Characterization of Extended-Spectrum ß-Lactamase-Producing Escherichia coli in Animal Farms in Hunan Province, China.

Multi-drug resistance of bacteria producing extended-spectrum ß-lactamase (ESBL) is a public health challenge. Thus, this study aimed to investigate the antimicrobial susceptibility of ESBL-producing Escherichia coli (ESBL-EC) in Hunan Province, China. A total of 1366 fecal samples were collected from pig, chicken, and cattle farms over a six-year period, which were assessed using strain isolation, 16S rRNA identification, polymerase chain reaction, drug sensitivity testing, whole-genome sequencing, and bioinformatics analysis. The results showed an overall prevalence of 6.66% for ESBL-EC strains, with ESBL positivity extents for pigs, chickens, and cattle isolates at 6.77%, 6.54%, and 12.5%, respectively. Most ESBL-EC isolates were resistant to cefotaxime, tetracycline, and trimethoprim-sulfamethoxazole; however, all the isolates were susceptible to meropenem, with relatively low resistance to amikacin and tigecycline. Various multi-locus sequence types with different origins and similar affinities were identified, with ST155 (n = 16) being the most common subtype. Several types of resistance genes were identified among the 91 positive strains, with beta-lactamase blaCTX-M-55 being the most common ESBL genotype. IncFIB was the predominant plasmid type. Widespread use of antibiotics in animal farming may increase antibiotic resistance, posing a serious threat to the health of farmed animals and, thus, to human food security and health.

A long-term retrospective analysis of management of cervical cancer during pregnancy.

OBJECTIVE: This study aims to describe cervical cancer during pregnancy (CCP) and investigate factors associated with survival outcomes. METHODS: This retrospective matched study included CCP patients from May 2007 to August 2021 and matched non-pregnant cervical cancer patients (1:2) based on age (±5 years), year at diagnosis (±2 years), histological type and stage (2018 FIGO). The Kaplan-Meier method and multivariate Cox regression analyses were used to assess the impact of pregnancy and clinicopathologic factors on prognosis. RESULTS: Thirty-eight CCP patients (stage IA to IIIC) and 76 non-pregnant patients were included. Most CCP patients were diagnosed in the first (31.6%) or second (47.4%) trimester. CCP patients had a longer waiting time than non-pregnant patients. Pregnancy continued in 42.1% (continuation of pregnancy [COP] group) and was terminated in 57.9% (termination of pregnancy [TOP] group) of patients. Survival analysis showed no significant differences in recurrence-free survival (RFS) or overall survival (OS) between pregnant and non-pregnant patients or between the COP and TOP groups. At the end of the follow-up period (range 12-178 months), 23 children born to CCP patients exhibited normal development. CONCLUSION: Pregnancy does not impact cervical cancer prognosis. The oncologic outcomes of the TOP and COP groups were comparable. A pregnancy-preserving strategy could be considered for managing CCP patients.

Zeaamine, a new amine from roots of Zea mays and its cytotoxic activity against CT26 and SW480 cell lines.

A new amine, zeaamine (1), along with nine known compounds (2-10), were isolated from the roots of Zea mays. Among these, compound 2 was first isolated from this plant, and compound 3 was first isolated from the roots. In the current investigation, the cytotoxicity against CT26 and SW480 cells of the compounds were evaluated. Zeaamine (1) exhibited moderately affected CT26 and SW480 cells with IC50 values of 17.91 and 10.21 µM.

Overexpression of TMEM150A in glioblastoma multiforme patients correlated with dismal prognoses and compromised immune statuses.

