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Objective To investigate the effect of cyclin D1 (with CCND1 as the gene name) on HBV replication and its potential mechanism. Methods With reference to GSE84044 dataset, the Spearman's rank correlation analysis was used to investigate the correlation between the expression levels of genes in liver tissue and serum HBV DNA load in patients with HBV-related liver fibrosis. Cyclin D1 and cyclin D1 T286A mutant were transiently expressed in the HBV cell replication model, and time-resolved immunofluorescence and quantitative real-time PCR were used to measure the levels of HBsAg/HBeAg and HBV DNA in cell culture supernatant; Western blot was used to measure the level of HBV core protein in cells; reverse-transcription quantitative real-time PCR was used to measure the level of HBV RNA in cells; dual-luciferase reporter assay was used to observe the effect of cyclin D1 on the activity of HBV basic core promoter (BCP). GSE83148 dataset was used to investigate the correlation between CCND1 and HBV-related regulatory factors. The independent samples t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. Results The analysis of GSE84044 data showed that 7 cell cycle genes were significantly negatively correlated with HBV DNA load in liver tissue of the patients with HBV-related liver fibrosis (all r < -0.3, all P < 0.05), which included the CCND1 gene ( r =-0.474, P < 0.001). Exogenous expression of cyclin D1 and cyclin D1 T286A mutant reduced the levels of HBsAg, HBeAg, and HBV DNA in culture supernatant of the HBV replication cell model, as well as the levels of HBV core protein and HBV RNA in cells. Exogenous expression of cyclin D1 significantly inhibited the transcriptional activity of HBV BCP. The expression level of CCND1 in liver tissue of chronic hepatitis B patients was significantly positively correlated with the expression of APOBEC3G ( r =0.575, P < 0.001), SMC5 ( r =0.341, P < 0.001), and FOXM1 ( r =0.333, P < 0.001) which inhibited HBV replication, while it was significantly negatively correlated with the expression of the HBV entry receptor NTCP ( r =-0.511, P < 0.001) and HNF1α as the transcription factor for positive regulation of HBV replication ( r =-0.430, P < 0.001). Overexpression of cyclin D1 in HepG2 cells reduced the transcriptional levels of HNF1α and NTCP. Conclusion Cyclin D1 inhibits HBV transcription and replication possibly by downregulating the expression of HNF1α and NTCP.
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Objective:To investigate the safety and dose of 4D template (real-time adjustable angle template) in the treatment of advanced malignant tumors with 125I seeds. Methods:98 patients with advanced malignant tumors admitted to Department of Thoracic Surgery of Shaanxi Provincial Tumor Hospital were treated with 4D template-navigated radioactive 125I seed implantation from June 2018 to December 2019. Preoperative TPS plan, intraoperative optimization, postoperative verification of immediate dose and postoperative evaluation of implantation dose were performed. The treatment results were observed. Results:All 98 patients completed the seed implantation. The implantation dose of GTV of implantation site receiving external irradiation was (12 489±414) cGy and the dose of no external irradiation was (15 036±514) cGy. V 100% was 84.7%-94.1%, and 88.2%-93.7%. The implantation dose of CTV was (7 450±621) cGy, and (9 080±761) cGy. The quality of dose implantation was evaluated as: excellent in 89 cases (91%, 89/98), good in 7 cases (7%, 7/98), fair in 2 cases (2%, 2/98), and poor in 0 case, respectively. The symptom relief rate of patients with pain was 92%(36/39). The 1-and 2-year local control rates were 61%, 36% and 82%, 54% in patients treated with and without external irradiation, respectively. The difference was statistically significant ( P=0.02). The incidence rates of pneumothorax and hemoptysis were 19%(9/48) and 10%(5/48). No corresponding complications were observed in other parts of the patients. Conclusion:4D template-assisted 125I seed therapy is safe and effective for malignant tumors, and intraoperative adjustment of needle angle and dose optimization can realize the precise control of implantation dose.
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Objective:To develop a multimodal MRI-based radiomics model for the differential diagnosis of benign and malignant lung lesions, and to compare the discriminative abilities of different models.Methods:Totally 114 patients with 115 lesions (44 benign and 71 malignant) in Nantong First Peoples′s Hospital from January 2014 to October 2019 were included in the study. All patients underwent non-enhanced MR examination, and textural features from T 1WI,T 2WI and apparent diffusion coefficient (ADC) imaging were extracted. The feature selection methods included L1 based, mutual information, tree based, recursive feature elimination and F-test. Then we constructed a prediction model by using logistic regression (LR), support vector machine (SVM), random forest (RF) and k-nearest neighbor (KNN) respectively. In order to control the number of modeling features and reduce the ininterpretability of the model, the new model was obtained by manually modifying some parameters of the hyperparameter model. One hundred and fourteen cases were rotated as training and validation sets. The performance of each model was evaluated by confounding matrix and receiver operating characteristic (ROC) curve. Results:The area under the curve (AUC) of T 2WI based LR model for the differential diagnosis of benign and malignant pulmonary nodules/masses was 0.71 and the F1 score was 0.57. Based on T 1WI images, LR and SVM model could be used to identify benign and malignant pulmonary nodules, the AUC before parameter adjustment were 0.77 and 0.78, the accuracy after parameter adjustment (LR a,SVM a) was 0.67, 0.70, and both the AUC were 0.72. However, no matter which feature or classifier was selected, both the AUC and accuracy of ADC-based model were less than 0.70. Conclusion:Multimodal MRI-based radiomics model is valuable for the differential diagnosis of benign and malignant pulmonary nodules/masses, and T 1WI-based model shows the best discrimination.
