Exploring the role of exosomal MicroRNAs as potential biomarkers in preeclampsia.

The complex pathogenesis of preeclampsia (PE), a significant contributor to maternal and neonatal mortality globally, is poorly understood despite substantial research. This review explores the involvement of exosomal microRNAs (exomiRs) in PE, focusing on their impact on the protein kinase B (AKT)/hypoxia-inducible factor 1-α (HIF1α)/vascular endothelial growth factor (VEGF) signaling pathway as well as endothelial cell proliferation and migration. Specifically, this article amalgamates existing evidence to reveal the pivotal role of exomiRs in regulating mesenchymal stem cell and trophoblast function, placental angiogenesis, the renin-angiotensin system, and nitric oxide production, which may contribute to PE etiology. This review emphasizes the limited knowledge regarding the role of exomiRs in PE while underscoring the potential of exomiRs as non-invasive biomarkers for PE diagnosis, prediction, and treatment. Further, it provides valuable insights into the mechanisms of PE, highlighting exomiRs as key players with clinical implications, warranting further exploration to enhance the current understanding and the development of novel therapeutic interventions.

Inflammation and Connexin 43 profiles in the prefrontal cortex are relevant to stress susceptibility and resilience in mice.

Depression is a major chronic mental illness worldwide, characterized by anhedonia and pessimism. Exposed to the same stressful stimuli, some people behave normally, while others exhibit negative behaviors and psychology. The exact molecular mechanisms linking stress-induced depressive susceptibility and resilience remain unclear. Connexin 43 (Cx43) forms gap junction channels between the astrocytes, acting as a crucial role in the pathogenesis of depression. Cx43 dysfunction could lead to depressive behaviors, and depression down-regulates the expression of Cx43 in the prefrontal cortex (PFC). Besides, accumulating evidence indicates that inflammation is one of the most common pathological features of the central nervous system dysfunction. However, the roles of Cx43 and peripheral inflammation in stress-susceptible and stress-resilient individuals have rarely been investigated. Thus, animals were classified into the chronic unpredictable stress (CUS)-susceptible group and the CUS-resilient group based on the performance of behavioral tests following the CUS protocol in this study. The protein expression of Cx43 in the PFC, the Cx43 functional changes in the PFC, and the expression levels including interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, IL-2, IL-10, and IL-18 in the peripheral serum were detected. Here, we found that stress exposure triggered a significant reduction in Cx43 protein expression in the CUS-susceptible mice but not in the CUS-resilient mice accompanied by various Cx43 phosphorylation expression and the changes of inflammatory signals. Stress resilience is associated with Cx43 in the PFC and fluctuation in inflammatory signaling, showing that therapeutic targeting of these pathways might promote stress resilience.

Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia Diagnosed Following Recurrent Epistaxis.

We present a rare case of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia (LPL/WM) diagnosed in a 65-year-old female initially presenting with recurrent bilateral epistaxis. Despite multiple cauterizations and a history of ineffective conventional treatments, comprehensive evaluations led to the diagnosis, underscoring the critical need for thorough investigation in persistent epistaxis cases, particularly when standard approaches fail. This case emphasizes the importance of considering indolent lymphomas in the differential diagnosis of recurrent epistaxis and showcases the diagnostic pathway leading to successful identification and treatment of a rare etiology. Laryngoscope, 2024.

Relationship between bleeding sites and clinical data: experience of 646 epistaxis cases in 8 years.

