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Objective:To study the effect and molecular mechanism of BRCA2 gene on the killing of lung cancer by immune cells.Methods:siRNA was designed to reduce BRCA2 gene in lung cancer cells;BRCA2 expression was detected by qPCR and Western blot;cell growth was detected by MTT and CCK-8 methods;peripheral blood mononuclear cells were co-cultured with lung cancer cells,and GFP fluorescence was detected by enzyme labeling method.Killing efficiency of lung cancer cells was evaluated.Results:BRCA2 gene was expressed in moderate abundance in lung cancer cells A549 and H1299,and there was no significant differ-ence compared with lung epithelial cells BEAS-2B(P>0.05).When the BRCA2 gene in A549 and H1299 cells was successfully knocked down,the cell proliferation rate was significantly increased compared with control group;the killing efficiency of peripheral blood mononuclear cells to lung cancer cells A549 and H1299 were significantly higher than that of the control group;the expression of ATM,RAD51 and RAD50 were significantly reduced,while the expression of P53 protein was 7.2 times of the control group.Con-clusion:After knockdown of BRCA2 gene,peripheral blood monocytes are more effective in killing lung cancer cells.Intervention of BRCA2 and monocytes can synergistically inhibit lung cancer and regulate the expression of ATM signaling pathway molecules.
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Objective To investigate the modulatory effect of Yulian Pills(composed of Coptidis Rhizoma and Euodiae Fructus)on splenic memory follicular T helper cell(mTfh)in mice with dextran sodium sulfate(DSS)-induced ulcerative colitis.Methods Forty BALB/c mice were randomly divided into normal group,model group,Yulian Pills group(0.5 g·kg-1)and Mesalazine group(0.3 g·kg-1),10 mice in each group.The mouse model of ulcerative colitis was induced by ad libitum drinking 3%DSS solution for 7 days.During the experiment,the mental state,faecal characteristics,blood in stool and body mass of the mice were recorded daily,and the length and mass of the colon were measured and the colon mass index was calculated;HE staining was used to observe the pathological and morphological changes of the colon tissue;ELISA was used to determine the expression levels of interleukin(IL)-6 and IL-15 in the colon tissues;flow cytometry was used to determine the mTfh cell subpopulation in the spleen tissue expression;Western Blot was used to determine the protein expression levels of Roquin-1,AMPK-α,p-AMPK-α in colon tissues.Results Compared with the normal group,the mice in the model group showed a significant decrease in body mass(P＜0.01),a significant shortening of colon length(P＜0.01),significant increase in colon mass(P＜0.05)and colon mass index(P＜0.01),and severe pathological damage to colon tissues;the expression levels of the pro-inflammatory cytokines IL-6 and IL-15 in the colon tissues were significantly increased(P＜0.01);cell expression levels of CD4+CCR7-CXCR5+CD62L+,CD4+CCR7+CXCR5+ GL7+,CD4+CCR7-CXCR5+GL7+ were significantly increased in spleen tissues(P＜0.01),whereas the expression level of CD4+CCR7+CXCR5+CD62L+ cell was significantly decreased(P＜0.01);and protein expression levels of Roquin-1,AMPK-α,p-AMPK-α were significantly reduced in the colonic tissues(P＜0.05).Compared with the model group,mice in the Yulian Pills group and Mesalazine group showed a significant increase in body mass(P＜0.05),a significant extension of colon length(P＜0.01),a significant reduction in colon mass(P＜0.05),a significant decrease in the colon mass index(P＜0.01),and a more obvious improvement in pathological damage of the colon tissues;a significant decrease in the expression levels of IL-6 and IL-15 in the colon tissues(P＜0.01);cell expression levels of CD4+CCR7-CXCR5+CD62L+,CD4+CCR7+CXCR5+GL7+,CD4+CCR7-CXCR5+GL7+ in splenic tissues was significantly reduced(P＜0.01),whereas the expression level of CD4+CCR7+CXCR5+CD62L+ cell was significantly increased(P＜0.01);the protein expression levels of Roquin-1,AMPK-α,and p-AMPK-α were significantly increased in colon tissues(P＜0.05,P＜0.01).Conclusion The therapeutic effect of Yulian Pills on DSS-induced ulcerative colitis mice can ameliorate the histopathological damage of colon,which may be related to the activation of the Roquin-1/MPK-α signalling pathway,the down-regulation of the expressions of inflammatory cytokines IL-6 and IL-15,and the modulation of the homeostasis of the mTfh cell subpopulation.
