Platycodon D protects human nasal epithelial cells from pyroptosis through the Nrf2/HO-1/ROS signaling cascade in chronic rhinosinusitis.

BACKGROUND: Pyroptosis has been demonstrated being closely associated with the inflammatory progression in chronic rhinosinusitis (CRS). However, platycodon D (PLD) has emerged as a key anti-inflammatory mediator in the inflammatory progression of various respiratory diseases. This study aims at investigating whether PLD could reduce inflammatory progression of CRS by inhibiting pyroptosis. METHODS: Nasal mucosal tissues from patients with CRS and the control group (simple nasal septal deviation) were analyzed for morphological difference using hematoxylin & eosin staining and for the expression of pyroptosis-related makers by immunofluorescence (IF). Human nasal epithelial cells (HNEpCs) were cultured and co-stimulated with lipopolysaccharide (LPS)/adenosine triphosphate (ATP) to construct an in vitro cellular model simulating CRS. After pretreatment with PLD, EthD-I staining, TUNEL staining, transmission electron microscopy (TEM), and GSDMD-NT detection were performed to evaluate pyroptosis markers. The NLRP3 inflammasome was detected by IF and western blotting (WB). Reactive oxygen species (ROS) were detected by H2DCFDA staining, and mitochondrial membrane potential was evaluated by JC-1 staining. Mitochondrial morphology and structure were observed using TEM. The Nrf2/HO-1 antioxidant signaling pathway was detected using WB. RESULTS: The nasal mucosa structure of patients with CRS exhibited significant damage, with a marked increase in the expression of pyroptosis-related proteins compared with the control group. LPS/ATP co-stimulation resulted in an increased expression of IL-18 and IL-1ß in HNEpCs, causing significant damage to nuclear and cell membranes, GSDMD-NT accumulation around the cell membrane, and intracellular NLRP3 inflammasome activation. Furthermore, it led to increased ROS expression, significantly decreased mitochondrial membrane potential, and damaged mitochondrial structure. However, pretreatment with PLD significantly reversed the aforementioned trends and activated the Nrf2/HO-1 antioxidant signaling pathway. CONCLUSIONS: The results of this study confirm that NLRP3-mediated pyroptosis plays a crucial role in the pathological process of nasal mucosal impairment in patients with CRS. PLD inhibits NLRP3-mediated pyroptosis, preventing inflammatory damage in HNEpCs of patients with CRS by activating the Nrf2/HO-1 antioxidant signaling pathway, which in turn reduces ROS production and ameliorates mitochondrial damage.

The effectiveness of hysteroscopy for the treatment of cesarean scar pregnancy: a retrospective cohort study.

BACKGROUND: Cesarean scar pregnancy (CSP) is a long-term complication of cesarean section characterized by the localization of a subsequent gestational sac within the scar area or niche developed as a result of a previous cesarean section. Its incidence has increased substantially because of the high global cesarean section rate in recent decades. Several surgical and drug treatments exist for this condition; however, there is currently no optimal treatment. This study compared the effectiveness of direct hysteroscopic removal of the gestational tissue and hysteroscopy combined with vacuum suction for the treatment of CSP. METHODS: From 2017 to 2023, 521 patients were diagnosed with CSP at our hospital. Of these patients, 45 underwent hysteroscopy. Among them, 28 underwent direct hysteroscopic removal (hysteroscopic removal group) and 17 underwent hysteroscopy combined with vacuum suction (hysteroscopic suction group). The clinical characteristics and outcomes of the hysteroscopic removal group and hysteroscopic suction group were analyzed. RESULTS: Among the 45 patients, the amount of bleeding and hospitalization cost were significantly higher in the hysteroscopic removal group than in the hysteroscopic suction group (33.8 mL vs. 9.9 mL, P < 0.001; and 8744.0 yuan vs. 5473.8 yuan, P < 0.001; respectively). The operation time and duration of hospitalization were significantly longer in the hysteroscopic removal group than in the hysteroscopic suction group (61.4 min vs. 28.2 min, P < 0.001; and 3.8 days vs. 2.4 days, P = 0.026; respectively). Three patients in the hysteroscopic removal group had uterine perforation and received laparoscopic repair during operation. No complications occurred in the hysteroscopic suction group. One patient in the hysteroscopic removal group received ultrasound-guided suction curettage due to postoperative moderate vaginal bleeding, and one patient in the hysteroscopic suction group received ultrasound-guided suction curettage due to postoperative gestational residue and elevated serum beta-human chorionic gonadotropin levels. Reproductive function was preserved in all patients. CONCLUSIONS: Hysteroscopy is an effective method for treating CSP. Compared with direct hysteroscopic removal, hysteroscopy combined with vacuum suction is more suitable for CSP. However, multicenter prospective studies with large sample sizes are required for verification of these findings.