PURPOSE: This study aims to investigate the bleeding sites and their relationship with clinical characteristics in hospitalized epistaxis patients. METHODS: We retrospectively reviewed the data of 646 hospitalized epistaxis patients. RESULTS: The bleeding sites were identified in 395 (61.1%) patients and unidentified in 251 (38.9%). We found that age > 50 years (P = 0.030) and the history of cardiovascular diseases (P = 0.027) were more frequent in patients with unidentified bleeding sites. Among patients with identified sites, inferior meatus (n = 130, 32.9%) was the most common site, followed by the septal surface of the olfactory region (n = 102, 25.8%), nasal septum (n = 80, 20.3%), middle meatus (n = 60, 15.2%), and others (n = 23, 5.8%). After dividing patients into five groups by the area of the bleeding sites, we found significant differences in age (P = 0.026), history of hypertension (P = 0.001), cardiovascular diseases (P = 0.032), and nasal packing (P = 0.011). The logistic regression also revealed that these four factors were predictors for different bleeding sites. CONCLUSION: The bleeding sites can be identified in most epistaxis patients. Age > 50 years and the history of cardiovascular diseases are more frequent in patients with unidentified bleeding sites. In our patients, the most common bleeding site is inferior meatus, followed by the septal surface of the olfactory region, nasal septum, and middle meatus. Age, histories of hypertension, cardiovascular diseases, and nasal packing are factors associated with the bleeding risks of different bleeding sites. According to the different clinical characteristics of patients, the order of the nasal endoscopic examination should be adjusted to develop their treatment plans.

Incidence, prognostic factors, and a nomogram of cervical cancer with lung metastasis: A SEER-based study.

AIMS: The purpose of this study was to investigate the incidence, survival and prognostic factors of cervical cancer with lung metastasis at the initial diagnosis and to develop a visual nomogram to predict the prognosis of these patients. METHODS: We used the Surveillance, Epidemiology and End Results (SEER) database to screen patients diagnosed with cervical cancer from 2010 to 2015. After strict inclusion and exclusion, the chi-square test was used to evaluate the differences in the clinical characteristics of patients with cervical cancer, and then we used Kaplan-Meier method to perform survival analysis among cervical cancer patients with lung metastasis. Next, univariate and multivariate Cox proportional hazard regression models were used to estimate prognostic factors of these patients and we developed a visualized and novel nomogram to judge the prognosis. RESULTS: 476 patients with lung metastasis and 12,016 patients without lung metastasis were included in this study. The incidence of lung metastasis was higher in unmarried white cervical cancer patients between the ages of 40 and 60, and grade III cervical squamous cell carcinoma patients were more likely to have lung metastasis. In addition, grade, surgery, radiotherapy, sequence of surgery and radiotherapy and chemotherapy were significantly related to the outcomes of cervical cancer patients with lung metastasis. Furthermore, our nomogram could predict the 3-year and 5-year overall survival (OS) of these patients. Finally, the AUC of 3-year OS and 5-year OS were confirmed to be 0.969 and 0.939 respectively by ROC curves, with good consistency. CONCLUSIONS: Age at diagnosis, race, marital status, and characteristics of the tumor can influence the incidence of lung metastasis in cervical cancer patients. Besides, grade, surgery, radiotherapy, sequence of surgery and radiotherapy and chemotherapy may deeply affect the prognosis of cervical cancer patients with lung metastasis. The nomogram built in this study may help clinicians to formulate individualized treatment strategies and encourage the development of more and more comprehensive and accurate predictive models.

The role of ZEB1 in regulating tight junctions in antrochoanal polyp.

Background: Antrochoanal polyp (ACP) is a benign nasal mass of unknown etiology. Tight junctions (TJs) are essential to the epithelial barrier that protects the body from external damage. However, the phenotype of tight junction in ACP is currently unclear. Methods: The samples were collected from 20 controls, 37 patients with ACP and 45 patients with chronic rhinosinusitis with nasal polyp (CRSwNP). Quantitative Real-Time PCR (qRT-PCR) and immunofluorescence staining (IF) were performed to analyze the expressions of TJs markers (ZO-1, claudin-3 and occludin) and ZEB1. hNEpCs were transfected with ZEB1 small interfering RNA (si-ZEB1) or ZEB1 over-expression plasmid (OE-ZEB1). qRT-PCR and Western blotting were used to determine the levels of TJs-related markers. Primary human nasal epithelial cells (hNECs) were stimulated with IL-17A and si-ZEB1, and the expression of epithelial barrier markers were measured by qRT-PCR and Western blotting. Results: Compared to the control group, ACP group showed a significant downregulation in both mRNA and protein levels of ZO-1, occludin, and claudin-3. Furthermore, disease severity correlates positively with the degree of disruption of tight junctions. In addition, higher expression levels of ZEB1, IL-17A, and IFN-γ were observed in the ACP group compared to controls. Overexpression of ZEB1 in hNEpCs led to impairments in the levels of ZO-1, occludin, and claudin-3, while silencing of ZEB1 expression was found to enhance the barrier function of epithelial cells. Finally, IL-17 stimulation of hNECs impaired the expression of TJs-associated molecules (ZO-1, occludin, and claudin-3), which was effectively reversed by the IL-17A + si-ZEB1 group. Conclusions: The tight junctions in ACP were extremely damaged and were correlated with the severity of the disease. ZEB1 was involved in the pathogenesis of ACP mediated by IL-17A through regulating tight junctions.

