ABSTRACT
BACKGROUND: Compared to photon beam, carbon-ion radiotherapy (CIRT) has both physical and biological advantages. AIM: To examine whether two-dimensional (2D) CIRT is dosimetrically superior to photon beam volume-modulated arc therapy (VMAT) in protecting the normal tissues for stage III non-small-cell lung cancer (NSCLC). SUBJECTS AND METHODS: A retrospective study was conducted. Thirteen patients with stage III NSCLC treated in our center with curative CIRT and a sham photon beam VMAT treatment planning with the same normal tissue dose constraints were included for analysis. Target dose distributions and the homogeneity index (HI) within the planning target volumes were compared. RESULTS: Both CIRT and VMAT plans have good tumor coverage with no significant differences in D98, D95, and D50 of Planning target volume 1 (PTV1) between the two plans. The HIs between the two plans are similar. The HI of PTV2 is superior in the CIRT plan (CIRT vs. VMAT: 0.08 vs. 0.16, P < 0.05). In general, CIRT results in a lower dose of the organ-at-risk (OAR) than the photon plans. The V5, V10, V20, V30, V40, and Dmean of the contralateral lung in the CIRT plan are significantly lower than that of the photon VMAT. For the ipsilateral lung, the V5 of CIRT is significantly lower. The CIRT also had significantly lower spinal cord Dmax, esophageal Dmean and V50, V10 and V30 of bone, and V50 of the trachea and bronchial tree. CONCLUSIONS: Compared with photon VMAT, 2D-CIRT using the passive beam scanning technique significantly reduces the radiation dose to the OARs in curative radiotherapy of stage III NSCLC, suggesting a better protection of the normal tissues.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Radiotherapy, Intensity-Modulated , Humans , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/radiotherapy , Radiotherapy, Intensity-Modulated/methods , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/radiotherapy , X-Rays , Retrospective Studies , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy Dosage , CarbonABSTRACT
OBJECTIVE: To explore the mechanism of the Chinese medicine Cigu Xiaozhi prescription (, CGXZ) in the treatment of the non-alcoholic fatty liver disease (NAFLD) by detoxification and phlegm-reducing, the effect of CGXZ prescription on ceramide-mediated lipid apoptosis in Hep G2 cells with NAFLD. METHODS: The experiment was randomly divided into 6 groups: normal control group, model group, CGXZ prescription medicated serum high, medium, and low dose groups, and pioglitazone positive control group. Using 500 µmol/L free fatty acid (FFA) mixture to induce Hep G2 cells to establish NAFLD cell model, respectively, with 2%, 4%, and 6% concentration of CGXZ prescription medicated serum intervention for 24 h. The changes in organelles and lipid droplet accumulation were observed under the electron microscope. Furthermore, TdT-mediated dUTP Nick-End Labeling method was used to assay hepatocyte apoptosis; Biochemical determination of glutamic-pyruvic transaminase, glutamic oxalacetic transaminase, triglycerides, and FFA levels in Hep G2 cells; the content of ceramide was determined by high-performance thin-layer chromatography. Finally, Western Blot and quantitative real-time polymerase chain reaction (qRT-PCR) were used to determine the protein and gene expression levels, such as inducible nitric oxide synthase (iNOS), nuclear factor κB (NF-κB), B cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax). RESULTS: Under the electron microscope, the cells in the model group showed moderate-to-severe steatosis, and apoptotic bodies could be seen. The model group had greater improvements in the apoptosis rate (P < 0.01), and the levels of ceramide C2 and FFA in the cytoplasm (P < 0.01) than the normal control group. The protein expressions of NF-κB, iNOS, and Bax were significantly up-regulated (P < 0.05), while the Bcl-2 had no significant change (P > 0.05). Compared with the model group, the levels of ceramide C2 and FFA (P < 0.01), the protein expressions of NF-κB, iNOS, and Bax (P < 0.05) in the CGXZ prescription treatment group and pioglitazone positive control group were significantly decreased; Only the Bcl-2 protein was significantly up-regulated in the high-dose Chinese medicine group (P < 0.05). The down-regulation of Bax mRNA expression in each Chinese medicine treatment group was significantly better than in the pioglitazone positive control group (P < 0.01). CONCLUSIONS: The CGXZ prescription, formulated with the method of detoxification and phlegm, can inhibit lipoapoptosis in the NAFLD cell model by down-regulating the levels of ceramide C2 and FFA, which may be achieved by regulating ceramide/iNOS/NF-κB signaling pathway.
