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.

S100 calc-binding protein A8/A9(S100A8/A9)can induce the migration of primary tumor cells to distant target organs by binding multiple channel proteins,promote the formation of tumor metastasis microenvironment,and play an important role in the immune and inflammatory response of the body.It provides a new target and idea for the prevention and treatment of tumor metastasis and invasion.This paper mainly reviewed the expression and mechanism of S100A8/A9 on related channel proteins in a variety of high incidence tumors,in order to provide a new strategy for tumor prevention,diagnosis and treatment.

This study design of specific identification primers for the ITS2 sequence of F. ussuriensis. The reaction system and conditions were optimized, and PCR-nucleic acid test strips were constructed to realize the visual detection of F. ussuriensis Bark. Through molecular cloning and sequencing technology, we constructed a positive control for F. ussuriensis DNA and formulated quality standards. The established method was evaluated for sensitivity, specificity and reproducibility, and the authenticity of the commercially available samples was identified. Results demonstrated that based on the ITS2 sequences, F. ussuriensis and its mixed forgeries could be distinguished. The PCR products of the authentic F. ussuriensis on test strips showed two bands in the T and C lines, while the pseudo products and negative control showed only one band in the C line, which was consistent with the results of agarose gel electrophoresis. The specificity was 100%, and the sensitivity of the PCR-nucleic acid test strip was up to 0.1 ng·μL^-1, which was 10 times higher than that of the gel electrophoresis assay. 11 out of 16 commercially available samples of F. ussuriensis were qualified, and 5 were unqualified. Collectively, the PCR-nucleic acid test strip method established in this study is specific, rapid, accurate and visualized, which can provide a new technical idea for the detection of F. ussuriensis.

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.

To determine the main components of the fishy smell of the Eupolyphaga Steleophaga, and to provide a theoretical basis for deodorizing the Eupolyphaga Steleophaga. METHODS Head space-solid phase microextraction-gas chromatography-mass spectrometry was used to identify the components of 10 batches of Eupolyphaga Steleophaga, and area normalization method and chemometrics method were used to analyze the smelly gas of different batches. Odor activity value(OAV) was used to evaluate the contribution of odor components and identify key odor components. RESULTS A total of 87 volatile odor components were identified, the key fishy smell compounds(OAV≥1) were m-methylphenol, dimethyltrisulfide, 4-methylphenol, 2-methyliso-borneol, 2-etzol, 4-methylvaleric acid, iso-valeric acid, etc. Modified fishy gas composition(0.1