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@#Objective: To explore the mechanism by which icariin alleviates viral myocarditis. Methods: CVB3-induced cardiomyocytes were used as an in vitro model of viral myocarditis to assess the effects of icariin treatment on cell viability, inflammation, and apoptosis. Moreover, the effects of icariin on ferroptosis and TLR4 signaling were assessed. After AC16 cells were transfected with TLR4 overexpression plasmids, the role of TLR4 in mediating the regulatory effect of icariin in viral myocarditis was investigated. Results: Icariin significantly elevated cell viability and reduced inflammatory factors TNF-α, IL-1β, IL-6, and IL-18. Flow cytometry revealed that icariin decreased apoptosis rate, and the protein expression of Bax and cleaved caspase 3 and 9 in CVB3-induced cardiomyocytes. Additionally, it suppressed ferroptosis including lipid peroxidation and ferrous ion, as well as the TLR4 signaling. However, TLR4 overexpression abrogated the modulatory effects of icariin. Conclusions: Icariin mitigates CVB3-induced myocardial injury by inhibiting TLR4-mediated ferroptosis. Further animal study is needed to verify its efficacy.
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Purpose To evaluate the diagnostic accuracy of abdominal plain scan and contrast-enhanced multi-slice CT after orally diluted iodide in time segment(Post-ODI ANCCE-MSCT)for gastrointestinal fistula(GIF)secondary to acute pancreatitis(AP).Materials and Methods A total of 108 patients with late AP in the prospective and continuously collected database of Hunan Provincial People's Hospital from January 2017 to December 2022 were retrospectively extracted.Their demographic information and clinical features were recorded and GIF were screened by Post-ODI ANCCE-MSCT.The comprehensive clinical diagnosis results within 5 days thereafter were used as reference standards.The sensitivity,specificity,positive predictive value,negative predictive value and accuracy of Post-ODI ANCCE-MSCT for diagnosing GIF secondary to AP were calculated using a four-cell table,and the consistency of the two methods was evaluated by Kappa test and McNemar's test.Results Sensitivity was 91.5%(95%CI 78.7%-97.2%),specificity was 98.4%(95%CI 90.0%-99.9%),positive predictive value was 97.7%(95%CI 86.5%-99.9%),negative predictive value was 93.8%(95%CI 84.0%-98.0%),and the accuracy was 95.4%(95%CI 91.4%-99.3%),respectively.The Kappa value was 0.905,and P value was 0.375 via McNemar's test.Conclusion Post-ODI ANCCE-MSCT can diagnose GIF secondary to AP in a simple,non-invasive,rapid and accurate way,and provide earlier,more accurate and reliable image basis for clinical diagnosis and treatment.
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Objective: To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL). Methods: A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children's Hospital, Capital Medical University and Baoding Children's Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients. Results: Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) (χ2=1.88, 1.47, P=0.170, 0.224). Conclusions: Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.
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Male , Child , Infant , Female , Humans , Retrospective Studies , In Situ Hybridization, Fluorescence , Prognosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Abnormal Karyotype , RecurrenceABSTRACT
Purpose To evaluate the classification criteria of triple negative breast cancer(TNBC)based on histomorphol-ogy and immunohistochemistry(IHC),and to provide theoreti-cal basis for the classification and treatment of TNBCs.Methods TNBC subtyping was performed according to the histomorphologi-cal characteristics and the expression of immune markers AR,CD8 and FOXC1,and the clinicopathological features and prog-nostic differences were compared.Results Among 93 cases of TNBC,there were 23 cases(24.7％)of luminal androgen re-ceptor subtypes,24 cases(25.8％)of immunomodulatory type,39 cases(42.0％)of basal immunosuppressive type,and 7 ca-ses(7.5％)of mesenchymal type.There were significant differ-ences in the clinicopathological features of subtypes,including pT stage(P=0.030),histological grade(P＜0.001),intersti-tial lymphocyte infiltration pattern(P＜0.001),expression of PD-L1(P＜0.001),and HER2-low(P=0.024).There was no significant difference in disease-free survival among the sub-types(P＞0.05).Univariate survival analysis showed there was significant difference in disease-free survival among the subtypes at pT1 stage(P=0.011),and other clinicopathological features were not independent prognostic factors.Conclusion The clini-copathological characteristics of TNBC subtypes are different,which are expected to be an alternative choice for complex gene expression profile analysis and to provide theoretical basis for subtypic therapy and targeted therapy.
