A case report of lymphangioleiomyomatosis with retroperitoneal masses in pregnancy.

Background: Lymphangioleiomyomatosis (LAM) is a rare, gradually advancing tumor of unknown origin. It is distinguished by the anomalous proliferation of pulmonary smooth muscle cells and predominantly manifests in women of childbearing age. In this study, we aim to present a noteworthy case of LAM accompanied by lymphangioleiomyoma in the retroperitoneal space during pregnancy, a scenario susceptible to misdiagnosis. Case presentation: A 31-year-old woman, facing an unintended pregnancy, presented during the 13th week with a cystic-solid mass exhibiting abundant blood signals in the pelvic cavity, as revealed by routine obstetrical ultrasound. Concurrently, her chest CT disclosed diffuse thin-walled cavities in both lungs. Despite the absence of clinical symptoms, the patient abandoned pregnancy and underwent a complete curettage. However, 24 days post-operation, she was readmitted for further assessment, revealing an enlargement of the mass encompassing the abdominal aorta and inferior vena cava, along with compression on the middle and lower segments of the ureter. After a multi-disciplinary discussion and patient explanation, an exploratory laparotomy was performed, resulting in the complete removal of the tumor. Intraoperative pathological examination and immunohistochemical staining indicated a retroperitoneal mass devoid of malignant evidence. The comprehensive morphologic and immunophenotypic features substantiated the diagnosis of lymphangioleiomyomatosis. The postoperative course was uneventful, culminating in the patient's discharge. Conclusion: The consideration of Lymphangioleiomyomatosis (LAM) with a retroperitoneal tumor is crucial in the differential diagnosis of pelvic and abdominal masses. The preoperative diagnosis of this tumor poses a challenge, as ultrasound or CT scans may not yield definitive results. Accurate diagnosis necessitates not only a pathological examination of the retroperitoneal mass but also the correlation with the patient's chest High-Resolution Computed Tomography (HRCT) findings and corresponding clinical manifestations. Optimal management involves radical surgery, with surgeons comprehensively factoring in both fetal and maternal conditions when formulating a treatment plan.

A Pyroptosis-Related Gene Panel for Predicting the Prognosis and Immune Microenvironment of Cervical Cancer.

Cervical cancer (CC) is one of the most common malignant tumors of the female reproductive system. And the immune system disorder in patients results in an increasing incidence rate and mortality rate. Pyroptosis is an immune system-related programmed cell death pathway that produces systemic inflammation by releasing pro-inflammatory intracellular components. However, the diagnostic significance of pyroptosis-related genes (PRGs) in CC is still unclear. Therefore, we identified 52 PRGs from the TCGA database and screened three Differentially Expressed Pyroptosis-Related Genes (DEPRGs) in the prognosis of cervical cancer: CHMP4C, GZMB, TNF. The least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate COX regression analysis were then used to construct a gene panel based on the three prognostic DEPRGs. The patients were divided into high-and low-risk groups based on the median risk score of the panel. According to the Kaplan-Meier curve, there was a substantial difference in survival rates between the two groups, with the high-risk group's survival rate being significantly lower than the low-risk group's. The PCA and t-SNE analyses revealed that the panel was able to differentiate patients into high-and low-risk groups. The area under the ROC curve (AUC) shows that the prognostic panel has high sensitivity and specificity. The risk score could then be employed as an independent prognostic factor using univariate and multivariate COX regression analyses paired with clinical data. The analyses of GO and KEGG functional enrichment of differentially expressed genes (DEGs) in the high-and low-risk groups revealed that these genes were primarily engaged in immune response and inflammatory cell chemotaxis. To illustrate immune cell infiltration in CC patients further, we used ssGSEA to compare immune-related cells and immune pathway activation between the high-and low-risk groups. The link between three prognostic DEPRGs and immune-related cells was still being discussed after evaluating immune cell infiltration in the TCGA cohort with "CIBERSORT." In addition, the GEPIA database and qRT-PCR analysis were used to verify the expression levels of prognostic DEPRGs. In conclusion, PRGs are critical in tumor immunity and can be utilized to predict the prognosis of CC.

