Meta-analysis of the efficacy and safety of OLIF and TLIF in the treatment of degenerative lumbar spondylolisthesis.

OBJECTIVE: To systematically evaluate the difference in clinical efficacy between two surgical approaches, oblique lateral approach and intervertebral foraminal approach, in the treatment of degenerative lumbar spondylolisthesis. METHODS: English databases, including PubMed, Cochrane, Embase, and Web of Science, were systematically searched using keywords such as "oblique lumbar interbody fusion" and "transforaminal lumbar interbody fusion." Concurrently, Chinese databases, including CNKI, WanFang data, VIP, and CBM, were also queried using corresponding Chinese terms. The search spanned from January 2014 to February 2024, focusing on published studies in both Chinese and English that compared the clinical efficacy of OLIF and TLIF. The literature screening was conducted by reviewing titles, abstracts, and full texts. Literature meeting the inclusion criteria underwent quality assessment, and relevant data were extracted. Statistical analysis and a meta-analysis of the observational data for both surgical groups were performed using Excel and RevMan 5.4 software. Findings revealed a total of 14 studies meeting the inclusion criteria, encompassing 877 patients. Of these, 414 patients were in the OLIF group, while 463 were in the TLIF group. Meta-analysis of the statistical data revealed that compared to TLIF, OLIF had a shorter average surgical duration (P < 0.05), reduced intraoperative bleeding (P < 0.05), shorter average hospital stay (P < 0.05), better improvement in postoperative VAS scores (P < 0.05), superior enhancement in postoperative ODI scores (P < 0.05), more effective restoration of disc height (P < 0.05), and better correction of lumbar lordosis (P < 0.05). However, there were no significant differences between OLIF and TLIF in terms of the incidence of surgical complications (P > 0.05) and fusion rates (P > 0.05). CONCLUSION: When treating degenerative lumbar spondylolisthesis, OLIF demonstrates significant advantages over TLIF in terms of shorter surgical duration, reduced intraoperative bleeding, shorter hospital stay, superior improvement in postoperative VAS and ODI scores, better restoration of disc height, and more effective correction of lumbar lordosis.

The potential of Paeonia lactiflora pall seeds oil as a pure natural cosmetics raw material: In Vitro findings.

BACKGROUND: As a traditional Chinese herbal medicine, Paeonia lactiflora Pall is rich in various active ingredients such as polysaccharides and total flavonoids while having ornamental value. It has potential application value in the development of food and cosmetics. OBJECTIVE: To study the in vitro efficacy of Paeonia lactiflora Pall seeds oil. METHODS: Firstly, the levels of linolenic acid and linoleic acid in Paeonia lactiflora Pall seeds oil were quantified using gas chromatography. The impact of Paeonia lactiflora Pall seeds oil on the proliferation rate of B16F10 cells was assessed through the CCK-8 method, while the melanin content of B16F10 cells was determined using the sodium hydroxide lysis method. The inhibitory effects of Paeonia lactiflora Pall seeds oil on elastase, collagenase and hyaluronidase were evaluated by biochemical techniques in vitro. Lastly, the hen's egg chorioallantoic membrane test (HET-CAM) was conducted to confirm the absence of eye irritation caused by Paeonia lactiflora Pall seeds oil. RESULTS: Paeonia lactiflora Pall seeds oil within a certain volume concentration range (0.5%-4%) had no effect on the proliferation of B16F10 cells. Paeonia lactiflora Pall seeds oil showed significant inhibition of elastase, collagenase and hyaluronidase. Notably, the highest concentration tested, 4% Paeonia lactiflora Pall seed oil, yielded the most pronounced outcomes without causing any irritation. CONCLUSION: A certain concentration of Paeonia lactiflora Pall seeds oil has a significant effect on decreasing the melanin content in B16F10 cells and inhibiting the activities of elastase, collagenase, and hyaluronidase, which can provide a reference for the development of pure natural cosmetics raw materials.

Integrated analysis of long non-coding RNAs and mRNAs associated with condyloma acuminatum.