Subject(s)
Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/metabolism , Liver , NF-kappa B/genetics , NF-kappa B/metabolism , bcl-2-Associated X Protein/metabolism , Ceramides/metabolism , Ceramides/pharmacology , Ceramides/therapeutic use , Pioglitazone/metabolism , Pioglitazone/pharmacology , Pioglitazone/therapeutic use , PrescriptionsABSTRACT
Objective: To analyze the clinical characteristics of patients with common cardiovascular diseases (CVD, including hypertension, coronary heart disease, atrial fibrillation, and heart failure) combined with mild cognitive impairment (MCI) and explore the potential risk factors of MCI in patients with CVD. Methods: A total of 2 294 patients with common cardiovascular diseases who met the criteria at Cardiology Medical Center in Beijing Anzhen Hospital, Capital Medical University, from June 1, 2021, to January 5, 2022, were retrospectively included. The patients were divided into the normal cognitive function group (1 107 cases) and the MCI group (1 187 cases). Demographic information and CVD status were collected. The information of cognitive function were collected using the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) scales. The difference between normal cognitive function and MCI were compared and analyzed. The logistic regression analysis was used to explored risk factors of MCI in CVD patients. Results: A total of 2 294 patients aged (60.6±10.4) years were included, among whom there were 29.99% (688 cases) females. Compared with patients in the normal cognitive function group, patients in the MCI group were older [ (57.9±11.4) vs (63.1±8.9) years old, P<0.001], with a higher proportion of women [26.47% (293 cases) vs 33.28% (395 cases), P<0.001]; there was a higher proportion of patients suffering from hypertension in the MCI group [59.62% (660 cases) vs 64.62% (767 cases), P=0.014ï¼½, and more components of CVD [(1.68±0.62) vs (1.74±0.65) components, P=0.017]. The risk factors of MCI in patients with common CVD were increased age, increased depression score, combined with hypertension, and ≥3 common components of CVD, with OR (95%CI) of 1.043 (1.032-1.054), 1.021 (1.004-1.037), 1.151 (1.142-3.439), and 1.137 (1.023-1.797), respectively (all P values <0.05). Increasing education level was observed to be associated with reduced risk of MCI with OR (95%CI) of 0.319 (0.271-0.378) (P<0.05). Conclusions: The incidence of MCI was high in CVD patients. The risk factors of MCI in CVD patients included hypertension and≥3 common components of CVD.
Subject(s)
Cardiovascular Diseases , Cognitive Dysfunction , Hypertension , Humans , Female , Middle Aged , Aged , Retrospective Studies , Hypertension/epidemiology , CognitionABSTRACT
Objective: To investigate the distribution and hantavirus (HV) carrying state in host animals of hemorrhagic fever with renal syndrome (HFRS) in Henan Province from 2019 to 2022. Methods: Host animal monitoring was carried out at the monitoring sites of HFRS in Henan Province. The real-time fluorescence quantitative PCR was used to detect hantavirus in rat lungs. The types of hantavirus were analyzed. The positive samples were sequenced and then sequence homology and variation were analyzed. Results: A total of 1 308 rodents were captured from 2019 to 2022, 16 specimens of rat lungs tested positive for hantavirus nucleic acid. The positive rate of HV was 1.22% (16/1 308). According to type, the positive rate of HV in Apodius agrarius was the highest (68.75%, 11/16). According to distribution, the positive rate of HV in field samples was the highest (2.50%, 12/480), and the positive rate of HV in residential samples was 0.53% (4/759). The typing results of 16 positive samples showed that all viruses were hantavirus type â (hantaan virus). The positive samples were sequenced and eight S gene fragments (GenBank number: OQ681444-OQ681451) and six M gene fragments (OQ681438-OQ681443) were obtained. The S and M gene fragments were similar to the Shaanxi 84FLi strain and Sichuan SN7 strain. Phylogenetic analysis of S and M gene fragments showed that they all belonged to the hantaan virus-H5 subtype. Amino acid sequence analysis revealed that, compared with the hantaan virus vaccine strain 84FLi, the 74th amino acid encoded by eight S fragments was replaced by aspartamide with serine. Tryptophan was replaced by glycine at the 14th position of Gn region in XC2022047, and isoleucine was replaced by alanine at the 359 position of XC2022022 and XC2022024. Conclusion: The hantavirus carried by host animals in Henan Province from 2019 to 2022 belongs to the type â (hantaan virus), and Apodemus agrarius is still the dominant host animal of the hantaan virus. Compared with the vaccine strains, amino acid sites are replaced in the immune epitopes of the S and M gene fragments.