Interaction between ozone and paternal smoking on fetal congenital heart defects among pregnant women at high risk: a multicenter maternal-fetal medicine study.

BACKGROUND: Evidence remains limited on the association between maternal ozone (O3) exposure and congenital heart defects (CHDs) in offspring, and few studies have investigated the interaction and modification of paternal smoking on this association. METHODS: Using a sample including pregnant women at high risk of fetal CHD (with metabolic disease, first-trimester viral infection, family history of CHD, etc.) from a maternal-fetal medicine study covering 1313 referral hospitals in China during 2013-2021, we examined the associations between maternal O3 exposure during 3-8 weeks of gestational age and fetal CHD in offspring and investigated the interaction and modification of paternal smoking on this association. CHD was diagnosed by fetal echocardiograms, maximum daily 8-hour average O3 exposure data at a 10 km × 10 km spatial resolution came from the Tracking Air Pollution in China dataset, and paternal smoking was collected using questionnaires. Logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 27,834 pregnant women at high risk of fetal CHD, 17.4% of fetuses were diagnosed with CHD. Each 10 µg/m3 increase in maternal O3 exposure was associated with a 17% increased risk of CHD in offspring (OR = 1.17, 95% CI = 1.14-1.20). Compared with paternal nonsmoking and maternal low O3 exposure, the ORs (95% CI) of CHD for smoking and low O3 exposure, nonsmoking and high O3 exposure, and smoking and high O3 exposure were 1.25 (1.08-1.45), 1.81 (1.56-2.08), and 2.23 (1.84-2.71), respectively. Paternal smoking cessation seemingly mitigated the increased risk of CHD. CONCLUSIONS: Maternal O3 exposure and paternal smoking were interactively associated with an increased risk of fetal CHD in offspring, which calls for effective measures to decrease maternal exposure to O3 pollution and secondhand smoke for CHD prevention.

Refractory and progressively worsening nasal obstruction: case report of nasal osteoblastoma and literature review.

Nasal osteoblastoma (OB) is a rare and locally aggressive osteogenic tumor that has rarely been reported, and there is a lack of effective evidence data for its diagnosis and treatment. In this study, we report a 31-year-old female patient who presented with nasal congestion and associated progressive painless swelling of the left maxillofacial region. A preoperative computed tomography (CT) examination of the paranasal sinuses was performed, and based on the imaging presentation, the surgeon was unable to differentiate between OB, osteoid osteoma (OO), fibrous dysplasia of bone (FDB) and osteoblastic fibroma (OF). After excluding contraindications to surgery, the patient underwent nasal endoscopic excision of the left nasal mass, which was found to be gravel-like and difficult to remove cleanly during the operation. The mass was brittle and bled easily, resulting in inadequate exposure of the operative field, prolonged operation time, and substantial intraoperative blood loss. This indicates that definite preoperative diagnosis (biopsy of deeper parts of the mass is recommended) and appropriate preoperative preparations (e.g., preoperative angiography and embolization, adequate blood preparation) are very important. The intraoperative frozen and postoperative pathological results clearly identified the tumor as OB. No local recurrence of the tumor was observed at the 11-month postoperative follow-up.

A multi-omics integrative analysis based on CRISPR screens re-defines the pluripotency regulatory network in ESCs.

A comprehensive and precise definition of the pluripotency gene regulatory network (PGRN) is crucial for clarifying the regulatory mechanisms in embryonic stem cells (ESCs). Here, after a CRISPR/Cas9-based functional genomics screen and integrative analysis with other functional genomes, transcriptomes, proteomes and epigenome data, an expanded pluripotency-associated gene set is obtained, and a new PGRN with nine sub-classes is constructed. By integrating the DNA binding, epigenetic modification, chromatin conformation, and RNA expression profiles, the PGRN is resolved to six functionally independent transcriptional modules (CORE, MYC, PAF, PRC, PCGF and TBX). Spatiotemporal transcriptomics reveal activated CORE/MYC/PAF module activity and repressed PRC/PCGF/TBX module activity in both mouse ESCs (mESCs) and pluripotent cells of early embryos. Moreover, this module activity pattern is found to be shared by human ESCs (hESCs) and cancers. Thus, our results provide novel insights into elucidating the molecular basis of ESC pluripotency.

