Interleukin-1 beta signals through the ERK signalling pathway to modulate human placental trophoblast migration and invasion in the first trimester of pregnancy.

INTRODUCTION: Interleukin-1 beta (IL-1ß) can promote cell migration, invasion and metastasis in various cancer cells. The mechanism of its role in human trophoblast has not been fully investigated. Therefore, we aimed to investigate the expression level of IL-1ß in first trimester decidua and placenta and its potential role in regulation of extravillous trophoblast cell (EVT) invasion and migration. METHODS: First trimester placenta and decidua were collected to study the expression levels of IL-1ß and its receptors by immunohistochemical staining. Primary isolates of first trimester EVT or the HTR-8/SVneo trophoblast like cell line were used to assess migration and invasion. Matrix metalloproteinase levels were assessed by gelatin zymography and ELISA. The phosphorylation profile of signaling pathway proteins was detected with the Proteome Profiler Human Phospho-Kinase Array Kit. Differentially expressed proteins in cells was detected and verified by Western Blot. RESULTS: IL-1ß, its receptors and antagonist are expressed in first trimester placenta and decidua, exogenous IL-1ß stimulates trophoblast cell outgrowth, migration and invasion through the ERK signaling pathway. IL-1ß was significantly increased in the placenta at 6-7 weeks gestation compared with 8-9 weeks gestation (P < 0.0001). Transwell and RTCA assays indicated that IL-1ß stimulates the invasion and migration of EVT. In addition, IL-1ß promoted the phosphorylation of ERK 1/2. It also promoted the expression of MMP2 and MMP9 in EVT as demonstrated by gelatin zymography assay and enzyme linked immunosorbent assay. DISCUSSION: This study demonstrated IL-1ß expression in placenta and decidua, and that it regulates EVT invasion and migration.

Prognostic value of a nomogram model for postoperative liver metastasis of colon cancer.

BACKGROUND: Colon cancer is one of the most common malignant tumors of the digestive system. Liver metastasis after colon cancer surgery is the primary cause of death in patients with colon cancer. AIM: To construct a novel nomogram model including various factors to predict liver metastasis after colon cancer surgery. METHODS: We retrospectively analyzed 242 patients with colon cancer who were admitted and underwent radical resection for colon cancer in Zhejiang Provincial People's Hospital from December 2019 to December 2022. Patients were divided into liver metastasis and non-liver metastasis groups. Sex, age, and other general and clinicopathological data (preoperative blood routine and biochemical test indexes) were compared. The risk factors for liver metastasis were analyzed using single-factor and multifactorial logistic regression. A predictive model was then constructed and evaluated for efficacy. RESULTS: Systemic inflammatory index (SII), C-reactive protein/albumin ratio (CAR), red blood cell distribution width (RDW), alanine aminotransferase, preoperative carcinoembryonic antigen level, and lymphatic metastasis were different between groups (P < 0.05). SII, CAR, and RDW were risk factors for liver metastasis after colon cancer surgery (P < 0.05). The area under the curve was 0.93 for the column-line diagram prediction model constructed based on these risk factors to distinguish whether liver metastasis occurred postoperatively. The actual curve of the column-line diagram predicting the risk of postoperative liver metastasis was close to the ideal curve, with good agreement. The prediction model curves in the decision curve analysis showed higher net benefits for a larger threshold range than those in extreme cases, indicating that the model is safer. CONCLUSION: Liver metastases after colorectal cancer surgery could be well predicted by a nomogram based on the SII, CAR, and RDW.

Exploring a novel HE image segmentation technique for glioblastoma: A hybrid slime mould and differential evolution approach.