Subject(s)
Hemorrhagic Fever with Renal Syndrome , Orthohantavirus , Vaccines , Animals , Hemorrhagic Fever with Renal Syndrome/epidemiology , Phylogeny , Orthohantavirus/genetics , Murinae , Amino Acids/geneticsABSTRACT
OBJECTIVES: The association between asthma and COVID-19 mortality remains inconclusive. We examined the association between asthma and clinical outcomes of patients with COVID-19. STUDY DESIGN: A case-control study based on a surveillance cohort in Harris County, Texas. METHODS: Using the data of 21,765 patients who reported having at least one chronic health condition, we investigated the association between asthma and COVID-19 severity, characterized primarily by hospitalization and death. Unconditional logistic regression models were used to estimate the multivariable odds ratio (mOR) and its 95 % confidence interval (CI) of COVID-19 severity associated with asthma and other chronic lung diseases, adjusting for demographic and other comorbidities. A P-value < 0.005 was considered statistically significant after correcting multiple testing. RESULTS: In total, 3034 patients (13.9 %) had asthma, and 774 (3.56 %) had other chronic lung diseases. The case death rate among patients with asthma and other chronic lung diseases was 0.75 % and 19.0 %, respectively. Compared to patients without the respective conditions, patients with asthma had lower odds of death (mOR = 0.44, 95 % CI: 0.27-0.69), while patients with other chronic lung diseases had higher odds of hospitalization (mOR = 2.02, 95 % CI: 1.68-2.42) and death (mOR = 1.95, 95 % CI: 1.52-2.49) (P-values < 0.005). Risk factors for COVID-19 mortality included older age, male gender, diabetes, obesity, hypertension, cardiovascular disease, active cancer, and chronic kidney disease. CONCLUSIONS: The public health surveillance data suggested that preexisting asthma was inversely associated with COVID-19 mortality.
Subject(s)
Asthma , COVID-19 , Humans , Male , COVID-19/epidemiology , Comorbidity , Case-Control Studies , SARS-CoV-2 , Asthma/epidemiology , Risk Factors , Hospitalization , Retrospective StudiesABSTRACT
Long-term tumour recurrence rates and complications of endoscope-assisted partial superficial parotidectomy (PSP) are rarely reported compared to traditional open approaches. This retrospective study included 306 patients with superficial parotid benign neoplasms who were divided into an endoscopy group (endoscope-assisted PSP, n = 102) and a control group (conventional PSP, n = 204). There were no significant differences in clinical and pathological characteristics between the two groups, except age (P = 0.001). Three patients had confirmed recurrence during a mean follow-up duration of 125.1 months. Ten (9.8%) patients in the endoscopy group and 22 (10.8%) in the control group developed transient facial nerve palsy (P = 0.792), and recovered 6 months after the operation. Nine (8.8%) and 19 (9.3%) patients, respectively, suffered from Frey syndrome (P = 0.889). A sensory deficit of the auricle occurred in 24 (23.5%) and 57 (27.9%) patients respectively (P = 0.410). Patients in the endoscopy group were more satisfied with the postoperative scar than those in the control group (P < 0.001). This study demonstrated that the endoscope-assisted PSP can be curative, with better cosmetic outcomes than the conventional approach, and does not increase the incidence of postoperative complications or the local recurrence rate.
Subject(s)
Heterocyclic Compounds , Organometallic Compounds , Parotid Gland , Parotid Neoplasms , Humans , Parotid Gland/surgery , Case-Control Studies , Retrospective Studies , Parotid Neoplasms/surgery , Endoscopes , Postoperative ComplicationsABSTRACT
AIM: To develop a clinical-radiological model to predict the malignancy of solitary pulmonary nodules (SPNs) and to evaluate the accuracy of chest computed tomography imaging characteristics of SPN in diagnosing pathological type. MATERIALS AND METHODS: The predictive model was developed using a retrospective cohort of 601 SPN patients (Group A) between July 2015 and July 2020. The established model was tested using a second retrospective cohort of 124 patients between August 2020 and August 2021 (Group B). The radiological characteristics of all adenocarcinomas in two groups were analysed to determine the correlation between radiological and pathological characteristics. RESULTS: Malignant nodules were found in 78.87% of cases and benign in 21.13%. Two clinical characteristics (age and gender) and four radiological characteristics (calcification, vascular convergence, pleural retraction sign, and density) were identified as independent predictors of malignancy in patients with SPN using logistic regression analysis. The area under the receiver operating characteristic curve (0.748) of the present model was greater than the other two reported models. Diameter, spiculation, lobulation, vascular convergence, and pleural retraction signs differed significantly among pre-invasive lesions, minimally invasive adenocarcinoma, and invasive adenocarcinoma. Only diameter and density were significantly different among invasive adenocarcinoma subtypes. CONCLUSIONS: Older age, male gender, no calcification, vascular convergence, pleural contraction sign, and lower density were independent malignancy predictors of SPNs. Furthermore, the pathological classification can be clarified based on the radiological characteristics of SPN, providing a new option for the prevention and treatment of early lung cancer.