[Clinical comprehensive evaluation of Jinsang Sanjie Pills/Capsules in treatment of vocal nodule/polyp of vocal cord].

This study used health technology assessment methods and multi-criteria decision analysis(MCDA) model, according to the guideline for clinical comprehensive evaluation of Chinese patent medicine, we developed this assessment tool. The comprehensive evaluation score of Jinsang Sanjie Pills/Capsules is calculated based on the additive model. This score is calculated by "quantitative evaluation software v1.0 for clinical comprehensive evaluation of Chinese patent medicines" which developed by the project team. The evaluation yielded the following results.(1)Effectiveness: compared with the control group, Jinsang Sanjie Pills/Capsules can improve the total effectiveness rate of vocal nodule/polyp of vocal cord, and improve the symptoms and signs.(2)Safety: Jinsang Sanjie Pills/Capsules did not show acute toxicity and long-term toxicity. The most common adverse reaction was gastrointestinal system damage, all of the adverse reactions were either improved or cured.(3)Economy: from the perspective of the health system, evaluating the single use or combination of Jinsang Sanjie Pills/Capsules with conventional medication in the treatment of vocal nodule/polyp of vocal cord is relatively effective and cost-effective compared to conventional medication, with a stable cost-effectiveness advantage.(4) Innovation: Jinsang Sanjie Pills/Capsules are used for the treatment of slow throat paralysis(vocal nodules, polyp of vocal cord, thickening of vocal mucosa) caused by heat toxin accumulation, Qi stagnation and blood stasis, and the resulting hoarseness. Jinsang Sanjie Pills/Capsules have good innovation and targeted indications.(5) Suitability: the investigated doctors, pharmacists and patients all believed that Jinsang Sanjie Pills/Capsules have good suitability.(6)Accessibility: Jinsang Sanjie Pills/Capsules are included in the category B of the National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance Drug Catalogue(2021 edition), which have good cost-effectiveness and affordability for medical insurance and self-paid patients. Jinsang Sanjie Pills/Capsules do not contain endangered animals and plants. The supply of raw materials can meet the demand of production at present. The comprehensive evaluation score is 76.06 points. Based on all dimensions of evidence, 71.4% experts consensus on Jinsang Sanjie Pills/Capsules is class A, which can be directly converted into decision making. This study comprehensively evaluated the clinical application value of Jinsang Sanjie Pills/Capsules in the treatment of vocal nodule/polyp of vocal cord, so as to provide evidence for their rational clinical use and regulatory decision-making.

Prognostic Modeling of Lung Adenocarcinoma Based on Hypoxia and Ferroptosis-Related Genes.

Background: It is well known that hypoxia and ferroptosis are intimately connected with tumor development. The purpose of this investigation was to identify whether they have a prognostic signature. To this end, genes related to hypoxia and ferroptosis scores were investigated using bioinformatics analysis to stratify the risk of lung adenocarcinoma. Methods: Hypoxia and ferroptosis scores were estimated using The Cancer Genome Atlas (TCGA) database-derived cohort transcriptome profiles via the single sample gene set enrichment analysis (ssGSEA) algorithm. The candidate genes associated with hypoxia and ferroptosis scores were identified using weighted correlation network analysis (WGCNA) and differential expression analysis. The prognostic genes in this study were discovered using the Cox regression (CR) model in conjunction with the LASSO method, which was then utilized to create a prognostic signature. The efficacy, accuracy, and clinical value of the prognostic model were evaluated using an independent validation cohort, Receiver Operator Characteristic (ROC) curve, and nomogram. The analysis of function and immune cell infiltration was also carried out. Results: Here, we appraised 152 candidate genes expressed not the same, which were related to hypoxia and ferroptosis for prognostic modeling in The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) cohort, and these genes were further validated in the GSE31210 cohort. We found that the 14-gene-based prognostic model, utilizing MAPK4, TNS4, WFDC2, FSTL3, ITGA2, KLK11, PHLDB2, VGLL3, SNX30, KCNQ3, SMAD9, ANGPTL4, LAMA3, and STK32A, performed well in predicting the prognosis in lung adenocarcinoma. ROC and nomogram analyses showed that risk scores based on prognostic signatures provided desirable predictive accuracy and clinical utility. Moreover, gene set variance analysis showed differential enrichment of 33 hallmark gene sets between different risk groups. Additionally, our results indicated that a higher risk score will lead to more fibroblasts and activated CD4 T cells but fewer myeloid dendritic cells, endothelial cells, eosinophils, immature dendritic cells, and neutrophils. Conclusion: Our research found a 14-gene signature and established a nomogram that accurately predicted the prognosis in patients with lung adenocarcinoma. Clinical decision-making and therapeutic customization may benefit from these results, which may serve as a valuable reference in the future.

