ABSTRACT
Periodontitis is a prevalent oral inflammatory disease that can result in tooth loss and is closely linked to type 2 diabetes (T2D). In this study, we analyzed the salivary proteome and intact N-glycopeptides (IGPs) of individuals with mild-moderate, severe, aggressive periodontitis, and periodontitis with T2D, including those treated with antidiabetic drugs, to identify specific signatures associated with the disease. Our results revealed that salivary proteins and glycoproteins were altered in all periodontitis groups (PRIDE ID: 1-20230612-72345), with fucose- and sialic acid-containing N-glycans showing the greatest increase. Additionally, differentially expressed proteins were classified into 9 clusters, including those that were increased in all periodontitis groups and those that were only altered in certain types of periodontitis. Interestingly, treatment with antidiabetic drugs reversed many of the changes observed in the salivary proteome and IGPs in T2D-related periodontitis, suggesting a potential therapeutic approach for managing periodontitis in patients with T2D. Consistent with MS/MS results, the expression of salivary IGHA2 and Fucα1-3/6GlcNAc (AAL) was significantly increased in MP. These findings provide new insights into the pathogenesis of periodontitis and highlight the potential of salivary biomarkers for diagnosis, prognosis, and monitoring of disease progression and treatment response.
Subject(s)
Diabetes Mellitus, Type 2 , Periodontitis , Humans , Proteome/genetics , Proteome/metabolism , Diabetes Mellitus, Type 2/metabolism , Glycopeptides/metabolism , Tandem Mass Spectrometry , Biomarkers/metabolism , Hypoglycemic Agents , Saliva/metabolismABSTRACT
The management of hypertrophic scars (HSs), characterized by excessive collagen production, involves various nonsurgical and surgical interventions. However, the absence of a well-defined molecular mechanism governing hypertrophic scarring has led to less-than-ideal results in clinical antifibrotic treatments. Therefore, our study focused on the role of decorin (DCN) and its regulatory role in the TGF-ß/Smad signalling pathway in the development of HSs. In our research, we observed a decrease in DCN expression within hypertrophic scar tissue and its derived cells (HSFc) compared to that in normal tissue. Then, the inhibitory effect of DCN on collagen synthesis was confirmed in Fc and HSFc via the detection of fibrosis markers such as COL-1 and COL-3 after the overexpression and knockdown of DCN. Moreover, functional assessments revealed that DCN suppresses the proliferation, migration and invasion of HSFc. We discovered that DCN significantly inhibits the TGF-ß1/Smad3 pathway by suppressing TGF-ß1 expression, as well as the formation and phosphorylation of Smad3. This finding suggested that DCN regulates the synthesis of collagen-based extracellular matrix and fibrosis through the TGF-ß1/Smad3 pathway.
Subject(s)
Cicatrix, Hypertrophic , Decorin , Smad3 Protein , Transforming Growth Factor beta , Decorin/genetics , Decorin/metabolism , Cicatrix, Hypertrophic/metabolism , Cicatrix, Hypertrophic/pathology , Transforming Growth Factor beta/metabolism , Signal Transduction , Gene Knockdown Techniques , Humans , Smad3 Protein/metabolism , Collagen Type I/metabolism , Collagen Type III/metabolism , Extracellular Matrix/metabolism , Cell Proliferation , Cell MovementABSTRACT
Neuroinflammation is being increasingly recognized as a vital factor in the development of various neurological and neuropsychiatric diseases. Lipopolysaccharides (LPS), an outer membrane component of gram-negative bacteria, can trigger innate immune responses, resulting in neuroinflammation and subsequent cognitive deficits. The expression of glutamate receptors (GluRs) on glial cells can induce glial activation. Therefore, we hypothesized that repeated LPS exposure can increase GluR levels, promoting microglial activation and ultimately affecting synaptic plasticity and cognitive function. In this study, C57/BL6 mice were repeatedly exposed to LPS to construct a neuroinflammation animal model. The levels of GluRs, inflammatory cytokines, ionized calcium-binding adaptor molecule 1, postsynaptic density protein 95, synaptophysin 38, NMDA receptor 2 A, and NMDA receptor 2B (GluN2B) were measured in the hippocampi. Furthermore, dendritic spine density in the CA1 hippocampal region was determined. Repeated LPS exposure induced cognitive impairments and microglial activation and increased GluR1 and GluR2 levels. This was accompanied by a significant decrease in GluN2B expression and dendritic spine density in the hippocampi. However, CFM-2, an α-amino-3- hydroxy-5-methyl-4-isoxazolepropionate receptor antagonist, reversed these anomalies. Furthermore, minocycline, a microglial inhibitor, reversed these anomalies and downregulated GluR2 but not GluR1 expression. In summary, we demonstrated that GluR2 plays an essential role in microglia-induced neuroinflammation, resulting in synaptic plasticity and cognitive impairment induced by repeated exposure to LPS.
