ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

Objective To investigate the effect of LAG-3 deficiency (LAG3^-/-) on natural killer (NK) cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis. Methods C57BL/6 mice, each weighing (20 ± 2) g, were divided into the LAG3^-/- and wild type (WT) groups, and each mouse in both groups was inoculated with 3 000 E. multilocularis protoscoleces via the hepatic portal vein. Mouse liver and spleen specimens were collected 12 weeks post-infection, sectioned and stained with sirius red, and the hepatic lesions and fibrosis were observed. Mouse hepatic and splenic lymphocytes were isolated, and flow cytometry was performed to detect the proportions of hepatic and splenic NK cells, the expression of CD44, CD25 and CD69 molecules on NK cell surface, and the secretion of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin (IL)-4, IL-10 and IL-17A. Results Sirius red staining showed widening of inflammatory cell bands and hyperplasia of fibrotic connective tissues around mouse hepatic lesions, as well as increased deposition of collagen fibers in the LAG3-/-group relative to the WT group. Flow cytometry revealed lower proportions of mouse hepatic (6.29% ± 1.06% vs. 11.91% ± 1.85%, P < 0.000 1) and splenic NK cells (4.44% ± 1.22% vs. 5.85% ± 1.10%, P > 0.05) in the LAG3^-/- group than in the WT group, and the mean fluorescence intensity of CD44 was higher on the surface of mouse hepatic NK cells in the LAG3^-/- group than in the WT group (t = −3.234, P < 0.01), while no significant differences were found in the mean fluorescence intensity of CD25 or CD69 on the surface of mouse hepaticNK cells between the LAG3^-/- and WT groups (both P values > 0.05). There were significant differences between the LAG3^-/- and WT groups in terms of the percentages of IFN-γ (t = −0.723, P > 0.05), TNF-α (t = −0.659, P > 0.05), IL-4 (t = −0.263, P > 0.05), IL-10 (t = −0.455, P > 0.05) or IL-17A secreted by mouse hepatic NK cells (t = 0.091, P > 0.05), and the percentage of IFN-γ secreted by mouse splenic NK cells was higher in the LAG3^-/- group than in the WT group (58.40% ± 1.64% vs. 50.40% ± 4.13%; t = −4.042, P < 0.01); however, there were no significant differences between the two groups in terms of the proportions of TNF-α (t = −1.902, P > 0.05), IL-4 (t = −1.333, P > 0.05), IL-10 (t = −1.356, P > 0.05) or IL-17A secreted by mouse splenic NK cells (t = 0.529, P > 0.05). Conclusions During the course of E. multilocularis infections, LAG3^-/- promotes high-level secretion of IFN-γ by splenic NK cells, which may participate in the reversal the immune function of NK cells, resulting in aggravation of hepatic fibrosis.

Objective To discuss the application of the"rotating guidewire and correcting the filter recovery hook direction technique"("rotation-correction loop technique"for short),a technique invented by the authors in clinical practice,in the retrieval of complex inferior vena cava filter(IVCF),and to discuss its technical skills and advantages.Methods The clinical data of 417 patients carrying an IVCF,who were admitted to the Department of Vascular Surgery of Second Hospital of Shanxi Medical University of China to retrieve IVCF between January 2022 and December 2022,were retrospectively analyzed.Taking the time spent on the retrieval of IVCF and the intraoperative radiation dose as the evaluation indicators,the advantages and disadvantages of the standard filter retrieval technique,the"rotation-correction loop technique"and the other loop-assisted techniques were compared.Results Both the intraoperative radiation dose and the time spent on the retrieval of IVCF using"rotation-correction loop technique"were remarkably lower than those of other loop-assisted techniques(P＜0.000 1).Conclusion For the retrieval of complex IVCF,especially for the IVCF which is heavily tilted and/or its recovered hook is attached to the vascular wall,the use of"rotation-correction loop technique"can shorten the time spent on the the retrieval of IVCF and reduce the intraoperative radiation dose.This technique carries high safety and practicability,the device is simple and it can be manipulated by single physician,which is conducive to clinical application and promotion.(J Intervent Radiol,2024,33:289-294)

