Objective:To investigate the role and possible mechanism of triggering receptor expressed on myeloid cells-1(TREM-1)in the inflammatory response of rat vascular smooth muscle cells(VSMCs)mediated by trimethylamine N-oxide(TMAO).Methods:VSMCs were treated with TMAO at different concentrations(0,100,300,600,900,1 200,1 500 μmol/L)for 24 hours.VSMCs were transfected with the siRNA interference plasmid targeting the TREM-1 gene(si-TREM-1)and its negative control interference plas-mid(si-NC),and 600 μmol/L TMAO was used to induce inflammatory response in VSMCs,combined with the intervention with the nuclear factor-kappa B(NF-κB)activator phorbol myristate acetate(PMA)for 24 hours.CCK-8 assay was used to measure cell prolif-erative activity;ELISA was used to measure the levels of interleu-kin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in cell supernatant;qRT-PCR was used to measure the mRNA expression levels of TREM-1,cyclooxygenase-2(COX-2),intercellular adhesion molecule-1(ICAM-1),IL-1β,IL-6,and TNF-α in cells,and Western blot was used to measure the protein expression levels of TREM-1,COX-2,ICAM-1,NF-κB p65,and p-NF-κB p65(Ser536)in cells.Results:Treatment with TMAO at different concentrations had no significant impact on the prolifera-tive activity of VSMCs(P=0.375),but it significantly upregulated the levels of IL-1β,IL-6,and TNF-α in supernatant and the mRNA and protein expression levels of TREM-1,COX-2,and ICAM-1 in cells(all P<0.01)in a concentration-dependent manner.Silencing of the TREM-1 gene significantly inhibited the increases in the levels of IL-1β,IL-6,and TNF-α in the supernatant of VSMCs in-duced by TMAO,and it also suppressed the upregulation of the mRNA expression levels of COX-2,ICAM-1,IL-1β,IL-6,and TNF-α and the ratio of p-NF-kB p65/NF-kB p65 in VSMCs(all P<0.01).However,PMA intervention significantly reversed the role of si-lencing the TREM-1 gene on TMAO-induced inflammatory response in VSMCs.Conclusion:Silencing of the TREM-1 gene can in-hibit TMAO-induced inflammatory response in VSMCs,possibly by inhibiting the activation of the NF-κB pathway.

Objective To study the effect of cobalt-60 gamma-ray (⁶⁰Co-γ) radiation on the structure of Nialamide, compare the anti-inflammatory activity of irradiation products, and explore the mechanism of action. Methods After ⁶⁰Co-γ irradiation of nialamide at a dose of 50 kGy, five known compounds were obtained (2-6). The viability of RAW 264.7 (mouse mononuclear macrophage leukemia) cells treated with these compounds was determined by CCK-8 assay. The secretion of interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE₂) and the content of nitric oxide (NO) were measured using enzyme-linked immunosorbent assay and Griess method. The production of reactive oxygen species (ROS) was detected using DCFH-DA fluorescent probe. The expression levels of cell-induced nitric oxide synthase (iNOS), cyclooxygenase (COX-2), nuclear transcription factor-κB (NF-κB), and IκB were detected using Western blot. Results The products of nialamide after irradiation did not significantly affect RAW264.7 cell viability (P > 0.05) but showed a strong anti-inflammatory effect (P < 0.01). Compared with nialamide, compounds 2, 3, 4, 6 significantly reduced NO content in LPS-induced RAW 264.7 cells (P < 0.01), and compound 4 had the most significant effect. Moreover, compound 4 significantly reduced the content of IL-6, TNF-α, PGE₂, and ROS (P < 0.05) as well as the expression of iNOS, COX-2, NF-κB, and IκB (P < 0.05) in LPS-induced RAW 264.7 cells. Conclusion The chemical structure of nialamide is changed after irradiation with ⁶⁰Co-γ, and its product compound 4 shows strong anti-inflammatory activity, which may be related to inhibiting the activation of NF-κB signaling pathway and reducing the release of inflammatory factors. Radiation technology can provide new insights into the changes of molecular structures and physiological properties of natural products.

