugs by gavage for 28 days. The serum levels of endogenous metabolites in rats were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF/MS）. The obtained data were processed by principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） to screen for differential metabolites and potential biomarkers. MetaboAnalyst 5.0 was used for pathway enrichment analysis to explain the metabolic regulation mechanism of the drug. ResultsCompared with the out-of-capsule control group， the in-capsule control group showed elevated levels of thirteen metabolites， including 14-hydroxyhexadecanoic acid， linoleic acid， and α-linolenic acid （P<0.05）， which suggested that the space capsule environment mainly affected the metabolism of α-linolenic acid and linoleic acid in the rats. Compared with the in-capsule control group， the model group showed lowered levels of fourteen metabolites， including 4-imidazolone-5-propionic acid， isocitric acid/citric acid， and L-tyrosine （P<0.05）， which were recovered after the treatment with Taikong Yangxin pills （P<0.05）. The pathway enrichment analysis revealed that weightlessness induced by tail suspension and drug intervention mainly involved the phenylalanine， tyrosine， and tryptophan biosynthesis， tyrosine metabolism， histidine metabolism， and citric acid cycle. ConclusionThe simulated space capsule environment and simulated weightlessness induced by tail suspension can both affect the metabolism level of rats. Taikong Yangxin pills can ameliorate the metabolic abnormality in the rat model of weightlessness by regulating various amino acids and energy metabolism-related pathways.

ObjectiveTo establish the fingerprints of 15 batches of Hengzhi Kechuan capsules， to quantitatively analyze 10 index components， and to evaluate the quality uniformity of samples from different batches. MethodsThe fingerprints and quantitative analysis of Hengzhi Kechuan capsules were established by a combination method of high performance liquid chromatography coupled with diode array detector and charged aerosol detector（HPLC-DAD-CAD）， adenosine， guanosine， vanillic acid， safflomin A， agarotetrol， naringin， hesperidin， militarine， ginsenoside Rb₁， and glycyrrhizic acid were selected as quality attribute indexes. A total of 15 batches of Hengzhi Kechuan capsules from 2022 to 2024（3 boxes per batch） were qualitatively and quantitatively analyzed， and the quality uniformity level of the manufacturers was characterized by parameters of intra-batch consistency（P_A） and inter-batch consistency（P_B）. The homogeneity and difference of quality attribute indexes of samples from different years were analyzed by heatmap clustering analysis. ResultsHPLC fingerprints and quantitative method of Hengzhi Kechuan capsules were established， and the methods could be used for qualitative and quantitative analysis of this preparation， which was found to be stable and reliable by method validation. The similarity of fingerprints of 15 batches of samples was 0.887-0.975， a total of 13 common peaks were calibrated， and 10 common peaks were designated， all of which were quality attribute index components. The results of quantitative analysis showed that the contents of the above 10 ingredients in the samples were 0.038-0.078， 0.115-0.251， 0.007-0.018， 0.291-0.673， 0.122-0.257， 0.887-1.905， 1.841-3.364， 1.412-2.450， 2.207-3.112， 0.650-1.161， respectively. And the contents of ginsenoside Rb₁ and glycyrrhizic acid met the limit requirements in the 2020 edition of Chinese Pharmacopoeia. For the samples from 15 batches， the P_A values of the 10 index components were all <10%， indicating good intra-batch homogeneity， and the P_B values ranged from 33.86% to 92.97%， suggesting that the inter-batch homogeneity was poor. Heatmap clustering analysis showed that the samples from different years were clustered into separate categories， and adenosine， guanosine， safflomin A， naringin， hesperidin and agarotetrol were the main differential components. ConclusionThe intra-annual quality uniformity of Hengzhi Kechuan capsules is good and the inter-annual quality uniformity is insufficient， which may be related to the quality difference of Pinellinae Rhizoma Praeparatum， Carthami Flos， Citri Sarcodactylis Fructus， Citri Reticulatae Pericarpium， Aquilariae Lignum Resinatum， Citri Fructus， etc. In this study， the fingerprint and multi-indicator determination method of Hengzhi Kechuan capsules was established， which can be used for more accurate and efficient quality control and standardization enhancement.