Modified membrane fixation technique in a severe continuous horizontal bone defect: A case report.

BACKGROUND: Continuous severe horizontal bone defect is common in the aesthetic maxillary anterior area, and presents a major challenge in implant dentistry and requires predictable bone augmentation to increase the width of the alveolar bone. CASE SUMMARY: A 24-year-old man, with a history of well-controlled IgA nephropathy, presented to the Dentistry Department of our hospital complaining of missing his right maxillary anterior teeth 1 mo ago. Severe horizontal alveolar bone defects at sites of teeth 12, 13 and 14 were diagnosed. A modified guided bone regeneration surgical approach stabilizing the absorbable collagen membrane and particulate graft materials by periosteal diagonal mattress suture (PDMS) combined with four corner pins was used for this severe continuous horizontal bone defect. The outcome revealed that the newly formed alveolar ridge dimension increased from 0.72 mm to 11.55 mm horizontally 10 mo postoperatively, with no adverse events. The implant surgery was successfully performed. CONCLUSION: This case highlights that PDMS combined with four corner pins is feasible to maintain the space and stabilize the graft and membranes in severe continuous horizontal bone defect.

Diagnostic and surgical challenges of progressive neck and upper back painless masses in Madelung's disease: A case report and review of literature.

BACKGROUND: Madelung's disease (MD) is a chronic alcoholism-associated metabolic syndrome characterized by symmetrical subcutaneous deposition of adipose tissue in the head, neck, shoulders, back, trunk, and nerve roots of the upper and lower limbs. It is relatively rare in Asian individuals and is prone to misdiagnosis. Herein, we report a case of a patient with MD who had undergone surgical management at our hospital, and we discuss the pathogenesis, diagnosis, and treatment of MD. CASE SUMMARY: We report a case of MD in a 65-year-old man of Han descent. The patient had multiple, painless progressive masses for more than five years in the neck and more than 30 years in the upper back. Because of neck mobility limitations and progressive cosmetic deformities caused by the masses, he was admitted to our hospital. He drank approximately 500 mL of liquor per day and smoked heavily for more than 30 years. Contrast-enhanced computed tomography of the neck and chest documented abundant unencapsulated, subcutaneous fatty deposits. We prepared a staged operation plan. The patient was diagnosed with MD; he was advised to abstain from alcohol and was followed up regularly. After a 3-month follow-up, no recurrence of fat accumulation was found in the surgical areas. CONCLUSION: This report presents a case of surgical treatment for MD to improve clinicians' understanding of the disease.

Genome-Wide CRISPR Screen Identifies Puf60 as a Novel Stemness Gene of Mouse Embryonic Stem Cells.

The mechanisms underlying self-renewal of embryonic stem cells (ESCs) hold great value in the clinical translation of stem cell biology and regenerative medicine research. To study the mechanisms in ESC self-renewal, screening and identification of key genes maintaining ESC self-renewal were performed by a genome-wide CRISPR-Cas9 knockout virus library. The mouse ESC R1 were infected with CRISPR-Cas9 knockout virus library and cultured for 14 days. The variation of single guide RNA (sgRNA) ratio was analyzed by high-throughput sequencing, followed by bioinformatics analysis to profile the altered genes. Our results showed 1375 genes with increased sgRNA ratio were found to be mainly involved in signal transduction, cell differentiation, and cell apoptosis; 2929 genes with decreased sgRNA ratio were mainly involved in cell cycle regulation, RNA splicing, and biological metabolic processes. We further confirmed our screen specificity by identifying Puf60, U2af2, Wdr75, and Usp16 as novel positive regulators in mESC self-renewal. Meanwhile, further analysis showed the relevance between Puf60 expression and tumor. In conclusion, our study screened key genes maintaining ESC self-renewal and successfully identified Puf60, U2af2, Wdr75, and Usp16 as novel positive regulators in mESC self-renewal, which provided theoretical basis and research clues for a better understanding of ESC self-renewal regulation.