Transmembrane proteins have exhibited a significant correlation with glioblastoma multiforme (GBM). The current study elucidates the roles of transmembrane protein 150A (TMEM150A) in GBM. Data on patients with GBM were collected from The Cancer Genome Atlas and Xena databases. The objective was to identify the expression levels of TMEM150A in patients with GBM, and evaluate its diagnostic and prognostic values, accomplished using the receiver operating characteristic and survival analyses. On a cellular level, Cell Counting Kit-8, Wound healing, and Transwell experiments were performed to gauge the impact of TMEM150A on cell growth and migration. The study further investigated the correlation between TMEM150A expression and immune status, along with ribonucleic acid (RNA) modifications in GBM. The findings demonstrated TMEM150A overexpression in the cancerous tissues of patients with GBM, with an area under the curve value of 0.95. TMEM150A overexpression was significantly correlated with poor prognostic indicators. TMEM150A overexpression and isocitrate dehydrogenase (IDH) mutation status were predictive of poor survival time among patients with GBM. In vitro experiments indicated that suppressing TMEM150A expression could inhibit GBM cell proliferation, migration, and invasion. Moreover, TMEM150A overexpression was associated with stromal, immune, and estimate scores, immune cells (such as the T helper (Th) 17 cells, Th2 cells, and regulatory T cells), cell markers, and RNA modifications. Therefore, TMEM150A overexpression might serve as a promising biomarker for predicting poor prognosis in patients with GBM. Inhibiting TMEM150A expression holds the potential for improving the survival time of patients with GBM.

Roots of Zea mays L.: As a Potential Source to Treat Sodium Oxalate-Induced Renal Cell Injury.

Zea mays L. is an annual grass of the Gramineae family and is known as one of the cereal crops. Its by-products exhibited significant medicinal properties. In some regions of China, water extracts of Z. mays roots (RM) are utilized to treat kidney stones, but no research has been reported. In our present study, a bioassay-guided isolation method was used to yield five new lignans (1-5) as well as 15 known components, among which 8-15 and 17-20 were first identified from the genus. The fractions and all components were evaluated for their abilities to inhibit sodium oxalate-induced injury to human proximal tubular HK-2 cells. Fraction 50W and compounds 3, 4, and 11 exhibited the most potent activities. Further investigation indicated that these potential agents inhibited the LDH release, decreased the MDA and H2O2 concentrations, and increased the level of SOD2 in HK-2 cells. These results indicated that RM is a promising and valuable crop waste for further development and utilization in nephrolithiasis pharmaceutical research.

Two New Alkaloids from Roots of Zea mays and Their Cytotoxic Activity against Hep3B and SW480 Cells.

Two undescribed alkaloids, along with seven known compounds, were isolated from the roots of Zea mays (RM). Their chemical structures were elucidated based on extensive analyses of HR-ESI-MS, 1D and 2D NMR, and CD spectra. Two new alkaloids exhibited moderate inhibition of Hep3B (IC50 values of 11.7±2.4 and 14.2±3.6 µM) and SW480 cells (IC50 values of 33.4±8.2 and 47.3±5.8 µM) compared to that of the positive control compound, Oxaliplatin, IC50 value of 8.4±1.7 and 45.8±5.6 µM, respectively.

HLA-DPA1 overexpression inhibits cancer progression, reduces resistance to cisplatin, and correlates with increased immune infiltration in lung adenocarcinoma.

PURPOSE: Human Leukocyte Antigen-DP alpha 1 (HLA-DPA1) is a critical gene in antigen-presenting cells and plays a significant role in immune regulation. The objective of this study was to comprehensively analyze the roles of HLA-DPA1 and its association with lung adenocarcinoma (LUAD). METHODS: We utilized bioinformatics and conducted a meta-analysis to examine the roles of HLA-DPA1 expression on the progression and immunity of LUAD. We also performed CCK-8, wound healing, and Transwell assays to validate the functions of HLA-DPA1 in LUAD. RESULTS: HLA-DPA1 expression is downregulated in LUAD tissues and is associated with gender, race, age, smoking history, clinical stage, histological type, lymph node metastasis, and prognosis of patients with LUAD. HLA-DPA1 is involved in immune responses, leukocyte cell-cell adhesion, and antigen processing and presentation. Overexpression of HLA-DPA1 inhibits cancer cell proliferation, migration, and invasion while promoting cell sensitivity to cisplatin in A549 and A549/DDP cells. Additionally, overexpression of HLA-DPA1 correlates with tumor purity, stromal, immune, and ESTIMATE scores, the abundance of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, dendritic cells, and neutrophils), and immune cell markers (programmed cell death 1, cytotoxic T-lymphocyte-associated protein 4, and cluster of differentiation 8A). CONCLUSIONS: Decreased HLA-DPA1 expression is associated with poor prognosis and immune infiltration in LUAD while HLA-DPA1 overexpression inhibits cancer cell proliferation and progression. Therefore, HLA-DPA1 shows potential as a prognostic biomarker and a therapeutic target for LUAD.