CT imaging features of lung ground-glass nodule patients with upgraded intraoperative frozen pathology.

PURPOSE: Intraoperative frozen section pathology (FS) is widely used to guide surgical strategies while the accuracy is relatively low. Underestimating the pathological condition may result in inadequate surgical margins. This study aims to identify CT imaging features related to upgraded FS and develop a predictive model. METHODS: Collected data from 860 patients who underwent lung surgery from January to December 2019. We analyzed the consistency rate of FS and categorized the patients into three groups: Group 1 (n = 360) had both FS and Formalin-fixed Paraffin-embedded section (FP) as non-invasive adenocarcinoma (IAC); Group 2 (n = 128) had FS as non-IAC but FP as IAC; Group 3 (n = 372) had both FS and FP as IAC. Clinical baseline characteristics were compared and propensity score adjustment was used to mitigate the effects of these characteristics. Univariate analyses identified imaging features with inter-group differences. A multivariate analysis was conducted to screen independent risk factors for FS upgrade, after which a logistic regression prediction model was established and a receiver operating characteristic (ROC) curve was plotted. RESULTS: The consistency rate of FS with FP was 84.19%. 26.67% of the patients with non-IAC FS diagnosis were upgraded to IAC. The predictive model's Area Under Curve (AUC) is 0.785. Consolidation tumor ratio (CTR) ≤ 0.5 and smaller nodule diameter are associated with the underestimation of IAC in FS. CONCLUSION: CT imaging has the capacity to effectively detect patients at risk of upstaging during FS.

Factors associated with human papillomavirus persistence after loop electrosurgical excision procedure in patients with cervical squamous intraepithelial lesion.

AIM: To seek the high-risk factors of human papillomavirus (HPV) persistence and residual lesion or recurrence after loop electrosurgical excision procedure (LEEP) focus on the predictive value of intraoperative human papilloma virus (IOP-HPV) testing. METHODS: Intraoperative endocervical sample was obtained with a cytobrush from the remained cervix of 292 patients immediately after LEEP. HPV Genotyping was performed using a polymerase chain reaction technique. All patients followed by HPV genotyping and cytology every 3-6 months. The IOP-HPV testing results and possible risk factors such as age, cytology grade, menopause status, margin involvement, preoperative HPV status, and cervical lesion grade were assessed in predicting persistence of HPV and residual lesion or recurrence after surgery. RESULTS: There were 61 (20.9%) patients presented persistent HPV infection. Multivariate analyses showed that IOP-HPV positive, post-menopause and preoperative HPV multiplex infection was strongly associated with HPV persistence after LEEP, IOP-HPV positive and post-menopause was also associated with residua or recurrent disease after LEEP. CONCLUSIONS: IOP-HPV positive, post-menopause, and preoperative HPV multiplex infection are independent predictors of HPV persistence in patients with cervical squamous intraepithelial lesion treated by LEEP. IOP-HPV test is a new approach that may potentially allow for early identification of patients at high risk of HPV persistence and residua or recurrent disease after LEEP, thereby possibly facilitate an attenuated follow-up schedule for negative patients those at low risk of persistent HPV infection.

miR-200a-3p regulates epithelial-mesenchymal transition and inflammation in chronic rhinosinusitis with nasal polyps by targeting ZEB1 via ERK/p38 pathway.