Subject(s)
Cognitive Dysfunction , Lipopolysaccharides , Mice, Inbred C57BL , Neuroinflammatory Diseases , Receptors, AMPA , Animals , Lipopolysaccharides/toxicity , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/chemically induced , Receptors, AMPA/metabolism , Male , Neuroinflammatory Diseases/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Mice , Hippocampus/metabolism , Hippocampus/drug effects , Microglia/metabolism , Microglia/drug effects , Neuronal Plasticity/drug effectsABSTRACT
OBJECTIVES: To determine the relationship between renal tumor complexity and vascular complications after partial nephrectomy using PADUA, RENAL, and ZS scores. METHODS: Between January 2007 and December 2018, a total of 1917 patients with available cross-sectional imaging were enrolled in the study. Logistic regressions were used to identify independent predictors of vascular complications. RESULTS: Of 1917 patients, 31 (1.6%) developed vascular complications, including 10 females and 21 males. The high-complexity category was significantly associated with a decreased risk of vascular complication in PADUA (OR = 0.256; 95%CI = 0.086-0.762; P = 0.014) and ZS score (OR = 0.279; 95%CI = 0.083-0.946; P = 0.040). Laparoscopic partial nephrectomy and robot-assisted laparoscopic partial nephrectomy were independent risk factors for vascular complications. Meanwhile, the incidence was significantly reduced in the recent 4 years in the high score tumor group alone in PADUA (0.2% [1/474] vs. 2.2% [3/139], P = 0.038) and ZS score (0.2% [1/469] vs. 2.7% [3/112], P = 0.024). In the first 8 years, laparoscopic partial nephrectomy and robot-assisted laparoscopic partial nephrectomy were the only two independent risk factors for vascular complications. In the recent 4 years, only the high-complexity category was significantly associated with a decreased risk of vascular complication in the PADUA score (OR = 0.110; 95%CI = 0.013-0.938; P = 0.044). CONCLUSION: The renal anatomic classification system cannot predict the occurrence of vascular complications after partial nephrectomy.
Subject(s)
Kidney Neoplasms , Laparoscopy , Robotic Surgical Procedures , Male , Female , Humans , Kidney/surgery , Nephrectomy/adverse effects , Nephrectomy/methods , Kidney Neoplasms/pathology , Robotic Surgical Procedures/adverse effects , Laparoscopy/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/pathology , Retrospective Studies , Treatment OutcomeABSTRACT
Hydrochlorofluorocarbons (HCFCs) are transitional substitutes for chlorofluorocarbons (CFCs). However, they still have the capacity to be ozone-depleting substances (ODSs). Therefore, they are scheduled to be phased out in China by 2030 under the Montreal Protocol. The emission estimates of HCFC-22 (CHClF2) and HCFC-142b (CH3CClF2) in China using atmospheric observations are lacking after 2017, making it hard to understand the effectiveness of the phase-out process of HCFCs in China. Here, we use flask and in situ measurements of HCFC-22 and HCFC-142b during 2018-2021 and inverse modeling to determine the emission magnitude and changes in China. It was determined that China's emissions were 172 ± 40, 154 ± 39, 160 ± 22, and 155 ± 33 Gg yr-1 of HCFC-22 and 8.3 ± 1.8, 7.8 ± 1.6, 7.4 ± 1.7, and 7.9 ± 1.7 Gg yr-1 of HCFC-142b from 2018 to 2021, respectively. Top-down estimates show that HCFC-22 emissions in China were stable, while HCFC-142b emissions were decreasing during 2013-2021, although both substances were in the stage of being phased out during 2013-2021. This study reveals that 46 and 39% of the global HCFC-22 and HCFC-142b emissions, respectively, cannot be traced to certain countries in 2020. We suggest that more studies on HCFC emissions around the world in the future are needed to better safeguard the ozone layer recovery and climate mitigation by ensuring compliance with the Montreal Protocol during HCFC phase-out processes.
