BACKGROUND:Troxerutin has been found to have a significant ameliorative effect on brain disorders,but there are fewer studies on the effects of troxerutin on the treatment of cerebral infarction and on neuronal cells. OBJECTIVE:To investigate the mechanism by which troxerutin regulates nuclear factor-κB signaling pathway to reduce brain injury and neuronal apoptosis in cerebral infarction rats. METHODS:Fifty clean grade rats were randomized into healthy group,model group,and troxerutin+nuclear factor-κB agonist group,troxerutin group,and nuclear factor-κB inhibitor group.Except for the healthy group,all other groups were used to establish a rat model of cerebral infarction by arterial ligation.The healthy and model groups were treated once a day with an equal amount of physiological saline by gavage.The troxerutin+nuclear factor-κB agonist group was intervened with 72 mg/kg troxerutin by gavage+20 mg/kg RANK intraperitoneally.The troxerutin group was treated with 72 mg/kg troxerutin by gavage.The nuclear factor κB inhibitor group was intervened intraperitoneally with 120 mg/kg nuclear factor κB inhibitor pyrrolidine disulfiram.Administration in each group was given once a day for 30 continuous days.Zea-longa was used to detect neurological damage in rats,hematoxylin-eosin staining was used to observe pathological changes,TUNEL was used to detect neuronal apoptosis,and immunoblotting and PCR were used to detect the expression of nuclear factor-κB p65 and nuclear factor-κB p50 at protein and mRNA levels,respectively. RESULTS AND CONCLUSION:Compared with the healthy group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65,nuclear factor-κB p50 mRNA and protein expression levels were elevated in the model group(P＜0.05).Compared with the model group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65 and nuclear factor-κB p50 mRNA and protein expression levels were decreased in the troxerutin+nuclear factor-κB agonist group(P＜0.05).Compared with the troxerutin+nuclear factor-κB agonist group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65 and nuclear factor-κB p50 mRNA and protein expression levels were reduced in the troxerutin group and nuclear factor-κB inhibitor group(P＜0.05).In addition,there was no difference between the troxerutin group and the nuclear factor-κB inhibitor group(P＞0.05).In the model group,there was a large number of cytoplasmic vacuolation,obvious edema and necrosis,and a large number of inflammatory cell infiltrations.In the troxerutin+nuclear factor-κB agonist,the swelling of brain tissue was reduced,and reticulate structures and condensed cells were reduced,still with some edema.In the troxerutin group and nuclear factor-κB inhibitor group,brain tissue swelling,neuronal edema degeneration,cytoplasmic vacuolation and neuronal nucleus consolidation were reduced,and the inflammatory cell infiltration was significantly decreased.To conclude,troxrutin can reduce the expression of neurological impairment,inhibit neuronal apoptosis and improve the pathological injury of brain tissue in rats with cerebral infarction,and its mechanism of action may be related to the modulation of nuclear factor-κB expression and related signaling pathways.

Neutrophil extracellular traps (NETs), intricate reticular structures released by activated neutrophils, play a pivotal regulatory role in the pathogenesis of malignant tumors. Lung cancer is one of the most prevalent malignancies globally, with persistently high incidence and mortality rates. Recent studies have revealed that NETs dynamically modulate the tumor microenvironment through unique pathological mechanisms, exhibiting complex immunoregulatory characteristics during the progression of lung cancer, and this discovery has increasingly become a focal point in tumor immunology research. This paper provides a comprehensive review of the latest advancements in NETs research related to lung cancer, offering an in-depth analysis of their impact on lung cancer progression, their potential diagnostic value, and the current state of research on targeting NETs for lung cancer prevention and treatment. The aim is to propose novel strategies to enhance therapeutic outcomes and improve the prognosis for lung cancer patients.
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Extracellular Traps/immunology* ; Humans ; Lung Neoplasms/metabolism* ; Neutrophils/metabolism* ; Animals ; Tumor Microenvironment

Colon cancer is one of the most common malignant tumors worldwide.When the conventional treatment methods provide survival benefits for patients,their side effects and limitations cannot be ignored.Many traditional Chinese medicines has attracted much attention from scholars at home and abroad because of its anti-tumor advantages of multi-target,multi-pathway and less toxic side effects.Many Chinese medicines and the active components extracted from them,represented by flavonoids,phenols and alkaloids,have played an effective role in anti-tumor.There mechanism is related to inhibiting tumor cell proliferation,inducing apoptosis,regulate autophagy,inhibiting tumor cell invasion and metastasis,inhibiting tumor angiogenesis.In this paper,the mechanism of inhibiting colon cancer by effective components of traditional Chinese medicine in recent years was reviewed in order to provide reference for the clinical treatment of colon cancer.