BACKGROUND: Several biological processes are regulated by miR-200a-3p, including cell proliferation, migration, and epithelial-mesenchymal transition (EMT). In this study we aimed to uncover the diagnostic value and molecular mechanisms of miR-200a-3p in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: The expressions of miR-200a-3p were detected by quantitative real-time polymerase chain reaction (qRT-PCR), Zinc finger E-box binding homeobox 1 (ZEB1) levels were examined by qRT-PCR and immunofluorescence staining. The interaction between miR-200a-3p and ZEB1 was predicted by TargetScan Human 8.0 and confirmed by dual-luciferase reporter assays. In addition, the effect of miR-200a-3p and ZEB1 on EMT-related makers and inflammation cytokines was assessed by qRT-PCR and Western blotting in human nasal epithelial cells (hNEpCs) and primary human nasal mucosal epithelial cells (hNECs). RESULTS: We found that miR-200a-3p was downregulated in non-eosinophilic and eosinophilic CRSwNP patients when compared with controls. The diagnostic value of miR-200a-3p in serum is reflected by the receiver operating characteristic curve and the 22-item Sino-Nasal Outcome Test. Bioinformatic analysis and luciferase reporter assay identified ZEB1 as a target of miR-200a-3p. ZEB1 was more highly expressed in CRSwNP than in controls. Furthermore, miR-200a-3p inhibitor or ZEB1 overexpression significantly suppressed the epithelial marker E-cadherin; promoted the activation of vimentin, α-spinal muscle atrophy, and N-cadherin; and aggravated inflammation in hNEpCs. Knockdown of ZEB1 significantly alleviated the cellular remodeling caused by miR-200a-3p inhibitor via the extracellular signal-regulated kinase (ERK)/p38 pathway in hNECs. CONCLUSIONS: miR-200a-3p suppresses EMT and inflammation by regulating the expression of ZEB1 via the ERK/p38 pathway. Our study presents new ideas for protecting nasal epithelial cells from tissue remodeling and finding a possible target for disease.

Difference of Antrochoanal Polyps Between Children and Adults in the Chinese Population.

OBJECTIVE: This study aims to find the difference in clinical and immunopathological characteristics between children and adults with antrochoanal polyps (ACPs) in the Chinese population. METHODS: The clinical data of 69 patients diagnosed with ACPs were retrospectively analyzed. Cytokine levels in 16 controls and 40 ACPs tissues were determined by quantitative real-time polymerase chain reaction (qPCR). The expression of matrix metalloproteinase (MMP)-9 was measured using qPCR, immunofluorescent staining, and western blot. RESULTS: There were 51 (73.9%) children (<18 years old) and 18 (26.1%) adults (≥18 years old). The sex ratio differed significantly between the two groups (p = 0.0032). There were no significant differences in the nasal side of ACPs and approaches to surgery between the two groups. In both groups, the most common symptom was nasal obstruction, followed by nasal discharge. As for associated nasal diseases, there was a significant difference between the two groups in septal deviation (p = 0.0223). Adult patients showed significantly higher expression of IL-8 mRNA than children (p = 0.0424). The mRNA and protein levels of MMP-9 were also significantly higher in adult patients than in children (p = 0.0498 and 0.0009, respectively). CONCLUSION: In the Chinese population, the comorbidities and immunopathological characteristics of adult ACP patients are different from those of children. The level of IL-8 and MMP-9 was significantly higher in ACPs of adults than in children, which may contribute to the more severe tissue remolding in adult ACP patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2093-2099, 2024.

Machine learning and experimental screening of chromatin regulator signatures and potential drugs in hepatitis B related hepatocellular carcinoma.