Simultaneous DHA and organic selenium production by Schizochytrium sp.: a theoretical basis.

Docosahexaenoic acid (DHA) and selenium (Se) are nutrients that confer several health benefits to both humans and animals. Widespread use of DHA in milk powder and health products requires large-scale mass production via Schizochytrium sp., while Se intended for human consumption is produced as organic Se via yeast. However, producing these nutrients on an industrial scale is constrained by various factors. We found that supplementing Schizochytrium sp. with Na2SeO3 (0.5 mg/L) improves its biomass and DHA production and also provides organic Se. De novo assembled transcriptome and biochemical indicators showed that Na2SeO3 promotes forming acetyl coenzyme A and L-cysteine via the glycerol kinase and cysteine synthase pathways, promoting DHA synthesis through the polyketide synthase pathway. However, high doses of Na2SeO3 (5 mg/L) limited the biomass of Schizochytrium sp. and DHA content. This study provided a theoretical basis for the simultaneous production of organic Se and DHA via Schizochytrium sp.

Machine learning developed a programmed cell death signature for predicting prognosis and immunotherapy benefits in lung adenocarcinoma.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide with poor prognosis. Programmed cell death (PCD) plays a crucial function in tumor progression and immunotherapy response in lung adenocarcinoma (LUAD). METHODS: Integrative machine learning procedure including 10 methods was performed to develop a prognostic cell death signature (CDS) using TCGA, GSE30129, GSE31210, GSE37745, GSE42127, GSE50081, GSE68467, GSE68571, and GSE72094 dataset. The correlation between CDS and tumor immune microenvironment was evaluated using various methods and single cell analysis. qRT-PCR and CCK-8 assay were conducted to explore the biological functions of hub gene. RESULTS: The prognostic CDS developed by Lasso + survivalSVM method was regarded as the optimal prognostic model. The CDS had a stable and powerful performance in predicting the clinical outcome of LUAD and served as an independent risk factor in TCGA and 8 GEO datasets. The C-index of CDS was higher than that of clinical stage and many developed signatures for LUAD. LUAD patients with low CDS score had a higher PD1&CTLA4 immunophenoscore, higher TMB score, lower TIDE score and lower tumor escape score, indicating a better immunotherapy benefit. Single cell analysis revealed a strong and frequent communication between epithelial cells and cancer-related fibroblasts by specific ligand-receptor pairs, including COL1A2-SDC4 and COL1A2-SDC1. Vitro experiment showed that SLC7A5 was upregulated in LUAD and knockdown of SLC7A5 obviously suppressed tumor cell proliferation. CONCLUSION: Our study developed a novel CDS for LUAD. The CDS served as an indicator for predicting the prognosis and immunotherapy benefits of LAUD patients.

TMEM41A overexpression correlates with poor prognosis and immune alterations in patients with endometrial carcinoma.

BACKGROUND: Expression levels of transmembrane protein 41A (TMEM41A) are related to the progression of malignant tumors. However, the association between TMEM41A expression and endometrial carcinoma (EC) remains unclear. This study aims to identify the roles of TMEM41A expression in the prognosis of patients with EC and its correlation with EC progression. METHODS: The TMEM41A expression and its correlation with the survival of patients with EC were assessed. Cox regression analysis was used to identify the prognostic factors, while nomograms were used to examine the association between the prognostic factors and the survival of patients with EC. Finally, the link between TMEM41A level and immune microenvironment and RNA modifications was investigated in EC. RESULTS: TMEM41A was overexpressed in EC. TMEM41A overexpression could diagnose the EC and evaluate the poor prognosis of patients. Overexpression of TMEM41A was associated with clinical stage, age, weight, histological subtype, tumor grade, and survival status of patients with EC. Clinical stage, age, tumor grade, radiotherapy, and TMEM41A overexpression were factors of poor prognosis in patients with EC. The nomograms revealed the correlation between the TMEM41A level and survival time of patients with EC at 1, 3, and 5 years. Furthermore, TMEM41A overexpression was significantly correlated with the level of the stromal score, immune score, estimate score, NK CD56 bright cells, iDC, NK cells, eosinophils, pDC, T cells, TReg, cytotoxic cells, mast cells, Th17 cells, neutrophils, aDC, NK CD56 dim cells, TFH, Th2 cells, CD8 T cells, macrophages, immune cell markers, and RNA modifications. CONCLUSIONS: TMEM41A is overexpressed in EC tissues and is associated with the prognosis, immune microenvironment, and RNA modification. Our preliminary studies indicate that overexpression of TMEM41A can potentially serve as a biomarker for EC treatment.