EIF4A3-regulated circ_0087429 can reverse EMT and inhibit the progression of cervical cancer via miR-5003-3p-dependent upregulation of OGN expression.

BACKGROUND: Circular RNAs (circRNAs) are noncoding RNAs with stable structures with high expression and tissue-specific expression. Studies have shown that circRNA dysregulation is closely related to the progression of tumours. However, the function and regulatory mechanism of most circRNAs in cervical cancer are still unclear.   METHODS: CircRNAs related to cervical cancer were screened through the Gene Expression Omnibus (GEO) database. qRT-PCR was used to verify the expression of circ_0087429 in cervical cancer tissues and cells. Then, in vivo and in vitro experiments were conducted to evaluate the role of circ_0087429 in the progression of cervical cancer. The role of the circ_0087429/miR-5003-3p/osteoglycin (OGN) axis in the epithelial to mesenchymal transition (EMT) was confirmed by rescue experiments, fluorescence in situ hybridization, luciferase reporter assays, immunofluorescence staining and western blotting. The inhibitory effect of Eukaryotic initiation factor 4A-III (EIF4A3) on the biogenesis of circ_0087429 was verified by RNA immunoprecipitation (RIP) assays and qRT-PCR. RESULTS: circ_0087429 is significantly downregulated in cervical cancer tissues and cells and negatively correlated with International Federation of Gynecology and Obstetrics (FIGO) staging and lymphatic metastasis in cervical cancer patients. circ_0087429 can significantly inhibit the proliferation, migration, invasion and angiogenesis of cervical cancer in vitro and tumour growth and metastasis in vivo. OGN is significantly downregulated in cervical cancer tissues and cells. circ_0087429 can upregulate the expression of OGN by competitively binding with miR-5003-3p, thereby reversing EMT and inhibiting the progression of cervical cancer. EIF4A3 can inhibit circ_0087429 expression by binding to its flanking regions. CONCLUSIONS: As a tumour suppressor, circ_0087429 regulated by EIF4A3 can reverse EMT and inhibit the progression of cervical cancer through the miR-5003-3p/OGN axis. It is expected to become a potential target for the treatment of cervical cancer.

Overexpressed CMTM6 Improves Prognosis and Associated With Immune Infiltrates of Ovarian Cancer.

Ovarian cancer (OV) is an epithelial malignancy that intrigues people for its high mortality and lack of efficient treatment. Chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing 6 (CMTM6) can be observed in various cancers, but its part in OV remains little known. Hence, the prognostic value and underlying mechanism of CMTM6 in OV were preliminarily evaluated. Here, we determined that CMTM6 expression was higher than that in normal controls. However, the upregulation of CMTM6 was associated with better prognosis. GSEA results suggested that CMTM6 is involved in the immune-related and metabolism-related pathways. GO/KEGG analysis of CMTM6 coexpressed genes was performed to survey the possible regulatory roles of CMTM6 in OV. Subsequently, CMTM6 expression was positively correlated with the infiltration levels of immune cells and the expression of diverse immune cell marker sets. Importantly, CMTM6 may influence prognosis partially by regulating immune infiltration in OV. Last, copy number variations (CNVs) and DNA methylation might prompt the abnormal CMTM6 expression in OV. In conclusion, CMTM6 can serve as a novel prognostic biomarker in patients with OV.

YLZ-F5, a novel polo-like kinase 4 inhibitor, inhibits human ovarian cancer cell growth by inducing apoptosis and mitotic defects.