Condyloma acuminatum (CA) is a prevalent sexually transmitted disease caused by low-risk human papillomavirus infection, characterized by high transmission and recurrence rates. Long non-coding RNAs (lncRNAs) play a crucial role in regulating gene transcription and are involved in various biological processes. Although recent studies have demonstrated the involvement of lncRNAs in cervical cancer, their expression profile and function in CA remain poorly understood. In this study, we aimed to identify messenger RNA (mRNA) and lncRNA expression patterns in CA using high-throughput lncRNA sequencing. We found that 3033 differentially expressed genes (DEGs) and 1090 differentially expressed lncRNAs (DELs) were significantly altered in CA compared to healthy controls. The results from quantitative reverse transcription polymerase chain reaction and immunohistochemical staining are in accordance with the observed trends in the sequencing data. Functional enrichment analysis revealed that upregulated DEGs in CA were involved in biological processes such as virus response, immune response, cell cycle regulation, the tumor necrosis factor signaling pathway, and the P53 signaling pathway. Co-expression network analysis identified potential target genes of DELs, with enrichment in biological processes such as cell differentiation, the intrinsic apoptotic signaling pathway, and pathways such as virus infection, pathways in cancer, T helper 17 cell differentiation, the mitogen-activated protein kinase signaling pathway, and the Wnt signaling pathway. Collectively, our findings indicate significant changes in the transcriptome profile, including mRNAs and lncRNAs, in CA compared to healthy controls. Our study provides new insights into the potential functions of lncRNAs in the pathogenesis of CA and identifies potential therapeutic targets for this disease.

ID2 promotes tumor progression and metastasis in thyroid cancer.

BACKGROUND: Inhibitor of DNA Binding 2 (ID2) plays a crucial role in tumor cell proliferation, invasion, metastasis, and stemness. Aberrant ID2 expression is associated with poor prognosis in various cancers. However, the specific function of ID2 in thyroid cancer remain unclear. METHOD: The TCGA database were utilized to explore the clinical relevance of ID2 in cancer. GO, KEGG, and TIMER were employed to predict the potential roles of ID2 in cancer. Functional analysis, including CCK-8, colony formation, transwell, wound healing, and sphere formation experiments, were conducted to determine the biological functions of ID2 in human cancers. Western blot (WB), RT-qPCR, and immunohistochemical (IHC) analyses were used to investigate the relationship between ID2 and downstream targets. RESULTS: Our study revealed significant overexpression of ID2 in various malignant tumor cells. Knocking ID2 significantly inhibited cancer cell proliferation and invasion, while overexpressing ID2 enhanced these capabilities. Additionally, ID2 mediates resistance of cancer cells to protein kinase B (or Akt) inhibitions. Further WB and IHC experiments indicated that ID2 promotes the phosphorylation activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, thereby upregulating the expression of downstream proliferation, epithelial-mesenchymal transition (EMT), and stemness-related markers. CONCLUSION: We found that ID2 significantly promotes thyroid cancer cell proliferation, migration, EMT, and stemness through the PI3K/Akt pathway. Moreover, ID2 plays a crucial role in regulating cancer immune responses. It may serve as a potential biomarker for enhancing the efficacy of chemotherapy, targeted therapy, and immunotherapy against cancer.

Plum blossom low molecular weight polypeptide protects HaCaT cells against UVB-induced oxidative damage in vitro and underlying mechanism.

BACKGROUND: Increasing amounts of ultraviolet radiation occur as ozone depletion causes the earth's ozone layer to be destroyed, making antioxidant efficacy a research hotspot. Previous studies on plum blossom have mostly focused on Volatile Oils, Flavonoids, Phenylpropanoids, and other compounds, whereas few studies have focused on low molecular weight polypeptide (LMWP) of plum blossom. This research provides a reference for the deep processing and utilization of plum blossom. OBJECTIVES: (a) Plum blossom low molecular weight polypeptides protect HaCaT cells against UVB-induced oxidative damage in vitro and the underlying mechanism. (b) Improve the theoretical basis for the intense processing and utilization of plum blossom. METHODS: The safe concentration of LMWP and the survival rate of HaCaT cells were determined using the CCK-8 experiment. The fluorescence intensity of reactive oxygen species (ROS) was identified using the dichlorofluorescin diacetate (DCFH-DA) method; Superoxide dismutase (SOD) and malondialdehyde (MDA) concentrations were measured in ruptured cells; Western blot analysis was used to examine the expression levels of three proteins: nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and benzoquinone oxidoreductase 1 (NQO-1). RESULTS: It was noted that a certain concentration of LMWP could promote cell proliferation. In oxidatively damaged HaCaT cells, SOD levels and survival rates were markedly reduced, but ROS and MDA levels were elevated. However, after treatment with LMWP, the survival rate of the cells and SOD levels were markedly increased, and the levels of ROS and MDA were markedly decreased. As shown by Western blotting, the model group exhibited lower levels of Nrf2, HO-1, and NQO-1 expression than the control group, whereas LMWP-treated cells had significantly higher levels of Nrf2, HO-1, and NQO-1 expression than their model-treated counterparts. CONCLUSIONS: LMMP can effectively protect HaCaT cells against oxidative damage in vitro induced by UVB, and the underlying mechanism is linked to the activation of the transcription factor Nrf2.