ABSTRACT
Water diversion can effectively alleviate water resource shortages and improve water environmental conditions, while also causing unknown ecological consequences, in particular, the assembly mechanism of zooplankton communities in the affected areas will become more complex after long-term water transfer. Taking Nansi Lake, the second largest impounded lake along the eastern route of China's South to North Water Diversion Project (SNWDP), as an example, the composition and diversity of zooplankton communities in the lake area and estuaries during the water diversion period (WDP) and non-water diversion period (NWDP) were studied. The potential assembly process of zooplankton communities was further explored, and the stability of communities in different regions during different periods was compared. The related results indicated that the changes in water quality conditions induced by water diversion had a relatively weak impact on the zooplankton communities. In the assembly mechanism of zooplankton communities, stochastic process played a more important role during both WDP or NWDP, and the proportion of deterministic process was relatively higher during NWDP, which may be related to the greater role of total nitrogen (TN) in the assembly of the zooplankton communities. The network analysis and cohesion calculation results showed that the stability of the zooplankton communities in the lake area sites was higher than that in the estuary sites, and the stability during NWDP was higher than that during WDP. In sum, the stability of zooplankton communities displayed a degree of change affected by water diversion activities, but the community assembly was not significantly influenced by the water quality fluctuations after about relatively long-term water diversion. This study provides an in-depth understanding of the ecological effects of water diversion on the biological communities in the affected lake, which is beneficial to the management and regulation of long-term water diversion projects.
Subject(s)
Lakes , Zooplankton , Animals , China , Water Quality , Nitrogen/analysisABSTRACT
BACKGROUND: Multiple supernumerary teeth, combined with numerous impacted teeth, can lead to various malocclusions, posing significant treatment challenges. While certain genes associated with syndromic cases of multiple supernumerary and impacted teeth have been identified, the etiologies of non-syndromic cases still largely remain elusive. CASE PRESENTATION: Here, we report a treatment of a 12-year-old boy who presented with 10 supernumerary teeth and 6 impacted teeth, accompanied by a genetic analysis to explore the underlying etiology. During the treatment, fifteen teeth were extracted, and various skilled techniques, including the closed-eruption technique and the application of by-pass arches, were utilized. Post-treatment, traction was successful for all the impacted teeth, without any tooth mobility or reduction in gingival height. Space closure, well-aligned teeth, and excellent functional occlusion were achieved. Furthermore, comprehensive genetic analysis was conducted through whole-exome sequencing on the patient and his parents, which revealed a potential link between the patient's numerous supernumerary teeth and abnormal mineralization. Notably, the p.Ser496Pro variant in the TCF7L2 gene was identified as a potential candidate variant in this patient. CONCLUSIONS: Overall, our findings not only report the treatment of a rare case involving multiple supernumerary and impacted teeth but also offer valuable insights into the molecular basis of supernumerary teeth.