Impairment mechanism of nasal mucosa after radiotherapy for nasopharyngeal carcinoma.

The nasal mucosa, which performs the crucial functions of filtering, humidifying and temperature regulation, is one of the most vulnerable areas of nasopharyngeal carcinoma (NPC) patients after radiotherapy (RT). Following RT, NPC patients experience a series of pathological changes in the nasal mucosa, ultimately leading to physiological dysfunction of the nasal epithelium. This article systematically reviews the clinical and pathological manifestations of RT-related nasal damage in NPC patients and summarizes the potential mechanism of damage to the human nasal epithelium by RT. Finally, we outline the current mechanistic models of nasal epithelial alterations after RT in NPC patients and provide additional information to extend the in-depth study on the impairment mechanisms of the nasal mucosa resulting from RT. We also describe the relationship between structural and functional alterations in the nasal mucosa after RT to help mitigate and treat this damage and provide insights informing future clinical and fundamental investigations.

Lymph or Chyle Leak After Neck Dissection in Patients With Thyroid Carcinoma: Results of a Study on 1724 Patients.

BACKGROUND: To discuss the prevention and treatment of lymph or chyle leak following neck dissection in patients with thyroid carcinoma. METHODS: A total of 1724 patients with thyroid carcinoma received neck dissection in the Sun Yat-sen University Cancer Center between November 2009 and October 2014. The incidence and management of leak were analyzed. RESULTS: A total of 92 (5.34%) patients developed leak, 28 (1.62%) developed lymph leak, 59 (3.42%) developed chyle leak, and 5 (.29%) developed chylothorax. Medical management to stop postoperative lymph or chyle leak included pressure dressing, reoperation, fasting, or low-fat diet therapy. CONCLUSIONS: Lymph or chyle leak may occur in thyroid carcinoma patients who underwent neck dissection. Clinicians should alert to leak when there were IV + VI region lymph node metastasis and should become aware of chylothorax after pressure dressing. A careful identification and ligation of lymphatic duct may be an effective way to avoid lymph or chyle leak.

MicroRNA-1246 Mediates Drug Resistance and Metastasis in Breast Cancer by Targeting NFE2L3.

MicroRNA (miR)-1246 is abnormally expressed and has pro-oncogenic functions in multiple types of cancer. In the present study, its functions in breast cancer and the underlying mechanisms were further elucidated. The clinical relevance of miR-1246 was analyzed and its expression in clinical specimens and cell lines was examined by reverse transcription-quantitat000000ive PCR analysis. FACS was used to detect cell apoptosis and mitochondrial transmembrane potential. A Transwell system was used to detect cell migration and invasion. Luciferase assay was used to confirm the target gene of miR-1246. Xenograft and metastasis mouse models were constructed to determine the function of miR-1246 in vivo. miR-1246 was found to be negatively associated with overall survival in breast cancer. miR-1246 inhibitor could effectively increase the cytotoxicity of docetaxel (Doc) by inducing apoptosis, and impair cell migration and invasion by suppressing epithelial-to-mesenchymal transition. Nuclear factor (erythroid 2)-like factor 3 (NFE2L3) was confirmed as a new target gene of miR-1246, and its overexpression was shown to reduce drug resistance and migration of MDA-MB-231 cells. More importantly, NFE2L3-silencing attenuated the effect of miR-1246 inhibitor. Finally, the inhibition of miR-1246 effectively enhanced the cytotoxicity of Doc in xenografts and impaired breast cancer metastasis. Therefore, miR-1246 may promote drug resistance and metastasis in breast cancer by targeting NFE2L3.

Research Progress on the SERPINE1 Protein and Chronic Inflammatory Diseases of the Upper Respiratory Tract: A Literature Review.

SERPINE1 protein is one important member of the serine proteinase inhibitor E superfamily that plays a crucial role in the fibrinolytic system. It has been identified which is related to chronic inflammatory lung diseases like allergic asthma and lung fibrosis. Recently, researchers have focused on the impact of SERPINE1 and its genetic polymorphisms on inflammatory diseases of the upper respiratory tract. In this review, we conclude that SERPINE1 is widely involved in the pathological process of chronic rhinosinusitis and allergic rhinitis (AR) and may play a pivotal role in tissue remodelling in chronic rhinosinusitis without nasal polyps. It is also found that the 4G allele of SERPINE1 gene is associated with the risk of upper respiratory diseases. More studies are needed to further clarify how SERPINE1 influences chronic rhinosinusitis and AR, which would be conducive to improving the therapeutic efficacy of treatments for upper respiratory diseases.