Objective:To investigate the mechanism of curcumin affecting HIV-1 infection co-receptor CCR5 by regulating transcription factor FOXP3.Methods:Binding sites of transcription factor FOXP3 on CCR5 promoter were predicted and analyzed by bioinformatics method.AutoDock 4.2 software was used to connect curcumin and FOXP3 flexibly.MTT assay was used to detect cyto-toxcity of curcumin on activity of Jurkat cells.qRT-PCR and Western blot were used to detect expression levels of CCR5 and FOXP3 mRNA and protein in Jurkat cells that were treated with different concentrations of curcumin.pcDNA3.1-FOXP3 expression vector was built and combined with the prediction results of transcription factors.The mutant CCR5 gene fragment was amplified by Overlap PCR,and the mutant CCR5 promoter recombinant vector pFireRluc-Mt-CCR5 was constructed.Binding site between transcription fac-tor FOXP3 and CCR5 promoter was verified by double luciferase reporter gene assay.Results:Results of JASPAR transcription factor prediction showed that there was a binding site between CCR5 promoter and transcription factor FOXP3;molecular docking results showed that curcumin could bind to the active region of FOXP3;MTT results showed that curcumin inhibited the activity of Jurkat cells after 24 hours,and the IC50 was 34.48 μmol/L.qRT-PCR and Western blot showed that expression levels of CCR5 and FOXP3 mRNA and protein were decreased in a dose-dependent manner after different concentrations of curcumin treated Jurkat cells;double luciferase reporter gene confirmed that FOXP3 could bind to CCR5 promoter,and the transcription factor FOXP3 could regulate the activity of CCR5 promoter;results of the recovery experiment of FOXP3 on curcumin showed that when the curcumin concentration was 60 μmol/L,relative value of luciferase activity in HEK293T cells with pcDNA3.1-FOXP3 and pFireRluc-Wt-CCR5 was signifi-cantly higher than that in pFireRluc-Wt-CCR5+curcumin-60 group(P<0.01).Conclusion:FOXP3 can regulate the activity of CCR5 promoter,and the mechanism may be that curcumin affects activity of CCR5 promoter by acting on binding site of FOXP3 and CCR5 promoter.

Objective:To analyze the application and regularity of acupoint selection of Sanyinjiao (SP 6) based on data mining.Methods:Search for literatures in CNKI, Wanfang, VIP, and Pubmed, the clinical researches of acupuncture on Sanyinjiao (SP 6) point were selected, according to the inclusion and exclusion criteria, and the retrieval period was from database construction to September 30th, 2021. Excel 2016, SPSS Statistics 25.0, SPSS Modeler 18.0 were used to perform descriptive analysis, association analysis and cluster analysis.Results:After literature screening, a total of 261 literatures were included, involving 73 kinds of diseases, mainly including mental and behavioral disorders, genitourinary diseases, endocrine and nutritional metabolism diseases and nervous system diseases. The most frequently used acupoints in Sanyinjiao (SP 6) compatibility are Zusanli (ST 36), Baihui (GV 20), Guanyuan (CV 4) and Taichong (LR 3), most of which focus on stomach meridian, conception channel, governor channel and bladder meridian. Seven categories were extracted among high-frequency acupoints by cluster analysis. The association rule analysis showed that the commonly used combination of Sanyinjiao (SP 6) were Zusanli (ST 36)-Sanyinjiao (SP 6), Baihui (GV 20)-Sanyinjiao (SP 6), and Guanyuan (CV 4)-Sanyinjiao (SP 6).Conclusions:Sanyinjiao (SP 6) is widely used in clinical application, and it is always compatible with stomach meridian, conception vessel, governor channel acupoints, especially those acupoints on the outer and inner meridians and the upper and lower parts. Sanyinjiao (SP 6) combined with other acupoints can treat diseases of multiple systems, such as insomnia, stroke, anxiety and depression, dysmenorrhea, infertility, etc. Clustering and association analysis found the core compatibility law of Sanyinjiao (SP 6), which can be used as a reference for clinical acupoint selection.

Objective:To investigate the value of combined detection of neutrophil gelatinase-associated lipocalin(NGAL), cystatin C(CysC)and heme oxygenase-1(HO-1)in the early diagnostic of acute kidney injury(AKI)caused by acute paraquat poisoning(APP)in elderly patients.Methods:One hundred and two elderly APP patients admitted to the emergency department of our hospital from May 2015 to June 2019 were assigned to the observation group, and 50 patients who took physical examinations served as the control group.The observation group was divided into the AKI sub-group(n=59)and the non-AKI sub-group(n=43)based on whether AKI occurred within 72 h of admission.Serum levels of NGAL, CysC, HO-1 and creatinine(Scr)were detected in all APP patients at 0 h(admission), 12 h, 24 h, 48 h and 72 h. Measurements of the same parameters were made on the day of physical examination for the control group.The correlations of serum levels of NGAL, CysC and HO-1 with the occurrence of AKI were analyzed.Relative operating characteristic curve(ROC)was drawn to analyze the diagnostic value of NGAL, CysC, HO-1 and the combination of the three for the early diagnosis of renal injury in APP patients.Results:Serum levels of NGAL, CysC, HO-1 and Scr at admission showed no significant difference between the AKI sub-group, non-AKI sub-group and control group( P>0.05). After admission, all the parameters showed an upward trend in the observation group.Serum levels of NGAL, CysC and HO-1 at 12 h after admission( P<0.05)and Scr levels at 72 h after admission( P<0.05)were significantly different between the AKI sub-group and the non-AKI sub-group.Correlation analysis showed that serum NGAL, CysC and HO-1 levels were positively correlated with the occurrence of AKI in APP patients at 12 h, 24 h, 48 h and 72 h after admission, with the best correlation at 48 h after admission(NGAL: r=0.203, 0.545, 0.707 and 0.560, P<0.05; CysC: r=0.242, 0.340, 0.754 and 0.467, P<0.05; HO-1: r=0.249, 0.536, 0.677 and 0.509, P<0.05). The area under ROC curve predicted by NGAL, CysC, HO-1, Scr and NGAL+ CysC+ HO-1 for AKI at 48 h after admission was 0.777, 0.718, 0.888, 0.602 and 0.969, respectively. Conclusions:Serum levels of NGAL, CysC and HO-1 are significantly elevated at 12 h after admission in elderly APP patients, and reach the peak at 48 h after admission.Each of them can give an earlier diagnosis for AKI than Scr, and the combination of the three provides a higher diagnostic accuracy for AKI.

Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.

Objective To discuss the effect of α-asarone on the expression level of Cyt-c,Smac,Caspase3 mRNA and protein in human esophageal carcinoma Eca-109 cell mitochondria. Methods The Eca-109 cells were cultured in vitro,and divided into the negative control group and the α-asarone treatment groups(final concentration:25,50,100 μg·mL-1).After 48 h,the morphological changes of Eca-109 cells were observed by fluorescence inversion microscope.The total RNA of cells were extracted by TRIzol method,the expressions of Cyt-c、Smac and Caspase3 were measured by RT-PCR and Western blotting. Results After Eca-109 cells were treated with different concentrations of α-asarone for 48 h,and obvious changes in the morphology were observed,the expressions of Cyt-c,Smac and Caspase3 genes and protein were increased significantly compared to the negative control group( P<0.05). Conclusion α-asarone can induce the human Eca-109 cells apoptosis by regulating expressions of mitochondrial apoptosis pathway correlation genes such as Cyt-c,Smac and Caspase3.

ObjectiveTo observe the effects of extract of Ginkgo biloba, Ginaton, on cerebral oxygen utilization coefficients (O2UCc) and lactate clearance rate (LCR) in patients with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP).Methods The 196 patients with DEACMP admitted to Harrison International Peace Hospital Affiliated to Hebei Medical University from January 2011 to March 2016 were enrolled, and they were randomly divided into a control group and an observation group, 98 cases in each groups. The control group received routine treatments such as hyperbaric oxygen, measures to prevent and treat cerebral edema, and promote brain cell metabolism, etc routine therapies: while in the observation group, besides the above routine treatments, additionally intravenous drip of Ginaton 70 mg (with 0.9% sodium chloride injection 250 mL added), once a day, for consecutive 2 weeks to complete one therapeutic course. At ambient air, before treatment and 6, 24 and 72 hours after treatment, the O2UCc and LCR and the changes of mini-mental state examination (MMSE) score, clinical efficacy and hospital mortality were observed and compared between two groups. Pearson correlation test was used to analyze the correlations between O2UCc, LCR and MMSE score.Results On the day of admission before treatment, there were no differences in O2UCc, lactate and MMSE score between the two groups (allP > 0.05). At 6 hours, 24 hours after treatment, the levels of O2UCc in observation group were obviously lower than those in control group [6 hours: (40.64±9.50)% vs. (45.78±7.94)%, P = 0.000; 24 hours: (30.51±6.76)% vs. (33.34±8.19)%,P = 0.009], while the levels of LCR were significantly higher than those in control group [6 hours: (14.93±2.27)% vs. (11.45±1.88)%,P = 0.000; 24 hours: (19.86±3.42)% vs. (13.73±2.35)%,P = 0.009]. There were no statistical significant differences in O2UCc and LCR at 72 hours after treatment between the two groups (P > 0.05). The MMSE scores at 6, 24 and 72 hours after treatment in observation group were higher than those in control group (6 hours: 15.52±3.61 vs. 11.60±2.49, 24 hours: 20.05±5.79 vs. 14.85±5.71,72 hours: 23.87±5.96 vs. 18.07±6.97, allP < 0.05). The total effective rate in observation group was significantly higher [77.55% (76/98) vs. 61.22% (60/98),P < 0.05], and the mortality [3.06% (3/98) vs. 10.20% (10/98),P < 0.05] was obviously lower than their own counterparts in control group. The correlation analysis showed that at different time points, the levels of O2UCc were negatively correlated to the corresponding MMSE scores (r6 h = -0.153,r24 h = -0.158, P6 h = 0.032,P24 h = 0.027), and there were positive correlations between the levels of LCR and MMSE scores (r6 h = 0.473, r24 h = 0.242,P6 h = 0.000,P24 h = 0.001) in patients with DEACMP.Conclusions The treatment of Ginaton in patients with DEACMP can effectively elevate the LCR and MMSE score, reduce O2UCc, decrease mortality and improve the prognosis, thus the clinical curative effect is distinct.