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Objective To explore the diagnostic value of Likert score and EPE grade score based on multiparameter magnetic resonance imaging(mpMRI)for extracapsular extension in prostate cancer(PCa).Methods The MR imaging and histopathology data from 272 PCa patients were analyzed retrospectively.All patients underwent mpMRI examination within 2 months before radical prostatectomy.Two radiologists with over 10 years of experience assessed the mpMRI images according to the Likert score and EPE grade score,respectively,and compared with pathological findings.The consistency between the two radiologists was evaluated by weighted Kappa test.The statistical analysis was performed using MedCalc 20.0 software.The sensitivity,specificity and other indicators were calculated to analyze the optimal cut-off value of Likert score and EPE grade score for diagnosing extracapsular extension in PCa.The area under the curve(AUC)was used to compare the diagnostic performance of the two scoring systems for extracapsular extension in PCa.Results Among 272 PCa patients,there were 45 cases with extracapsular extension and 227 cases without extracapsular extension.The weighted Kappa coefficients were 0.730 and 0.820 for Likert score and EPE grade score,respectively,indicating good consistency.The optimal cut-off values for diagnosing extracapsular extension in PCa were Likert score 3 and EPE grade score 2.The sensitivity and specificity were 68.8%and 77.5%for Likert score 3,and 64.4%and 84.5%for EPE grade score 2,respectively.Both Likert score(AUC=0.780)and EPE grade score(AUC=0.797)had high accuracy in predicting extracapsular extension in PCa,with no significant difference(P>0.05).Conclusion Both Likert score and EPE grade score have good diagnostic performance in detecting extracapsular extension in PCa,which provides important diagnostic basis for clinical staging of PCa.
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Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.
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Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression. These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.
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Animals , Humans , Squamous Cell Carcinoma of Head and Neck , Carcinogenesis/genetics , Cell Transformation, Neoplastic , Wnt Signaling Pathway , Disease Models, Animal , Head and Neck Neoplasms/genetics , Wnt Proteins , Frizzled Receptors/genetics , Janus Kinase 1 , STAT3 Transcription FactorABSTRACT
Objective:To explore the immunological characteristics of peripheral blood and genetic variations of 11 immunodeficiency virus(HIV)-negative children with Talaromyces marneffei(TM) infection, thus enhancing the diagnostic and therapeutic levels of TM infection in children. Methods:Clinical data of 11 HIV-negative children with TM infection who presented to Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from January 2010 to December 2022 were retrospectively analyzed, including clinical characteristics, peripheral immune profile and genetic test results.Results:A total of 11 HIV-negative children with TM infections were recruited, involving 9 males and 2 females with a median age of 19 months.The main clinical manifestations were fever (10/11, 90.91%), cough (10/11, 90.91%) and hepatomegaly (7/11, 63.64%). Common severe complications included acute respiratory distress syndrome (7/11, 63.64%) and septic shock (5/11, 45.45%). Finally, 2 children died.Transient neutropenia occurred in 6 cases (6/11, 54.55%), and lymphocytopenia combined with serum immunoglobulin (Ig) G decrease was observed in 4 cases (4/11, 36.36%). IgA decrease, IgM decrease, IgE decrease, IgM increase and IgE increase were observed in 6 cases, 3 cases, 5 cases, 3 cases, and 2 cases, respectively.Both T-lymphocyte and B-lymphocyte counts decreases was observed in 1 case.Genetic testing was performed in all recruited children, and genetic variations were detected in all of them.Inborn errors of immunity (IEIs) were diagnosed in 8 cases, including 4 diagnosed as CD 40 ligand deficiency with CD40LG variation, 1 of severe combined immunodeficiency with IL2RG variation, 1 of Signal transduction and activator of transcription 3(STAT3)-hyper-IgE syndrome with STAT3 variation and 1 of familial candidiasis type 2 with CARD9 compound heterozygous mutations.In the other 3 cases, 2 carried genetic variations that were likely pathogenic, and 1 case was considered uncertain. Conclusions:The clinical manifestations of HIV-negative children with TM infection are atypical, which is characterized as serious complications and high mortality.Early identification and gene testing to detect potential IEIs can improve the prognosis of TM infection.