Glioblastoma is a primary brain tumor with high incidence and mortality rates, posing a significant threat to human health. It is crucial to provide necessary diagnostic assistance for its management. Among them, Multi-threshold Image Segmentation (MIS) is considered the most efficient and intuitive method in image processing. In recent years, many scholars have combined different metaheuristic algorithms with MIS to improve the quality of Image Segmentation (IS). Slime Mould Algorithm (SMA) is a metaheuristic approach inspired by the foraging behavior of slime mould populations in nature. In this investigation, we introduce a hybridized variant named BDSMA, aimed at overcoming the inherent limitations of the original algorithm. These limitations encompass inadequate exploitation capacity and a tendency to converge prematurely towards local optima when dealing with complex multidimensional problems. To bolster the algorithm's optimization prowess, we integrate the original algorithm with a robust exploitative operator called Differential Evolution (DE). Additionally, we introduce a strategy for handling solutions that surpass boundaries. The incorporation of an advanced cooperative mixing model accelerates the convergence of BDSMA, refining its precision and preventing it from becoming trapped in local optima. To substantiate the effectiveness of our proposed approach, we conduct a comprehensive series of comparative experiments involving 30 benchmark functions. The results of these experiments demonstrate the superiority of our method in terms of both convergence speed and precision. Moreover, within this study, we propose a MIS technique. This technique is subsequently employed to conduct experiments on IS at both low and high threshold levels. The effectiveness of the BDSMA-based MIS technique is further showcased through its successful application to the medical image of brain glioblastoma. The evaluation of these experimental outcomes, utilizing image quality metrics, conclusively underscores the exceptional efficacy of the algorithm we have put forth.

Multi-threshold Image Segmentation based on an improved Salp Swarm Algorithm: Case study of breast cancer pathology images.

Breast cancer poses a significant risk to women's health, and it is essential to provide proper diagnostic support. Medical image processing technology is a key component of all supporting diagnostic techniques, with Image Segmentation (IS) being one of its primary steps. Among various methods, Multilevel Image Segmentation (MIS) is considered one of the most effective and straightforward approaches. Many researchers have attempted to improve the quality of image segmentation by combining different metaheuristic algorithms with MIS. However, these methods often suffer from issues such as low convergence accuracy and a proclivity for converging towards Local Optima (LO). To overcome these challenges, this study introduces an integrated approach that combines the Salp Swarm Algorithm (SSA), Slime Mould Algorithm (SMA) and Differential Evolution (DE) algorithm. In this manuscript, we introduce an innovative hybrid MIS model termed SDSSA, which leverages elements from the SSA, SMA and DE algorithms. The SDSSA model fundamentally relies on non-local means 2D histogram and 2D Kapur's entropy. To evaluate the proposed method effectively, we compare it initially with similar algorithms using the IEEE CEC2014 benchmark functions. The SDSSA showcases enhanced convergence velocity and precision relative to similar algorithms. Furthermore, this paper proposes an excellent MIS method. Subsequently, IS experiments were conducted separately at both low and high threshold levels. The test results demonstrate that the segmentation outcomes of MIS, at both low and high threshold levels, outperform other methods. This validates SDSSA as a superior segmentation technique that provides practical assistance for future research in breast cancer pathology image processing.

HPV infection and vaginal microecological disorders in women with intrauterine adhesion: cross-sectional study in a Chinese population.

BACKGROUND: The purpose of this study was to evaluate the vaginal microecology and the distribution of human papillomavirus (HPV) subtypes in patients with uterine adhesions and explore the correlation between HPV infection and vaginal microecology imbalance and the occurrence of intrauterine adhesion (IUA). METHODS: A total of 479 women were enrolled in the study, including 259 in the normal group and 220 in the IUA group. Vaginal microecological and HPV analyses were performed on all participants. Significant differences between the two groups were analyzed, and Spearman correlation analysis was performed. RESULTS: The incidence of IUA in patients between 31 and 40 years of age was high. The I-II degree of vaginal cleanliness in the IUA group was significantly lower than that in the normal group, and the number of III-IV degree was significantly higher than that in the normal group. Moreover, the incidences of VVC (vulvovaginal candidiasis) and vaginal disorders and infections with HPV 16 and HPV 52 subtypes were significantly higher in the IUA group than in the normal group. The incidence of high-risk HPV infection combined with vaginal disorders in the IUA group was higher than that in the normal group. Correlation analysis showed that the occurrence of IUAs was positively correlated with HPV infection and negatively correlated with PH and vaginal microecological imbalance. CONCLUSION: The HPV infection rate and vaginal microecology disorders affect the occurrence of IUAs. For patients with IUAs, control of the HPV infection rate and the prevention of vaginal microecological disorders should be improved.

Clinical application of superselective transarterial embolization of renal tumors in zero ischaemia robotic-assisted laparoscopic partial nephrectomy.