Subject(s)
Tooth, Impacted , Tooth, Supernumerary , Humans , Tooth, Supernumerary/genetics , Tooth, Impacted/genetics , Male , Child , Tooth Extraction , Exome SequencingABSTRACT
Local retroperitoneal recurrence (RPR) after radical nephrectomy (RN) is rare in patients with renal cell carcinoma (RCC); however, it is associated with poor prognosis and lacks standard treatment. Our study aimed to assess oncological outcomes and prognostic factors of patients that underwent targeted therapy for RPR after RN, and to evaluate the role of presurgical targeted therapy in this context. This was a retrospective multicenter study of 85 patients with RPR treated with targeted therapy for RPR after RN (July 2008-October 2020). Clinical and pathological characteristics were reported using descriptive statistics. Cancer-specific survival (CSS) was examined using the Cox proportional hazards model. The median follow-up time was 50 months (95% confidence interval [CI]: 33.3-66.7) after the RPR diagnosis. The median CSS was 96 months in the presurgical targeted therapy followed by surgical resection group and 42 months (95% CI: 28.8-55.2) in the targeted therapy alone group (P = .0011). In multivariate analysis, International Metastatic RCC Database Consortium classification intermediate/poor risk, number of recurrence lesions and surgical resection were independent predictors of CSS. Presurgical targeted therapy may increase the feasibility of tumor resection for RPR after RN. Patients who underwent surgical resection following presurgical targeted therapy had better CSS than those treated with targeted therapy alone.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Retroperitoneal Neoplasms , Humans , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Retroperitoneal Neoplasms/etiology , Retroperitoneal Neoplasms/secondary , Neoplasm Recurrence, Local/pathology , Nephrectomy/adverse effects , Retrospective StudiesABSTRACT
OBJECTIVE: We aimed to retrospectively investigate whether the neutrophil to lymphocyte ratio (NLR) and the monocyte to lymphocyte ratio (MLR) can predict the prognosis of patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib or sorafenib. METHODS: We retrospectively identified 210 patients with mRCC treated with sunitinib or sorafenib from 2007 to 2017 at Fudan University- and Hexi University-affiliated hospitals. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method. Multivariate regression analysis was used to evaluate predictors of PFS and OS. RESULTS: Low NLR (<2.85) and MLR (<.30) were strongly associated with increased PFS and OS. Multivariable analyses verified that the NLR and MLR were both independent prognostic factors. Additionally, the NLR was negatively correlated with CD8+ and CD4+ T-cell infiltration in tumors. CONCLUSION: In patients with mRCC treated with sunitinib and sorafenib, an NLR <2.85 and MLR <.30 was associated with superior PFS and OS, which may be related to the reduced lymphocytic infiltration of tumors.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Sunitinib/therapeutic use , Sorafenib/therapeutic use , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Retrospective Studies , Biomarkers , Prognosis , Lymphocytes/pathologyABSTRACT
The posttranscriptional control of gene expression mediated by RNA-binding proteins (RBPs) is essential to determine tumor cell fate. HuR is an RBP with increased expression in various cancer types. This study aimed to clarify the regulatory mechanism of HuR's contribution to breast cancer (BC) cell proliferation by inducing RAB5C expression. First, we analyzed the expression level of HuR and RAB5C in BC tissues and cell lines by immunohistochemistry, qRT-PCR, and western blot. Next, to further investigate the effect of HuR on RAB5C expression, we used short hairpin RNAs (shRNAs) to silence endogenous HuR expression in BC cell lines MCF7 and MDA-MB-231. The binding site of RAB5C mRNA and HuR was confirmed by RNA immunoprecipitation. Finally, the function of RAB5C was investigated using flow cytometry, colony formation, and MTT assays. We found that the expression of HuR and RAB5C was significantly upregulated in BC tissues and MCF-7 and MDA-MB231 cell lines. Importantly, RAB5C mRNA stability was increased through binding of HuR to its 3'UTR. Inhibition of HuR expression using shRNA decreased RAB5C mRNA, suggesting that HuR plays a role in regulating RAB5C expression level. In addition, suppression of RAB5C expression reduced BC cell growth. These results suggest RAB5C functions as an oncogene in BC cells, HuR promoted BC cell survival by facilitating RAB5C expression. Our findings suggest that HuR and RAB5C play important roles in BC cell survival.