Objective To evaluate the impact of optimizing the stroke green channel on the efficiency of acute ischemic stroke management in a county hospital. Methods A retrospective analysis of the emergency stroke green channel treatment data from Sixian People’s Hospital from May 2020 to April 2021 (before optimization of the green channel) and from May 2021 to April 2022 (after optimization of the green channel) was conducted. The rates of intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) patients, as well as door-to-needle time (DNT), door-to-puncture time (DPT), and the modified Rankin scale (mRS) scores of patients three months post-treatment before and after the optimization of the stroke green channel were compared. Results Within one year before and after optimization of the green channel, the number of acute visits for ischemic stroke was 3 143 and 2 623, respectively. Before optimization, 84 and 51 underwent IVT and MT, respectively. After optimization of the green channel, the ratios of patients underwent IVT (n＝215) and MT (n＝103) significantly increased, and both DNT and DPT were significantly shortened (P＜0.000 1); the proportion of MT patients with an mRS score of 0-2 at 3 months post-discharge significantly increased (46/99 vs 13/46, P＝0.038). Conclusion After optimizing the green channel at Sixian People’s Hospital, the efficiency of stroke treatment has significantly improved, and the patients’ prognosis improved.

Purpose: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti–programmed cell death-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT. Materials and Methods: This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child-Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles. Results: During a median follow-up of 11.23 months (range, 3.07 to 34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The 2-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively. Conclusion Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.

【Objective】 To explore the relationship between the storage time of leukodepleted red blood cells and transfusion adverse reactions by analyzing the occurrence of transfusion adverse reactions of patients after leukodepleted red blood cells transfusion from four hospitals. 【Methods】 By using the electronic medical record management system, the collection and transfusion dates of leukodepleted red blood cells from four hospitals in Enshi Prefecture from 2018 to 2022, as well as the information on transfusion adverse reactions, were retrieved. 【Results】 From 2018 to 2022, a total of 697 61 bags of leukodepleted red blood cells were transfused in four hospitals, resulting in 166 cases of transfusion adverse reactions, among which 93 were allergic reactions, 63 were non hemolytic febrile reactions, and 10 were others, with a total incidence rate of transfusion adverse reactions at 0.24%. The average storage time of leukodepleted red blood cells with and without transfusion adverse reactions was (20.25±6.31) and (19.88±5.50) days, respectively. With a storage time of 7 days as the threshold, the incidence of transfusion adverse reactions was the lowest for a storage time of 15~21 days. The incidence of transfusion adverse reactions of leukodepleted red blood cells in two groups (with storage days ≤21 days and >21 days) was not statistically significant(P>0.05). 【Conclusion】 Allergic reactions were the main type of transfusion adverse reaction caused by leukodepleted red blood cells, and the incidence of transfusion adverse reactions decreased and then increased with the prolongation of the storage time of leukodepleted red blood cells. There was no significant difference in the incidence of transfusion adverse reactions with leukodepleted red blood cells stored for ≤ 21 days and >21 days.

Objective:To investigate the prevention and risk factors of deep vein thrombosis (DVT) in the lower extremity after medial open wedge high tibial osteotomy (HTO).Methods:A total of 128 patients who underwent medial open wedge HTO in the Third Hospital of Hebei Medical University from January 2020 to October 2022 were retrospectively analyzed, including 45 males and 83 females, aged 59.3±6.8 years (range, 44-87 years). Postoperative anticoagulation with enoxaparin sodium was applied at a randomized dose of 4,000 AXaIU/d or 6,000 AXaIU/d. Gender, age, history of chronic diseases (hypertension, diabetes), smoking history, body mass index, and body fat percentage were collected. On admission, the risk of DVT was assessed using the Caprini scale and calf circumference was measured. Hemoglobin, D-dimer, antithrombin III, activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), fibrinogen degradation products (FDP), glutathione, glutathione, urea, creatinine, uric acid were recorded. Patients were divided into DVT group and non-DVT group according to whether DVT occurred after operation. Binary logistic regression was used to analyze the independent risk factors of DVT after HTO. The receiver operating characteristic (ROC) curve was plotted, and the area under curve (AUC) was calculated to analyze the predictive value of the postoperative Caprini scale in the occurrence of DVT after HTO.Results:A total of 128 patients were enrolled, 83 patients were treated with enoxaparin sodium 4 000 AXaIU/d and 45 patients were treated with enoxaparin sodium 6 000 AXaIU/d. According to the results of color Doppler examination of bilateral lower extremity veins on the third day after operation, DVT occurred in 39% (50/128) of patients, including 39 cases of calf intermuscular thrombosis, 6 cases of peroneal vein thrombosis, 4 cases of posterior tibial vein thrombosis, and 1 case of popliteal vein thrombosis. DVT occurred in 36% (30/83) of patients receiving 4 000 AXaIU/d enoxaparin sodium and 44% (20/45) of patients receiving 6 000 AXaIU/d enoxaparin sodium, with no statistically significant difference (χ 2=0.84, P=0.358). Univariate analysis showed that smoking history, postoperative Caprini scale≥8, and female may be associated with the development of DVT after HTO ( P<0.05). They were included in the binary logistic regression, and the results showed that postoperative Caprini scale≥8 was an independent risk factor for DVT after HTO. The ROC curve of postoperative Caprini scale for predicting DVT after HTO was drawn, and the AUC was 0.847 (95% CI: 0.73, 0.96), the optimal cut-off value was 8, and the sensitivity and specificity were 84.2% and 77.6%, respectively. Conclusion:Caprini scale≥8 is an independent risk factor for DVT after medial open wedge HTO. Caprini scale has a good value in predicting the occurrence of DVT after HTO. The recommended dose of enoxaparin sodium is 4 000 AXaIU/d for the prevention of postoperative DVT, and increasing the dose is not associated with a decreased risk of DVT.