The natural product lapiferin inhibits cell proliferation and promotes cell apoptosis in gingival squamous cell carcinoma via P21 regulation.

Gingival squamous cell carcinoma (GSCC) is responsible fora large proportion of oral cavity malignancies. GSCC is characterized by rapid cell growth, and progressive invasion and migration. P21 is a widely recognized tumor suppressor, which is induced by P53 activation; however, drugs that aim to promote P21­mediated tumor suppression remain to be identified. A natural compound library was used to perform broad­spectrum screening of drugs that could promote P21 expression. Subsequently, the effects of the screened drug on GSCC cell proliferation and apoptosis were evaluated. The results of the present study suggested that lapiferin was the most effective natural compound that promoted the expression of P21 at both mRNA and protein levels. Lapiferin inhibited proliferation and enhanced apoptosis of YD­38 GSCC cells in a dose­dependent manner. Furthermore, following treatment with lapiferin, the critical cell cycle regulators cell division cycle 25C and cyclin B1 and tumor cell proliferation markers proliferating cell nuclear antigen and Ki67 were markedly decreased. In addition, pro­apoptotic proteins were promoted following treatment of YD­38 cells with lapiferin. Following the depletion ofP21 expression, lapiferin­mediated inhibition of cell proliferation and enhancement of cell apoptosis were significantly reduced. These results indicated that lapiferin may exert potent antitumor effects on GSCC via regulation of P21; therefore, lapiferin may be considered a potential, natural therapeutic agent for the treatment of GSCC.

Synovial chondromatosis of the temporomandibular joint with 400 loose bodies: a case report and literature review.

Synovial chondromatosis (SC) is a benign condition characterized by the formation of metaplastic cartilage in the synovial membrane of the joint, resulting in numerous attached and unattached osteocartilaginous bodies. SC mostly affects the large synovial joints, especially the knee, hip, elbow, and ankle, whereas involvement of the temporomandibular joint (TMJ) is rare. Approximately 240 cases of SC of the TMJ have been reported in the English-language literature to date. The number of loose bodies varies among patients but usually ranges from the dozens to around 100. We herein report a case of SC of the TMJ accompanied by approximately 400 loose bodies in a healthy 53-year-old woman. Such a high number of loose bodies within a small space is extremely rare. We also include a brief discussion about the differential diagnoses and current diagnostic approaches to SC of the TMJ. Notably, delayed diagnosis or misdiagnosis is common because of the nonspecific nature of the presenting complaints.

The Association of New-Onset Atrial Fibrillation and Risk of Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: There are distinct results for the relationship between new-onset atrial fibrillation (NOAF) and subsequent incident cancer. To date, no systematic analysis has been conducted on this issue. This study aims to explore the relationship between NOAF and the risk of developing cancer through a meta-analysis with a large sample size. METHODS: Electronic databases, such as PubMed and EMBASE, were searched for published relevant studies on NOAF patients diagnosed with cancer after and during follow-ups, including reported records of baseline information and the statistical result of morbidity. Two investigators independently reviewed the articles and extracted the data using uniform standards and definitions. The meta-analysis was conducted using the Cochrane Program Review Manager. RESULTS: This meta-analysis consisted of five cohort studies and one case-control study, which comprised 533,514 participants. The pooled relative risk (RR) for incident cancer was 1.24 (95% CI: 1.10-1.39, P=0.0003). The temporal trend analysis demonstrated that an increased risk of cancer was observed during the initial 90 days (RR: 3.44, 95% CI: 2.29-5.57, P < 0.00001), but not after that. Lung cancer (RR: 1.51, 95% CI: 1.47-1.55, P < 0.00001) was associated with NOAF, but not colorectal cancer and breast cancer. CONCLUSION: This meta-analysis provides evidence that NOAF is associated with increased risk of cancer. The risk of incident cancer particularly increases within 90 days after NOAF diagnosis, but not after that.

Identification and functional comparison of Bcl2 splicing isoforms in mouse embryonic stem cells.