Many evidences have confirmed that chromatin regulator factors (CRs) are involved in the progression of cancer, but its potential mechanism of affecting hepatitis B related hepatocellular carcinoma still needs to be studied. Our study detected the CRs that affect hepatitis B related hepatocellular carcinoma (HBV-HCC) through machine learning analysis, conducted the analysis of immune cells, constructed the relevant risk model and immune function infiltration, and predicted the potential therapeutic drugs. We found that these CRs were significantly related to the immune cells of Macrophages, B cells, CD8+T cells, etc., and PBK, AURKA, TOP2A and AURKB were the potential risk CRs of HBV-HCC. The expression levels of these four CRs increased in HepG2.2.15 cells and the liver of HBV-HCC patients, consistent with the predicted risk model. Subsequently, ten potential drugs closely related to the risk CRs were finally obtained, experimental research on resveratrol has shown that it can inhibit the proliferation of HepG2.2.15 cells and potentially inhibit the occurrence and development of HBV-HCC. Our study provides novel insights into the function of CRs in HBV-HCC and certain ideas for more accurate targeted therapy.Communicated by Ramaswamy H. Sarma.

A Rare Case of Metastatic Clear Cell Renal Cell Carcinoma to the Petroclival Region Presenting as Posterior Cranial Neuropathies.

We present a case of metastatic renal cell carcinoma (RCC) to the petroclival region with clinical symptoms manifested as posterior cranial neuropathies. A 65-year-old male presented with headache symptom for over 1 year, during which time he was diagnosed with RCC and underwent right nephrectomy. However, the headache symptom and cranial neuropathies had been attributed to cranial neuritis all the time until the surgical removal of metastatic tumor in the petroclival region led to the diagnosis of metastatic RCC. RCC has a tendency for metastasis early. The incidence of spread of RCC to brain is a rarity in clinical practice. When a patient presents with cranial nerve neuropathies, the possibility of metastatic RCC should be sought. Brain metastases display nonspecific presentations, and it is useful to examine with magnetic resonance imaging and computed tomography scans radiologically.

Clinical Characteristics of Sphenoid Sinus Fungus Ball: A Nine-year Retrospective Study of 77 Cases.

OBJECTIVE: This study aimed to investigate the clinical characteristics of sphenoid sinus fungus ball (SSFB) to help increase the accuracy of diagnosis and efficiency of treatment. METHODS: We retrospectively analyzed the data of 77 patients who were histopathologically diagnosed with SSFB. RESULTS: The mean age of SSFB patients was 52.4 years (range 25-84), and 47 patients (61.0%) were female. Compared to age-matched and sex-matched chronic rhinosinusitis (CRS) patients, headache was more common in SSFB patients (79.2%; p < 0.0001). SSFB patients also had higher prevalence of diabetes than CRS (p = 0.0420). The features of computed tomography (CT) were sphenoid sinus opacification (100%), sclerosis (93.5%), calcification (76.6%), and bone erosion (41.6%). Functional endoscopic sinus surgery (FESS) was the best treatment option, and the trans-ethmoid (n = 64, 83.1%) was the most commonly used approach. No one experienced a recurrence of SSFB in 44 successfully contacted patients. Six months after FESS, 91.0% of patients (40/44) established proper drainage in the sphenoid sinus. The recovery rates for headache and nasal symptoms were 91.7% (33/36) and 77.8% (7/9) respectively. CONCLUSION: SSFB is more prevalent in older women and usually presents as unilateral headache. Diabetes is a potential risk factor for SSFB. CT findings provide evidence for diagnosis and suggestions for surgical approaches. FESS is the optimal treatment for SSFB. After FESS, most patients had good prognosis with no recurrence of SSFB. However, regular endoscopic follow-up is required due to the possibility of the postoperative closure of sphenoid ostium. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3292-3298, 2023.

Soil Inoculation and Blocker-Mediated Sequencing Show Effects of the Antibacterial T6SS on Agrobacterial Tumorigenesis and Gallobiome.