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Objective To identify the differentially expressed proteins in different liver tissues in the mouse model of alveolar echinococcosis using high-resolution mass spectrometry with data independent acquisition (DIA), and to identify the key proteins contributing to the pathogenesis of alveolar echinococcosis. Methods Protoscoleces were isolated from Microtus fuscus with alveolar echinococcosis and the experimental model of alveolar echinococcosis was established in female Kunming mice aged 6 to 8 weeks by infection with Echinococcus multilocularis protoscoleces. Mice were divided into the experimental and control groups, and animals in the experimental group was injected with approximately 3 000 protoscoleces, while mice in the control group were injected with the same volume of physiological saline. Mouse liver specimens were sampled from both groups one year post-infection and subjected to pathological examinations. In addition, the lesions (the lesion group) and peri-lesion specimens (the peri-lesion group) were sampled from the liver of mice in the experimental group and the normal liver specimens (the normal group) were sampled from mice in the control group for DIA proteomics analysis, and the differentially expressed proteins were subjected to bioinformatics analysis. Results A total of 1 020 differentially expressed proteins were identified between the lesion group and the normal group, including 671 up-regulated proteins and 349 down-regulated proteins, and 495 differentially expressed proteins were identified between the peri-lesion group and the normal group, including 327 up-regulated proteins and 168 down-regulated proteins. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that these differentially expressed proteins were involved in peroxisome, peroxisome proliferator-activated receptor (PPAR) and fatty acid degradation pathways, and the peroxisome and PPAR signaling pathways were found to correlate with liver injury. Several differentially expressed proteins that may contribute to the pathogenesis of alveolar echinococcosis were identified in these two pathways, including fatty acid binding protein 1 (Fabp1), Acyl-CoA synthetase long chain family member 1 (Acsl1), Acyl-CoA oxidase 1 (Acox1), Enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (Ehhadh) and Acetyl-Coenzyme A acyltransferase 1B (Acaa1b), which were down-regulated in mice in the experimental group. Conclusion A large number of differentially expressed proteins are identified in the liver of the mouse model of alveolar echinococcosis, and Fabp1, Acsl1, Acox1, Ehhadh and Acaa1b may contribute to the pathogenesis of alveolar echinococcosis.
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Objective To identify the differentially expressed proteins in different liver tissues in the mouse model of cystic echinococcosis (CE), so as to provide insights into the research and development of therapeutic drugs targeting CE. Methods Female Kunming mice at ages of 6 to 8 weeks were randomly assigned into the CE group and the control group. Mice in the CE group were intraperitoneally infected with 2 000 Echinococcus multilocularis protoscoleces, while mice in the control group were injected with the same volume of physiological saline. All mice in both groups were sacrificed after breeding for 350 d, and the lesions (the lesion group) and peri-lesion specimens (the peri-lesion group) were sampled from the liver of mice in the CE group and the normal liver specimens (the normal group) were sampled from mice in the control group for data independent acquisition (DIA) proteomics analysis, and the differentially expressed proteins were subjected to Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results A total of 26 differentially expressed proteins were identified between the lesion group and the normal group and between the peri-lesion group and the normal group, including 8 up-regulated proteins and 18 down-regulated proteins. GO term enrichment analysis showed that these differentially expressed proteins were predominantly enriched in endoplasmic reticulum membrane (biological components), oxidoreductase activity (molecular function) and oxoacid metabolic process and monocarboxylic acid metabolic process (biological processes). KEGG pathway enrichment analysis revealed that the differentially expressed protein Acyl-CoA oxidase 1 (Acox1), which contributed to primary bile acid biosynthesis during the fatty acid oxidation, was involved in peroxisome signaling pathway, and the differentially expressed protein fatty acid binding protein 1 (Fabp1), which contributed to fatty acid transport, was involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Conclusion Differentially expressed proteins are identified in the liver specimens between mouse models of CE and normal mice, and some differentially expressed proteins may serve as potential drug targets for CE.