Embryonic stem cells (ESCs) provide an ideal model for investigating developmental processes and are great sources for developing regenerative medicine. Harnessing apoptosis facilitates accurate recapitulation of signalling events during embryogenesis and allows efficient expansion of the ESCs during differentiation. Bcl2, a key regulator of intrinsic anti-apoptotic pathway, encodes two splicing isoforms. However, the identification and functional comparison of Bcl2 splicing isoforms in mouse ESCs (mESCs) remains to be elucidated. Here, we provide the evidence that both Bcl2 splicing variants are expressed in mESCs. Despite the structural difference, they have similar subcellular localisation. Both Bcl2α and Bcl2ß enhance differentiation efficiency of the ESCs and effectively improve the survival and growth of ESCs under serum-free conditions. However, the functional effect of Bcl2α was more potent than that of Bcl2ß. Moreover, only Bcl2α could maintain the long-term expansion and pluripotency of ESCs cultured in serum-free medium. Taken together, our results demonstrate previously unknown functional differences in Bcl2 alternative splicing isoforms in ESCs, and lay the foundation for future efforts to engineer ESCs for regenerative medicine.

Investigation of optimal pathways for preeclampsia using network-based guilt by association algorithm.

This study investigated optimal pathways for preeclampsia (PE) utilizing the network-based guilt by association (GBA) algorithm. The inference method consisted of four steps: preparing differentially expressed genes (DEGs) between PE patients and normal controls from gene expression data; constructing co-expression network (CEN) for DEGs utilizing Spearman's correlation coefficient (SCC) method; and predicting optimal pathways by network-based GBA algorithm of which the area under the receiver operating characteristics curve (AUROC) was gained for each pathway. There were 351 DEGs and 61,425 edges in the CEN for PE. Subsequently, 53 pathways were obtained with a good classification performance (AUROC >0.5). AUROC for 9 was >0.9 and defined as optimal pathways, especially microRNAs in cancer (AUROC=0.9966), gap junction (AUROC=0.9922), and pathogenic Escherichia coli infection (AUROC=0.9888). Nine optimal pathways were identified through comprehensive analysis of data from PE patients, which might shed new light on uncovering molecular and pathological mechanism of PE.

Recombinant Expression and Bioactivity Comparison of Four Typical Fungal Immunomodulatory Proteins from Three Main Ganoderma Species.

BACKGROUND: More than a dozen of fungal immunomodulatory proteins (FIPs) have been identified to date, most of which are from Ganoderma species. However, little is known about the similarities and differences between different Ganoderma FIPs' bioactivities. In the current study, two FIP genes termed FIP-gap1 and FIP-gap2 from G. applanatum, along with LZ-8 and FIP-gsi, another two representative Ganoderma FIP genes from G. lucidum and G. sinense were functionally expressed in Pichia. Subsequently, bioactivities of four recombinant Ganoderma FIPs were demonstrated and compared. RESULTS: All the four Ganoderma FIP genes could be effectively expressed in P. pastoris GS115 at expression levels ranging from 197.5 to 264.3 mg L- 1 and simply purified by one step chromatography using HisTrap™ FF prepack columns. Amino acid sequence analysis showed that they all possessed the FIP conserved fragments. The homologies of different Ganoderma FIPs were from 72.6 to 86.4%. In vitro haemagglutination exhibited that FIP-gap1, FIP-gsi and LZ-8 could agglutinate human, sheep and mouse red blood cells but FIP-gap2 agglutinated none. Besides, the immunomodulation activities of these Ganoderma FIPs were as: rFIP-gap2 > rFIP-gap1 > rLZ-8 and rFIP-gsi in terms of proliferation stimulation and cytokine induction on murine splenocytes. Additionally, the cytotoxic activity of different FIPs was: rFIP-gap1 > rLZ-8 > rFIP-gsi > rFIP-gap2, examined by their inhibition of three human carcinomas A549, Hela and MCF-7. CONCLUSIONS: Taken together, four typical Ganoderma FIP genes could be functionally expressed in P. pastoris, which might supply as feasible efficient resources for further study and application. Both similarities and differences were indeed observed between Ganoderma FIPs in their amino acid sequences and bioactivities. Comprehensively, rFIP-gaps from G. applanatum proved to be more effective in immunomodulation and cytotoxic assays in vitro than rLZ-8 (G. lucidum) and rFIP-gsi (G. sinense).