The type VI secretion system (T6SS) is deployed by many proteobacteria to secrete effector proteins into bacterial competitors for competition or eukaryotic cells for pathogenesis. Agrobacteria, a group of soilborne phytopathogens causing crown gall disease on various plant species, deploy the T6SS to attack closely and distantly related bacterial species in vitro and in planta. Current evidence suggests that the T6SS is not essential for pathogenesis under direct inoculation, but it remains unknown whether the T6SS influences natural disease incidence or the microbial community within crown galls (i.e., the gallobiome). To address these two key questions, we established a soil inoculation method on wounded tomato seedlings that mimics natural infections and developed a bacterial 16S rRNA gene amplicon enrichment sequencing platform. By comparing the Agrobacterium wild-type strain C58 with two T6SS mutants, we demonstrate that the T6SS influences both disease occurrence and gallobiome composition. Based on multiple inoculation trials across seasons, all three strains induced tumors, but the mutants had significantly lower disease incidences. The season of inoculation played a more important role than the T6SS in shaping the gallobiome. The influence of the T6SS was evident in summer, during which two Sphingomonadaceae species and the family Burkholderiaceae were enriched in the gallobiome induced by the mutants. Further in vitro competition and colonization assays demonstrated the T6SS-mediated antagonism to a Sphingomonas sp. R1 strain isolated from tomato rhizosphere in this study. In conclusion, this work demonstrates that the Agrobacterium T6SS promotes tumorigenesis in infection processes and provides competitive advantages in gall-associated microbiota. IMPORTANCE The T6SS is widespread among proteobacteria and used for interbacterial competition by agrobacteria, which are soil inhabitants and opportunistic bacterial pathogens causing crown gall disease in a wide range of plants. Current evidence indicates that the T6SS is not required for gall formation when agrobacteria are inoculated directly on plant wounding sites. However, in natural settings, agrobacteria may need to compete with other bacteria in bulk soil to gain access to plant wounds and influence the microbial community inside crown galls. The role of the T6SS in these critical aspects of disease ecology have remained largely unknown. In this study, we successfully developed a soil inoculation method coupled with blocker-mediated enrichment of bacterial 16S rRNA gene amplicon sequencing, named SI-BBacSeq, to address these two important questions. We provided evidence that the T6SS promotes disease occurrence and influences crown gall microbiota composition by interbacterial competition.

Incidence, prognostic factors and a nomogram of cervical cancer with distant organ metastasis: a SEER-based study.

This study was to investigate the incidence, survival and prognostic factors of cervical cancer with distant organ metastasis, and to develop a nomogram to predict the prognosis of cervical cancer. We used the Surveillance, Epidemiology and End Results (SEER) database to screen patients diagnosed with cervical cancer from 2010 to 2014. The chi-squared test was used to analyse the differences in clinical characteristics, and we used Kaplan-Meier methods to perform survival analysis. Univariate and multivariate Cox proportional hazard regression models were used to estimate prognostic factors, and we developed a visual nomogram to judge the prognosis. We found that lung metastasis was the most common in cervical cancer patients with distant organ metastasis. Age, race, characteristics of the tumour, and therapy should be considered when analysing the prognosis of cervical cancer patients. The findings of this study may help clinicians to formulate individualised treatment strategies.Impact StatementWhat is already known on this subject? Distant organ metastasis of cervical cancer mainly involves lung, bone, liver and brain. Once it occurs, the survival and prognosis will be threatened seriously.What the results of this study add? 4176 patients were included, and lung metastasis was the most common in cervical cancer with distant organ metastasis (3.5%). Additionally, age, race, tumour grade, histological type, T-stage, N-stage, lung, liver and bone metastasis and the treatment mode are significantly related to the outcomes of cervical cancer patients. Furthermore, we developed a nomogram that could predict the probability of three-year and five-year OS.What the implications are of these findings for clinical practice and/or further research? The findings of this study may drive more and more studies focussing on the comprehensive prognostic assessment, diagnosis, and treatment of distant metastasis of cervical cancer. Besides, clinicians can utilise these findings to formulate individualised treatment strategies.