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OBJECTIVE@#To explore the characteristics and rules of acupoint sensitization phenomena based on knee osteoarthritis (KOA), one of the clinical dominant diseases of acupuncture-moxibustion.@*METHODS@#In combination with literature and expert experiences, the acupoints with the highest use frequency in treatment of KOA were screened, e.g. Heding (EX-LE 2), Liangqiu (ST 34), Mingmen (GV 4), Neixiyan (EX-LE 4), Ququan (LR 8) and Dubi (ST 35). In 814 patients with KOA and 217 healthy subjects, the acupoint temperature, mechanic pain threshold and pressure pain threshold were detected separately. Using machine learning method, the sensitization was judged at each acupoint.@*RESULTS@#Compared with healthy subjects, the acupoint temperature was increased and the mechanic pain threshold and pressure pain threshold were reduced in KOA patients (P<0.05). Besides, the cut-off value was presented to distinguish whether the acupoint was sensitized or not. The results of machine learning showed that the highest prediction accuracy of acupoint sensitization was 86.7% (Shenshu [BL 23]) and the lowest one was 73.9% (Heding [EX LE 2]). The prediction accuracy at the third clinical stage trial was higher, the highest was 93.3% (Ququan [LR 8]) in KOA patients.@*CONCLUSION@#It is confirmed that the acupoint sensitization reflects the characteristics of disease and is correlative with the conditions of illness, which may provide the reference for the auxiliary diagnosis and condition assessment of KOA.
Subject(s)
Humans , Acupuncture Points , Acupuncture Therapy , Moxibustion , Osteoarthritis, Knee/therapy , Treatment OutcomeABSTRACT
OBJECTIVES@#After renal transplantation, patients need to take various immunosuppressant, but the drug compliance is poor. The theory of planned behavior suggests that the past medication behavior and subjective norms of individuals are closely related to medication compliance. This study aims to explore the change of medication compliance behavior and its influenting factors for renal transplantation patients at different stages.@*METHODS@#This study was a prospective longitudinal study. The Basel Assessment of Adherence with Immunosuppressive Medication Scale (BAASIS), Medication Belief Scale, Social Support Scale and Quality of Life Scale were used to dynamically follow up renal transplantation patients at pre-operation and 1-month, 6-month, and 12-month after transplantation.@*RESULTS@#A total of 300 patients completed the whole follow-up. The percentage of patients with good medication compliance was 97.60%, 87.30% and 84.30% at 1-month, 6-month and 12-month after transplantation respectively. The life quality of the patients was decreased at 6 months after the operation, and the patients with better self-reported life quality had poor medication compliance. After adjusting for demographic data, the risk of medication incompliance in patients with poor medication compliance before operation was 37.646 times than those with good compliance. Patients who did not use medication reminders had high risk (odds ratio=2.467) of drug non-adherence. The risk of drug non-adherence in patients with more postoperative misgivings was 1.265 times compared with that in patients with less postoperative misgivings.@*CONCLUSIONS@#The medication compliance decreases with the time of transplantation, but the medication compliance of patients with good self-reported life quality is poor. Medication concerns reduce the compliance behavior. Preoperative medication behavior has a significant predictive effect on postoperative behavior. Medication reminder is a protective factor for promoting compliance. Medical staff should pay more attention to preoperative medication belief, behaviors and reminder of using drug so as to provide precise intervention in the renal transplantation patients.
Subject(s)
Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/adverse effects , Longitudinal Studies , Medication Adherence , Prospective Studies , Quality of LifeABSTRACT
Adenosine is a metabolite produced abundantly in the tumor microenvironment, dampening immune response in inflamed tissues via adenosine A2A receptor (A2AR) which is widely expressed on immune cells, inhibiting anti-tumor immune response accordingly. Therefore, blocking adenosine signaling pathway is of potential to promote anti-tumor immunity. This review briefly introduces adenosine signaling pathway, describes its role in regulating tumor immunity and highlights A2AR blockade in cancer therapy. Prospective anti-tumor activity of adenosine/A2AR inhibition has been revealed by preclinical data, and a number of clinical trials of A2AR antagonists are under way. Primary results from clinical trials suggest that A2AR antagonists are well tolerated in cancer patients and are effective both as monotherapy and in combination with other therapies. In the future, finding predictive biomarkers are critical to identify patients most likely to benefit from adenosine pathway blockade, and further researches are needed to rationally combine A2AR antagonists with other anti-tumor therapies. .
Subject(s)
Humans , Adenosine/therapeutic use , Adenosine A2 Receptor Antagonists/therapeutic use , Lung Neoplasms , Receptor, Adenosine A2A/metabolism , Tumor MicroenvironmentABSTRACT
Objective@#To investigate the prevalence and influencing factors of electronic cigarette (e-cigarette) use among adolescents in Haidian District, Beijing, so as to provide insights into tobacco control among adolescents.@*Methods@#The students in junior high school, high school and vocational high school were recruited from Haidian District using the stratified cluster random sampling method in October of 2019, and subjects' demographic features and use of e-cigarettes were collected using the Questionnaire for Survey on Tobacco Prevalence among Adolescents in China in 2019. The factors affecting e-cigarette use were identified among adolescents using the multivariable logistic regression analysis.@*Results@#A total of 658 adolescents were investigated, including 315 junior high school students ( 47.87% ), 221 high school students ( 33.59% ), and 122 vocational high school students ( 18.54% ), and there were 261 boys ( 39.66% ), and 397 girls ( 60.34% ). There were 605 students that had heard of electronic cigarettes ( 91.95% ), 63 students that had used e-cigarettes (9.57%), and 23 students with current use of e-cigarettes ( 3.50% ), and there were 39 students that had never used electronic cigarettes but had a tendency of use in the future ( 6.55% ). Multivariable logistic regression analysis identified parental smoking ( OR=2.408, 95%CI: 1.179-4.916 ), close friends' smoking ( OR=3.597, 95%CI: 1.715-7.544 ) and cigarette smoking ( OR=23.029, 95%CI: 11.092-47.812 ) as factors affecting e-cigarette use among adolescents.@*Conclusions@#The prevalence of electronic cigarette uses is 9.57% among adolescents in Haidian District, Beijing. Parental smoking, peer smoking and use of cigarettes may facilitate the use of e-cigarettes among adolescents.