Analysis of Pediatric Surgical Disease Spectrum in a Tertiary Hospital.

Objective: To analyze the main disease composition of children hospitalized in pediatric surgery, explore the correlation between disease types and gender, and provide a reference for hospital management and pediatric disease prevention. Methods: Using ICD-10 codes as the classification standard for disease diagnosis, a statistical analysis was conducted on the disease composition of children hospitalized in the Pediatric Surgery Department of the Second Affiliated Hospital of Xi'an Jiaotong University from January 1, 2015, to December 31, 2015, followed by the establishment of a clinical database. A total of 1647 male patients and 817 female patients were enrolled in the study, resulting in a male-to-female ratio of 2:1. The age range of the patients spanned from 0 to 18 years, with a marked imbalance in patient distribution among the various age groups. Statistical analysis was conducted using SPSS version 18.0 software. A chi-square test was performed to analyze the differences in the composition of disease systems and the composition of major diseases in terms of sex and age. Results: Pediatric patients were admitted with complex and diverse diseases in 2015, involving 15 systems of the human body and 400 diseases. Digestive system diseases, tumors, congenital malformations, and genitourinary system diseases were the top four diseases accounting for 83.5% of all pediatric cases. 561 patients were aged 0 years, accounting for 22.3% of all cases, while 1,801 patients fell within the 0-5 years age group, constituting 73.1% of the total. The differences in disease system composition among different sex and age groups of pediatric surgical inpatients were statistically significant (P = .001). There are statistically significant differences in the length of hospital stay and hospitalization costs among pediatric surgical inpatients in different age groups (P = .001). Conclusion: To strengthen the diagnosis and treatment of pediatric surgical diseases, we should strengthen the construction of key departments, optimize the consultation process according to the characteristics of children's disease spectrum, and improve the level of diagnosis and treatment of pediatric surgical diseases.

Timing of endoscopy for acute variceal bleeding in patients with cirrhosis (CHESS1905): A nationwide cohort study.

BACKGROUND: Endoscopy plays an important role in the management of acute variceal bleeding (AVB) in patients with cirrhosis. This study aimed at determining the optimal endoscopy timing for cirrhotic AVB. METHODS: Patients with cirrhosis with AVB across 34 university hospitals in 30 cities from February 2013 to May 2020 who underwent endoscopy within 24 hours were included in this study. Patients were divided into an urgent endoscopy group (endoscopy <6 h after admission) and an early endoscopy group (endoscopy 6-24 h after admission). Multivariable analysis was performed to identify risk factors for treatment failure. Primary outcome was the incidence of 5-day treatment failure. Secondary outcomes included in-hospital mortality, need for intensive care unit, and length of hospital stay. A propensity score matching analysis was performed. In addition, we performed an analysis, in which we compared the 5-day treatment failure incidence and the in-hospital mortality among patients with endoscopy performed at <12 hours and 12-24 hours. RESULTS: A total of 3319 patients were enrolled: 2383 in the urgent endoscopy group and 936 in the early endoscopy group. After propensity score matching, on multivariable analysis, Child-Pugh class was identified as an independent risk factor for 5-day treatment failure (HR, 1.61; 95% CI: 1.09-2.37). The incidence of 5-day treatment failure was 3.0% in the urgent endoscopy group and 2.9% in the early group ( p = 0.90). The in-hospital mortality was 1.9% in the urgent endoscopy group and 1.2% in the early endoscopy group ( p = 0.26). The incidence of need for intensive care unit was 18.2% in the urgent endoscopy group and 21.4% in the early endoscopy group ( p = 0.11). The mean length of hospital stay was 17.9 days in the urgent endoscopy group and 12.9 days in the early endoscopy group ( p < 0.05). The incidence of 5-day treatment failure in the <12-hour group was 2.3% and 2.2% in the 12-24 hours group ( p = 0.85). The in-hospital mortality was 2.2% in the <12-hour group and 0.5% in the 12-24 hours group ( p < 0.05). CONCLUSIONS: The data suggest that performance of endoscopy within 6-12 or within 24 hours of presentation among patients with cirrhosis with AVB led to similar treatment failure outcomes.