OBJECTIVES: Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) mainly characterized by inflammation, ulceration and erosion of colonic mucosa and submucosa. Transient receptor potential vanilloid 1 (TRPV1) is an important mediator of visceral pain and inflammatory bowel disease. This study aims to investigate the protective effect of water soluble propolis (WSP) on UC colon inflammatory tissue and the role of TRPV1. METHODS: Male SD rats were randomly divided into 6 groups (n=8): a normal control (NC) group, an ulcerative colitis model (UC) group, a low-WSP (L-WSP) group, a medium-WSP (M-WSP) group, a high-WSP (H-WSP) group, and a salazosulfapyridine (SASP) group. The rats in the NC group drank water freely, and the other groups drank 4% dextran sulfate sodium (DSS) solution freely for 7 d to replicate the ulcerative colitis model. Based on the successful replication of the UC, the L-WSP, M-WSP, and H-WSP groups were given 50, 100, and 200 mg/kg of water-soluble propolis by gavage for 7 d, and the SASP group was given 100 mg/kg of sulfasalazine by gavage for 7 d. The body weight of rats in each group was measured at the same time every day, the fecal traits and occult blood were observed to record the disease activity index (DAI). After intragastric administration, the animals were sacrificed after fasted 24 h. Serum and colonic tissue were collected, and the changes of MDA, IL-6 and TNF-α were detected. The pathological changes of colon tissues were observed by HE staining, and the expression of TRPV1 in colon tissues was observed by Western blotting, immunohistochemistry, and immunofluorescence. RESULTS: The animals in each group that drank DSS freely showed symptoms such as weight loss, decreased appetite, depressed state, and hematochezia, indicating that the model was successfully established. Compared with the NC group, DAI scores of other groups were increased (all P<0.05). MDA, IL-6, TNF-α in serum and colon tissues of the UC group were increased compared with the NC group (all P<0.01), and they were decreased after WSP and SASP treatment (all P<0.01). The results of showed that the colon tissue structure was obviously broken and inflammatory infiltration in the UC group, while the H-WSP group and the SASP group significantly improved the colon tissue and alleviated inflammatory infiltration. The expression of TRPV1 in colon tissues in the UC group was increased compared with the NC group (all P<0.01), and it was decreased after WSP and SASP treatment. CONCLUSIONS WSP can alleviate the inflammatory state of ulcerative colitis induced by DSS, which might be related to the inhibition of inflammatory factors release, and down-regulation or desensitization of TRPV1.
Animals ; Male ; Rats ; Antineoplastic Agents/therapeutic use* ; Colitis, Ulcerative/chemically induced* ; Colon/pathology* ; Disease Models, Animal ; Interleukin-6/pharmacology* ; Propolis/therapeutic use* ; Rats, Sprague-Dawley ; Sulfasalazine/therapeutic use* ; TRPV Cation Channels ; Tumor Necrosis Factor-alpha/pharmacology*

Objective:To explore risk factors for clinical onset in children with uncontrolled self-limited epilepsy with centrotemporal spikes (SeLECTS) managed by 2 anti-seizure medications (ASMs).Methods:A total of 112 children with SeLECTS who were diagnosed at the Department of Pediatric Neurology of the Third Affiliated Hospital of Zhengzhou University from January 2018 to May 2021 were retrospectively reviewed.All of them were treated with conventional ASMs, and regularly followed up for 1-2 years.Types of therapeutic drugs, clinical seizure control status, presence of new seizure forms, electroencephalogram (EEG) were reviewed at follow-up visits.According to whether the seizures were controlled after the use of no more than 2 ASMs, patients were divided into poor response group (43 cases) and good response group (69 cases), and their clinical data and EEG characteristics were compared.Multivariate Logistic regression analysis was used to explore the risk factors for seizures that were uncontrolled by 2 ASMs. Results:There were significant differences in the age of onset ( χ2=8.919, P=0.003), seizure form ( χ2=4.218, P=0.040), seizure frequency ( Z=-7.664, P<0.001), EEG background slowing ( χ2=10.284, P=0.001), emergence of electrical status epilepticus during slow-wave sleep (ESES)( χ2=11.921, P=0.001), discharge generalization ( χ2=25.377, P<0.001), and presence of epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS)( χ2=54.334, P<0.001) between groups.Multivariate Logistic regression analysis showed that seizure frequency ( P<0.001, OR=0.086, 95% CI: 0.022-0.329), discharge generalization ( P=0.006, OR=9.942, 95% CI: 1.918-51.527) and EEG background slowing ( P=0.041, OR=6.648, 95% CI: 1.077-41.038) were the 3 main risk factors associated with poor response to short-term medications of ASMs. Conclusions:Seizures are easily controlled in most SeLECTS patients medicated with ASMs with a favorable prognosis.Seizure frequency, discharge generalization and EEG background slowing are risk factors for the poor response to short-term pharmacotherapy in children with SeLECTS.