Subject(s)
Adenocarcinoma , Calcinosis , Lung Neoplasms , Solitary Pulmonary Nodule , Humans , Male , Solitary Pulmonary Nodule/pathology , Retrospective Studies , Radiography , Lung Neoplasms/pathology , Adenocarcinoma/diagnostic imagingABSTRACT
Objective: To investigate the role and related mechanism of the highly expressed circular RNA molecule 103124 (hsa_circRNA_103124) in macrophage differentiation, pyroptosis and inflammation in peripheral blood mononuclear cells (PBMC) of patients with active Crohn's disease (CD). Methods: Patients with active CD (CD group) admitted to the Affiliated Suzhou Hospital of Nanjing Medical University from April to September 2018 and healthy people (control group) from the physical examination center of the hospital from July to October 2018 were retrospectively selected. The levels of hsa_circRNA_103124 and Toll-like receptor 4 (TLR4) in PBMC of the two groups were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Tohoku hospital pediatrics-1 (THP1) cell line was used as a model for the study of hsa_circRNA_103124 regulating macrophage differentiation. Lentivirus infection was used to construct hsa_circRNA_103124 overexpressed or down-regulated THP1 cells to induce macrophage-like differentiation. According to the expression level of hsa_circRNA_103124, THP1 cell lines were divided into the following four groups: pLC5-ciR was overexpression control group; hsa_circRNA_103124 OE was the overexpression group; ShRNActrl was down-regulated expression control group; hsa_circRNA_103124 ShRNA was the down-regulated expression group. Flow cytometry was used to detect levels cluster of differentiation (CD) 68, CD80, interleukin (IL)-6, tumor necrosis factor α (TNF-α) and reactive oxygen species (ROS). The expression levels of IL-6, TNF-α, IL-1ß, TLR4 and myeloid differentiation factor 88 (MyD88) were detected by RT-qPCR. The levels of gasdermin D (GSDMD), IL-18 and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) were determined by immunofluorescence and RT-qPCR. Pearson correlation analysis was used to analyze the correlation between the abundance of hsa_circRNA_103124 and TLR4 expression level or Crohn's disease activity index (CDAI). Results: A total of 50 patients were included in the CD group, including 36 males and 14 females, aged (35±10) (19-64) years. A total of 30 subjects were included in the control group, including 22 males and 8 females, aged (38±9) (24-64) years. hsa_circRNA_103124 [(0.009±0.016) vs (0.003±0.002), P=0.042] and TLR4 [(0.005±0.003) vs (0.001±0.001), P<0.001] were all upregulated in the PBMC of patients in the CD group, compared with the control group. And hsa_circRNA_103124 was positively correlated with TLR4 (r=0.40, P=0.004). hsa_circRNA_103124 level was positively correlated with CDAI (r=0.32, P=0.024). The expression of CD68 (P=0.002) and CD80 (P<0.001) were enhanced. hsa_circRNA_103124 promoted production of ROS and the expression of IL-6, TNF-α, IL-1ß, TLR4, MyD88, GSDMD, IL-18 and NLRP3 in macrophage-like M1 differentiated THP1 cells (all P<0.05). Conclusion: High expresion of hsa_circRNA_103124 in PBMC of patients with active CD may promote macrophage M1 differentiation, pyroptosis and inflammation through enhancing the expression of TLR4, MyD88, NLRP3 and GSDMD.
Subject(s)
Crohn Disease , Male , Female , Child , Humans , RNA, Circular , Leukocytes, Mononuclear/metabolism , Interleukin-18/metabolism , Toll-Like Receptor 4/metabolism , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6/metabolism , Pyroptosis , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Retrospective Studies , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/metabolism , Reactive Oxygen Species/metabolism , Inflammation , Macrophages/metabolism , Macrophages/pathologyABSTRACT
To investigate two clusters of severe fever with thrombocytopenia syndrome virus (SFTSV) in Xinyang City, Henan Province, in 2022, and analyze their causes, transmission route, risk factors, and the characteristics of virus genetic variation. Case search and case investigation were carried out according to the case definition. Blood samples from cases, family members and neighbors and samples of biological vectors were collected for RT-PCR to detect SFTSV. The whole genome sequencing and bioinformatics analysis were performed on the collected positive samples. A total of two clustered outbreaks occurred, involving two initial cases and ten secondary cases, all of which were family recurrent cases. Among them, nine secondary cases had close contact with the blood of the initial case, and it was determined that close contact with blood was the main risk factor for the two clustered outbreaks. After genome sequencing analysis, we found that the SFTSV genotype in two cases was type A, which was closely related to previous endemic strains in Xinyang. The nucleotide sequence of the SFTSV in the case was highly homologous, with a total of nine amino acid mutation sites in the coding region. It was not ruled out that its mutation sites might have an impact on the outbreak of the epidemic.