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Objective:To evaluate the clinical efficacy of Gushen Jianpi Huashi Decoction combined with irbesartan in the treatment of spleen and kidney deficiency syndrome of diabetic nephropathy (DN).Methods:According to random number table method, 97 patients with DN who met the inclusion criteria and from January 2018 to September 2020 were randomly divided into two groups, 48 in the control group and 49 in the study group. The control group took irbesartan on the basis of routine treatment of western medicine, and the study group took Gushen Jianpi Huashi Decoction on the basis of the control group. Both groups were treated for 14 days as a course of treatment, a total of 6 courses of treatment. Traditional Chinese Medicine (TCM) syndrome scores were performed before and after treatment, BUN and SCr levels were detected by automatic biochemical instrument, and serum IL-6, TNF-α, and CRP levels were detected by ELISA. The Urinary microalbumin excretion rate (UAER) was measured by radioimmunoassay, and the clinical efficacy was evaluated and adverse reactions were recorded.Results:The total effective rate was 91.8% (45/49) in the study group and 75.0% (36/48) in the control group, and there was significant difference between the two groups ( χ2=4.99, P=0.025). The scores of TCM syndrome in the study group was significantly lower than that of the control group ( t=29.75, P<0.01). After treatment, the serum BUN [(4.49 ± 0.68) mmol/L vs. (5.16 ± 0.61) mmol/L, t=5.11], SCr [(63.42 ± 4.09) μmol/L vs. (69.01 ± 4.35) μmol/L, t=6.52] and UAER [(72.58 ± 5.88) μg/min vs. (85.63 ± 6.49) μg/min, t=10.44] in the study group were significantly lower than those in the control group ( P<0.01), the serum IL-6, CRP and TNF-α levels in the study group were significantly lower than those in the control group ( t values were 9.44, 7.24 and 18.08, respectively, P<0.01). During the treatment, the incidence of adverse reactions was 14.6% (7/48) in the control group and 16.3% (8/49) in the study group, but there was no significant difference between two groups ( χ2=0.06, P=0.812). Conclusion:The Gushen Jianpi Huashi Decoction combined with irbesartan can improve the renal function of DN patients, reduce the level of inflammatory cytokines and improve the clinical effect.
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Objective:To investigate the preventive effect of Xiyanping injection on radioactive esophagitis in patients with radical radiotherapy and chemotherapy for esophageal cancer.Methods:A total of 70 patients with esophageal cancer undergoing radical radiotherapy and chemotherapy were selected from the Department of Radiation Oncology of Jiangsu Provincial People′s Hospital from January to September 2020. They were divided into experimental group ( n=35) and control group ( n=35) according to random number table method. The control group received standard concurrent radiotherapy and chemotherapy, and the experimental group received concurrent radiotherapy and chemotherapy combined with Xiyanping. The white blood cell count, neutrophil count, procalcitonin (PCT) and interleukin-6 (IL-6) levels before and after treatment were compared between the two groups, as well as the occurrences of radioactive esophagitis and radioactive pneumonia during radiotherapy. Results:Before treatment, there were no significant differences in white blood cell count [4.57 (2.52)×10 9/L vs. 5.59 (2.23)×10 9/L] and neutrophil count [2.95 (1.66)×10 9/L vs. 3.69 (1.56)×10 9/L] between the control group and experimental group ( Z=1.44, P=0.151; Z=1.52, P=0.130). After treatment, there were no statistically significant differences in white blood cell count [4.28 (2.50)×10 9/L vs. 4.25 (1.88)×10 9/L] and neutrophil count [2.99 (2.50)×10 9/L vs. 2.94 (1.61)×10 9/L] between the two groups ( Z=0.67, P=0.503; Z=0.69, P=0.489). There were no statistically significant differences in white blood cell count and neutrophil count between the patients after treatment and before treatment in the two groups ( Z=0.77, P=0.443; Z=1.08, P=0.279; Z =1.06, P=0.289; Z=0.68, P=0.495). Before treatment, there were no statistically significant differences in serum inflammation indexes PCT [0.02 (0.03) μg/L vs. 0.02 (0.05) μg/L] and IL-6 [0.04 (0.21) μg/L vs. 0.04 (0.12) μg/L] between the two groups ( Z=0.70, P=0.482; Z=0.77, P=0.439). After treatment, there were statistically significant differences in serum inflammation indexes PCT [0.06 (0.17) μg/L vs. 0.03 (0.08) μg/L] and IL-6 [0.10 (0.25) μg/L vs. 0.01 (0.08) μg/L] between the two groups ( Z=2.08, P=0.038; Z=2.92, P=0.003). There were no statistically significant differences in serum inflammation indexes PCT and IL-6 in the experimental groups after treatment compared with before treatment ( Z=1.20, P=0.230; Z=1.19, P=0.235). In the control group, the serum inflammation index PCT level increased after treatment compared with before treatment, with a statistically significant difference ( Z=2.82, P=0.005), and the serum inflammation index IL-6 level increased compared with before treatment, but with no statistically significant difference ( Z=1.41, P=0.158). During the treatment, the incidence of radioactive esophagitis in the two groups was mainly grade Ⅰ-Ⅱ, with 24 cases in