Despite the advancement of treatments, adults with relapsed/refractory (R/R) B-lineage acute lymphoblastic leukemia (B-ALL) have poor prognosis, with an expected five-year overall survival (OS) rate of 10%‒20% (Nguyen et al., 2008; Oriol et al., 2010). Extramedullary relapse of B-ALL is regarded as a high-risk factor generally associated with poor survival, occurring in about 15% to 20% of all relapsed patients (Ding et al., 2017; Sun et al., 2018). The central nervous system (CNS) and the testes are the most common sites of extramedullary relapse of B-ALL. In addition, extramedullary leukemia can appear in the skin, eyes, breasts, bones, muscles, and abdominal organs. The prognosis of relapsed extramedullary B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is extremely poor (Spyridonidis et al., 2012; Dahlberg et al., 2019). Conventional chemotherapy or radiation is often ineffective in such patients. At present, there are no optimal treatment strategies for treating extramedullary leukemia after allo-HSCT.
Adult ; Antigens, CD19 ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunotherapy, Adoptive/adverse effects* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Receptors, Chimeric Antigen ; Recurrence

Objective:To analyze any changes in the functional connectivity between the seed points of the dorsolateral prefrontal cortex (DLPFC) and the whole brain, as well as any fluctuations in the low-frequency amplitude among persons with post-stroke depression (PSD). The aim was to develop correlations among functional imaging results, clinical scales, and inflammation indicators including high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), interleukin 2 (IL-2), interleukin 10 (IL-10), interleukin 17a (IL-17a) and interferon-γ (IFN-γ).Methods:Between 2016 and 2020, 55 ischemic stroke survivors were tested. The 28 scoring 7 or more on the Hamilton Depression Scale (HAMD-17) formed the PSD group, while the 27 others formed the control group. Functional magnetic resonance images were collected, and serum inflammation indicators were determined.Results:When seed points in the left DLPFC were used, in the PSD group the frontal cortex (FC) decreased in one cluster, with a voxel of 129mm3 and the MNI coordinates (x=9, y=30, z=33) indicating that the anatomical automatic labeling (AAL) brain regions were the Cingulum_Ant_L, Cingulum_Mid_R and the frontal_Sup_Medial_L. When the right DLPFC was used as the seed point the FC again decreased in one cluster, with voxels of 44mm 3 and the MNI coordinates (x=-27, y=12, z=47) referring to the AAL brain region of the frontal_Mid_L. In the PSD group, the FC value of abnormal brain areas with the R-DLPFC as the seed point was positively correlated with time since stroke. In the control group, the FC value of abnormal brain areas with L-DLPFC as the seed point was negatively correlated with MoCA, while with R-DLPFC as the seed point it was positively correlated with IFN-γ. The FC values of abnormal areas of the brain showed no significant correlation with other clinical scales, inflammation indicators or lesion volume. Conclusion:Abnormal functional connections within the executive control network and between the salience networks may participate in the mechanism of PSD, and may be related to the time since stroke, cognitive functioning, and IFN-γ levels.