OBJECTIVE Designing and synthesizing ursolic acid prodrugs to improve the water solubility and anti-multiple sclerosis(MS) activity of ursolic acid. METHODS succinic acid, dipeptide amino acid and the amino acids segments of side chains of isavuconazole wers selected according to the prodrug strategy, combined with 3-position hydroxyl of ursolic acid via condensation and esterification reaction. Using ultraviolet-visible spectrophotometry to determine the water solubility of prodrugs, and establish the experimental allergic encephalomyelitis mice model for its anti-MS efficacy evaluation. RESULTS Three prodrugs were synthesized and their structures were confirmed by 1H-NMR, 13C-NMR and LCMS(ESI). The water solubility of prodrugs 1 and 2 was over 110 times higher than ursolic acid, and that of prodrug 3 was over 200 times higher than ursolic acid. The in vivo anti-MS activity results showed that the three prodrugs showed significant anti-MS activity, among which prodrug 1 showed significantly better anti-MS activity than ursolic acid group. The mechanism might be through inhibition of peripheral inflammatory cell infiltration into the center and anti-demyelination, so as to exert the anti-MS activity. The metabolism of prodrug 1 in vivo showed that the exposure of prodrug 1 in vivo was 6 times that of ursolic acid, indicating that prodrug 1 might exert anti-MS activity mainly as sodium prototype. CONCLUSION Prodrug 1 has great anti-MS potential, which is worthy of further study. This study provides some basis and useful guidance for the development of ursolic acid prodrugs with anti-MS activity.

Objective:To explore the relationship between the maternal dietary patterns during pregnancy and the early childhood BMI change trajectory.Methods:The subjects were 1 241 pairs of pregnant women and their children in Ma'anshan maternal and infant health cohort. The food frequency questionnaire was used to collect the maternal diet data during pregnancy. The cohort children were followed up at birth, month 3, 6, 12, 18 and 24, respectively. The body height and weight data of the cohort children were collected. The principal component analysis was used to determine the categories of maternal dietary patterns during pregnancy, group-based multi-trajectory modeling was used to fit the early childhood BMI change trajectory, and the multiple classification logistic regression model was used to evaluate the relationship between the maternal dietary patterns during pregnancy and the early childhood BMI change trajectory.Results:The maternal dietary patterns during pregnancy included protein type, healthy type, vegetarian type, processing type and beverage type, which could explain 50.04% of the total dietary variation. Among them, the protein type, main dietary pattern, could explain 21.34% of the total dietary variation. The early childhood BMI change trajectory was from thinnish stature to average stature, then to mild obesity, accounting for 42.9%, 45.6% and 11.5% respectively. After controlling the potential confounding factors, it was found that there was a statistical correlation between healthy type and beverage type of maternal dietary patterns during pregnancy and early childhood BMI change trajectory ( P<0.05). Comparison of change trajectories between thinnish type and average stature type, children in the low-level group of healthy diet pattern tended to have a thinnish type change trajectory in early life ( OR=1.286, 95% CI: 1.002-1.651). Comparison of change trajectories between mild obesity type and average stature type, children in the high-level group of beverage diet pattern tended to have a mild obesity type change trajectory in early life ( OR=0.565, 95% CI: 0.342-0.935). The other dietary patterns had no statistical correlation with the early childhood BMI change trajectory. Conclusions:Maternal dietary patterns during pregnancy can affect the early childhood BMI change trajectory, and the low-level healthy type diet is an independent risk factor for thinnish type change trajectory, and the high-level beverage type diet is an independent risk factor for the mild obesity type change trajectory.