Objective To investigate the risk factors for secondary infection in patients with acute ischemic stroke(AIS)undergoing intravenous thrombolysis,and to construct a nomogram model.Methods A retrospective analysis was performed for the clinical data of 391 patients with AIS who underwent intravenous thrombolysis in Nanjing Drum Tower Hospital retrospectively from December 2016 to December 2021,and according to the presence of absence of secondary in-fection,they were divided into infection group with 75 patients and non-infection group with 316 patients.Results Age[odds ratio(OR)=1.049,95%confidence interval(CI)1.017-1.082],history of renal insufficiency(OR=3.76,95%CI 1.382-9.966),history of antihypertensive drugs(OR=0.298,95%CI 0.144-0.562),hemorrhagic transforma-tion after thrombolysis(OR=2.851,95%CI 1.05-7.36),white blood cell count(WBC)on admission(OR=1.17,95%CI 1.045-1.313),prothrombin time(PT)on admission(OR=1.585,95%CI 1.206-2.167),and dysphagia(OR=8.309,95%CI 4.091-17.269)were independent risk factors for secondary infection.The nomogram predictive model based on these risk factors had an area under the ROC curve of 0.867 and a cutoff value of 0.180,suggesting that the model had good discriminatory ability and calibration.According to the cutoff value of the nomogram,the patients were di-vided into high-risk and low-risk groups based on the risk of secondary infection,and the low-risk group had a significantly higher cumulative survival rate than the high-risk group(P<0.000 1).Conclusion Age,history of renal insufficiency,his-tory of antihypertensive drugs,hemorrhagic transformation after thrombolysis,WBC on admission,PT on admission,and dysphagia on admission are risk factors for secondary infection in AIS patients after intravenous thrombolysis,and the nomo-gram predictive model constructed based on the above risk factors has a good value in predicting secondary infection and 90-day survival.

T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFNγ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed on TAMs can attenuate T cell proliferation. Therefore, targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor tissues. We herein developed reduction-responsive nanoparticles (NPs) made with poly (disulfide amide) (PDSA) and lipid-poly (ethylene glycol) (lipid-PEG) for systemic delivery of Siglec15 siRNA (siSiglec15) and IFNγ for enhanced cancer immunotherapy. After intravenous administration, these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages (TAMs). With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFNγ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.

Objective:To explore the influence of head nurse empowerment on nurses′ voice behavior and the mediating and moderating effects of nurses′ job crafting and proactive personality.Methods:A total of 805 nurses from the 4 grade A hospitals in Shandong province from February to March 2022 were selected by convenience sampling method, the Nurse Managers′ Empowering Behavioral Scale For Staff Nurses, Job Crafting Scale, Voice Behavior Scale and Proactive Personality Scale were used for cross-sectional survey. The mediating effect was analyzed by SPSS 26.0 and Process 3.4 macro.Results:The total score of nurses′ perception of head nurse empowerment was (4.01 ± 0.57) points, the total score of nurses′ job crafting was (4.19 ± 0.66) points, the total score of nurses′ voice behavior was (4.12 ± 0.62) points, and the total score of nurses′ proactive personality was (6.07 ± 0.90) points. Head nurse empowerment, nurse job crafting, voice behavior and proactive personality were positively correlated with each other ( r values were 0.483-0.824, all P<0.01). The mediating effect of job crafting was 0.541, accounting for 86.4% of the total effect; proactive personality had a positive moderating effect on the first half path of the mediation model ( ? R 2=0.163, P<0.01). Conclusions:Head nurse empowerment influenced voice behavior of nurses directly and indirectly through the mediating role of job crafting, proactive personality can moderate the effect of head nurse empowerment on nurse job crafting. It is suggested that the head nurse appropriately delegate power to the nurses and actively authorize them, identify nurses with high proactive personality, stimulate their job remodeling and voice behavior, and improve the quality of nursing work.