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Objective: To assess the safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use on different immunization procedures in healthy people aged 9-65 years. Methods: A randomized, blind, positive-controlled clinical study was conducted in March 2015. The eligible residents aged 9-65 were recruited in Dengfeng city and Biyang County, Henan Province. A total of 1 956 subjects were enrolled. The subjects were randomly (1∶1∶1) assigned to 5-dose control group, 4-dose trial group and 5-dose trial group, with 652 subjects in each group. The subjects of 5-dose control group were immunized with control vaccine on days 0, 3, 7, 14 and 28. The subjects of 4-dose trial group were immunized with trial vaccine on days 0, 7 and 21 (2-1-1 phases) and the subjects of 5-dose trial group were immunized with trial vaccine on days 0, 3, 7, 14 and 28. A combination of regular follow-up and active reporting was used to observe local and systemic adverse reactions till 30 days after the first and full immunization, and the incidence rate of adverse reactions in three groups was analyzed and compared. The venous blood was collected before the first immunization, 7 days after the first immunization, 14 days after the first immunization and 14 days after the full immunization. The neutralizing antibody of rabies virus was detected by rapid fluorescent focus inhibition test (RFFIT), and the seropositive conversion rate and geometric mean concentration (GMC) of antibody were calculated. Results: The adverse reaction rates in 5-dose control group, 4-dose trial group and 5-dose trial group were 41.87% (273/652), 35.43% (231/652) and 34.97% (228/652), respectively. The adverse reaction rates of 4-dose trial group and 5-dose trial group were lower than those of the 5-dose control group (P<0.05). The local reactions were mainly pain, itching, swelling and redness in injection site, while the systemic reactions were mainly fever, fatigue, headache and muscle pain. The severity of adverse reactions was mainly mild (level 1), accounting for 85.33% (518/607), 89.02% (373/419) and 88.96% (427/480) of the total number of adverse reactions in each group. At 14 days after the first immunization and 14 days after the full immunization, the antibody positive conversion rates of three groups were all 100%. At 7 days, 14 days after the first immunization and 14 days after the full immunization, the GMCs of three groups were 0.60, 0.72, 0.59 IU/ml, 20.42, 23.99, 24.38 IU/ml and 22.95, 23.52, 24.72 IU/ml, respectively, with no significant difference (P>0.05). Conclusion: The freeze-dried rabies vaccine (Vero-cells) for human use has good safety and immunogenicity when inoculated according to 5-dose and 4-dose immunization procedures.
Subject(s)
Humans , Rabies Vaccines , Antibodies, Viral , Antibodies, Neutralizing , Rabies virus , Vaccination , Rabies/prevention & controlABSTRACT
This study explored the effects of propofol on the activity of glutamatergic neurons in the paraventricular thalamus (PVT) and the underlying mechanisms at the molecular level using whole-cell patch-clamp techniques. Acute brain slices containing the PVT were obtained from 8 weeks old C57BL/6J mice. The electrophysiological characteristics of PVT neurons were recorded in current-clamp mode, then single-cell sequencing was used to identify neuronal types. The firing frequencies before, during, and after propofol or intralipid application were recorded as FB, FD and FW; and the membrane potentials were recorded as MPB and MPD. Picrotoxin (PTX) was used to block inhibitory gamma-aminobutyric acid type A (GABAA) receptors during the application of propofol at 10 μmol·L-1. Then, GABAA receptor-mediated spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) were recorded, and the effects of 10 μmol·L-1 propofol were investigated. The animal experiments were approved by the Medical Animal Administrative Committee of Shanghai Medical College Fudan University. The results showed that there were no significant differences in FB, FD and FW during intralipid and 2 μmol·L-1 propofol application. With propofol at 5, 10 and 20 μmol·L-1, FD decreased significantly when compared with FB, and FW increased significantly as compared with FD (P < 0.01). The inhibition degree of the three concentration groups was significantly different (P < 0.01). In addition, with propofol at 20 μmol·L-1, MPD hyperpolarized significantly (P < 0.01). In the presence of PTX, 10 μmol·L-1 propofol could not suppress the firing frequency of PVT glutamatergic neurons. Propofol at 10 μmol·L-1 prolonged the decay time of sIPSCs (P < 0.01) and mIPSCs (P < 0.05), and increased the amplitude (P < 0.01) of mIPSCs of PVT glutamatergic neurons. Together, these results indicate that propofol can inhibit the activity of PVT glutamatergic neurons in a concentration-dependent and reversible manner, and the effect is likely to be mediated by postsynaptic GABAA receptors.