Evidence that oncostatin M synergizes with IL-4 signaling to induce TSLP expression in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Oncostatin M (OSM) may promote type 2 inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) by inducing thymic stromal lymphopoietin (TSLP). OBJECTIVE: We sought to study the impact of OSM on TSLP synthesis and release from nasal epithelial cells (NECs). METHODS: OSM receptors, IL-4 receptors (IL-4R), and TSLP were evaluated in mucosal tissue and primary NECs from patients with CRSwNP by quantitative PCR and immunofluorescence. Air-liquid interface-cultured NECs were stimulated with cytokines, including OSM, and quantitative PCR, ELISA, Western blot, and flow cytometry were used to assess the expression of OSM receptors, IL-4R, and TSLP. RESULTS: Increased levels of OSM receptor ß chain (OSMRß), IL-4Rα, and TSLP were observed in nasal polyp tissues and primary epithelial cells from nasal polyps of patients with CRSwNP compared with control tissues or cells from control subjects. The level of expression of OSMRß in tissue was correlated with levels of both IL-4Rα and TSLP. OSM stimulation of NECs increased the expression of OSMRß and IL-4Rα. Stimulation with IL-4 plus OSM augmented the production of TSLP; the response was suppressed by a signal transducer and activator of transcription 6 inhibitor. Stimulation of NECs with IL-4 plus OSM increased the expression of proprotein convertase subtilisin/kexin 3, an enzyme that truncates and activates TSLP. CONCLUSIONS: OSM increases the expression of IL-4Rα and synergizes with IL-4 to induce the synthesis and release of TSLP in NECs. Because the combination of IL-4 and OSM also augmented the expression of proprotein convertase subtilisin/kexin 3, these results suggest that OSM can induce both synthesis and posttranslational processing/activation of TSLP, promoting type 2 inflammation.

Development and validation of a nomogram model for the prediction of 4L lymph node metastasis in thoracic esophageal squamous cell carcinoma.

Objectives: The left tracheobronchial (4L) lymph nodes (LNs) are considered as regional LNs for esophageal squamous cell carcinoma (ESCC), but there is a controversy about routine prophylactic 4L LN dissection for all resectable ESCCs. This study aimed to develop a nomogram for preoperative prediction of station 4L lymph node metastases (LNMs). Methods: A total of 522 EC patients in the training cohort and 370 in the external validation cohort were included. The prognostic impact of station 4L LNM was evaluated, and multivariable logistic regression analyses were performed to identify independent risk factors of station 4L LNM. A nomogram model was developed based on multivariable logistic regression analysis. Model performance was evaluated in both cohorts in terms of calibration, discrimination, and clinical usefulness. Results: The incidence of station 4L LNM was 7.9% (41/522) in the training cohort. Patients with station 4L LNM exhibited a poorer 5-year overall survival rate than those without (43.2% vs. 71.6%, p < 0.001). In multivariate logistic regression analyses, six variables were confirmed as independent 4L LNM risk factors: sex (p = 0.039), depth of invasion (p = 0.002), tumor differentiation (p = 0.016), short axis of the largest 4L LNs (p = 0.001), 4L conglomeration (p = 0.006), and 4L necrosis (p = 0.002). A nomogram model, containing six independent risk factors, demonstrated a good performance, with the area under the curve (AUC) of 0.921 (95% CI: 0.878-0.964) in the training cohort and 0.892 (95% CI: 0.830-0.954) in the validation cohort. The calibration curve showed a good agreement on the presence of station 4L LNM between the risk estimation according to the model and histopathologic results on surgical specimens. The Hosmer-Lemeshow test demonstrated a non-significant statistic (p = 0.691 and 0.897) in the training and validation cohorts, which indicated no departure from the perfect fit. Decision curve analysis indicated that the model had better diagnostic power for 4L LNM than the traditional LN size criteria. Conclusions: This model integrated the available clinical and radiological risk factors, facilitating in the precise prediction of 4L LNM in patients with ESCC and aiding in personalized therapeutic decision-making regarding the need for routine prophylactic 4L lymphadenectomy.