Multiple sclerosis (MS) is an idiopathic inflammatory demyelinating diseases of the central nervous system, the underlying cause of which has not been cleared. Previous studies have shown that the pathogenesis of MS is related to the destruction of blood brain barrier, furthermore the drugs used to treat MS have a certain protective effect on the function of blood brain barrier. Therefore, this review combines the research progress at home and abroad to clarify the relationship between the blood brain barrier and MS in pathogenesis and treatment, proposing possible orientation of development.

Objective:To prospectively investigate the prevalence of heparin-induced thrombocytopenia (HIT) in critically ill children during extracorporeal membrane oxygenation(ECMO) and explore the clinical characteristics and prognosis of HIT during ECMO.Methods:A total of 22 critically ill children, who had received ECMO support for more than 96 hours in the Intensive Care Unit at the Children′s Hospital of Fudan University from March 2019 to December 2020, were enrolled.According to the 4T score and the heparin/platelet factor 4(PF4) antibody, children whose 4T scores were not less than 6 and heparin/ PF4 antibodies were positive, were classified into HIT group ( n=6), and non-HIT group ( n=16). The clinical outcomes and the incidence of thrombotic events were compared between two groups. Results:The incidence of HIT during ECMO in critically ill children was 27% in this study.The incidence of thrombosis in the ECMO circuit in the HIT group was higher (100% vs.63%, P=0.133), and the average time to the first thrombosis in ECMO circuit in the HIT group was shorter than that in the non-HIT group (3.70 d vs.5.44 d, P=0.06). During the first 14 days of ECMO, the proportion of children with thrombotic events no less than twice was higher in the HIT group (67% vs.19%, P=0.054). There was no significant difference regarding the survival rate at 28 days after ECMO withdrawal between two groups (33% vs.50%, P=0.664). Conclusion:The prevalence of HIT during ECMO in critically ill children is high.Thrombosis events tend to occur earlier and more extensively in children with HIT during ECMO.No significant effect of HIT on the survival rate of children during ECMO is found.Whether HIT has effect on the survival rate of children with ECMO requires a prospective and large clinical study.

Objective To compare the clinical effects of interscalene brachial plexus block and superior trunk block in arthroscopic shoulder surgery with 0.25% ropivacaine. Methods 46 patients undergoing shoulder arthroscopy surgery were included and randomly divided into group ISB (n=23) and group ST (n=23). Patients in group ISB received 10 ml 0.25% ropivacaine on the lateral side of C5 and C6. Patients in group ST were treated with 5 ml 0.25% ropivacaine on both sides of the superior trunk of brachial plexus. The diaphragmatic excursion, Numerical Rating Scale(NRS), duration of the block, handgrip strength were recorded at different time. Results No statistical difference was detected between the two groups in the reduction of diaphragmatic excursion within 30 min after block (P>0.05). Compared with ISB patients, ST patients had significantly less diaphragmatic excursion at 3 h after block（P<0.05). 30 minutes after block, 8.7% patients in ISB group reached complete HDP and 52.2% patients reached partial HDP. At the same time, no complete HDP and 26.1% partial HDP were detected in ST group. 3 hours after block, patients in ST group had lower complete HDP rate (0.0% vs 17.4%) and lower partial HDP rate (39.1% vs 65.2%) than patients in ISB group. At 30 minutes and 3 h after block, the reduction of grip strength in ST group was significantly lower than that in ISB group (P<0.001). ST group had lower NRS than ISB group (P<0.05). The average block time in ISB group (8.3±1.97 )h was significantly lower than that in ST group (10.9±1.26)h (P<0.01). Conclusion Superior trunk block with 10 ml 0.25% ropivacaine is superior compared to interscalene brachial plexus block in occurrence of HDP, decrease of grip strength, postoperative pain and block duration.