Objective: To assess the feasibility and safety of zero ischaemia robotic-assisted laparoscopic partial nephrectomy (RALPN) after preoperative superselective transarterial embolization (STE) of T1 renal cancer. Methods: We retrospectively analyzed the data of 32 patients who underwent zero ischaemia RALPN after STE and 140 patients who received standard robot-assisted laparoscopic partial nephrectomy (S-RALPN). In addition, we selected 35 patients treated with off-clamp RALPN (O-RALPN) from September 2017 to March 2022 for comparison. STE was performed by the same interventional practitioner, and zero ischaemia laparoscopic partial nephrectomy (LPN) was carried out by experienced surgeon 1-12 hours after STE. The intraoperative data and postoperative complications were recorded. The postoperative renal function, routine urine test, urinary Computed Tomography (CT), and preoperative and postoperative glomerular filtration rate (GFR) data were analyzed. Results: All operations were completed successfully. There were no cases of conversion to opening and no deaths. The renal arterial trunk was not blocked. No blood transfusions were needed. The mean operation time was 91.5 ± 34.28 minutes. The mean blood loss was 58.59 ± 54.11 ml. No recurrence or metastasis occurred. Conclusion: For patients with renal tumors, STE of renal tumors in zero ischaemia RALPN can preserve more renal function, and it provides a safe and feasible surgical method.

Knockdown of heat shock protein family D member 1 (HSPD1) promotes proliferation and migration of ovarian cancer cells via disrupting the stability of mitochondrial 3-oxoacyl-ACP synthase (OXSM).

BACKGROUND: Heat shock protein 60 (HSP60) is essential for the folding and assembly of newly imported proteins to the mitochondria. HSP60 is overexpressed in most types of cancer, but its association with ovarian cancer is still in dispute. SKOV3 and OVCAR3 were used as experimental models after comparing the expression level of mitochondrial HSP60 in a normal human ovarian epithelial cell line and four ovarian cancer cell lines. RESULTS: Low HSPD1 (Heat Shock Protein Family D (HSP60) Member 1) expression was associated with unfavorable prognosis in ovarian cancer patients. Knockdown of HSPD1 significantly promoted the proliferation and migration of ovarian cancer cells. The differentially expressed proteins after HSPD1 knockdown were enriched in the lipoic acid (LA) biosynthesis and metabolism pathway, in which mitochondrial 3-oxoacyl-ACP synthase (OXSM) was the most downregulated protein and responsible for lipoic acid synthesis. HSP60 interacted with OXSM and overexpression of OXSM or LA treatment could reverse proliferation promotion mediated by HSPD1 knockdown. CONCLUSIONS: HSP60 interacted with OXSM and maintained its stability. Knockdown of HSPD1 could promote the proliferation and migration of SKOV3 and OVCAR3 via lowering the protein level of OXSM and LA synthesis.

Ezrin accelerates breast cancer liver metastasis through promoting furin-like convertase-mediated cleavage of Notch1.

BACKGROUND: Ezrin, known as a crosslinker between the plasma membrane and actin cytoskeleton, is closely associated with breast cancer (BC) progression. Here, we explored a novel role of ezrin in breast cancer liver metastasis (BCLM). METHODS: The clinical relevance of ezrin was evaluated using in silico tools and confirmed in BC specimens. The effect of ezrin on proliferation, migration and invasion was examined in vitro and in vivo using murine primary liver-metastatic breast cancer cells (mLM). The molecular mechanism involved in ezrin-mediated activation of the Notch1 signaling pathway was elucidated using in vitro models. RESULTS: Data-mining demonstrated that ezrin mRNA and protein expression is up-regulated in breast cancer cohorts and has prognostic significance. Ezrin overexpression promotes cell proliferation, migration and invasion in vitro and in vivo. Hairy and enhancer of split-1 (Hes1) is one of the most significantly enriched candidates of differentially expressed genes in ezrin overexpression and control mLM cells. Ezrin can positively regulate Hes1 mRNA and protein expression, and their coexpression was associated with poor prognosis in BC patients. Ezrin promoted BC cell proliferation in a Hes1-dependent manner without directly interacting with Hes1. The functional link between ezrin and Hes1 is dependent on Notch1 activation through promotion of furin-like convertase cleavage. CONCLUSION: Our results demonstrated that ezrin drives BCLM through activation of the Notch signaling pathway via furin-like convertase. These findings provide a better understanding of the mechanism of ezrin in breast cancer progression, with the goal of discovering a novel target for the treatment of BCLM in the future.

Portal vein gas combined with pneumatosis intestinalis and emphysematous cystitis: A case report and literature review.