Subject(s)
Bunyaviridae Infections , Phlebovirus , Severe Fever with Thrombocytopenia Syndrome , Thrombocytopenia , Humans , Severe Fever with Thrombocytopenia Syndrome/complications , Severe Fever with Thrombocytopenia Syndrome/epidemiology , Bunyaviridae Infections/complications , Bunyaviridae Infections/epidemiology , Thrombocytopenia/epidemiology , Thrombocytopenia/genetics , Thrombocytopenia/complications , Phlebovirus/genetics , Disease Outbreaks , China/epidemiologyABSTRACT
The European Association for the Study of Liver Diseases issued the "Clinical Practice Guidelines for the Management of Hepatic Encephalopathy" in 2022, which included recommendations for clinical diagnosis, assessment, treatment, management, and prevention. The Society's "Hepatic Encephalopathy Clinical Practice Guidelines in Chronic Liver Disease," which was last published in 2014, and the "Guidelines for the Diagnosis and Treatment of Hepatic Encephalopathy in Cirrhosis," which the Chinese Society of Hepatology, Chinese Medical Association, released in 2018, have certain differences and updates in terms of comparison to terminology, grading and classification, diagnosis, clinical evaluation and treatment, management, and prevention. Herein, the updated points of this guideline and the differences between it and our nation's guidelines are summarized in order to refine and understand the guiding role of the new version of the guideline for the clinical treatment of hepatic encephalopathy and provide aid for standardizing clinical diagnosis and treatment.
Subject(s)
Gastroenterology , Liver Diseases , Humans , Asian People , China , Gastroenterology/standards , Hepatic Encephalopathy/diagnosis , Hepatic Encephalopathy/therapy , Hepatic Encephalopathy/complications , Liver Cirrhosis , European People , Liver Diseases/diagnosis , Liver Diseases/therapy , EuropeABSTRACT
Atopic dermatitis(AD)is a chronic, recurrent, inflammatory skin disease in children. The disease is characterized by dryness, chronic eczema-like lesions and obvious itching, seriously affecting the quality of life of children and their families. The pathogenesis of AD is not yet to be clear, and it might be the interaction of genetic susceptibility and environmental exposure to induce skin barrier impairment and immune system dysfunction. In recent years, the role of maternal factors or intrauterine environment exposure on childhood allergic diseases has been attracted attention, and the hypothesis that allergic diseases originate from the fetal period has been postulated. Maternal exposures called "early life exposure", such as nutritional factors during pregnancy (folate, vitamin D, vitamin E and polyunsaturated fatty acid) and tobacco exposure, home environmental exposure may be related with childhood atopic dermatitis. This article would focus on the recent research about maternal nutritional factors and family environmental exposure during pregnancy on offspring's atopic dermatitis.
Subject(s)
Dermatitis, Atopic , Child , Female , Pregnancy , Humans , Quality of Life , Environmental Exposure/adverse effects , Maternal Exposure/adverse effects , FamilyABSTRACT
Dental caries is a dynamic disease induced by the unbalance between demineralization of dental hard tissues caused by biofilm and remineralization of them; however, although various effective remineralization methods have been well documented, it is a challenge to reestablish the balance by enhancing remineralization alone while ignoring the antibacterial therapy. Therefore, the integration of remineralizing and antibacterial technologies offers a promising strategy to halt natural caries progression in clinical practice. Here, the conception of interrupting dental caries (IDC) was proposed based on the development of dual-functional coating with remineralizing and antibacterial properties. In this study, bovine serum albumin (BSA) loaded octenidine (OCT) successfully to form a BSA-OCT composite. Subsequently, through fast amyloid-like aggregation, the phase-transited BSA-OCT (PTB-OCT) coating can be covered on teeth, resin composite, or sealant surfaces in 30 min by a simple smearing process. The PTB-OCT coating showed satisfactory effects in promoting the remineralization of demineralized enamel and dentin in vitro. Moreover, this coating also exerted significant acid-resistance stability and anti-biofilm properties. Equally importantly, this coating exhibited promising abilities in reducing the microleakage between the tooth and resin composite in vitro and preventing primary and secondary caries in vivo. In conclusion, this novel dual-functional PTB-OCT coating could reestablish the balance between demineralization and remineralization in the process of caries, thereby potentially preventing or arresting caries.