Objective:Assess the relationship between elevated antiphospholipid antibodies and thrombosis in hospitalized patients.Methods:Case control study. A total of 385 patients (149 males and 236 females, aged from 1 to 105 years, with a median age of 37 years) who were hospitalized in Peking University First Hospital from January 2015 to December 2019 and tested positive for any one of the anti-phospholipid antibodies were included in the study. All subjects were divided into thrombotic group and non-thrombotic group according to whether thrombus was detected by imaging examination during hospitalization. In thrombosis group, there were 66 males and 36 females, aged from 3 to 105 years, with a median age of 58 years. In non-thrombosis group, there were 83 males and 200 females, aged from 1 to 94 years, with a median age of 31 years. Clinical data and laboratory data of patients were recorded. ACL-IgM/IgG and anti-β2GPI-IgM/IgG were detected by ELISA and LA was detected by dRVVT and SCT on automatic coagulation analyzer. The rates of age, gender, smoking, obesity, hypertension, hyperlipidemia, diabetes and the median level of antiphospholipid antibodies were compared between two groups. Logistic multivariate regression analysis was used to determine the risk factors for thrombotic events. The mid-to-high titer value of aCL was established by the χ 2-trend test and verified by logistic regression. Results:The median age (58 years) and the rates of male (64.7%), smoking (16.7%), hypertension (63.7%) and diabetes (28.4%) in thrombus group were significantly higher than those in non-thrombus group ( Z=7.685, χ2=38.077, 16.312, 37.769, 24.749 respectively; P<0.01). The positive rate of anti-β2GPI-IgG and dRVVT in thrombosis group (11.8% and 78.4%) was significantly higher than that in non-thrombosis group (5.3% and 60.1%), as well as the median level of dRVVT (1.29 RU/ml vs 1.23 RU/ml) (χ2=3.864 and 10.309, Z=3.539; P<0.05). The median level of aCL-IgM was higher in non-thrombosis group (2.3 MPL vs 2.0 MPL). The positive rate of aCL-IgG was slightly higher in thrombosis group (18.6% vs 10.6%). Logistic regression analysis showed that men, hypertension, diabetes, advanced age, elevated dRVVT, and elevated anti-β2GPI-IgG are risk factors for thrombosis. Taking 36 GPL as the medium-to-high titer value of aCL-IgG, the risk of thrombosis increased by 2.45 times. Conclusions:In the anti-phospholipid antibody profile, LA detected by dRVVT method, anti-β2GPI-IgG and aCL-IgG may be valuable laboratory indicators for inpatient thrombotic events. The mid-to-high titer value of aCL-IgG is set at 36 GPL to distinguish the risk of thrombosis.

Objective:To identify new prognostic markers and therapeutic targets for gastric adenocarcinoma.Methods:The public datasets of gastric adenocarcinoma collected from GEO database (GSE33335 and GSE63089) were downloaded for analysis. There were 70 GC tissues and paired normal tissues in the two profile datasets. Differentially expressed genes (DEGs) between GC tissues and normal stomach tissues were selected by the R software. Protein-protein interaction (PPI) of these DEGs were visualized by the Search Tool for the Retrieval of Interacting Genes (STRING). The key gene sets were analyzed by Cytoscape and Molecular Complex Detection (MCODE). The mRNA and protein expression levels of prognosis related genes identified by public database were confirmed by using GC tissues and paired normal tissues collected from July 2019 to September 2019 in Affiliated Hospital of Nantong University.Results:DEGs were identified in the two datasets by using R software. A total of 128 DEGs were detected, including 85 up-regulated genes ( log2FC>1.2 and FDR<0.01) and 43 down-regulated genes ( log2FC<-1.2 and FDR<0.01) in the GC tissues. PPI network model and MCODE model were established by using the Online String tool and Cytoscape software, and 27 key genes were obtained, including 25 genes related with prognosis of GC patients ( P<0.05). We identified 14 significant DEGs in GC tissues, including cyclin B1 (CCNB1), polo-like kinase 1 (PLK1) and pituitary-tumor transforming gene (PTTG1), which were significantly enriched in the cell cycle pathway through KEGG pathway enrichment analysis. The positive expression rate of PTTG1 in GC tissues was 68.8% (22/32), significantly higher than 18.8% (6/32) in normal gastric tissues ( P<0.05). Conclusions:The expression of PTTG1 is different in GC and gastric tissues, implicates it is the key gene in gastric carcinogenesis. The prognoses of GC patients with higher PTTG1 expression are worse. PTTG1 might participate in the development of gastric adenocarcinoma by regulating cell cycle.