Thiol oxidative stress-dependent degradation of transglutaminase2 via protein S-glutathionylation sensitizes 5-fluorouracil therapy in 5-fluorouracil-resistant colorectal cancer cells.

5-Fluorouracil (5-Fu) is a first-line drug for colorectal cancer (CRC) therapy. However, the development of 5-Fu resistance limits its chemotherapeutic effectiveness and often leads to poor prognoses of CRC. Transglutaminase 2 (TGM2), a member of the transglutaminase family, is considered to be associated with chemoresistance through apoptotic prevention in various cancers including CRC. TGM2 was found to be overexpressed in two 5-Fu-resistant CRC cell lines and down-regulated by increased thiol oxidative stress induced by inhibition of glutathione reductase (GR). The present study aimed to explore the role of TGM2 in 5-Fu-resistant CRC and the mechanism of action by which the elevated thiol oxidative stress down-regulates TGM2 protein level. The results revealed that 5-Fu-resistance induced by overexpression of TGM2 in CRC cells was reversed through up-regulation of thiol oxidative stress. Knockdown of TGM2 increased the chemosensitivity of CRC cells to 5-Fu. Thiol oxidative stress potentially enhanced the therapeutic effect of 5-Fu in the resistant CRC cells by promotion of 5-Fu-induced apoptosis through down-regulation of TGM2. The elevated thiol oxidative stress increased the S-glutathionylation of TGM2 and led to proteasomal degradation of TGM2. Furthermore, Cys193 was identified as the S-glutathionylation site in TGM2, and its mutation resulted in thiol oxidative stress-mediated CRC cell apoptotic resistance. TGM2-induced EMT was also suppressed by the elevated thiol oxidative stress. A xenograft tumor model confirmed the effect of thiol oxidative stress in the reversal of 5-Fu resistance in CRC cells in vivo. TGM2 protein expression level was found to be significantly higher in human CRC specimens than in non-cancerous colorectal tissues. Taken together, the present data suggest an important role of TGM2 in 5-Fu resistance in CRC cells. Up-regulation of thiol oxidative stress could be a potential therapeutic approach for treating 5-Fu-resistant CRC and TGM2 may serve as a potential therapeutic target of thiol oxidative stress.

Comparative analysis of three common imaging modalities for nasolabial cysts.

OBJECTIVE: To compare the clinical diagnostic value of ultrasonography (USG), computed tomography (CT), and magnetic resonance imaging (MRI) for nasolabial cysts. METHODS: The clinical and imaging data of 20 patients with 21 nasolabial cysts confirmed surgically and histopathologically were retrospectively analyzed. RESULTS: The largest cyst was 3.4 × 2.7 × 2.3 cm, and the smallest cyst was 1.1 × 0.7 × 0.5 cm. All cysts were located in the soft tissue between the nasolabial fold and maxillary bone. USG showed sensitivity of 95%, accuracy of 95%, and a missed diagnosis rate of 5%; CT showed sensitivity of 80%, accuracy of 80%, and a missed diagnosis rate of 20%; and MRI showed sensitivity of 85%, accuracy of 85%, and a missed diagnosis rate of 15%. CONCLUSIONS: USG showed higher sensitivity and accuracy and a lower missed diagnosis rate than CT and MRI. Therefore, USG is worth popularizing on a large scale for the diagnosis of nasolabial cysts.

ESE1/AGR2 axis antagonizes TGF-ß-induced epithelial-mesenchymal transition in low-grade pancreatic cancer.