Impacts of ovarian preservation on the prognosis of neuroendocrine cervical carcinoma: a retrospective analysis based on machine learning.

BACKGROUND: Neuroendocrine cervical carcinoma (NECC) is a rare but aggressive malignancy with younger patients compared to other common histology types. This study aimed to evaluate the impacts of ovarian preservation (OP) on the prognosis of NECC through machine learning. METHODS: Between 2013 and 2021, 116 NECC patients with a median age of 46 years received OP or bilateral salpingo-oophorectomy (BSO) and were enrolled in a retrospective analysis with a median follow-up of 41 months. The prognosis was estimated using Kaplan-Meier analysis. Random forest, LASSO, stepwise, and optimum subset prognostic models were constructed in training cohort (randomly selected 70 patients) and tested in 46 patients through receiver operator curves. Risk factors for ovarian metastasis were identified through univariate and multivariate regression analyses. All data processing was carried out in R 4.2.0 software. RESULTS: Among 116 patients, 30 (25.9%) received OP and showed no significantly different OS compared with BSO group (p = 0.072) and got better DFS (p = 0.038). After construction of machine learning models, the safety of OP was validated in lower prognostic risk group (p > 0.05). In patients ≤ 46 years, no impacts of OP were shown for DFS (p = 0.58) or OS (p = 0.67), and OP had no impact on DFS in different relapse risk population (p > 0.05). In BSO group, regression analyses showed that later stage, para-aortic LNM, and parametrial involvement were associated with ovarian metastasis (p < 0.05). CONCLUSIONS: Preserving ovaries had no significant impact on prognosis in patients with NECC. OP should be considered cautiously in patients with ovarian metastasis risk factors.

By-Products of Zea mays L.: A Promising Source of Medicinal Properties with Phytochemistry and Pharmacological Activities: A Comprehensive Review.

Zea mays (Z. mays) is one of the main cereal crops in the world, and it's by-products have exhibited medicinal properties to explore. This article intends to review the chemical compositions and pharmacological activities of by-products of Z. mays (corn silks, roots, bract, stems, bran, and leaves) which support the therapeutic potential in the treatment of different diseases, with emphasis on the natural occurring compounds and detailed pharmacological developments. Based on this review, 231 natural compounds are presented. Among them, flavonoids, terpenes, phenylpropanoids, and alkaloids are the most frequently reported. The by-products of Z. mays possess diuretic effects, hepatoprotective, anti-diabetic, antioxidant, neuroprotective, anti-inflammatory, anti-cancer, plant protection activity, and other activities. This article reviewed the phytochemistry and pharmacological activities of Z. mays for comprehensive quality control and the safety and effectiveness to enhance future application.

Verniciflavanol A, a profisetinidin-type-4-arylflavan-3-ol from toxicodendron vernicifluum protects SH-SY5Y cells against H2O2-Induced oxidative stress.

Eleven undescribed derivatives of flavan, including flavan-3,4-diols vernicinosides A-H and profisetinidin-type-4-arylflavan-3-ols verniciflavanols A-C, together with eight known compounds were purified from the heartwood of Toxicodendron vernicifluum. The chemical structures of the undescribed compounds were characterized by spectroscopic data interpretation, including NMR (1H and 13C NMR HSQC and HMBC) and HRESIMS analysis. CD data analysis was conducted to assign the absolute configurations of the undescribed compounds and the active compound verniciflavanol A was also confirmed by ECD experiment. The absolute configuration of the sugar moiety was identified by GC analysis of chiral derivatives in the hydrolysate. MTT assay was applied to test these compounds against H2O2-induced oxidative stress in human neuroblastoma SH-SY5Y cells. Results found that verniciflavanol A demonstrated the best potential in protecting SH-SY5Y cells against H2O2-induced oxidative stress by inhibiting cell apoptosis and attenuate reactive oxygen species (ROS) level and mitochondrial dysfunction. And the underlying mechanism was confirmed to be associated with Nrf2-antioxidant response element signaling and IL-6 cell survival pathways.