Subject(s)
Breast Neoplasms , ELAV-Like Protein 1 , Female , Humans , 3' Untranslated Regions , Breast Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation , ELAV-Like Protein 1/genetics , ELAV-Like Protein 1/metabolism , Gene Expression Regulation, Neoplastic , rab5 GTP-Binding Proteins/genetics , rab5 GTP-Binding Proteins/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Small Interfering/metabolismABSTRACT
Having the highest ozone-depleting potential among hydrochlorofluorocarbons (HCFCs), the production and consumption of HCFC-141b (1,1-dichloro-1-fluoroethane, CH3CCl2F) are controlled by the Montreal Protocol. A renewed rise in global HCFC-141b emissions was found during 2017-2020; however, the latest changes in emissions across China are unclear for this period. This study used the FLEXible PARTicle dispersion model and the Bayesian framework to quantify HCFC-141b emissions based on atmospheric measurements from more sites across China than those used in previous studies. Results show that the estimated HCFC-141b emissions during 2018-2020 were on average 19.4 (17.3-21.6) Gg year-1, which was 3.9 (0.9-7.0) Gg year-1 higher than those in 2017 (15.5 [13.4-17.6] Gg year-1), showing a renewed rise. The proportion of global emissions that could not be exactly traced in 2020 was reduced from about 70% reported in previous studies to 46% herein. This study reconciled the global emission rise of 3.0 ± 1.2 Gg year-1 (emissions in 2020 - emissions in 2017): China's HCFC-141b emissions changed by 4.3 ± 4.5 Gg year-1, and the combined emissions from North Korea, South Korea, western Japan, Australia, northwestern Europe, and the United States changed by -2.2 ± 2.6 Gg year-1, while those from other countries/regions changed by 0.9 ± 5.3 Gg year-1.
Subject(s)
Chlorofluorocarbons , Chlorofluorocarbons/analysis , Bayes Theorem , Chlorofluorocarbons, Ethane , ChinaABSTRACT
Venous thromboembolism (VTE) is a multifactorial disease, and pulmonary hypertension (PH) is a serious condition characterized by pulmonary vascular remodeling leading with increased pulmonary vascular resistance, ultimately leading to right heart failure and death. Although VTE and PH have distinct primary etiologies, they share some pathophysiologic similarities such as dysfunctional vasculature and thrombosis. In both conditions there is solid evidence that EVs derived from a variety of cell types including platelets, monocytes, endothelial cells and smooth muscle cells contribute to vascular endothelial dysfunction, inflammation, thrombosis, cellular activation and communications. However, the roles and importance of EVs substantially differ between studies depending on experimental conditions and parent cell origins of EVs that modify the nature of their cargo. Numerous studies have confirmed that EVs contribute to the pathophysiology of VTE and PH and increased levels of various EVs in relation with the severity of VTE and PH, confirming its potential pathophysiological role and its utility as a biomarker of disease severity and as potential therapeutic targets.
Subject(s)
Extracellular Vesicles , Hypertension, Pulmonary , Thrombosis , Venous Thromboembolism , Humans , Hypertension, Pulmonary/metabolism , Hypertension, Pulmonary/therapy , Venous Thromboembolism/metabolism , Endothelial Cells/metabolism , Extracellular Vesicles/metabolismABSTRACT
Hypothermic oxygenated machine perfusion (HOPE) can enhance organ preservation and protect mitochondria from hypoxia-ischemic injury; however, an understanding of the underlying HOPE mechanism that protects mitochondria is somewhat lacking. We hypothesized that mitophagy may play an important role in HOPE mitochondria protection. Experimental rat liver grafts were exposed to 30 min of in situ warm ischemia. Then, grafts were procured, followed by cold storage for 3 or 4 h to mimic the conventional preservation and transportation time in donation after circulatory death (DCD) in clinical contexts. Next, the grafts underwent hypothermic machine perfusion (HMP) or HOPE for 1 h through portal vein only perfusion. The HOPE-treated group showed a better preservation capacity compared with cold storage and HMP, preventing hepatocyte damage, nuclear injury, and cell death. HOPE can increase mitophagy marker expression, promote mitophagy flux via the PINK1/Parkin pathway to maintain mitochondrial function, and reduce oxygen free radical generation, while the inhibition of autophagy by 3-methyladenine and chloroquine could reverse the protective effect. HOPE-treated DCD liver also demonstrated more changes in the expression of genes responsible for bile metabolism, mitochondrial dynamics, cell survival, and oxidative stress. Overall, HOPE attenuates hypoxia-ischemic injury in DCD liver by promoting mitophagy flux to maintain mitochondrial function and protect hepatocytes. Mitophagy could pave the way for a protective approach against hypoxia-ischemic injury in DCD liver.