PURPOSE: Polo-like kinase 4 (PLK4), a member of the polo-like kinase family, plays several important roles in mitotic regulation, including centrosome duplication, spindle formation, and cytokinesis. PLK4 overexpression is frequently detected in many human cancers, including ovarian cancer, and the inhibition of PLK4 activity results in cancer cell mitotic arrest and apoptosis. Therefore, PLK4 might be a valid therapeutic target for antitumor therapy. In the present study, we aimed to determine if YLZ-F5, a potent small-molecule inhibitor of PLK4, inhibits ovarian cancer cell growth. METHODS AND RESULTS: MTT assay showed that YLZ-F5 inhibited ovarian cancer cell proliferation in a concentration- and time-dependent manner. The results of colony formation assays were consistent with those of the MTT assay results. In addition, YLZ-F5 induced ovarian cancer cell apoptosis that was associated with activation of caspase-3/caspase-9. Moreover, YLZ-F5 caused aberrant in centriole duplication that was associated with the inhibition of PLK4 phosphorylation. Notably, we showed that YLZ-F5 promoted the accumulation of ovarian cancer cells with mitotic defects (> 4 N DNA content) in a concentration-dependent manner. Furthermore, YLZ-F5 markedly inhibited the migration of A2780 cells. CONCLUSION: Taken together, these findings suggest that YLZ-F5 is a potential drug candidate for human ovarian cancer.

Long non-coding RNA FLJ33360 participates in ovarian cancer progression by sponging miR-30b-3p.

BACKGROUND: Long noncoding RNAs (lncRNAs) have been reported to play a key role in the development and progression of human malignancies. FLJ33360 is an lncRNA with unknown functions. This study was designed to determine the clinical significance and mechanism of FLJ33360 in ovarian cancer. MATERIALS AND METHODS: The clinical significance of FLJ33360 in ovarian cancer was determined using the Gene Expression Profiling Interactive Analysis (GEPIA) database, Kaplan-Meier Plotter database, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and statistical analysis. The regulatory relationships between FLJ33360 and miR-30b-3p were explored through bioinformatics, the Gene Expression Omnibus (GEO) database, the ArrayExpress database and meta-analysis. The possible pathways were predicted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In addition, the key target genes were identified using a protein-protein interaction (PPI) network, the Cancer Genome Atlas (TCGA) database, and correlation analysis. RESULTS: FLJ33360 expression was significantly downregulated in ovarian cancer tissue (P=0.0011) and was closely associated with International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.027) and recurrence (P=0.002). FLJ33360 may have potential value in detecting ovarian cancer (area under the curve =0.793). Function analysis demonstrated that FLJ33360 can act as a molecular sponge of miR-30b-3p to regulate the expression of target genes that are mainly involved in positive regulation of smooth muscle cell migration, the unsaturated fatty acid metabolic process, and positive regulation of the epithelial to mesenchymal transition. Among these target genes, BCL2 is the hub gene. CONCLUSION: FLJ33360 is a potential biomarker for early diagnosis and prognostic assessment in ovarian cancer and may regulate the expression of genes by sponging miR-30b-3p and thus participate in the development of ovarian cancer.

Clinical significance and oncogene function of long noncoding RNA HAGLROS overexpression in ovarian cancer.

PURPOSE: To explore the clinical significance and mechanism of long noncoding RNA (lncRNA) HAGLROS in ovarian cancer. METHODS: The expression of HAGLROS in ovarian cancer was verified by online databases and quantitative reverse transcription polymerase chain reaction (qRT-PCR), and its relationship with clinicopathological parameters was analysed. Pearson correlation analysis was used to study the correlation between HAGLROS and miR-100 in ovarian cancer. Meta-analysis was used to explore the expression of miR-100 in ovarian cancer. In addition, we used bioinformatics to explore the target genes of miR-100 and perform functional analysis. RESULTS: HAGLROS was significantly upregulated in ovarian cancer (P < 0.001) and was closely related to disease stage (P = 0.033), tumour size (P = 0.032) and poor prognosis (P = 0.019). HAGLROS had a certain diagnostic value in ovarian cancer (area under the curve = 0.751). MiR-100 was negatively correlated with HAGLROS (r = 0.167, P = 0.001) and significantly downregulated in ovarian cancer. Bioinformatics analysis predicted a total of 31 potential target genes that interact with miR-100. These target genes were mainly involved in the regulation of cellular catabolic process, proteoglycan biosynthetic process and positive regulation of proteasomal ubiquitin-dependent protein catabolic process. Among them, mTOR and ZNRF2 are hub genes. CONCLUSION: HAGLROS is a potential biomarker for early diagnosis and prognosis evaluation of ovarian cancer. It can be used as a molecular sponge of miR-100 to regulate the expression of mTOR and ZNRF2 and affect the signal transduction of the mTOR pathway. HAGLROS is expected to be a new target for the treatment of ovarian cancer.