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. 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). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Objective:To investigate the level of serum lipoprotein a [Lp (a)] in patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance.Methods:A retrospective cohort study was performed. The clinical data of 87 patients with DLBCL who were treated at Changshu No.2 People's Hospital from January 2017 to June 2022 (the newly treated DLBCL group) were retrospectively analyzed, and 78 healthy physical examination subjects were selected as the control group. The level of Lp(a) in the two groups and the level of Lp(a) in DLBCL patients achieving different therapeutic effects after treatment were compared. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of serum Lp(a) in predicting the therapeutic effect of DLBCL patients, and the area under the curve (AUC) was calculated to determine the optimal critical value. Based on the optimal critical value, patients with DLBCL were divided into low Lp(a) group and high Lp(a) group, and the clinicopathological characteristics of DLBCL patients with different Lp(a) levels were compared. Cox proportional hazards model was used to analyze the factors affecting the prognosis of DLBCL patients. Kaplan-Meier method was used to compare the relapse-free survival (RFS) and overall survival (OS) of DLBCL patients with different Lp(a) levels.Results:The level of Lp (a) in the newly treated DLBCL group was higher than that in the control group[ (0.24±0.09) g/L vs. (0.09±0.06) g/L], and the difference was statistically significant ( t = 3.61, P = 0.019). Among 87 patients, 54 achieved complete remission (CR), 23 achieved partial remission (PR), and 10 achieved progression of the disease (PD). The Lp (a) levels of patients achieving CR, PR, and PD were (0.09±0.09) g/L, (0.12±0.08) g/L, and (0.25±0.15) g/L, respectively. The Lp (a) levels in patients achieving CR and PR were lower than those in the newly treated DLBCL patients [(0.24±0.09) g/L], and the differences were statistically significant (all P < 0.05). There was no statistically significant difference in the Lp (a) levels between patients achieving PD and the newly treated DLBCL patients ( P > 0.05). The ROC curve results showed that the optimal critical value of serum Lp (a) in predicting the efficacy of DLBCL patients was 0.25 g/L, AUC was 0.776 (95% CI: 0.676-0.876, P < 0.05), and its sensitivity and specificity was 66.67%, 82.76%, respectively. According to the optimal critical value of Lp (a) (0.25 g/L), patients were divided into the low Lp (a) group (≤ 0.25 g/L) (57 cases) and the high Lp (a) group (>0.25 g/L) (30 cases). The proportion of patients with lactate dehydrogenase level >227 U/L, Ann Arbor stage Ⅲ-Ⅳ, and extranodal organ involvement >1 in the high Lp (a) group was higher than that in the low Lp (a) group, and the differences were statistically significant (all P < 0.05). Cox multivariate analysis results showed that Ann Arbor stage Ⅲ-Ⅳ, international prognostic index (IPI) score 3-5, and Lp (a)>0.25 g/L were independent risk factors for OS in DLBCL patients (all P < 0.05); Ann Arbor stage Ⅲ-Ⅳ and IPI score 3-5 were independent risk factors for RFS in DLBCL patients (all P < 0.05). The median OS in the low Lp (a) group was not reached; the median OS of the high Lp (a) group was 21 months, and there was a statistically significant difference in OS between the two groups ( P = 0.001). The median RFS time was not reached in the low Lp (a) group and the high Lp (a) group; and there was no statistically significant difference in RFS between the two groups ( P = 0.102) . Conclusions:Lp(a) level of DLBCL patients is increased, and Lp(a) could be a factor influencing the prognosis of DLBCL.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective To investigate the effect of galangin on cardiac remodeling and cardiac func-tion after myocardial infarction(MI).Methods A total of 32 male C57/BL6 mice(8-10 weeks old)were subjected for MI modeling,and finally 24 mice were assigned into control group[sham operation+hydroxycellulose sodium(CMC-Na)],model group(MI+CMC-Na),and experimental group(MI+galangin),with 8 mice in each group.After MI modeling,the mice of the experimen-tal group were given 40 mg/kg galangin by gavage for 4 weeks,and those of the control group and the model group were given the same volume(0.4 ml)of CMC-Na solution.HE staining was used to observe the size of the infarct area.The mRNA levels of inflammatory factors in the heart were detected by qRT-PCR,and protein levels of related signaling pathway proteins were measured with Western blotting.Immunofluorescence(IF)assay was applied to detect the infiltration of in-flammatory cells in the infarct border zone.TUNEL staining was employed to detect cell apoptosis in the infarct border zone.Results At 4 weeks after modeling,larger infarct size,enhanced expression levels of IL-1β,IL-6,TNF-α,p-P65,p-IκBα and Bax,elevated apoptotic rate,decreased cardiac function indicators such as FS and LVEF,and reduced Bcl-2 expression level were observed in the model group than the control group(P＜0.05).The experimental group had sig-nificant smaller myocardial infarct size[(11.64±0.64)％vs(21.84±1.94)％],less CD3 positive T cells[(3.10±0.46)％vs(6.28±0.24)％],F4-80 positive macrophages[(1.98±0.50)％vs(5.35±0.62)％]and LY6G positive neutrophils[(6.33±0.67)％vs(11.33±1.77)％],decreased expression levels of IL-1β,IL-6,TNF-α,p-P65,p-IκBα and Bax,reduced apoptotic rate[(21.45± 1.62)％vs(35.68±0.88)％],and increased FS and LVEF values and Bcl-2 expression level when compared with the model group(P＜0.05).Conclusion Galangin improves myocardial remode-ling and cardiac dysfunction after MI by inhibiting inflammatory response and cell apoptosis.

Hepatocellular carcinoma(HCC),commonly known as primary liver cancer,is a major cause of malignant tumors and cancer-related deaths in China,accounting for approximately 85％of all cancer cases in the country.Several guidelines have been used to diagnose and treat liver cancer.However,these guidelines provide a broad definition for classifying advanced liver cancer,with an emphasis on a singular approach,without considering treatment options for individual patients.Therefore,it is necessary to establish a comprehensive and practical expert consensus,specifically for China,to enhance the diagnosis and treatment of HCC using the Delphi method.The classification criteria were refined for Chinese patients with HCC,and the corresponding optimal treatment regimen recommendations were developed.These recommendations took into account various factors,including tumor characteristics,vascular tumor thrombus grade,distant metastasis,liver function status,portal hypertension,and the hepatitis B virus replication status of patients with primary HCC,along with treatment prognosis.The findings and rec-ommendations provide detailed,scientific,and reasonable individualized diagnosis and treatment strategies for clinicians.