Corrigendum: Study of quality of life and its correlated factors in patients after lumbar fusion for lumbar degenerative disc disease.

[This corrects the article DOI: 10.3389/fsurg.2022.939591.].

Trilobolide-6-O-isobutyrate exerts anti-tumor effects on cholangiocarcinoma cells through inhibiting JAK/STAT3 signaling pathway.

Trilobolide-6-O-isobutyrate exhibits significant antitumor effects on cholangiocarcinoma (CCA) cells by effectively inhibiting the JAK/STAT3 signaling pathway. This study aims to investigate the mechanisms underlying the antitumor properties of trilobolide-6-O-isobutyrate, and to explore its potential as a therapeutic agent for CCA. This study illustrates that trilobolide-6-O-isobutyrate efficiently suppresses CCA cell proliferation in a dose- and time-dependent manner. Furthermore, trilobolide-6-O-isobutyrate stimulates the production of reactive oxygen species, leading to oxidative stress and initiation of apoptosis via the activation of the mitochondrial pathway. Data from xenograft tumor assays in nude mice confirms that TBB inhibits tumor growth, and that there are no obvious toxic effects or side effects in vivo. Mechanistically, trilobolide-6-O-isobutyrate exerts antitumor effects by inhibiting STAT3 transcriptional activation, reducing PCNA and Bcl-2 expression, and increasing P21 expression. These findings emphasizes the potential of trilobolide-6-O-isobutyrate as a promising therapeutic candidate for the treatment of CCA.

Downregulation of dermatopontin in cholangiocarcinoma cells suppresses CCL19 secretion of macrophages and immune infiltration.

OBJECTIVE: The tumor microenvironment (TME) in cholangiocarcinoma (CHOL) is typically characterized by a low level of immune infiltration, which accounts for the dismal prognosis of this patient population. This study sought to investigate the mechanisms underlying the reduced infiltration of immune cells into the CHOL TME. METHODS: We constructed a Least Absolute Shrinkage and Selection Operator (LASSO) regression model to identify prognosis-related differentially expressed genes (DEGs). The 'Corrplot' package was employed to analyze the correlation between dermatopontin (DPT) and immune infiltration in CHOL. The Tumor and Immune System Interaction Database (TISIDB) was used to evaluate the association between DPT and immunology. Single-cell analysis was conducted to localize CCL19 secretions. Western blot and qPCR were utilized to detect DPT expression, while immunofluorescence was performed to investigate the cellular localization of DPT. Additionally, ELISA analysis was employed to assess the alteration in CCL19 secretion in cancer-associated fibroblasts (CAFs) and macrophages. RESULTS: Our findings revealed that CHOL patients with low DPT expression had a poorer prognosis. Enrichment analysis demonstrated a positive correlation between DPT levels and the infiltration of immunomodulators and immune cells. Moreover, high DPT levels were associated with enhanced anti-PD-1/PD-L1 immunotherapeutic responses. Furthermore, DPT expression impacted the landscape of gene mutations, showing a negative association with tumor grade, stage, and lymph node metastasis. Based on the results of protein peptides analysis and cell experiments, it was inferred that the downregulation of DPT in CHOL cells effectively suppressed the secretion of CCL19 in macrophages. CONCLUSIONS: DPT is a novel prognosis-related biomarker for CHOL patients, and this study provides preliminary insights into the mechanism by which DPT promotes the infiltration of immune cells into the CHOL TME.

[Screen of key characteristic genes of nasopharyngeal carcinoma (NPC) base on machine learning and analysis of their correlation with immune cells].