[Short-term effect of HeartCon left ventricular assist device on the treatment of 20 adult patients with end-stage heart failure].

OBJECTIVE: To investigate and evaluate the efficacy of HeartCon left ventricular assist device (LVAD) in the treatment of adult patients with end-stage heart failure (ESHF). METHODS: A prospective and observational study was conducted. Patients with ESHF who underwent LVAD implantation in the department of cardiac surgery of Teda International Cardiovascular Hospital from September 2020 to August 2021 were selected. The left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) classification, N-terminal pro-B type natriuretic peptide (NT-proBNP), and six minute walk distance (6MWD) before operation and 90 days after operation were compared. The incidence of equipment failures and major adverse events within 90 days after operation were recorded. RESULTS: A total of 20 patients with ESHF were included, with 15 males and 5 females. Patients' age ranged from 20 to 67 years old, with an average of (50.2±13.6) years old. The range of body weight was 49.8-106.1 kg, with an average of (67.9±15.5) kg, and the body surface area (BSA) was from 1.49 to 2.32 m2, with an average of (17.6±0.22) m2. The operation process of all the patients were successful. The length of hospital stay ranged from 33 to 90 days, and the average was 56.0 (42.8, 75.0) days. Complications within 90 days after operation as follows, 2 cases with pericardial tamponade (10%), 1 case with cerebral hemorrhage (5%), 1 case with mediastinum infection (5%), 3 cases with acute renal injury (AKI, 15%), 5 cases with gastrointestinal bleeding (25%). There were no mechanical failure of LVAD and hemolysis events, right ventricular failure (RVF), cerebral infarction and death occurred. Compared with preoperative, the LVEDD significantly decreased (mm: 67.50±13.98 vs. 77.40±9.73), LVEF significantly increased (%: 34.80±9.76 vs. 22.70±5.62), NT-proBNP significantly decreased (ng/L: 2 028.65±1 752.05 vs. 4 796.45±4 355.40), 6MWD significantly increased (m: 385.20±144.12 vs. 85.81±63.50) at 90 days after operation, and the differences were statistically significant (all P < 0.05). 18 cases (90%) of the 20 patients reached NYHA classification I and 2 cases (10%) reached NYHA classification II, which were significantly improved compared with those before surgery (all patients' NYHA classification were IV before surgery). CONCLUSIONS: HeartCon LVAD can effectively improve the life quality of patients with ESHF, which has been proved safe and effective in clinical trials, but its long-term effects and complications need further observation and study.

A New Risk Model Based on 7 Quercetin-Related Target Genes for Predicting the Prognosis of Patients With Lung Adenocarcinoma.

Background: Studies have reported that quercetin inhibits the growth and migration of lung adenocarcinoma (LUAD). This study aimed to explore the roles and mechanisms of quercetin target genes in the progression of LUAD. Methods: The quercetin structure and potential target genes of quercetin were explored in the Traditional Chinese Medicine Systems Pharmacology and SwissTargetPrediction databases. The differentially expressed quercetin target genes were identified in The Cancer Genome Atlas (TCGA) database, and the clinical values of quercetin target genes were explored. Subsequently, a risk model was constructed via the Cox regression and survival analysis to evaluate the potential effects and possible mechanisms of quercetin target genes. Results: The quercetin differential target genes involved in biological processes such as the oxidation-reduction process, cell proliferation, G2/M transition of the mitotic cell cycle, and were related to the lung cancer. NEK2, TOP2A, PLK1, CA4, CDK5R1, AURKB, and F2 were related to the prognosis, and were independent factors influencing the prognosis of LUAD patients. The risk model was related to the gender, clinical stage, T stage, lymph node metastasis, and survival status of LUAD patients, and was independent risk factor associated with poor prognosis. In the high-risk group, the risk model involved signaling pathways such as cell cycle, DNA replication, spliceosome, and homologous recombination. Conclusion: The quercetin potential target genes NEK2, TOP2A, PLK1, CA4, CDK5R1, AURKB, and F2 were related to the diagnosis and prognosis of LUAD patients. A risk model based on 7 quercetin target genes could be used to assess the prognosis of patients with LUAD.