Objective:To explore the clinical value of extra-long subcutaneous tunnel ventricular drainage in patients with hydrocephalus.Methods:From March 2016 to March 2020, 33 patients who were not suitable for ventriculoperitoneal shunt, who would have expected time of external ventricular drainage longer than 7 d, who had external ventricular drainage reaching for 7 d and still could not expect for drainage tube drawing for the next 7 d, or who had hydrocephalus after external ventricular drainage were chosen in our study. These patients accepted extra-long subcutaneous tunnel ventricular drainage. The curative effects in the patients were analyzed retrospectively.Results:The drainage tube was kept for a maximum of 24 months and the shortest time was 13 d, with average of 69.3 d; 32 patients (97%) had drainage time longer than 14 d. There was no secondary infection after operation.Conclusion:Extra-long subcutaneous tunnel extraventricular drainage tube has a long duration of catheter placement, could avoid multiple drainage and secondary intracranial infection, so it is a safe and effective new technology for hydrocephalus.

Chimeric antigen receptor T (CAR-T) cell therapy, which adoptively transfers engineered T cells expressing synthetic receptors to target specific antigens, has achieved great clinical success in treating hematological malignancies. Though FDA has approved two CAR-T products, CAR-T therapy can cause some side effects, such as cytokine release syndrome (CRS), neurotoxicity and B cell aplasia. Meanwhile, lacking tumor specific antigen and the suppressive tumor environment limit the efficacy of CAR-T therapy in solid tumor. This review focuses on the structural components, clinical applications and synthetic biology approaches on CAR-T cell design, and summarizes the challenges and perspectives of CAR-T therapy as a revolutionary cancer immunotherapy.
Cell- and Tissue-Based Therapy ; Child ; Humans ; Immunotherapy ; Immunotherapy, Adoptive ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen ; T-Lymphocytes

Objective To observe the clinical efficacy of acupuncture in treating Oxycodone hydrochloride-induced constipation in cancer pain patients.Method Sixty cancer pain patients with Oxycodone hydrochloride-induced constipation were randomized into a treatment group and a control group, 30 cases in each group. The treatment group was intervened by acupuncture, while the control group was by oral administration of lactulose oral solution. The therapeutic efficacies were compared after 2-week treatment, and the quality of life was evaluated before and after treatment.Result The total effective rate was 90.0% in the treatment group versus 73.3% in the control group, and the difference was statistically significant (P<0.05). The Karnofsky Performance Status (KPS) score was significantly changed in the treatment group after intervention (P<0.05). There was a significant difference in comparing the KPS score between the two groups after treatment (P<0.05).Conclusion Acupuncture can produce a significant efficacy in treating Oxycodone hydrochloride-induced constipation, and also improve the patients’ quality of life.

OBJECTIVE:To systematically review the efficacy of ursodeoxycholic acid(UDCA)in the prevention ofulcerative colitisassociated colorectal cancer (UC-CRC) and dysplasia (UC-Dys),and provide evidence-based reference for clinic. METH-ODS:Retrieved from Cochrane Library,EMBase,PubMed,CJFD,CBM,VIP and Wanfang Database,randomized controlled tri-als(RCT)or cohort studies about UDCA(test group)versus placebo(control group)in the prevention of UC-CRC and UC-Dys were collected. Meta-analysis was performed by using Rev Man 5.3 software after quality evaluation and data extraction by Co-chrane Manual 5.1.0. RESULTS:Totally 7 studies(3 randomized controlled trials and 4 cohort studies)were included in the analy-sis,involving 672 patients. Results of Meta-analysis of 3 RCT showed that there was no significant difference in the incidence of UC-CRC and UC-Dys between 2 groups [OR=0.95,95%CI(0.17,5.12),P=0.95];results of Meta-analysis of 4 cohort studiess-howed that there was no significant difference in the incidence of UC-CRC and UC-Dys between 2 groups[OR=0.74,95%CI(0.30, 1.84),P=0.52]. Results of subgroup analysis showed,the incidence of UC-CRC and UC-Dys in test group with low-dose UDCA (<15 mg/kg) was significantly lower than control group,the difference was statistically significant [OR=0.19,95%CI(0.08, 0.49),P<0.001];there were no signifficant diferences in the incidence of UC-CRC and UC-Dys in high-dose UDCA group[OR=1.97,95%Cl(0.53,7.25),P=0.31](≥15 mg/kg). There was no significant difference in the incidence of adverse reactions(P>0.05). CONCLUSIONS:UDCA can not decease the incidence of UC-CRC and UC-Dys,it only prompts a possible trend toward decreased UC-CRC and UC-Dys risk in low-doseUDCA.