the control group and 28 cases in the experimental group. There were 8 patients with grade Ⅲ-Ⅳ radioactive esophagitis in the control group and 1 in the experimental group. There was a statistically significant difference in the occurrence of radioactive esophagitis between the two groups ( χ2=10.34, P=0.035). During the treatment period, most patients with radioactive pneumonia were rated as grade 0. There were 10 cases of mild radioactive pneumonia (grade Ⅰ-Ⅱ) in the control group had and 6 cases in the experimental group. There were 2 cases of grade Ⅲ radioactive pneumonia in the control group and experimental group respectively. There was no grade Ⅳ radioactive pneumonia in either group. There was no significant difference in radioactive pneumonia between the two groups ( χ2=1.34, P=0.720). Conclusion:Xiyanping injection can prevent the rise of serum inflammatory index PCT and reduce the severity of radioactive esophagitis in patients with esophageal cancer after treatment.
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AIM: To investigate the correlation between meibomian gland dysfunction(MGD)and serum lipid in patients with type 2 diabetes mellitus(T2DM).METHODS: A case-control study was performed which recruited 184 patients with T2DM admitted to hospital from July 2020 to October 2021. After completing the ocular surface examination, subjects were divided into MGD group(94 cases)and control group(90 cases)according to whether MGD was combined. The body mass index(BMI), fasting blood glucose(FBG), glycosylated hemoglobin A1c(HbA1c), total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were examined for the condition of meibomian glands and collected between the two groups of patients. The relationship between MGD and blood lipid levels was compared between the two groups. Multivariate Logistic regression was used to analyze the risk factors of MGD.RESULTS: The HbA1c, TC, TG, LDL-C in MGD group were 8.30%±1.95%, 5.72±1.21, 2.16±1.05, 3.42±1.10mmol/L, all significantly higher than control group(7.26%±1.18%, 4.82±1.19, 1.48±0.71, 2.75±1.00mmol/L, all P<0.001), there were no statistically significant in HDL-C between the two groups(P>0.05). Multivariate Logistic regression analysis revealed that the risk factors for the onset of MGD was significantly associated with higher blood levels of TC(OR: 5.846; 95%CI: 1.867-18.306; P<0.001)and the higher blood levels of TG(OR: 5.822; 95%CI: 2.654-12.774; P=0.002).CONCLUSION: T2DM patients with MGD are related to a number of dyslipidemias, and the TC hyperlipidemia and TG hyperlipidemia are significantly associated with an increase risk of MGD in patients with T2DM.
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To study the protective effect of Ershiwuwei Zhenzhu Pills on ischemic stroke rats. Ninety 4-weeks-old SPF male SD rats were randomly divided into 6 groups(n=15):sham operation group, model group, nimodipine group(12 mg·kg~(-1)), Ershiwuwei Zhenzhu Pills high-dose group(400 mg·kg~(-1)), Ershiwuwei Zhenzhu Pills medium-dose group(200 mg·kg~(-1)), Ershiwuwei Zhenzhu Pills low-dose group(100 mg·kg~(-1)).The permanent middle cerebral artery occlusion model(PMCAO) was established in the model group, nimodipine group, and Ershiwuwei Zhenzhu Pills groups by the improved thread plug method, while the sham operation group did not insert the thread plug.Nimodipine group and Ershiwuwei Zhenzhu Pills groups were given intragastric administration once a day for 24 days before the modeling operation, and once 1 hour before the modeling operation, while sham operation group and model group were given equal volumes of distilled water.The neuroethology of the surviving rats was measured; The volume of cerebral infarction in rats was measured by TTC method; The histopathology of rat brain was observed by HE method; The expression levels of tumor necrosis factor α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),malondialdehyde(MDA),superoxide dismutase(SOD) and catalase(CAT) in serum were detected by ELISA;The mRNA expressions of Notch 1,Jagged 1,Hes 1 and Bcl-2 in rat brain were detected by RT-PCR;Western blot was used to detect the expression levels of caspase-3 protein in rat brain; the expression levels of vascular endothelial growth factor(VEGF) and CD34 positive cells in rat brain were detected by immunofluorescence.The low, medium and high dose groups of Ershiwuwei Zhenzhu Pills and nimodipine group could significantly reduce the neurobehavioral score and cerebral infarction volume of rats with permanent middle cerebral artery occlusion, reduce the morphological changes of nerve cells, decrease the expression of TNF-α,IL-1β and IL-6 in rat serum, increase the activity of SOD and CAT,and reduce the level of MDA.Furthermore, the expression levels of Notch l, Jagged l, Hes l and Bcl-2 mRNA were significantly increased, and the expression level of caspase-3 protein was decreased.Meanwhile, the number of VEGF and CD34 positive cells increased in the treatment group.The differences were statistically significant. Ershiwuwei Zhenzhu Pills has a protective effect on ischemic stroke rats, and its mechanism may be related to anti-inflammation, anti-oxidation, promotion of nerve cell proliferation, inhibition nerve cell apoptosis and promotion of angiogenesis.