MiR-30a-3p Suppresses the Growth and Development of Lung Adenocarcinoma Cells Through Modulating GOLM1/JAK-STAT Signaling.

A considerable amount of people succumbs to lung adenocarcinoma (LUAD) due to its high incidence and mortality. This study attempted to reveal the impacts of GOLM1 on LUAD. This work analyzed GOLM1 expression in LUAD and normal tissue and studied its prognostic value utilizing data from The Cancer Genome Atlas. RNA and protein levels were, respectively, determined utilizing qRT-PCR and western blot. Cell-aggressive behaviors were assessed employing Cell Counting Kit-8, scratch healing, and Transwell assays. The targetting relationship between GOLM1 and miR-30a-3p was assayed by dual-luciferase method. GOLM1 up-regulation in LUAD was found in TCGA and it was also a negative factor for survival in patients. GOLM1 overexpression promoted cell progression in LUAD. Down-regulated miR-30a-3p in LUAD was an upstream regulatory miRNA of GOLM1 in terms of molecular mechanism. Further, rescue assays illustrated that miR-30a-3p overexpression attenuated the GOLM1 facilitating impacts on LUAD progression. Finally, we proved that miR-30a-3p/GOLM1 regulated progression of LUAD cells via JAK-STAT pathway. Collectively, the inhibitory impacts of miR-30a-3p on LUAD growth may be mediated by GOLM1/JAK-STAT, which may contribute to the diagnosis of LUAD therapy and the development of therapeutic tools.

A comprehensive review on ethnobotanical, phytochemical and pharmacological aspects of Rhus chinensis Mill.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhus chinensis Mill., firstly recorded as herbal medicine in Shan Hai Jing, have been used for thousands of years to treat various diseases. AIM OF THIS REVIEW: This review targets on the ethnomedicinal applications of R. chinensis and to gather the phytochemical, pharmacological and toxicological data which support the therapeutic potential of R. chinensis in treatment on different diseases, with emphasis on the naturally occurring compounds and detailed pharmacological developments. MATERIALS AND METHODS: The information of R. chinensis was collected based on a variety of popular databases such as Scifinder, PubMed, Web of Science, ScienceDirect, Springer, Wiley, ACS, CNKI, Baidu Scholar, Google Scholar and other published materials (books and Ph.D. and M. Sc. Dissertations). The keywords "Rhus chinensis", "Rhus amela", "Rhus javanica", "Rhus osbeckii", "Rhus semialata", and "Schinus indicus" were applied to search the literature related in this review. RESULTS: 152 natural compounds of R. chinensis belong to different classes are presented in this review, including flavonoids, lignans, coumarins, simple phenolics, urushiols, tannins, triterpenoids, steroids and other types of constituents. Among them, flavonoids, lignans, and triterpenoids are most frequently reported components. The pharmacological effects of R. chinensis were numerous and complicated, including anti-viral, anti-bacterial, anti-diarrheal, hepatoprotective, anti-proliferation, enzyme-inhibiting, anti-oxidants and so on. CONCLUSION: In order to discover more compounds with novel structures to both enrich chemical context of genus Rhus and expand the variety of constituents, the phytochemical research is urgent and indispensable. Anti-diarrhea, the most widely application of R. chinensis traditionally, is insufficient in underlying mechanism exploration. And for other activities, in-depth studies on the mechanism of pharmacological effects in vivo and in vitro are both needed. Meanwhile, pharmacokinetics, toxicology, quality control and preclinical and clinical data are urgent to assess the rationale and safety of the medicinal and food application of R. chinensis.

Ubiquitin C-terminal hydrolase L1 promotes lymph node metastasis in small cell neuroendocrine carcinomas of the cervix.