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Orbital fracture often leads to facial collapse, diplopia, enophthalmos, and even blindness. Traditional surgery relies on the experiences of physicians to achieve fracture reduction and orbital wall reconstruction, but the repair effect is not satisfactory. In recent years, with the development of digital technology, technologies such as computer-assisted surgery, 3D printing, surgical navigation systems, and intraoperative CT imaging have become increasingly widespread in the field of orbital reconstruction. Such techniques can avoid dependence on physicians′ experiences and make it easy for estimating and positioning the implantation sites, which subsequently contributes to better surgery efficiency and precise reconstruction of the orbit, improving aesthetics and visual function of patients. To this end, the authors reviewed the recent progress in application of digital technology for orbital fracture reconstruction, so as to provide reference and theoretical basis for clinical practice.
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Objective:To investigate the functional connectivity of default mode network (DMN) and limbic system, the expression level of inflammatory cytokine and their correlation in bipolar disorder type Ⅱ(BDⅡ) patients with depressive episodes.Methods:Thirty-three BD Ⅱ patients with depressive episodes and forty-six healthy controls were recruited to complete the resting-state functional magnetic resonance imaging (rs-fMRI). After image preprocessing, the DMN and limbic system were extracted from the image data by independent component analysis (ICA), so as to compare the differences of functional connectivity of resting brain network between the patients and the controls.Serum levels of inflammatory cytokines interleukin-6 (IL-6), interleukin-8(IL-8), interleukin-10(IL-10), tumor necrosis factor-α (TNF-α), and C-C motif chemokine ligand 4 (CCL4) in patients and healthy controls were detected.The correlation between functional connectivity of different brain regions and inflammatory cytokines was analyzed.SPSS 17.0 software was used for data statistical analysis.The two samples were compared using t-test or Mann-Whitney U-test, and Spearman was used for correlation testing. Results:In BDⅡ patients, the functional connectivity of the right medial prefrontal cortex(cluster-size=7 voxel, cluster-level PGRF<0.05, MNI: x=6, y=54, z=9, t=-3.765) and the left superior frontal gyrus(cluster-size=10 voxel, cluster-level PGRF<0.05, MNI: x=-21, y=54, z=15, t=-4.139) in DMN decreased, while the left cerebellum Ⅳ and Ⅴ lobules of limbic system (cluster-size=21 voxel, cluster-level PGRF<0.05, MNI: x=-15, y=-24, z=-30, t=4.468) and cerebellar tonsil of left cerebellum posterior lobe(cluster-size=8 voxel, cluster-level PGRF<0.05, MNI: x=-15, y=-51, z=-45, t=4.138) in the limbic system increased.Compared with the healthy controls, the serum levels of IL-10(7.39 (6.33, 9.32) pg/mL vs 6.54 (5.84, 7.39) pg/mL, Z=-2.937, P=0.003)and CCL4 (39.31 (25.77, 68.70) pg/mL vs 31.30 (20.32, 40.89) pg/mL, Z=-2.209, P=0.027) were higher in BDⅡ patients.The functional connectivity of the left cerebellum Ⅳ and Ⅴ lobules was positively correlated with the serum levels of IL-10 ( r=0.432, P=0.031) and that of the cerebellar tonsil of left cerebellum posterior lobe was positively correlated with the serum levels of IL-10 ( r=0.429, P=0.032) and CCL4 ( r=0.402, P=0.046). Conclusion:The functional connectivity of DMN and limbic system in BDⅡ patients with depressive episode is abnormal in resting-state fMRI.The expression level of inflammatory cytokines in patients' serum increases, and has correlation with the functional connection of limbic system.