BACKGROUND: Portal venous gas (PVG) is a rare clinical condition usually indicative of severe disorders, including necrotizing enterocolitis, bowel ischemia, or bowel wall rupture/infarction. Pneumatosis intestinalis (PI) is a rare illness characterized by an infiltration of gas into the intestinal wall. Emphysematous cystitis (EC) is relatively rare and characterized by intramural and/or intraluminal bladder gas best depicted by cross-sectional imaging. Our study reports a rare case coexistence of PVG presenting with PI and EC. CASE SUMMARY: An 86-year-old woman was admitted to the emergency room due to the progressive aggravation of pain because of abdominal fullness and distention, complicated with vomiting and stopping defecation for 4 d. The abdominal computed tomography (CT) plain scan indicated intestinal obstruction with ischemia changes, gas in the portal vein, left renal artery, superior mesenteric artery, superior mesenteric vein, some branch vessels, and bladder pneumatosis with air-fluid levels. Emergency surgery was conducted on the patient. Ischemic necrosis was found in the small intestine approximately 110 cm below the Treitz ligament and in the ileocecal junction and ascending colon canals. This included excision of the necrotic small intestine and right colon, fistulation of the proximal small intestine, and distal closure of the transverse colon. Subsequently, the patient displayed postoperative short bowel syndrome but had a good recovery. She received intravenous fluid infusion and enteral nutrition maintenance every other day after discharge from the community hospital. CONCLUSION: Emergency surgery should be performed when CT shows signs of PVG with PI and EC along with a clinical situation strongly suggestive of bowel ischemia.

Synthesis, biological evaluation and cellular localization study of fluorescent derivatives of Jiyuan Oridonin A.

Jiyuan Oridonin A (JOA) is a naturally occurring ent-kaurane diterpenoid that exhibits significant potential in the field of anti-tumor drug development. However, its detailed anti-cancer mechanism of action has not been fully understood. In order to investigate its anticancer mode of action, two series of novel fluorescent derivatives of JOA conjugated with naphthalimide dyes were synthesized, and their antitumor activity against five selected cancer cell lines (MGC-803, SW1990, PC-3, TE-1 and HGC-27) was evaluated. Compared with JOA, the anti-tumor activity of the vast majority of compounds were improved. Among them, B12 exhibited promising anti-proliferative activity against HGC-27 cells with IC50 value of 0.39 ± 0.09 µM. Fluorescence imaging studies demonstrated that probe B12 could enter HGC-27 cells in a dose-dependent and time-dependent manner and was mainly accumulated in mitochondria. Preliminary biological mechanism studies indicated that B12 was able to inhibit cell cloning and migration. Further studies suggested that B12-induced apoptosis was related to the mitochondrial pathway. Overall, our results provide new approaches to explore the molecular mechanism of the natural product JOA, which would contribute to its further development as an antitumor agent.

An Autophagy-Related Gene-Based Prognostic Risk Signature for Hepatocellular Carcinoma: Construction and Validation.

BACKGROUND: Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer. Treatment is dramatically difficult due to its high complexity and poor prognosis. Due to the disclosed dual functions of autophagy in cancer development, understanding autophagy-related genes devotes into novel biomarkers for HCC. METHODS: Differential expression of genes in normal and tumor groups was analyzed to acquire autophagy-related genes in HCC. These genes were subjected to GO and KEGG pathway analyses. Genes were then screened by univariate regression analysis. The screened genes were subjected to multivariate Cox regression analysis to build a prognostic model. The model was validated by the ICGC validation set. RESULTS: To sum up, 42 differential genes relevant to autophagy were screened by differential expression analysis. Enrichment analysis showed that they were mainly enriched in pathways including regulation of autophagy and cell apoptosis. Genes were screened by univariate analysis and multivariate Cox regression analysis to build a prognostic model. The model constituted 6 feature genes: EIF2S1, BIRC5, SQSTM1, ATG7, HDAC1, and FKBP1A. Validation confirmed the accuracy and independence of this model in predicting the HCC patient's prognosis. CONCLUSION: A total of 6 feature genes were identified to build a prognostic risk model. This model is conducive to investigating interplay between autophagy-related genes and HCC prognosis.