OBJECTIVE: To screen for specific differentially expressed genes in small cell neuroendocrine carcinoma of the cervix (SCNEC) and to further explore their roles and mechanisms in tumor progression. METHODS: Differentially expressed genes in SCNEC compared with squamous cell carcinoma (SCC) and adenocarcinoma (AC) were screened by microarray and immunohistochemical analyses. The biological functions of the identified genes were examined in a SCNEC cell line using RNA interference and over-expression plasmid-transfection technologies. Co-expression network analysis and immunoprecipitation technology were used to explore the potential mechanisms. RESULTS: Compared with SCC and AC, UCHL1 (encoding ubiquitin C-terminal hydrolase L1) was identified as a specific differentially expressed gene in SCNEC, which was positively related to lymph node metastasis (LNM). Migration and invasion of SCNEC tumor cells were induced by UCHL1 over-expression and suppressed by UCHL1 down-regulation, as shown by scratch and transwell invasion assays. Co-expression network analysis suggested that Prospero homeobox protein 1 (PROX1) might interact with UCHL1, and in vivo immunoprecipitation and western blots verified that levels of ubiquitinated PROX1 were significantly decreased following UCHL1 overexpression. CONCLUSION: UCHL1 is a potential biomarker of LNM in SCNEC. UCHL1 might promote SCNEC cell migration and invasion by reducing PROX1 ubiquitination.

The value of erlotinib related target molecules in kidney renal cell carcinoma via bioinformatics analysis.

OBJECTIVE: Erlotinib was found to be an effective treatment for metastatic kidney renal cell carcinoma (KIRC). This study employed bioinformatics to explore the value of erlotinib's target molecules in KIRC. METHODS: We screened GSE25698 dataset for differentially expressed genes (DEGs) following erlotinib treatment, followed by analyzing their underlying functional mechanisms. The value of DEGs was identified in TCGA database to construct risk model and nomogram, and possible mechanisms underlying model factors and their relationship with KIRC immune infiltration were analyzed. RESULTS: Following erlotinib treatment, DEGs were involved in antigen binding, myeloid leukocyte activation, JAK-STAT signaling pathway, etc. COL11A1, EMCN, GLYATL1, HHLA2, IGFN1, LIPA, LRRC19, PANK1, PRAME, and TNFSF14 were independent factors influencing poor prognosis in KIRC patients. Age, grade, and risk score were independent risk factors influencing poor prognosis of KIRC patients. The risk score was associated with immune cells such as T cells regulatory, T cells follicular helper, macrophages M0, etc., and participated signaling mechanisms such as ERBB, insulin, mTOR, PPAR, apoptosis, MAPK, T cell receptor, etc. CONCLUSIONS: The expression levels of COL11A1, EMCN, GLYATL1, HHLA2, IGFN1 LIPA, LRRC19, PANK1, PRAME, and TNFSF14 were associated with KIRC prognosis and immune cell infiltration. The risk model and nomogram based on erlotinib's target molecules were expected to be a tool for evaluating the prognosis of KIRC patients.

Data from small cell neuroendocrine carcinoma of the cervix: FIGO 2018 staging is more accurate than FIGO 2009.

OBJECTIVE: To compare the prognostic value of International Federation of Gynecology and Obstetrics (FIGO) 2009 and 2018 staging systems in surgical patients with small cell neuroendocrine carcinoma of the cervix (SCNEC). METHODS: We re-staged 64 surgical IB-IIA (FIGO 2009) SCNEC patients according to the FIGO 2018 system and refined stage IIIC of FIGO 2018 based on tumor local invasion. The prognostic factors were analyzed, and the advantages of FIGO 2018 were compared with 2009. RESULTS: The 5-year overall survival rate (OS) was 78.5% for stage I and 22.2% for stage II (FIGO 2009). In FIGO 2018, there was no difference between stage I and II, and the 5-year OS was 74.1%, 60.2%, and 0% for stage I/II, IIIC1, and IIIC2. After combining stage IIIC with the local invasion stage (T1 was limited to the cervix and vagina; T2 involved the parametrium; T3 involved the pelvic or abdominal cavity), the 5-year OS for stage IIICT1, IIICT2, and IIICT3 was 83.3%, 30.0%, and 0%, respectively. CONCLUSIONS: For stage II SCNEC patients, FIGO 2009 underestimated the prognosis, while FIGO 2018 was more accurate. For stage IIIC, FIGO 2018 might be more individualized and accurate after combining stage IIIC with tumor local invasion.