Subject(s)
Animals , Male , Rats , Caspase 3/metabolism , Drugs, Chinese Herbal/pharmacology , Infarction, Middle Cerebral Artery/drug therapy , Interleukin-6/metabolism , Ischemic Stroke/drug therapy , Nimodipine/pharmacology , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA, Messenger , Rats, Sprague-Dawley , Superoxide Dismutase/metabolism , Tumor Necrosis Factor-alpha/metabolism , Vascular Endothelial Growth Factor A/metabolismABSTRACT
More and more studies have shown that NOD-like receptor protein 3 (NLRP3) inflammasome has become the regulatory factor of inflammatory response and protective immunity, and the assembly and activation of NLRP3 inflammasomes are closely related to the anti-tumor immunity effect. Depending on the cell type and stimuli, activation of the NLRP3 inflammasome can induce immune cells to become polarized, hyperactive, or pyroptotic, releasing interleukin (IL)-1β and IL-18, which leads to cascade immune or inflammatory responses, and its role in tumor immunity has received extensive attention. Here, we review the mechanisms of the NLRP3 inflammasome enhancing CD8+ T cells-mediated anti-tumor immunity by inducing the pyroptosis of tumor cell, the pyroptosis or hyperactive state of dendritic cells (DCs), and the pyroptosis or polarization of the macrophages. Different anti-tumor immune roles of NLRP3 inflammasome activation in tumor cells and immune cells provide new directions for future research and may influence the development of next-generation immunotherapy.
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OBJECTIVE@#To explore the therapeutic mechanism of tanshinone IIA in the treatment of pulmonary arterial hypertension (PAH) in rats.@*METHODS@#A total of 100 male SD rats were randomized into 5 groups (n=20), and except for those in the control group with saline injection, all the rats were injected with monocrotaline (MCT) on the back of the neck to establish models of pulmonary hypertension. Two weeks after the injection, the rat models received intraperitoneal injections of tanshinone IIA (10 mg/kg), phosphatidylinositol 3 kinase (PI3K) inhibitor (1 mg/kg), both tanshinone IIA and PI3K inhibitor, or saline (model group) on a daily basis. After 2 weeks of treatment, HE staining and α-SMA immunofluorescence staining were used to evaluate the morphology of the pulmonary vessels of the rats. The phosphorylation levels of PI3K, protein kinase B (PKB/Akt) and endothelial nitric oxide synthase (eNOS) in the lung tissue were determined with Western blotting; the levels of eNOS and NO were measured using enzyme-linked immunosorbent assay (ELISA).@*RESULTS@#The results of HE staining and α-SMA immunofluorescence staining showed that tanshinone IIA effectively inhibited MCT-induced pulmonary artery intimamedia thickening and muscularization of the pulmonary arterioles (P < 0.01). The results of Western blotting showed that treatment with tanshinone IIA significantly increased the phosphorylation levels of PI3K, Akt and eNOS proteins in the lung tissue of PAH rats; ELISA results showed that the levels of eNOS and NO were significantly decreased in the rat models after tanshinone IIA treatment (P < 0.01).@*CONCLUSION@#Treatment with tanshinone IIA can improve MCT-induced pulmonary hypertension in rats through the PI3K/Akt-eNOS signaling pathway.