Metagenomic Next-Generation Sequencing in the Diagnosis of Infectious Fever During Myelosuppression Among Pediatric Patients with Hematological and Neoplastic Diseases.

Purpose: To analyze the contribution of metagenomic next-generation sequencing (mNGS) in the guidance of clinical treatment and outcomes of infection during myelosuppression among children with hematological and neoplastic diseases. Patients and Methods: The clinical data and results of mNGS assay of febrile patients suspected of infection were retrospectively collected. The characteristics of pathogenic microorganisms and clinical course of myelosuppressed children with hematological diseases were summarized. Results: Our study included 70 patients (45 males) with a median age of 5 years (range: 0.5 to 13 y). During the study period, there were 96 events of suspected infection. According to comprehensive clinical diagnosis, 73 blood infections, 43 pneumonia and 2 urinary tract infections occurred. The positive rate of mNGS was significantly higher than that of traditional microbial detection (83.3% vs 17.7%). The main pathogens detected by mNGS were Pseudomonas aeruginosa, Acinetobacter, human herpesvirus, Candida and Aspergillus. The average duration of fever was 4.9 days and 11.6 days (P < 0.05), and the average cost of anti-infection treatment was RMB ¥28,077 and 39,898 (P < 0.05) among children received mNGS within 48 hours and more than 48 hours after the onset of infection symptoms. Conclusion: mNGS contributes to clinical management of children with infection during myelosuppression, especially among patients with negative traditional microbial detection. Early implementation of mNGS in children with symptoms has a tendency to reduce the time of infection, fever and the cost of treatment.

Dizziness Result From Anomalous Origin of Left Common Carotid Artery.

BACKGROUND: The anomalous origin of the left common carotid artery from the pulmonary artery is extremely scarce. At present, there are few relevant research and medical treatment data. This case is intended to provide relevant information and share treatment experiences. Case information: A 6-year-old child was diagnosed with patent ductus arteriosus and underwent surgery five years ago with occasional dizziness. After examination, it was found that the abnormality of her left common carotid artery originated from the pulmonary artery, and the patient underwent arterial ligation with the monitoring of cerebral oxygen consumption by near-infrared spectroscopy after careful preoperative evaluation. At present, it has been two years after the operation, and the patient is in good condition and has received regular follow-up. CONCLUSION: For patients with an abnormal left common carotid artery from the pulmonary artery, after careful preoperative evaluation such as cerebral angiography, under the monitoring of cerebral oxygen consumption by near-infrared spectroscopy, ligation of the proximal end of the artery of abnormal origin is safe and feasible.

A Novel ATM Antisense Transcript ATM-AS Positively Regulates ATM Expression in Normal and Breast Cancer Cells.

OBJECTIVE: The ataxia telangiectasia mutated (ATM) gene is a master regulator in cellular DNA damage response. The dysregulation of ATM expression is frequent in breast cancer, and is known to be involved in the carcinogenesis and prognosis of cancer. However, the underlying mechanism remains unclear. The bioinformatic analysis predicted a potential antisense transcript ATM-antisense (AS) from the opposite strand of the ATM gene. The purpose of this study was to identify ATM-AS and investigate the possible effect of ATM-AS on the ATM gene regulation. METHODS: Single strand-specific RT-PCR was performed to verify the predicted antisense transcript ATM-AS within the ATM gene locus. qRT-PCR and Western blotting were used to detect the expression levels of ATM-AS and ATM in normal and breast cancer cell lines as well as in tissue samples. Luciferase reporter gene assays, biological mass spectrometry, ChIP-qPCR and RIP were used to explore the function of ATM-AS in regulating the ATM expression. Immunofluorescence and host-cell reactivation (HCR) assay were performed to evaluate the biological significance of ATM-AS in ATM-mediated DNA damage repair. Breast cancer tissue samples were used for evaluating the correlation of the ATM-AS level with the ATM expression as well as prognosis of the patients. RESULTS: The ATM-AS significantly upregulated the ATM gene activity by recruiting KAT5 histone acetyltransferase to the gene promoter. The reduced ATM-AS level led to the abnormal downregulation of ATM expression, and impaired the ATM-mediated DNA damage repair in normal breast cells in vitro. The ATM-AS level was positively correlated with the ATM expression in the examined breast cancer tissue samples, and the patient prognosis. CONCLUSION: The present study demonstrated that ATM-AS, an antisense transcript located within the ATM gene body, is an essential positive regulator of ATM expression, and functions by mediating the binding of KAT5 to the ATM promoter. These findings uncover the novel mechanism underlying the dysregulation of the ATM gene in breast cancer, and enrich our understanding of how an antisense transcript regulates its host gene.