Subject(s)
Dental Caries , Tooth Demineralization , Humans , Dental Caries/prevention & control , Dental Caries Susceptibility , Tooth Demineralization/prevention & control , Dental Enamel , Composite Resins , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Tooth Remineralization/methodsABSTRACT
OBJECTIVE: To investigate the molecular mechanism of osteoporosis caused by ketogenic diet (KD) using transcriptomic analysis. METHODS: Sixteen 8-week-old female C57BL/6J mice were divided into KD group and sham group for feeding with KD and normal diet for 3 months, respectively. Body weight, blood glucose and blood ketone levels of the mice were measured every two weeks. Microstructure of the cancellous bone in the distal femur was observed with Micro-CT. Total RNA was extracted from bone marrow cells for transcriptomic analysis and bioinformatics analysis. RT-qPCR was used to verify the expression levels of the genes with significant differential expression between the groups. RESULTS: KD obviously weakened the microstructure of the cancellous bone in mice. Compared with those in the sham group, the mice in KD group showed 165 differentially expressed genes (94 up-regulated and 71 down-regulated ones), including Acot1, Mpig6b, Gp9, Ppbp, Slc2a9, etc. KEGG pathway enrichment analysis showed obvious enrichment of the Apelin signaling pathway, PI3K- Akt signaling pathway and ECM-receptor interaction signal transduction pathway with greater number of differential genes. RTqPCR results showed that the 5 differential genes screened by transcriptomics were significantly upregulated in KD group, among which Acot1, Mpig6b and Ppbp were upregulated by over two folds (2.49 ± 0.665, 2.58 ± 0.470, and 2.59 ± 0.611, respectively), suggesting their involvement in KD-induced osteoporosis. CONCLUSION: The differentially expressed genes and enriched pathways identified in the mouse models provide new clues for studying the molecular mechanism and prevention of KD-induced osteoporosis.
Subject(s)
Diet, Ketogenic , Osteoporosis , Female , Animals , Mice , Mice, Inbred C57BL , Transcriptome , Diet, Ketogenic/adverse effects , Gene Expression Profiling , Osteoporosis/geneticsABSTRACT
OBJECTIVE: To investigate the characteristics of exosomes derived from dental pulp stem cells (DPSCs) in the direction of odontogenic differentiation, to analyze the differences in microRNA expression profile between exosomes derived from undifferentiated and odontogenic DPSCs, and to analyze their possible signal transduction pathways. METHODS: (1) DPSCs were cultured in α minimum Eagle' s medium (α-MEM), and odontogenic DPSCs were cultured in odontogenic differentiation medium for 21 days, using alizarin red staining and alkaline phosphatase staining to identify the odontogenic differentiation. Exosomes from the cell supernatant were isolated respectively, named as dental pulp stem cells-exosomes (DPSCs-Exo) and dental pulp stem cells-odontogenic-exosomes (DPSCs-OD-Exo). The exosomes were identified by transmission electron microscopy, nanoparticle tracking analysis and Western blot. (2) The microRNA expression profiles of DPSCs-Exo and DPSCs-OD-Exo were investigated by microRNA microarray. To validate the result of the microRNA microarray, real-time quantitative polymerase chain reaction (real-time PCR) assay was applied on 3 most significantly differential expressed microRNA. Pathway analysis was taken to detect enriched pathways associated with the predicted target genes of microRNA. RESULTS: (1) The DPSCs were isolated and cultured in vitro showed typical fibroblast-like morphology. The odontogenic differentiated DPSCs were spindle-shaped, polygonal, and uniform in size. Odontogenic differentiation group showed a large number of dark deposits in alizarin red staining and the cells were darkly stained in alkaline phosphatase staining, while the cells in normal culture medium group did not show obvious dyeing. The DPSCs-Exo and DPSCs-OD-Exo had the same morphology, both showed bilayer membrane and cup-shape. The peak sizes of DPSCs-Exo and DPSCs-OD-Exo were (114.67±9.07) nm and (134.00±8.54) nm, respectively. The difference between the two was statistically significant. DPSCs-Exo and DPSCs-OD-Exo both expressed the markers of exosomes, tumor susceptibility gene (TSG)101 and CD63. (2) microRNA microarray results showed that the expression profiles of DPSCs-Exo and DPSCs-OD-Exo were different. Nineteen increased by more than two times, and one decreased by 64%. Real-time PCR results showed that the expression levels of microRNA-1246, microRNA-1246-100-5p and microRNA-1246-494-3p in DPSCs-OD-Exo were significantly up-regulated. The difference was statistically significant. microRNA target prediction database and gene signaling pathway database were used to analyze differentially expressed microRNA, and it was predicted that differentially expressed microRNA could target axis inhibition protein 2(AXIN2) gene and Wnt/ß-catenin signaling pathway. CONCLUSION: DPSCs-OD-Exo and DPSCs-Exo had differences in their microRNA expression profile. Those differentially expressed microRNA may be involved in the regulation of DPSCs odontogenic differentiation.