Subject(s)
Animals , Male , Rats , Abietanes , Hypertension, Pulmonary/drug therapy , Monocrotaline/toxicity , Nitric Oxide Synthase Type III/therapeutic use , Phosphatidylinositol 3-Kinase/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Pulmonary Artery , Rats, Sprague-Dawley , Signal TransductionABSTRACT
Objective: To observe the changes of olfactory function, intranasal trigeminal nerve function and taste function in patients with upper respiratory tract post-viral olfactory dysfunction (PVOD), and to explore the correlation of chemosensory function. Methods: The clinical data of 42 patients with PVOD who visited to the Olfactory and Taste Center of Otorhinolaryngology Head and Neck Surgery Department of Beijing Anzhen Hospital from January to December of 2019 were analyzed retrospectively, including 20 males and 22 females, aging (48.86±11.47) years (x¯). Twenty subjects in normal control group were selected according to the sex ratio of PVOD patients. Sniffin' Sticks olfactory tests were performed on the subjects, including threshold test (T), discrimination test (D) and identification test (I), and the sum of the above three test scores was the TDI value. At the same time, olfactory event-related potentials (oERPs), trigeminal event-related potentials (tERPs) and taste function test were performed. According to the taste function test, the patients were divided into normal gustation (NG) group and gustatory dysfunction (GD) group. The results of olfaction, taste and intranasal trigeminal nerve function tests were compared among different groups, and the correlation analysis was carried out. SPSS statistical software was used for statistical analysis. Results: GD was present in 14 (33.3%) of 42 PVOD patients with a course of PVOD of 5 (3, 6) months (M (Q1, Q3)). The gustatory function of patients with PVOD was related to gender (r=0.565, P<0.001), smoking status (r=-0.512, P=0.001), duration (r=-0.357, P=0.020) and olfactory function (all P<0.05). The olfactory function of GD group was worse than that of NG group, and the differences of TDI value and T value between the two groups were statistically significant (10.25±4.58 vs 13.35±3.61, 1.54±0.66 vs 2.10±0.88, t value was 2.40 and 2.10 respectively, both P<0.05). The amplitudes of oERPs and tERPs were significantly lower in GD group than those in NG group (all P<0.05). Conclusion: In patients with PVOD, the subjective and objective olfactory function, intranasal trigeminal nerve function and taste function were decreased, and there was a correlation, suggesting that there was a synergistic effect between the chemosensory functions of PVOD patients.
Subject(s)
Female , Humans , Male , Nose , Olfaction Disorders/etiology , Retrospective Studies , Smell , TasteABSTRACT
Objective: To compare the clinical efficacy and quality of life between uncut Roux-en-Y and Billroth II with Braun anastomosis in laparoscopic distal gastrectomy for gastric cancer patients. Methods: A retrospective cohort study was performed. Inclusion criteria: (1) 18 to 75 years old; (2) gastric cancer proved by preoperative gastroscopy, CT and pathological results and tumor was suitable for D2 radical distal gastrectomy; (3) postoperative pathological diagnosis stage was T1-4aN0-3M0 (according to the AJCC-7th TNM tumor stage), and the margin was negative; (4) Eastern Cooperative Oncology Group (ECOG) physical status score <2 points, and American Association of Anesthesiologists (ASA) grade 1 to 3; (5) no mental illness; (6) able to answer questionnaires independently; (7) patients agreed to undergo laparoscopic distal gastrectomy and signed an informed consent. Exclusion criteria: (1) patients with severe chronic diseases and American Association of Anesthesiologists (ASA) grade >3; (2) patients with other malignant tumors; (3) patients suffered from serious mental diseases; (4) patients received neoadjuvant chemotherapy or immunotherapy. According to the above criteria, clinical data of 200 patients who underwent laparoscopic distal gastrectomy at the Department of General Surgery of the First Affiliated Hospital of Army Medical University from January 2016 to December 2019 were collected. Of the 200 patients, 108 underwent uncut Roux-en-Y anastomosis and 92 underwent Billroth II with Braun anastomosis. The general data, intraoperative and postoperative conditions, complications, and endoscopic evaluation 1 year after the surgery were compared. Besides, the quality of life of two groups was also compared using the Chinese version of the European Organization For Research and Treatment of Cancer (EORTC) quality of life questionnaire-Core 30 (QLQ-C30) and quality of life questionnaire-stomach 22 (QLQ-STO22). Results: There were no significant differences in baseline data between the two groups (all P>0.05). All the 200 patients successfully underwent laparoscopic distal gastrectomy without intraoperative complications, conversion to open surgery or perioperative death. There were no significant differences between two groups in operative time, intraoperative blood loss, postoperative complications, time to flatus, time to removal of gastric tube, time to liquid diet, time to removal of drainage tube or length of postoperative hospital stay (all P>0.05). Endoscopic evaluation was conducted 1 year after surgery. Compared to Billroth II with Braun group, the uncut Roux-en-Y group had a significantly lower incidences of gastric stasis [19.8% (17/86) vs. 37.0% (27/73), χ(2)=11.199, P=0.024], gastritis [11.6% (10/86) vs. 34.2% (25/73), χ(2)=20.892, P<0.001] and bile reflux [1.2% (1/86) vs. 28.8% (21/73), χ(2)=25.237, P<0.001], and the differences were statistically significant. The EORTC questionnaire was performed 1 year after surgery, there were no significant differences in the scores of QLQ-C30 scale between the two groups (all P>0.05), while the scores of QLQ-STO22 showed that, compared to the Billroth II with Braun group, the uncut Roux-en-Y group had a lower pain score (median: 8.3 vs. 16.7, Z=-2.342, P=0.019) and reflux score (median: 0 vs 5.6, Z=-2.284, P=0.022), and the differences were statistically significant (all P<0.05), indicating milder symptoms. Conclusion: The uncut Roux-en-Y anastomosis is safe and reliable in laparoscopic distal gastrectomy, which can reduce the incidences of gastric stasis, gastritis and bile reflux, and improve the quality of life of patients after surgery.