Resveratrol: A new approach to ameliorate hyperhomocysteinaemia-induced renal dysfunction.

Hypertension is a common cause of kidney injury and renal damage occurs earlier and is more serious in patients with hypertension and hyperhomocysteinaemia (HHCY). Folic acid (FA) is widely used to ameliorate the organ damage caused by HHCY. However, the effective dose of FA remains controversial and certain studies have suggested that FA increases the risk of cancer. Therefore, it is necessary to identify a safe, effective drug. Resveratrol (RSV) is a natural polyphenol antioxidant. Therefore, the present study explored the effects of RSV on renal damage in spontaneously hypertensive rats (SHRs) with HHCY and its potential underlying mechanism. SHRs were divided randomly into control, HHCY, HHCY + FA and HHCY + RSV groups. Blood pressure, plasma homocysteine, indexes of oxidative stress [serum malondialdehyde (MDA) and superoxide dismutase (SOD) levels] and indexes of renal function [glomerular filtration rate (GFR) and urinary albumin creatinine ratio (UACR)] were assessed. The mRNA and protein expression levels of nephrin and NAPDH oxidase (NOX)2 and NOX4 were detected via reverse transcription-quantitative PCR and western blotting. The results demonstrated that there was no significant difference in BP (blood pressure) among the groups, while the levels of homocysteine (HCY) in the HHCY intervention groups were significantly increased compared with the control. Both FA and RSV decreased the level of HCY, but the decrease was more obvious in the HHCY + FA group. Compared with the control the serum SOD levels and GFR were significantly decreased in the HHCY group, whereas the serum MDA levels and UACR were significantly increased. Moreover, the NOX2 and NOX4 expression levels were significantly increased, whereas those of nephrin were significantly decreased in the HHCY group. The changes caused by HHCY were significantly counteracted in both the HHCY + FA and HHCY + RSV groups and the antioxidant effect was markedly stronger in the HHCY + RSV group. In conclusion, RSV, like FA, potentially improved the renal function damage aggravated by HHCY in SHRs. Furthermore, RSV improved renal function mainly via the inhibition of oxidative stress. RSV may be a potential safe and effective treatment for HHCY-induced hypertensive renal damage.

Disruption of GMNC-MCIDAS multiciliogenesis program is critical in choroid plexus carcinoma development.

Multiciliated cells (MCCs) in the brain reside in the ependyma and the choroid plexus (CP) epithelia. The CP secretes cerebrospinal fluid that circulates within the ventricular system, driven by ependymal cilia movement. Tumors of the CP are rare primary brain neoplasms mostly found in children. CP tumors exist in three forms: CP papilloma (CPP), atypical CPP, and CP carcinoma (CPC). Though CPP and atypical CPP are generally benign and can be resolved by surgery, CPC is a particularly aggressive and little understood cancer with a poor survival rate and a tendency for recurrence and metastasis. In contrast to MCCs in the CP epithelia, CPCs in humans are characterized by solitary cilia, frequent TP53 mutations, and disturbances to multiciliogenesis program directed by the GMNC-MCIDAS transcriptional network. GMNC and MCIDAS are early transcriptional regulators of MCC fate differentiation in diverse tissues. Consistently, components of the GMNC-MCIDAS transcriptional program are expressed during CP development and required for multiciliation in the CP, while CPC driven by deletion of Trp53 and Rb1 in mice exhibits multiciliation defects consequent to deficiencies in the GMNC-MCIDAS program. Previous studies revealed that abnormal NOTCH pathway activation leads to CPP. Here we show that combined defects in NOTCH and Sonic Hedgehog signaling in mice generates tumors that are similar to CPC in humans. NOTCH-driven CP tumors are monociliated, and disruption of the NOTCH complex restores multiciliation and decreases tumor growth. NOTCH suppresses multiciliation in tumor cells by inhibiting the expression of GMNC and MCIDAS, while Gmnc-Mcidas overexpression rescues multiciliation defects and suppresses tumor cell proliferation. Taken together, these findings indicate that reactivation of the GMNC-MCIDAS multiciliogenesis program is critical for inhibiting tumorigenesis in the CP, and it may have therapeutic implications for the treatment of CPC.