Dexamethasone suppresses cochlear Hes1 expression after noise exposure.

CONCLUSION: Dexamethasone provides protection against noise-induced hearing loss (NIHL) possibly by suppressing cochlear Hes1 expression via a glucocorticoid receptor (GR)-dependent mechanism. OBJECTIVES: The purpose of the present study was to explore whether hairy and enhancer of split 1 (Hes1) was involved in the protective effect of dexamethasone against NIHL. METHODS: Guinea pigs, which were administered intraperitoneal injections of either saline, 1.0 mg/kg dexamethasone, 20.0 mg/kg RU38,486, or a combination of both drugs (dexamethasone plus RU38,486) for 5 consecutive days, were exposed to white-band noise (115 dB sound pressure level). The expression level of Hes1 in cochleae was compared using real-time RT-PCR and Western blot analysis. RESULTS: Noise exposure for 3 h induced auditory brainstem response (ABR) threshold elevations, outer hair cell losses, and increase of Hes1 expression. Dexamethasone pretreatment prevented the NIHL with decreased Hes1 expression, which could be blocked by GR antagonist RU38,486.

Up-regulation of cochlear Hes1 expression in response to noise exposure.

Hes1, a hairy and enhancer of split homolog, negatively regulates inner ear hair cell differentiation. The main objective of this study was to investigate the status of the Hes1 gene in the noise-damaged cochlea in relation to the degree of noise-induced hearing loss (NIHL). Adult albino guinea pigs were exposed to white-band noise (115 dB sound pressure level). Noise exposure for either 1 or 3 hours induced significant elevations of threshold in auditory brainstem response (ABR) compared with unexposed controls. Succinate dehydrogenase staining showed that white-band noise exposure caused significant outer hair cell losses. In addition, we found significant up-regulations of cochlear Hes1 mRNA and protein expressions following acoustic trauma, and Hes1 mRNA expression was positively correlated with NIHL. These findings suggest that up-regulation of Hes1 expression in response to noise exposure may be one of the underlying mechanisms of NIHL.

Intratympanic administration of methylprednisolone reduces impact of experimental intensive impulse noise trauma on hearing.

CONCLUSION: The present findings demonstrated that intratympanic methylprednisolone (MP) reduces the impact of impulse noise trauma on hearing and in part preserves the hair cells from death 1 h after exposure to intensive impulse noise. OBJECTIVE: To examine the treatment efficiency of intratympanic MP (IT-MP) with different methods of administration on cochlear injury induced by exposure to intensive impulse noise. MATERIALS AND METHODS: Fifty-five guinea pigs were assigned into six groups and exposed to intensive impulse noise, i.e. 60 impulses at 165 dB SPL peak pressure with 0.5 ms duration and 2 s intervals. The auditory brainstem response (ABR) was used to examine the hearing thresholds. Cochlear morphology was examined to estimate the inner and outer hair cell loss induced by impulse noise exposure. MP was applied as a rescue agent via different modalities of administration. RESULTS: The ABR threshold value of IT-MP1 or IT-MP4 groups significantly decreased at 4 weeks as compared with the IT-NS (IT 0.9% physiological saline) group. The ABR threshold value of the group that received intramuscular administration of MP (IM-MP) also decreased at 4 weeks as compared with the IT-NS group. Significant hair cell loss was observed at the region 40-50% from the apex in the present model. Within this region, the residual hair cell number in the IT-MP1 or IT-MP4 groups was significantly greater than that in the IT-NS group.