Gene Model Related to m6A Predicts the Prognostic Effect of Immune Infiltration on Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive solid tumor. Because most studies have focused on the intrinsic carcinogenic pathways of tumors, we focused on the relationship between N6-methyladenosine (m6A) and the prognosis of HNSCC in the tumor immune microenvironment. We downloaded RNA-seq data from the TCGA dataset and used univariate Cox regression to screen m6A-related lncRNAs. The expression value of LASSO-screened genes was the sum of LASSO regression coefficients. We then evaluated relationships between the risk score and cellular components or cellular immune response. Differences in immune response under various algorithms were visualized with heat maps. The GSVA package in R was used to analyze GO, BP, KEGG, and hallmark gene sets of immune checkpoint clusters and immune checkpoint scores. The GSEA analysis was performed with the cluster profile package, yielding 21 m6A genes. Related lncRNAs were screened with Pearson's correlations, and the resulting 442 lncRNAs were screened using single-factor analysis. Eight lncRNAs closely related to prognosis were identified through survival random forest. Survival analysis showed that patients with a high risk score had a poor prognosis. Low- and high-risk-score groups differed significantly in m6A gene expression. Prognostic scores from different algorithms were significantly correlated with B cells, T cells, and memory cells in the immune microenvironment. Expression of immune checkpoints and signal pathways differed significantly across risk-score groups, suggesting that m6A could mediate lncRNA-induced immune system dysfunction and affect HNSCC development. A comprehensive study of tumor-cell immune characteristics should provide more insight into the complex immune microenvironment, thus contributing to the development of new immunotherapeutic agents.

Disease burden of liver cancer attributable to specific etiologies in China from 1990 to 2019: An age-period-cohort analysis.

Temporal trends of total liver cancer have been well reported in China, especially the trends caused by hepatitis B (HBV); however, the trends of liver cancer attributable to specific etiologies have rarely been reported in China. Thus, this study aims to describe the temporal trends in the incidence, mortality and DALYs of total and etiology-specific liver cancer in China from 1990 to 2019. We extracted the incidence, mortality and disability-adjusted life years (DALYs) of total and etiology-specific liver cancer in China from 1990 to 2019 from global disease burden (GBD) 2019. We plotted the trends in the age-standardized rates for incidence, mortality, and DALYs using locally weighted regression (LOESS)-smoothed data from 1990 to 2019. The age-standardized rate for the incidence of liver cancer was analyzed with an age-period-cohort method. The age-standardized rates for incidence, death, and DALYs decreased by -58.8%, -63.8%, and -65.6%, respectively, between 1990 and 2019. The age-standardized rates of incidence, mortality, and DALYs of total liver cancer showed similar temporal patterns, presenting an overall decline, with the average annual percentage change (AAPC) ranging from -3.3% to -3.8%. People in the period before 2007 had a higher risk, and people after 2007 had a lower risk. The cohort risk ratios (RRs) showed decreasing patterns, with the most rapid decline observed in the 1910 to 1960 cohorts. Our study generally revealed favorable decreasing trends for total and etiology-specific liver cancer in China from 1990 to 2019. Despite the overall decline in liver cancer due to heavy alcohol use and obesity from 1990 to 2019, there have been apparent upward trends since 2006. Planned population-wide interventions targeting heavy alcohol use and obesity may mitigate the increasing trends in liver cancer attributable to alcohol use and NASH.

Evaluation of anti-tumor effects of crocin on a novel 3D tissue-engineered tumor model based on sodium alginate/gelatin microbead.

Crocin, as one of the biologically active components of saffron, has anti-inflammatory, anti-oxidant, anti-depressant and auxiliary anti-tumor effects. Studies have shown that crocin could promote breast cancer cell apoptosis. However, conventional methods are mainly based on two-dimensional (2D) cell culture models, which are difficult to reproduce the tumor environment in vivo due to space constraints. In this study, we prepared a three-dimensional (3D) cell model in vitro based on sodium alginate/gelatin to evaluate the inhibitory effect of crocin on MCF-7 cells, which could bridge the gap in crocin drug evaluation between 2D and 3D cell model in vitro. Different from the 2D culture, the cells were found to aggregate in a spherical shape in the 3D microgel beads. And the CCK-8 assay showed that the growth of MCF-7 cells exposed to crocin was inhibited in a time-related and concentration-related manner. Compared with 2D culture (IC50 that MCF-7 cells treated with crocin at 24 h, 48 h, 72 h: 3.68, 2.55 and 1.53 mg/mL, respectively), the IC50 value of 3D culture (IC50 that MCF-7 cells treated with crocin at 24 h, 48 h, 72 h: 10.12, 6.89 and 6.64 mg/mL, respectively) was significantly increased by 2.77, 2.70, 4.34 times, respectively. Besides, live/dead staining and scanning electron microscope (SEM) revealed that the 2D cultured cells shrank and ruptured after crocin treatment, and the number of living cells was considerably reduced; the size of the cell colonies in the 3D microgel beads decreased.