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Objective:To compare the cost-effectiveness before and after using an artificial intelligence gastroscopy-assisted system for early gastric cancer screening.Methods:The gastroscopy cases before (non-AI group) and after (AI group) the use of artificial intelligence gastroscopy-assisted system were retrospectively collected in Renmin Hospital of Wuhan University from January 1, 2017 to February 28, 2022. The proportion of early gastric cancer among all gastric cancer was analyzed. Costs were estimated based on the standards of Renmin Hospital of Wuhan University and the 2021 edition of Wuhan Disease Diagnosis-related Group Payment Standards. Cost-effectiveness analysis was conducted per 100 thousand cases with and without the system. And the incremental cost-effectiveness ratio was calculated.Results:For the non-AI group, the proportion of early gastric cancer among all gastric cancer was 28.81% (70/243). The cost of gastroscopy screening per 100 thousand was 54 598.0 thousand yuan, early gastric treatment cost was 221.8 thousand yuan, and a total cost was 54 819.8 thousand yuan. The direct effectiveness was 894.2 thousand yuan, the indirect effectiveness was 1 828.2 thousand yuan and the total effectiveness was 2 722.4 thousand yuan per 100 thousand cases. For the AI group, the early gastric cancer diagnositic rate was 36.56%(366/1 001), where gastroscopy cost was 53 440.0 thousand yuan, early gastric treatment cost 315.8 thousand yuan, the total cost 53 755.8 thousand yuan. The direct effectiveness was 1 273.5 thousand yuan, indirect effectiveness 2 603.1 thousand yuan and the total effectiveness 3 876.6 thousand yuan per 100 thousand cases. The use of the system reduced the cost of early gastric cancer screening by 1 064.0 thousand yuan, and increased the benefit by 1 154.2 thousand yuan per 100 thousand cases. The incremental cost-effectiveness ratio was -0.92.Conclusion:The use of artificial intelligence gastroscopy-assisted system for gastric early cancer screening can reduce medical costs as well as improve the efficiency of screening, and it is recommended for gastroscopy screening .
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Objective@#This study uses structural magnetic resonance imaging to explore changes in the cerebellar lobules in patients with autism spectrum disorder (ASD) and further analyze the correlation between cerebellar structural changes and clinical symptoms of ASD. @*Methods@#A total of 75 patients with ASD and 97 typically developing (TD) subjects from Autism Brain Imaging Data Exchange dataset were recruited. We adopted an advanced automatic cerebellar lobule segmentation technique called CEREbellum Segmentation to segment each cerebellar hemisphere into 12 lobules. Normalized cortical thickness of each lobule was recorded, and group differences in the cortical measures were evaluated. Correlation analysis was also performed between the normalized cortical thickness and the score of Autism Diagnostic Interview-Revised. @*Results@#Results from analysis of variance showed that the normalized cortical thickness of the ASD group differed significantly from that of the TD group; specifically, the ASD group had lower normalized cortical thickness than the TD group. Post-hoc analysis revealed that the differences were more predominant in the left lobule VI, left lobule Crus I and left lobule X, and in the right lobule VI and right lobule Crus I. Lowered normalized cortical thickness in the left lobule Crus I in the ASD patients correlated positively with the abnormality of development evident at or before 36 months subscore. @*Conclusion@#These results suggest abnormal development of cerebellar lobule structures in ASD patients, and such abnormality might significantly influence the pathogenesis of ASD. These findings provide new insights into the neural mechanisms of ASD, which may be clinically relevant to ASD diagnosis.