Subject(s)
Liver Transplantation , Rats , Animals , Mitophagy , Liver/metabolism , Hepatocytes , Perfusion , Organ PreservationABSTRACT
The aim was to determine whether lipid molecules can be used as potential biomarkers for idiopathic pulmonary arterial hypertension (IPAH), providing important reference value for early diagnosis and treatment. Liquid chromatography-mass spectrometry-based lipidomic assays allow for the simultaneous detection of a large number of lipids. In this study, lipid profiling was performed on plasma samples from 69 IPAH patients and 30 healthy controls to compare the levels of lipid molecules in the 2 groups of patients, and Cox regression analysis was used to identify meaningful metrics, along with receiver operator characteristic curves to assess the ability of the lipid molecules to predict the risk of disease in patients. Among the 14 lipid subclasses tested, 12 lipid levels were significantly higher in IPAH patients than in healthy controls. Free fatty acids (FFA) and monoacylglycerol (MAG) were significantly different between IPAH patients and healthy controls. Logistic regression analysis showed that FFA (OR: 1.239, 95%CI: 1.101, 1.394, p < 0.0001) and MAG (OR: 3.711, 95%CI: 2.214, 6.221, p < 0.001) were independent predictors of IPAH development. Among the lipid subclasses, FFA and MAG have potential as biomarkers for predicting the pathogenesis of IPAH, which may improve the early diagnosis of IPAH.
Subject(s)
Hypertension, Pulmonary , Humans , Familial Primary Pulmonary Hypertension , Hypertension, Pulmonary/pathology , Lipid Metabolism , Biomarkers/metabolism , LipidsABSTRACT
PURPOSE: The purpose of this article is to discuss the effective management of mandibular fractures in pediatric patients during the growing phase of the mandible using splint fiber and ligature wire. METHODS: A retrospective study examined pediatric patients with mandibular fractures who were treated using the splint (Quartz) fiber and ligature wire technique at the Stomatology Hospital of Xi'an Jiaotong University from August 2021 to January 2023. Data on gender, age, location or site of the fracture, and development of tooth stage were collected from the patient's medical records. Descriptive statistics were used to analyze the data and evaluate the effectiveness of the splint (Quartz) fiber technique for treating mandibular fractures in pediatric patients. RESULTS: Out of 256 subjects, 6 pediatric patients with mandibular fractures were selected, resulting in an incidence rate of 2.34% with an equal sex ratio. Mental or symphysis fracture was the most common site for fracture in children, accounting for 100% of cases. Right mandibular angle fracture was observed in 16.7% of patients, while 50% of the group (3 individuals) suffered from left condylar fracture and 16.7% had a bilateral condylar fracture. Treatment with Quartz splint fiber and circumdental arch wiring using ligature wire was successful with no observed post-treatment complications or malocclusion. The splint fiber was worn for 30 days and the circumdental arch wiring was for the same. Healing of bone fracture yields good results after 12 weeks. Follow-up care is crucial to monitor for complications, in this study, no post-treatment complications were observed. CONCLUSION: The treatment of pediatric mandibular fractures is complex and requires careful consideration of various factors. Conservative management should be the first choice, with open reduction and internal fixation reserved for specific cases. The use of quartz splint fiber and ligature wire is an effective treatment option for stabilizing the mandible and providing occlusal stability in growing children. A fiber splint along with ligature wire can also be used as an alternative treatment to avoid any adverse effects on the growth and development of the mandible and permanent teeth. A multidisciplinary approach is essential to achieving the best outcomes for pediatric patients with mandibular fractures.