Studies on activation and regulation of the coagulation cascade in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Increased activation of the coagulation cascade and diminished fibrinolysis combine to promote fibrin deposition and polyp formation in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP). More information is needed concerning mechanisms of coagulation in CRSwNP. OBJECTIVE: We investigated the mechanisms as well as the initiation and regulation of coagulation cascade activation in CRS. METHODS: Samples were collected from 135 subjects with CRSwNP, 80 subjects with chronic CRS without nasal polyps (NP), and 65 control subjects. The levels of activated factor X (FXa), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex, tissue factor (TF), and TF pathway inhibitor (TFPI) were monitored in CRS by real-time PCR, ELISA, immunohistochemistry, or immunofluorescence. Heteromeric complexes of TF with activated factor VII (FVII) and TF with activated FVII and FXa were assessed by coimmunoprecipitation and Western blotting. RESULTS: Increased levels of FXa, F1+2, and thrombin-antithrombin complex were detected in NP tissue compared to uncinate tissue from CRS and control subjects. Although free TF protein levels were not increased in NP, immunoprecipitation of TF in NP tissue revealed increased complexes of TF with FVII. Local expression of FVII was detected in sinonasal mucosa, and the ratio of TFPI to FXa was lower in NP tissue. CONCLUSION: The coagulation cascade is associated with NP compared to control and uncinate tissue from CRS patients, and TF and FVII are produced locally in sinonasal mucosa in patients. TF and FVII can activate the extrinsic coagulation pathway, suggesting that this pathway may activate fibrin deposition in CRSwNP. Reduced formation of the complex of FXa and TFPI in NP may reduce natural suppression of the extrinsic coagulation pathway in CRSwNP.

Global interpretation of novel alternative splicing events in human congenital pulmonary airway malformations: A pilot study.

Little is known about differentially expressed genes (DEGs) and alternative splicing (AS) landscapes in congenital lung malformations (CLMs). We applied reference-based assembly of sequencing reads from RNA sequencing (RNA-seq) libraries to identify DEGs and AS landscapes in the lesions and normal lung tissue from the most common types of CLMs, including congenital pulmonary airway malformation-Ⅰ (CPAM-Ⅰ), CPAM-Ⅱ, intralobar sequestration (ILS), and ILS with CPAM (ILS-CPAM). We analyzed the expression profiles and related biological functions of AS events (ASEs). We further constructed a co-expression regulatory network between RNA binding protein (RBP) genes and corresponding ASEs to explore the related pathways in the regulated network. Ten DEGs were identified in the four types of CLMs, including eight upregulated genes and two downregulated genes. Additionally, 16 differential ASEs were detected, including the genes MACF1, RFX2, and FBXL4. Gene ontology (GO) enrichment was mainly observed in embryonic visual malformation and apoptotic process, and the KEGG pathway mainly enriched in the PI3K/AKT signaling pathway. We also detected 13 differentially expressed RBPs among 1979 DEGs in CPAM-I, in which ASEs in the MACF1 gene and RBP genes TLR8 and PTRH1 were closely associated. Moreover, we confirmed that the expression levels of PTRH1, NSUN7, and DZIP1L abundantly increased and the expression levels of TLR8, MEF2A, and NIPBL decreased in the CPAM-I lung tissue compared with the controls. It is suggested that ASEs in different types of CLMs is prominently different from normal controls, and ASEs differences occurring in CPAM-I malformation tissue are dramatically different from other types, which demonstrates the complex pathogenesis of CLMs and provides foundations for future studies to elucidate the mechanisms of developing CLMs.