Application of serum protein fingerprinting coupled with artificial neural network model in diagnosis of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma tends to present at a late clinical stage with poor prognosis. Therefore, it is urgent to explore and develop a simple, rapid diagnostic method, which has high sensitivity and specificity for hepatocellular carcinoma at an early stage. In this study, the serum proteins in patients with hepatocellular carcinoma or liver cirrhosis and in normal controls were analysed. Surface enhanced laser desorption/ionization time-of-flight mass (SELDI-TOF-MS) spectrometry was used to fingerprint serum protein using the protein chip technique and explore the value of the fingerprint, coupled with artificial neural network, to diagnose hepatocellular carcinoma. METHODS: Of the 106 serum samples obtained, 52 were from patients with hepatocellular carcinoma, 22 from patients with liver cirrhosis and 32 from healthy volunteers. The samples were randomly assigned into a training group (n = 70, 35 patients with hepatocellular carcinoma, 14 with liver cirrhosis, and 21 normal controls) and a testing group (n = 36, 17 patients with hepatocellular carcinoma, 8 with liver cirrhosis, and 11 normal controls). An artificial neural network was trained on data from 70 individuals in the training group to develop an artificial neural network diagnostic model and this model was tested. The 36 sera in the testing group were analysed with blind prediction by using the same flowchart and procedure of data collection. The 36 serum protein spectra were clustered with the preset clustering method and the same mass/charge (M/Z) peak values as those in the training group. Matrix transfer was performed after data were output. Then the data were input into the previously built artificial neural network model to get the prediction value. The M/Z peaks of the samples with more than 2000 M/Z were normalized with biomarker wizard of ProteinChip Software version 3.1 for noise filtering. The first threshold for noise filtering was set at 5, and the second was set at 2. The 10% was the minimum threshold for clustering. The statistical analysis of the data of serum protein mass spectrum was performed in the groups (normal vs. hepatocellular carcinoma, and liver cirrhosis vs. hepatocellular carcinoma) with the t test. RESULTS: Comparison between the groups of hepatocellular carcinoma and normal control: The mass spectra from 56 samples (hepatocellular carcinoma and normal controls) in the training group were analysed and 241 peaks were obtained. In addition, 21 peaks from them were used for comparison between the groups of hepatocellular carcinoma and normal controls (P < 0.01). Only 2 peaks at 3015 M/Z and 5900 M/Z were selected with significant difference (P < 10 (-9)). A model was developed based on these two proteins with different M/Z. It was confirmed that this artificial neural network model can be used for comparison between the groups of hepatocellular carcinoma and normal controls. The sensitivity was 100% (17/17), and the specificity was 100% (11/11). Comparison between the groups of hepatocellular carcinoma and liver cirrhosis: The mass spectra from 49 samples in the training group (including patients with hepatocellular carcinoma and liver cirrhosis) were analysed and 208 peaks were obtained. In addition, 21 peaks from them were used for comparison between the groups of hepatocellular carcinoma and liver cirrhosis (P < 0.01). Only 2 peaks at 7759 M/Z, 13134 M/Z were selected with significant difference (P < 10 (-9)). A model was developed based on these two proteins with different M/Z. It was confirmed that this artificial neural network model can be used for comparison between the groups of hepatocellular carcinoma and liver cirrhosis. The sensitivity was 88.2% (15/17), and the specificity was 100% (8/8). CONCLUSIONS: The specific biomarkers selected with the SELDI technology could be used for early diagnosis of hepatocellular carcinoma.

[Using ANN and serum protein pattern models in liver cancer diagnosis].

OBJECTIVE: To set up a method for the detection of the serum protein fingerprint pattern by using the protein chip technology for exploration of serum protein fingerprint pattern models based on the artificial neural network in diagnosis of liver cancer. METHODS: One hundred and six serum samples form subjects with liver cancer, hepatocirrhosis, and healthy individuals were detected with protein biochip surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) for protein fingerprint pattern, and analyzed with the artificial neural network. The 106 samples were randomly put into a training group (n = 70, 35 patients with liver cancer, 14 patients with hepatocirrhosis, and 21 healthy individuals) and a blind test group (n = 36, 17 patients with liver cancer, 8 patients with hepatocirrhosis, and 11 healthy individuals). RESULTS: The serum protein fingerprint pattern model obtained by the artificial neural network from training group was used to detect the 36 unknown serum samples. The sensitivity and specificity of this method in detection of liver cancer were 88.2% (15/17) and 94.6% (18/19) respectively. CONCLUSION: In comparison with the traditional methods, this new method has higher sensitivity and specificity in diagnosis of liver cancer and should be further studied.