Low Serum-Free Testosterone Concentration in Chinese Male Patients with Uncomplicated Acute Type B Aortic Dissection.

OBJECTIVE: Although aortic dissection occurs predominantly in men, its association with androgens is unknown. The aim of this study was to evaluate the androgen levels in Chinese male patients with uncomplicated, acute type B aortic dissection. STUDY DESIGN: Cross-sectional study. MATERIALS AND METHODS: A total of 192 age-matched male patients with uncomplicated, acute type B aortic dissection or essential hypertension were recruited between 2016 and 2018. The demographic and clinical data were analyzed. RESULTS: Male patients with uncomplicated, acute type B aortic dissection had lower serum total testosterone and free testosterone than male patients with essential hypertension (7.6 ± 3.7 nmol/L vs. 10.9 ± 3.8 nmol/L, P < 0.001; 36.0 ± 19.8 pmol/L vs. 56.4 ± 19.2 pmol/L, P < 0.001). Lower free testosterone level was significantly associated with uncomplicated, acute type B aortic dissection (univariate odds ratio 0.948, P < 0.001; multivariate odds ratio = 0.966, P = 0.002). No statistical difference was observed for free testosterone between younger patient groups (aged < 51 years; aged 51-60 years) and older patient groups (aged 61-70 years; aged >70 years) with uncomplicated, acute type B aortic dissection (33.7 ± 19.8 pmol/L vs. 38.5 ± 19.8 pmol/L, P = 0.239). CONCLUSIONS: Lower free testosterone was independently associated with uncomplicated, acute type B aortic dissection in the Chinese male population with hypertension. Additional studies are needed to clarify whether earlier onset in Chinese patients with aortic dissection is associated with androgen deficiency.

MiR-182 promotes glioma progression by targeting FBXW7.

OBJECTIVE: MicroRNAs (miRNAs) are widely considered to play an important role in the tumor progression. In this study, we aimed to investigate the potential biological effects of miR-182 and its target FBXW7 on glioma development. METHODS: Expression data of glioma were procured from TCGA database. Differential analysis was performed to identify the potential differentially expressed miRNA (DEmiRNA), and bioinformatics databases were utilized for target genes prediction. qRT-PCR was conducted to detect miR-182 and western blot was performed to test FBXW7 in protein level. Then the cells were processed for proliferation determination by CCK-8, migration test through wound healing assay, invasion detection via Transwell and apoptosis measurement by flow cytometry. In addition, dual-luciferase reporter gene assay was carried out for evaluation of the targeted relationship between the miR-182 and FBXW7. RESULTS: MiR-182 was found to be up-regulated in glioma cells while FBXW7 was down-regulated. Besides, miR-182 was predicted to targeted bind with FBXW7 on 3'UTR via bioinformatics methods, and their targeted relationship was further validated by dual-luciferase assay. MiR-182 mimic could significantly promote cell proliferation, migration, invasion and inhibit cell apoptosis, while miR-182 inhibitor had the negative effect. Moreover, FBXW7 knockdown could reverse the inhibitory effect of miR-182 inhibitor on glioma cells. CONCLUSION: MiR-182 promotes cell proliferation, migration, invasion and inhibits cell apoptosis in glioma by targeting FBXW7.

Upregulation of Insulin-Like Growth Factor-1 Receptor (IGF-1R) Reverses the Inhibitory Effect of Let-7g-5p on Migration and Invasion of Nasopharyngeal Carcinoma.