Epithelium-specific ETS transcription factor 1 (ESE1) has been implicated in epithelial homeostasis, inflammation, as well as tumorigenesis, and cancer progression. However, numerous studies have reported contradictory roles-as an oncogene or a tumor suppressor of ESE1 in different cancers, and its function in the development and progression of pancreatic ductal adenocarcinoma (PDAC) has remained largely unexplored. Herein, we report that ESE1 was found upregulated in primary PDAC compared to normal pancreatic tissue, but high expression of ESE1 correlated to better relapse-free survival in patients with PDAC. Interestingly, ESE1 was found to exhibit dual roles in regulation of malignant properties of PDAC cells in that its overexpression promoted cell proliferation, whereas its downregulation enhanced epithelial-mesenchymal transition (EMT) phenotype. In the context of TGF-ß-induced EMT, ESE1 is markedly downregulated at post-transcriptional level, and reconstituted ESE1 expression partially reversed TGF-ß-induced EMT marker expression. Furthermore, we identify AGR2 as a novel transcriptional target of ESE1 that participates in TGF-ß-induced EMT in PDAC. Collectively, our findings reveal an ESE1/AGR2 axis that interacts with TGF-ß signaling to modulate EMT phenotype in PDAC.

Diagnostic value of non-coding RNAs in ovarian cancer.

The type of primary tumour of the ovary ranks first among all organs in the body. Although the incidence of malignant ovarian tumour ranks third among gynaecological malignancies, it is the most fatal type. A lack of effective diagnostic methods for early ovarian cancer remains, and the efficacy of advanced ovarian cancer is often unsatisfactory; the five-year survival rate of stage III-IV is less than 30%. Non-coding RNA is RNA that does not have protein-coding potential and was once considered as 'junk DNA'. However, increasing number of studies have shown that the disorder of non-coding RNA is related to a variety of diseases, including the occurrence and development of tumours. We summarised the dysregulated non-coding RNAs (miRNAs, circRNAs, and lncRNAs) reported currently in ovarian cancer and their functional mechanisms, and the clinical value of different types of ncRNAs as diagnostic or predictive markers for ovarian cancer, providing further evidence for non-coding RNAs to be considered as biomarkers of ovarian cancer.

Predictive Value of Adenoid-Nasopharyngeal Ratio in the Diagnosis of Secretory Otitis Media.

OBJECTIVES: To explore the associated factors of otitis media with effusion (OME) and analyze the diagnostic value of the adenoid-nasopharyngeal (A/N) ratio to OME. METHODS: Patients with adenoid hypertrophy (AH) recently in 2 years were collected, including sex, age, duration, with/without rhinosinusitis, and examination results, including Cone Beam Computerized Tomography (CBCT) sinus imaging, tympanometry, pure tone audiometry (PTA), blood test, and allergen detection. According to Liden/Jerger's classification, the patients were divided into two groups: Type B and type C, which were defined as the tympanometry abnormal group (TAG), and the rest were classified as the tympanometry normal group (TNG). RESULTS: A total of 316 children were included in this study. Age and duration were significantly younger and shorter in TAG (6.0(4.0-9.0) vs.5.0(4.0-7.0)); 12.0(4.0-24.0) vs.6.0(2.0-12.0)). Compared to TNG, the allergen test results of fx5 (protein, milk, cod, wheat, peanut, and soybean) in TAG were higher (0.09(0.04-0.25) vs.0.14(0.05-0.45)), but eosinophilia in blood was lower (count: 0.21(0.13-0.35) vs. 0.18(0.12-0.27); ratio: 3.10 (1.90-4.70) vs. 2.50 (1.65-3.80)). A/N ratio and Visual obstruction ratio had a statistical difference (Z = -3.770, P < .01) but the two ratios didn't have too much disparity (0.82(0.74-0.88) VS 0.80(0.75-0.80)), and they had a positive correlation (r = 0.345, P < .01). A/N ratio of TAG was higher than TNG (0.78(0.70-0.85) vs. 0.86(0.82-0.90)) and had a positive correlation with increasing negative middle ear pressure (r = -3.777, P < .01). A/N ratio was an associated factor of OME (OR:1355.611, P = .006), the cut-off value of A/N ratio was 0.815(sensitivity: 75.3%, specificity: 64.3%, area under the curve (AUC): 0.747). CONCLUSIONS: A/N ratio indirectly reflected the abnormality of tympanometry in this study. When A/N ratio reaches 0.815, patients are at a higher risk of having OME so it could be a predictor of OME in patients with adenoid hypertrophy.