Subject(s)
Mandibular Fractures , Humans , Child , Mandibular Fractures/therapy , Conservative Treatment , Quartz , Retrospective Studies , SplintsABSTRACT
BACKGROUND: Enucleation, a surgical procedure, is commonly used to treat large jaw cysts, unicystic ameloblastomas and keratocysts. However, it remains unclear to what extent the jaw bone regenerates after enucleation. We aimed to evaluate the percentage and the survival analysis of jaw bone regeneration, in terms of cavity volume residual (CVR), in patients who underwent enucleation of large jaw cysts, unicystic ameloblastomas and keratocysts. METHODS: We collected data longitudinally from 75 patients who underwent jaw cystic lesions enucleation at the Stomatological Hospital of Xi'an Jiaotong University, between January 2015 and June 2021. All patients had both preoperative and postoperative cone-beam computed tomography (CBCT) imaging data. CBCT images were analyzed using Image J. Changes in the CVR were assessed at various follow-up time points, and the Kaplan-Meier method was utilized to evaluate the CVR over time. RESULTS: The patients had a mean age of 31.7 years (range: 5.5-72 years) with 58.66% of them being male. The postoperative CVR was 32.20% at three months, 21.10% at six months, 15.90% at 12 months, and 5.60% at 24 months. The percentage of CVR during follow-up periods for the initial size Quartile (Q)1 (212.54-1569.60 mm3) was substantially lower than those of Q2 and Q3 at and after seven months of follow-up and became statistically significant at the 12-month mark. CONCLUSION: This study demonstrates that spontaneous bone regeneration can occur after enucleation of large jaw cysts, unicystic ameloblastomas and keratocysts, even without the use of filler materials. The initial size of the lesion had a significant impact on the outcome of cystic lesion enucleation over time. To minimize the risks associated with radiation exposure and expenses, we recommend reducing the frequency of CT imaging follow-ups for patients with small initial cavity sizes (ranging from 212.54 to 1569.60 mm3).
Subject(s)
Ameloblastoma , Dental Caries , Jaw Cysts , Odontogenic Cysts , Adult , Female , Humans , Male , Bone Regeneration , Cone-Beam Computed Tomography , Odontogenic Cysts/diagnostic imaging , Odontogenic Cysts/surgery , Child , Adolescent , Young Adult , Middle Aged , AgedABSTRACT
Vaccines can stimulate the immune system to protect individuals from infectious diseases. Moreover, vaccines have also been applied to the prevention and treatment of cancers. Due to advances in genetic engineering technology, cancer vaccines could be genetically modified to increase antitumor efficacy. Various genes could be inserted into cells to boost the immune response, such as cytokines, T cell costimulatory molecules, tumor-associated antigens, and tumor-specific antigens. Genetically modified cancer vaccines utilize innate and adaptive immune responses to induce durable antineoplastic capacity and prevent the recurrence. This review will discuss the major approaches used to develop genetically modified cancer vaccines and explore recent advances to increase the understanding of engineered cancer vaccines.
Subject(s)
Cancer Vaccines , Neoplasms , Antigens, Neoplasm , Cytokines , Humans , Immune System , Neoplasms/genetics , Neoplasms/prevention & controlABSTRACT
BACKGROUND: Our previous study showed that circular RNA-gamma-secretase-activating protein (circGSAP) was down-regulated in pulmonary microvascular endothelial cells (PMECs) in response to hypoxia, and regulated the cell cycle of PMECs via miR-942-5p sponge in pulmonary hypertension (PH). However, the mechanism whether circGSAP affects the dysfunction of PEMCs through other microRNAs (miRNAs) remains largely unknown. Therefore, we aimed to demonstrate the underlying mechanisms of circGSAP regulating PMECs dysfunction by absorbing other miRNAs to regulate target genes in idiopathic pulmonary arterial hypertension (IPAH). METHODS: Quantitative real-time polymerase chain reaction, immunofluorescence staining, Cell Counting Kit-8, Calcein-AM/PI staining, Transwell assay, dual-luciferase reporter assay, and ELISA were used to elucidate the roles of circGSAP. RESULTS: Here we showed that plasma circGSAP levels were significantly decreased in patients with IPAH and associated with poor outcomes. In vivo, circGSAP overexpression improved survival, and alleviated pulmonary vascular remodeling of monocrotaline-induced PH (MCT-PH) rats. In vitro, circGSAP overexpression inhibited hypoxia-induced PMECs proliferation, migration and increased mortality by absorbing miR-27a-3p. BMPR2 was identified as a miR-27a-3p target gene. BMPR2 silencing ameliorated the effect of the miR-27a-3p inhibitor on PMECs proliferation,migration and mortality. The levels of BMPR2 were upregulated in circGSAP-overexpressed PMECs and lung tissues of MCT-PH rats. CONCLUSION: Our findings demonstrated that circGSAP alleviated the dysfunction of PMECs via the increase of BMPR2 by competitively binding with miR-27a-3p, and mitigated pulmonary vascular remodeling of MCT-PH rats, providing potential therapeutic strategies for IPAH.