Subject(s)
Exosomes , MicroRNAs , Exosomes/metabolism , Alkaline Phosphatase/metabolism , Dental Pulp/metabolism , Odontogenesis/genetics , Cell Differentiation/physiology , MicroRNAs/genetics , MicroRNAs/metabolism , Stem Cells/metabolism , Cells, Cultured , Cell ProliferationABSTRACT
OBJECTIVE: The aim of this study was to document the association between malnutrition and mortality as well as functional outcomes in patients with stroke. MATERIALS AND METHODS: PubMed, Embase and Scopus databases were systematically searched for observational studies that had used either of the three nutritional indices, geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), and controlling nutritional status score (CONUT), and examined the association between malnutrition and outcomes of interest in patients with stroke. The primary outcome was mortality and secondary outcomes were risk of recurrence and functional disability. Analysis was performed using STATA 16.0 software (College Station, TX, USA) and pooled effect sizes were reported as either hazards ratio (HR) or as odds ratio (OR). Random effects model was used for the analysis. RESULTS: A total of 20 studies were included, of which, 15 were focused on acute ischemic stroke (AIS) patients. Among patients with AIS, moderate to severe malnutrition, assessed using CONUT (OR 4.80, 95% CI: 2.31, 9.98), GNRI (OR 3.57, 95% CI: 2.08, 6.12) and PNI (OR 8.10, 95% CI: 4.69, 14.0), was associated with increased risk of mortality within 3 months and at 1-year follow-up (CONUT: OR 2.74, 95% CI: 1.96, 3.83; GNRI: OR 2.26, 95% CI: 1.34, 3.81; PNI: OR 3.32, 95% CI: 2.24, 4.93). Patients with moderate to severe malnutrition, assessed using any of the three indices, had an increased risk of having an unfavourable outcome [modified Rankin Score (mRS) score of 3 to 6, denoting major disability and/or death] within 3 months and at 1-year follow-up. Only one study reported the risk of recurrence. CONCLUSIONS: Assessing malnutrition in stroke patients at the time of hospital admission using any of the three nutritional indices is useful due to the observed association of malnutrition with survival and functional outcomes. However, due to a limited number of studies, there is a need for large prospective studies to validate the findings observed in this meta-analysis.
Subject(s)
Ischemic Stroke , Malnutrition , Stroke , Humans , Aged , Nutrition Assessment , Prospective Studies , Risk Factors , Nutritional Status , Prognosis , Malnutrition/diagnosis , Malnutrition/complications , Stroke/diagnosis , Stroke/complications , Retrospective StudiesABSTRACT
Objective: To explore the effect of blood lipids on the lesion distribution pattern in patients with acute ischemic stroke by using MRI technology based on population standard spatial analysis. Methods: The MRI data of 1 202 patients with acute ischemic stroke in General Hospital of Eastern Theater Command from January 2015 to December 2020 and Nanjing First Hospital from January 2013 to December 2021 were retrospectively collected, including 871 males and 331 females, aged 26 to 94 (64±11) years. According to the condition of blood lipids, they were divided into the dyslipidemia group (n=683) and the normal blood lipids group (n=519). After the automatic segmentation of diffusion-weighted imaging (DWI) images by artificial intelligence, the infarct sites were registered to the standard space which was used to draw the frequency heat map. The chi-square test was used to compare the difference in lesion location between the two groups. Generalized linear model regression analysis was used to observe the correlation between each blood lipid index and lesion site, and inter-group comparison and correlation analysis were used to observe the relationship between each blood lipid index and lesion volume. Results: Compared with the normal blood lipid group, the lesions in the dyslipidemia group were more extensive, mostly distributed in the occipital temporal region of the right posterior cerebral artery and the frontal region of the left middle cerebral artery. The brain regions of higher triglyceride(TG) and higher low-density lipoprotein cholesterol(LDL-C) groups were concentrated in the posterior circulation. The brain regions in the higher total cholesterol(TC) and lower high-density lipoprotein cholesterol(HDL-C) groups were concentrated in the anterior circulation(all P<0.05). In the anterior circulation infarct volume, the higher TC group was significantly higher than the normal TC group[(27.58±5.34) vs (17.73±1.18)ml, P=0.029]. In the posterior circulation infarct volume, the higher LDL-C group and the TG group were significantly higher than the normal LDL-C and TG groups[(7.55±2.51) vs (3.55±0.31) ml; (5.76±1.19) vs (3.36±0.30) ml](both P<0.05). Correlation analysis showed that TC and LDL-C were non-linearly (U-shaped) correlated with anterior circulation infarct volume (both P<0.05). Conclusions: Different blood lipids have effects on the distribution pattern and volume of ischemic stroke infarcts. Different hyperlipidemia is related to the specific distribution site and the larger extent of infarction.