Subject(s)
Adolescent , Adult , Aged , Humans , Middle Aged , Young Adult , Anastomosis, Roux-en-Y/adverse effects , Anastomosis, Surgical/adverse effects , Gastrectomy/methods , Gastroenterostomy/adverse effects , Laparoscopy/methods , Postoperative Complications/epidemiology , Quality of Life , Retrospective Studies , Stomach Neoplasms/pathology , Treatment OutcomeABSTRACT
The accurate diagnosis of burn wound depth is particularly important for evaluating the disease prognosis of burn patients. In the past, the diagnosis of burn wound depth often relied on the subjective judgment of doctors. With the continuous development of diagnostic technology, the methods for judging the depth of burn wound have also been updated. This paper mainly summarizes the research progress in the applications of indocyanine green angiography, laser Doppler imaging, laser speckle contrast imaging, and artificial intelligence in the diagnosis of burn wound depth, and compares the advantages and disadvantages of these techniques, so as to provide ideas for accurate diagnosis of burn wound depth.
Subject(s)
Humans , Angiography , Artificial Intelligence , Burns/diagnosis , Laser-Doppler Flowmetry/methods , Skin , Wound HealingABSTRACT
Objective: To investigate the related factors associated with the structure of the gut microbial community in HIV infection/AIDS cases (HIV/AIDS) in Henan province. Methods: The convenience sampling method was used to select 122 cases who were receiving Antiviral Treatment (ART) or ART-naive in Henan. Whole blood and stool specimens were collected. Genomic DNA of stool samples was extracted, and the V3-V4 hypervariable regions of the 16S rRNA gene were sequenced using Illumina NovaSeq 6000 high-throughput sequencing system. The analysis was performed mainly at the genus level, and the 30 genera with the highest abundance were selected as a measure of the gut microbial community structure. The correlation between community structure and related factors was analyzed using redundancy analysis and Envfit function. Results: 122 cases were finally completed sequencing and analysis, the average BMI was (23.62±2.78) kg/m2 and the average age was (47±13) years. Among them, male accounted for 66.39% (81/122), and heterosexual transmission route constituted the largest ratio, accounting for 51.64% (63/122). 36 cases were treatment naive (29.51%, 36/122). The top five dominant genera of the total population (122 cases) were Prevotella, Roseburia, Megamonas, Bacteroides and Faecalibacterium and the top five dominant genera of the ART population (86 cases) were Prevotella, Megamonas, Bacteroides, Roseburia and Faecalibacterium. The top five dominant genera of the ART-naive population (36 cases) appeared as Prevotella, Faecalibacterium, Roseburia, Bacteroides and Megamonas. In the total population, ART (P<0.001) was the most significant factors of community structure. Other significant factors were: duration of diagnosis (P=0.009), viral load (P=0.022) and anti-HCV (P=0.018). ART was positively correlated with Megamonas and negatively correlated with Prevotella, Roseburia and Faecalibacterium, while the other three factors of duration of diagnosis, viral load and anti-HCV were positively correlated with Prevotella, Roseburia and Faecalibacterium and negatively correlated with Megamonas. In the ART-naive population, duration of diagnosis (P=0.003) were the factors significantly associated with community structure. Duration of diagnosis was positively correlated with Roseburia, Faecalibacterium, Megamonas and Prevotella and negatively correlated with Bacteroides. Conclusion: ART and duration of diagnosis were factors significantly associated with gut microbial community structure and had a significant impact on multiple high-abundance genera.
Subject(s)
Adult , Humans , Male , Middle Aged , Acquired Immunodeficiency Syndrome/epidemiology , Gastrointestinal Microbiome/genetics , HIV Infections/epidemiology , Microbiota , RNA, Ribosomal, 16S/geneticsABSTRACT
Objective:To study the value of autoregressive integrated moving average (ARIMA) and autoregressive (AR) models in predicting the daily number of ambulances in prehospital emergency medical services demand in Guangzhou.Methods:Matlab simulation software was used to analyze the emergency dispatching departure records in Guangzhou from January 1, 2021 to December 31, 2021. A time series for the number of ambulances per day was calculated. After identifying the time series prediction model, ARIMA(1,1,1), AR(4) and AR(7) models were obtained. These models were used to predict the number of ambulances per day. ARIMA(1,1,1) model divided the time series into the training set and test set. Prony method was used for parameter calculation, and the demands of number of ambulances of the next few months were forecasted. AR(4) and AR(7) models used uniformity coefficient to forecast the demands of number of ambulances on that very day.Results:ARIMA(1,1,1), AR(4) and AR(7) can effectively predict the number of ambulances per day. The prediction fitting error of ARIMA (1,1,1) decreased with the extension of prediction time. The mean absolute percentage error (MAPE) of forecast results of daily vehicle output of emergency dispatching within two months was less than 6% and the predicted results were almost within the 95% confidence interval. The residual analysis of the model verified that the model was significantly effective.Conclusions:ARIMA model can make a long-term within two months and effective prediction fitting of the daily vehicle output of emergency dispatching, and AR model can make a short-term and effective prediction of the daily vehicle output of emergency dispatching.