Objective Machine learning was used to screen the key characteristic genes of nasopharyngeal carcinoma (NPC) and analyze their correlation with immune cells. Methods Download the NPC training datasets (GSE12452 and GSE13597) and the validation dataset (GSE53819) from the Gene Expression Omnibus (GEO). Firstly, the training data sets were merged and screened for differentially expressed genes (DEGs); Secondly, the DEGs were analyzed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), and immune cell infiltration analysis. Next, the least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM) algorithms were used to identify NPC-related genes in the training datasets and examined in the validation dataset, to further identify key genes using the area under curve (AUC) of receiver operating characteristic curve (ROC); Finally, the correlation between the key genes and immune cells was analyzed. Results A total of 55 DEGs were obtained, including 43 down-regulated genes and 12 up-regulated genes. The GO functions were enriched in humoral immune response, cell differentiation, neutrophil activation and chemokine receptor binding. The KEGG were mainly enriched in the IL-17 signaling pathway. The GSEA was enriched in cell cycle, extracellular matrix receptor interactions, cancer pathways and DNA replication. Immune infiltration analysis showed that the expression of naive B cells, memory B cells, and resting memory CD4+ T cells was significantly lower in NPC, while CD8+ T cells, naive CD4+ T cells, activated memory CD4+ T cells, follicular helper T cells, M0 macrophages and M1 macrophages were highly expressed in NPC. Among the feature genes screened by LASSO and SVM, only CCDC19, LAMB1, SPAG6 and RAD51AP1 genes' AUC were greater than 0.9 in both the training and validation datasets and were closely associated with immune cell infiltration. Conclusion The key genes CCDC19, LAMB1, SPAG6 and RAD51AP1 in NPC development are screened by machine learning algorithms, and are closely associated with immune cell infiltration.

RARγ promotes the invasion and metastasis of thyroid carcinoma by activating the JAK1-STAT3-CD24/MMPs axis.

The nuclear receptor superfamily RAR is generally considered to play a crucial role in the development of tumors by regulating the transcription of target genes. Nevertheless, whether RARγ performs tumor-promoting or tumor-suppressing functions and its specific mechanism in thyroid carcinoma (TC) remain unknown. Here, our study demonstrated that RARγ was abnormally overexpressed in TC tissues compared with normal thyroid tissues. Moreover, RARγ expression was remarkably correlated with cell phenotypes such as cell proliferation, migration and invasion. Mechanistically, RARγ knockdown effectively decreased the phosphorylation levels of JAK1 and STAT3, leading to decreased expression of the membrane protein CD24. In a coculture system, TC cells with high levels of CD24 in the membrane were more likely to escape phagocytosis by macrophages via the combination of CD24 with the inhibitory receptor Siglec-10 in the membrane of macrophages. In contrast, the ability of macrophages to engulf TC cells was notably elevated through exogenous addition of CD24 antibody. Collectively, our study revealed a previously undiscovered molecular mechanism of RARγ in promoting the development of TC, shedding light on RARγ as a promising therapeutic target for TC.

In-depth exploration of toxicity mechanism of nanoscale zero-valent iron and its aging products toward Escherichia coli under aerobic and anaerobic conditions.

The bacteria toxicity of nanoscale zero-valent iron (nZVI) can be changed during its application in water treatment but the toxicity mechanism is still not well understood, particularly under anaerobic conditions. Here, the toxicity of nZVI and its aging products towards Escherichia coli (E. coli) and the mechanisms of extracellular and intracellular reactive oxygen species (ROS) damage were deeply probed in the presence and absence of oxygen in ultrapure water. Under aerobic conditions, the ROS damage primarily caused by the generation of extracellular free •OH can be a major contributor to the toxicity of nZVI to E. coli. By contrast, in anaerobic nZVI treatment system, the intracellular •OH can be quenched by benzoic acid which is a cell permeable quencher and the electron spin resonance (ESR) signals of 5,5-dimethy-1-pyrroline (DMPO)- •OH were evidently observed in system with the addition of F- which could desorb the surface •OH into solution. It indicated that the intracellular •OH adsorbed on the particle surface can also play an indispensable role in inactivating cells under anaerobic conditions. Moreover, nZVI can steeply decline the membrane potential, causing severe membrane disruption and therefore resulting in the stronger toxicity in anaerobic conditions. Furthermore, the chemical composition transformation of nZVI and generation of benign iron corrosion products (e.g., Fe3O4, γ-Fe2O3, γ-FeOOH) are mainly responsible for the reduced toxicity with the increasing aging time. These results provide insights into the extracellular and intracellular ROS damage occurred in aerobic and anaerobic nZVI treatment systems, offering more perspective to the risk assessment of nZVI application.

Effect of Body Size Change on Off-Center Cervical Point and Face Doses in Patients Undergoing Nasopharyngeal Carcinoma Radiotherapy.