Subject(s)
Anterior Wall Myocardial Infarction , Ischemic Stroke , Female , Male , Humans , Artificial Intelligence , Cholesterol, LDL , Retrospective Studies , Lipids , Magnetic Resonance ImagingABSTRACT
Objective: To investigate the diagnostic and evaluation value of plasma interleukin 9 (IL9) in the mucosal healing (MH) in patients with inflammatory bowel disease (IBD) treated with biological agents. Methods: Cohort study. IBD patients (137 cases) treated in the Affiliated Suzhou Hospital to Nanjing Medical University (Suzhou Municipal Hospital) from September 2019 to January 2022 were prospective selected. Each patient was treated with biological agents [Infliximab (IFX, 56 cases), Adalimumab (ADA, 20 cases), Ustekinumab (UST, 18 cases), Vedolizumab (VDZ, 43 cases)]. According to different therapeutic drugs, the IFX, ADA, UST, and VDZ group were divided. Clinical symptoms, inflammatory indicators and imaging examinations etc. were evaluated every 8 weeks, and the degree of MH was evaluated by endoscopy at the 54th week. The expression of plasma IL9 was detected by ELISA after initial enrollment (W 0) and 8 weeks of biological treatment (W 8). Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of IL9 for MH. Select the cut off value for the optimal ROC threshold based on the highest value of the Youden index. Spearman's rank correlation was used to analyze the correlation between IL9 and Simple Endoscopic Score for CD (SES-CD) and Mayo Endoscopic Score (MES), so as to evaluate the predictive value of IL9 for MH in IBD patients treated with biologic agents. Results: Among the 137 patients, there were 97 Crohn's disease (CD) patients, 53 males and 44 females, aged (31.6±10.3) years (18-60 years). There were 40 ulcerative colitis (UC) patients, 22 males and 18 females, aged (37.5±14.7) years (18-67 years). Among the CD patients, 42 cases (43.3%) achieved MH on endoscopy at the 54th week, and 60 patients (61.9%) achieved clinical remission. Among the UC patients, 22 cases (55.0%) achieved MH and 30 cases (75.0%) achieved clinical remission. At W 0, the relative expression of IL9 in patients in IBD patients who achieved MH after 54 weeks of biological treatment was lower than that in the non-MH patients [x¯±s, (127.42±34.43) vs (146.82±45.64) ng/L, (113.01±44.88) vs (146.12±48.66) ng/L, respectively, both P<0.05]. At W 8, the relative expression of IL9 in the MH group was lower than that in the non-MH patients (both P<0.05). The relative expression of IL9 in the MH patients after IFX treatment was lower than that in the non-MH group (P<0.05). There was no significant difference among the other groups between MH and non-MH patients (all P>0.05). IL9 at W 8 showed high value in predicting MH in IBD [CD patients: area under curve (AUC)=0.716(95%CI: 0.616-0.817, P<0.001), sensitivity and specificity were 80.77%(95%CI:67.64%-88.45%) and 48.89%(95%CI: 35.53%-64.47%), respectively; UC patients: AUC=0.821, sensitivity and specificity were 77.78% and 72.73%, respectively]. At W 8, the cut off values for CD and UC patients were IL9>80.77 ng/L and IL9>77.78 ng/L, respectively. IL9 was positively correlated with endoscopic MH score parameters [M(Q1,Q3),SES-CD: 3.0(8.5, 18.5); MES: 2.0(1.0, 3.0)] (r=0.55, 0.72, respectively, both P<0.001) at W8. Conclusion: The plasma IL-9 at the week 8 after biological agents treatment can be used to diagnose and evaluate the MH of patients with IBD.