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This study investigated the effect of multi-glycosides of Tripterygium wilfordii(GTW) on renal injury in diabetic kidney disease(DKD) rats through Nod-like receptor protein 3(NLRP3)/cysteine-aspartic acid protease-1(caspase-1)/gsdermin D(GSDMD) pyroptosis pathway and the mechanism. To be specific, a total of 40 male SD rats were randomized into the normal group(n=8) and modeling group(n=34). In the modeling group, a high-sugar and high-fat diet and one-time intraperitoneal injection of streptozotocin(STZ) were used to induce DKD in rats. After successful modeling, they were randomly classified into model group, valsartan(Diovan) group, and GTW group. Normal group and model group were given normal saline, and the valsartan group and GTW group received(ig) valsartan and GTW, respectively, for 6 weeks. Blood urea nitrogen(BUN), serum creatinine(Scr), alanine ami-notransferase(ALT), albumin(ALB), and 24 hours urinary total protein(24 h-UTP) were determined by biochemical tests. The pathological changes of renal tissue were observed based on hematoxylin and eosin(HE) staining. Serum levels of interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected by enzyme-linked immunosorbent assay(ELISA). Western blot was used to detect the expression of pyroptosis pathway-related proteins in renal tissue, and RT-PCR to determine the expression of pyroptosis pathway-related genes in renal tissue. Compared with the normal group, the model group showed high levels of BUN, Scr, ALT, and 24 h-UTP and serum levels of IL-1β and IL-18(P<0.01), low level of ALB(P<0.01), severe pathological damage to kidney, and high protein and mRNA levels of NLRP3, caspase-1, and GSDMD in renal tissue(P<0.01). Compared with the model group, valsartan group and GTW group had low levels of BUN, Scr, ALT, and 24 h-UTP and serum levels of IL-1β and IL-18(P<0.01), high level of ALB(P<0.01), alleviation of the pathological damage to the kidney, and low protein and mRNA levels of NLRP3, caspase-1, and GSDMD in renal tissue(P<0.01 or P<0.05). GTW may inhibit pyroptosis by decreasing the expression of NLRP3/caspase-1/GSDMD in renal tissue, thereby relieving the inflammatory response of DKD rats and the pathological injury of kidney.
Subject(s)
Rats , Male , Animals , Diabetic Nephropathies/genetics , Interleukin-18/metabolism , Glycosides/pharmacology , Tripterygium , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Rats, Sprague-Dawley , Caspase 1/metabolism , Pyroptosis , Uridine Triphosphate/pharmacology , Kidney , Valsartan/pharmacology , RNA, Messenger/metabolism , Diabetes MellitusABSTRACT
Objective To clarify the effect and mechanism of tumor antigen-loaded dendritic cells (Ag-DCs) combined with cytokine-induced killers (CIKs) on the killing of esophageal cancer tumor cells. Methods Peripheral blood DCs and CIKs were induced and cultured, and the DCs were loaded with tumor antigen to obtain Ag-DCs, and Ag-DCs were co-cultured with CIKs. The experiment was divided into CIK group, DC combined with CIK group, Ag-DC combined with CIK group. Flow cytometry was used to detect the phenotype of cells. MTT assay was employed to determine the killing activity against EC9706 cells. Annexin V-FITC/PI double staining was used to detect the apoptosis rate of cells, immunofluorescence staining to detect the expression of phosphorylated apoptotic signal-regulated kinase 1 (p-ASK1) and Western blot analysis to detect the expression of ASK1 pathway related proteins. A nude mouse model of esophageal cancer transplantation tumor was constructed and divided into control group, DC combined with CIK group and Ag-DC combined with CIK group. The corresponding immune cells were injected into the tail vein for treatment and the tumor volume was measured every 2 days. After 21 days, all nude mice were sacrificed with the tumors taken out. HE staining was used to observe the tumor pathological changes and immunohistochemical staining was performed to detect the expression of ki67 and ASK1 in the tumor tissue. Results Comparedwith the CIK group alone and the DC combined with CIK group, the ratio of CD3+ CD8+ and CD3+ CD56+ in the cells significantly increased after Ag-DCs and CIKs co-culture, along with the increased killing rate of EC9706 cells, increased apoptosis rate of EC9706 cells, and the improved activation level of ASK1. Compared with the CIK group and the DC combined with CIK group, the growth of the transplanted tumor in nude mice treated with Ag-DCs combined with CIKs was significantly inhibited, and after 21 days, it was observed that the tumor tissue mass in this group was relatively smaller, with sparsely arranged cells in the tumor tissue and a decline in the positive rate of ki67 in tumor tissue, while the positive rate of ASK1 was significantly increased. Conclusion Co-cultivation of tumor antigen-loaded DCs with CIKs can significantly increase the killing activity of esophageal cancer tumor cells. The mechanism of action may be related to the activation of the ASK1 pathway.