Subject(s)
Hypertension, Pulmonary , MicroRNAs , Rats , Animals , Endothelial Cells/metabolism , Hypertension, Pulmonary/genetics , Hypertension, Pulmonary/metabolism , Vascular Remodeling , MicroRNAs/metabolism , Familial Primary Pulmonary Hypertension , Hypoxia/genetics , Hypoxia/metabolism , Bone Morphogenetic Protein Receptors, Type II/geneticsABSTRACT
BACKGROUND: Vesical Imaging-Reporting and Data System (VI-RADS) has been shown to be effective in diagnosing muscle invasion of bladder cancer (BC) in primary patients. PURPOSE: To evaluate the diagnostic efficacy of VI-RADS in a BC target population which included post-treatment patients, and to determine the repeatability. STUDY TYPE: Prospective. POPULATION: Seventy-three patients (42 with primary BC, 31 with post-treatment BC). FIELD STRENGTH/SEQUENCE: 3.0 T MRI with propeller fast spin-echo T2 WI, echo planer imaging diffusion-weighted imaging (DWI), and dynamic contrast-enhanced imaging (DCEI). ASSESSMENT: VI-RADS scores were independently assessed by five radiologists with different levels of experience. The diagnostic efficiency in each group (primary and post-treatment) and of each radiologist was assessed. STATISTICAL TESTS: Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), and area under the curve (AUC) in receiver operating characteristic curve analysis were calculated to evaluate VI-RADS diagnostic performance. Interobserver agreement was assessed using weighted Kappa statistics. A P value <0.05 was considered statistically significant. RESULTS: At the corresponding cut-off, AUC values of three groups range from 0.936 to 0.947 and AUC values of five observers range from 0.901 to 0.963. There was no significant difference between the AUCs in the primary and post-treatment groups (P = 0.870). The cut-off of the whole group and the post-treatment group was ≥4, and the cut-off of the primary group was ≥3. The Kappa values of interobserver agreements range from 0.709 to 0.923. CONCLUSIONS: After expanding the target population to include post-treatment patients, VI-RADS still has good diagnostic efficacy and repeatability. VI-RADS could potentially be a preoperative staging tool for post-treatment patients. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.
Subject(s)
Urinary Bladder Neoplasms , Diffusion Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging , Prospective Studies , Research Design , Urinary Bladder Neoplasms/diagnostic imagingABSTRACT
Hexafluoro-2-butyne (C4F6) is a potential eco-friendly alternative gas in plasma, refrigerants, and electrical insulation applications. Mechanisms for the reactions of C4F6 with OH/O2 have been revealed in detail using various theoretical methods including ROCBS-Q, RCCSD(T), multireference RS2C, and extrapolations to the complete basis-set limit with Aug-cc-pVnZ (n = T, Q, 5) basis sets. Rate coefficients and product branching ratios were predicted for a wide range of temperatures and pressures using the solution of master equations. The vibrationally adiabatic ground-state barrier for the initial C4F6 + OH association was best estimated to be 1.53-2.26 kcal/mol. Energetically preferable decomposition paths for the conformation-dependent C4F6OH adducts include six-center HF elimination, four-center proton migration, and C-C bond cleavage, but the collisional deactivation is dominant under ambient conditions. The subsequent oxidation of C4F6OH by O2 bifurcates in two orientations and proceeds without any well-defined barrier followed by the successive isomerization/elimination steps, forming perfluorobiacetyl to regenerate OH radicals or trifluoroacetic acid with trifluoroacetyl radicals. The OH-recycling path accounts for a branching ratio of 70% under ambient conditions. Theoretical rate coefficients are in good agreement with the available experimental results. The effect of fluorination on the reactivity of alkynes toward OH/O2 is discussed.