BACKGROUND Let-7 microRNAs (miRNAs) have the effects of inhibiting tumor growth and metastasis, however, the research in nasopharyngeal carcinoma (NPC) is limited. This study focused on the effects of Let-7 on NPC migration and invasion and the mechanism of action. MATERIAL AND METHODS Plasmid transfection was used to upregulate the expression levels of Let-7g-5p and insulin-like growth factor-1 receptor (IGF-1R). Cell counting kit-8 (CCK-8) assay was applied to test the cell viability. Scratch assay and Transwell assay were performed to detect the migration and invasion abilities. Bioinformatics prediction and luciferase reporter assay were used to determine and verify the downstream target genes for Let-7g-5p. Protein and mRNA were detected by western blot and real-time quantitative polymerase chain reaction (RT-qPCR), respectively. RESULTS Let-7g-5p was under-expressed in human NPC cells. Overexpression of Let-7g-5p could inhibit cell viability and inhibit the migration and invasion of SUNE1 cells. The dual-luciferase reporter assay showed that IGF-1R was a direct target gene of Let-7g-5p, which was directly regulated IGF-1R expression by 3'UTR. Let-7g-5p overexpression could inhibit the expression of IGF-1R gene, and upregulation of IGF-1R gene expression reversed the inhibitory effect of Let-7g-5p on cell viability and epithelial-mesenchymal transition processes. CONCLUSIONS Let-7g-5p is lowly expressed in NPC and it was the first to discover that IGF-1R was a target gene of let-7g-5p in NPC. Upregulation of IGF-1R reversed the inhibitory effect of Let-7g-5p on epithelial-mesenchymal transition.

Novel aminopyrimidinyl benzimidazoles as potentially antimicrobial agents: Design, synthesis and biological evaluation.

A series of novel aminopyrimidinyl benzimidazoles as potentially antimicrobial agents were designed, synthesized and characterized by IR, NMR and HRMS spectra. The biological evaluation in vitro revealed that some of the target compounds exerted good antibacterial and antifungal activity in comparison with the reference drugs. Noticeably, compound 7d could effectively inhibit the growth of A. flavus, E. coli DH52 and MRSA with MIC values of 1, 1 and 8 µg/mL, respectively. Further studies revealed that pyrimidine derivative 7d could exhibit bactericidal mode of action against both Gram positive (S. aureus and MRSA) and Gram negative (P. aeruginosa) bacteria. The active molecule 7d showed low cell toxicity and did not obviously trigger the development of resistance in bacteria even after 16 passages. Furthermore, compound 7d was able to beneficially regulate reactive oxygen species (ROS) generation for an excellent safety profile. Molecular docking study revealed that compound 7d could bind with DNA gyrase by the formation of hydrogen bonds. The preliminary exploration for antimicrobial mechanism disclosed that compound 7d could effectively intercalate into calf thymus DNA to form a steady supramolecular complex, which might further block DNA replication to exert the powerful bioactivities. The binding investigation of compound 7d with human serum albumins (HSA) revealed that this molecule could be effectively transported by HSA.

[Surgery of ventilation tube insertion in the middle ear and the external auditory canal for chronic secretory otitis media in children].

OBJECTIVE: To study the therapeutic effect of ventilation tube insertion in the middle ear and the external auditory canal on chronic secretory otitis media in children. METHODS: A retrospective study on 30 patients (40 ears) with chronic secretory otitis media and who underwent the operation of middle ear exploration and ventilation tube insertion in the middle ear and the external auditory canal was performed. Poor tympanic membrane, even with adhesion, was seen in 23 ears. Ten patients had evidence of bilateral secretory otitis media. From this group one ear was first injected with drugs (dexamethasone, mucosolvin, etc) and then tube insertion into the auditory tube was performed; the other ear only received drug injections into the auditory tube. The remaining 20 patients who had evidence of unilateral secretory otitis media only received drug injections into the auditory tube. RESULTS: The tubes inserting into the auditory tube all dropped out 5-8 days after operation. None of the ventilation tubes into the middle ear dropped out and the patients' tympanum recovered after the ventilation tubes were removed (6-8 months after operation). The total cure rate was 87.5% (35/40) and the improvement rate was 12.5% (5/40). The operation of inserting tubes into the auditorytube did not improve the therapeutic effects. In the 0.5-2 years postoperative follow-up, middle ear effusions recurred in one ear, and three ears were transferred from type C to type A. CONCLUSIONS: The surgery of ventilation tube insertion in the middle ear and the external auditory canal for chronic secretory otitis media can prevent the tympanic membrane from damage and dropping out of the ventilation tube and reduce recurrence in children. It is a preferred selection for the patients with poor tympanic membrane or adhesive tympanic membrane. It is no use to insert the tube into the auditory tube for the improvement of therapeutic effects.