Subject(s)
Animals , Humans , Mice , Antigens, Neoplasm , Cytokine-Induced Killer Cells , Cytokines/metabolism , Cytotoxicity, Immunologic , Dendritic Cells , Esophageal Neoplasms/therapy , Ki-67 Antigen , Mice, NudeABSTRACT
OBJECTIVE@#To investigate the spectrum-effect relationship between the total anthraquinone extract of Cassia seeds and fluorouracil (5-Fu)-induced liver injury in mice and identify the effective components in the extract.@*METHODS@#A mouse model of liver injury was established by intraperitoneal injection of 5-Fu, with bifendate as the positive control. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and myeloperoxidase (MPO), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) in the liver tissue were detected to investigate the effect of the total anthraquinone extract of Cassia seeds (0.4, 0.8 and 1.6 g/kg) on liver injury induced by 5-Fu. HPLC fingerprints of 10 batches of the total anthraquinone extracts were established to analyze the spectrum- effectiveness of the extract against 5- Fu- induced liver injury in mice and screen the effective components using the grey correlation method.@*RESULTS@#The 5- Fu- treated mice showed significant differences in liver function parameters from the normal control mice (P < 0.05), suggesting successful modelling. Compared with those in the model group, serum ALT and AST activities were decreased, SOD and T- AOC activities significantly increased, and MPO level was significantly lowered in the mice treated with the total anthraquinone extract (all P < 0.05). HPLC fingerprints of the 31 components in the total anthraquinone extract of Cassia seeds showed good correlations with the potency index of 5-Fu-induced liver injury but with varying correlation strengths. The top 15 components with known correlations included aurantio-obtusina (peak 6), rhein (peak 11), emodin (peak 22), chrysophanol (peak 29) and physcion (peak 30).@*CONCLUSION@#The effective components in the total anthraquinone extract of Cassia seeds, including aurantio-obtusina, rhein, emodin, chrysophanol, and physcion, are coordinated to produce protective effects against 5-Fu-induced liver injury in mice.
Subject(s)
Animals , Mice , Emodin , Cassia , Chemical and Drug Induced Liver Injury, Chronic , Anthraquinones , Antioxidants , Fluorouracil/adverse effects , Plant Extracts/pharmacologyABSTRACT
ObjectiveTo establish and validate a clinical prediction model for 1-year major adverse cardiovascular events（MACEs）risk after percutaneous coronary intervention （PCI） in coronary heart disease （CHD） patients with blood stasis syndrome. MethodThe consecutive CHD patients diagnosed with blood stasis syndrome in the Department of Integrative Cardiology at China-Japan Friendship Hospital from September 1， 2019 to March 31， 2021 were selected for a retrospective study， and basic clinical features and relevant indicators were collected. Eligible patients were classified into a derivation set and a validation set at a ratio of 7∶3， and each set was further divided into a MACEs group and a non-MACEs group. The factors affecting the outcomes were screened out by least absolute shrinkage and selection operator （Lasso） and used to establish a logistic regression model and identify independent prediction variables. The goodness-of-fit of the model was evaluated by the Hosmer-Lemeshow test， and the area under curve （AUC） of the receiver operating characteristic （ROC） curve， calibration curve， decision curve analysis （DCA）， and clinical impact curve （CIC） were employed to evaluate the discrimination， calibration， and clinical impact of the model. ResultA total of 731 consecutive patients were assessed and 404 eligible patients were enrolled， including 283 patients in the derivation set and 121 patients in the validation set. Lasso identified ten variables influencing outcomes， which included age， sex， fasting plasma glucose （FPG）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， homocysteine （Hcy）， brachial-ankle pulse wave velocity （baPWV）， flow-mediated dilatation （FMD）， left ventricular ejection fraction （LVEF）， and Gensini score. The multivariate Logistic regression preliminarily identified age， FPG， TG， Hcy， LDL-C， LVEF， and Gensini score as the independent variables that influenced the outcomes. Of these variables， male， high FMD and high LVEF were protective factors， and the rest were risk factors. The prediction model for 1-year MACEs risk after PCI in CHD patients with blood stasis syndrome showed χ2=12.371 （P=0.14） in Hosmer-Lemeshow test and the AUC of 0.90. With the threshold probability > 10%， the model showed better prediction performance for 1-year MACEs risk after PCI in CHD patients with blood stasis syndrome than for that in all the patients. With the threshold probability > 60%， the estimated value was much closer to the real number of patients. ConclusionThe established clinical prediction model facilitates the early prediction of 1-year MACEs risk after PCI in CHD patients with blood stasis syndrome， which can provide ideas for the precise treatment of CHD patients after PCI and has guiding significance for improving the prognosis of the patients. Meanwhile， multi-center studies with larger sample sizes are expected to further validate， improve， and update the model.