Nasopharyngeal carcinoma (NPC) is a clinically multiple malignant tumor. At present, with the increase in the infection rate of Epstein-Barr virus, the incidence of nasopharyngeal carcinoma is also increasing day by day. To explore the effect of body size change on off-center cervical point and face doses in patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy, in total, 100 patients with NPC from January 2019 to May 2020 in our hospital were selected for retrospective analysis, and they all received intensity-modulated radiation therapy. Bodyweight, horizontal longitudinal diameter of the odontoid process, longitudinal diameter of the third cervical spine, maximum radiation dose, and average radiation dose of normal organs in the first and last treatments were assessed, and the correlation between normal organ irradiation dose and body size was analyzed. Bodyweight, horizontal longitudinal diameter of the odontoid process, and longitudinal diameter of the third cervical spine in the last treatment were lower than those in the first treatment, with a statistically significant difference. There was no statistically significant difference in the maximum normal organ irradiation dose to the left eyeball, right eyeball, left crystalline lens, right crystalline lens, and maximum irradiation dose to optic nerve between the last treatment and the first treatment. In the last treatment, the maximum dose to the left parotid gland, right parotid gland, spinal cord, and brain stem was higher than that in the first treatment. The average irradiation dose to the left eye bulb, right eye bulb, left lens, right lens, optic nerve in the last treatment, and that in the first treatment showed no significant difference. The average dose to the left parotid gland, right parotid gland, spinal cord, and brain stem in the last treatment was higher than that in the first treatment. The irradiation dose to the left parotid gland, right parotid gland, spinal cord, and brain stem was significantly negatively correlated with body weight, horizontal longitudinal diameter of the odontoid process, and longitudinal diameter of the third cervical spine. After NPC radiotherapy, the body size of patients can change, which can have different effects on irradiation doses. Therefore, the target area and dose should be corrected during treatment to ensure the efficacy and safety of the treatment.

Association between Cystatin C and Cardiac Function in Acute Myocardial Infarction Patients: A Real-World Analysis.

Background: Acute myocardial infarction (AMI), as well as its long-term and short-term complications, is known to present with high morbidity and mortality. Cardiac function deterioration and ventricular remodelling after AMI are known to be correlated to worse long-term outcomes. However, the underlying mechanism remains elusive and there is a shortage of serum prediction markers. This study investigates the relationship between in-hospital Cystatin C (CysC) and cardiac function and subsequent prognosis among AMI patients. Research Design and Methods. We measured admission CysC and cardiac function parameters, including ejection fraction (EF) and pro-BNP value in 5956 patients diagnosed with AMI. Simple and multiregression analyses were performed to investigate the correlation between CysC and cardiac function in AMI patients. Major adverse cardiovascular events (MACE), cardiovascular, and all-cause mortality were documented, and 351 participants with high cystatin (≥1.09 mg/L) and 714 low cystatin (<1.09 mg/L) were investigated for survival analysis during a 48-month follow-up. Results: 5956 patients with AMI were enrolled in the initial observational analysis, and 1065 patients of the whole cohort were included in the follow-up survival analysis. The admission CysC level was found to be significantly positively correlated to the pro-BNP level (R square = 0.2142, 95% CI 4758 to 5265, p < 0.0001) and negatively correlated to the EF value (R square = 0.0095, 95% CI -3.503 to -1.605, p < 0.0001). Kaplan-Meier survival analysis revealed significantly increased MACE incidence (HR = 2.293, 95% CI 1.400 to 3.755, p < 0.0001), cardiovascular mortality (HR = 3.016, 95% CI 1.694 to 5.371, p = 0.0002), and all-cause mortality (HR = 3.424, 95% CI 2.010 to 5.835, p < 0.0001) in high-admission CysC cohort with AMI at the end of 4-year follow-up. Conclusions: Admission CysC is negatively correlated with cardiac function in AMI patients and acts as a novel predictor for MACE incidence in the whole population. Further studies are needed to investigate the specific mechanism of CysC in the cardiac function deterioration among AMI patients.

Association of Four Nutritional Scores With All-Cause and Cardiovascular Mortality in the General Population.

Background and Aims: Malnutrition is a well known risk factor for adverse outcomes in patients with cancer, cardiovascular disease (CVD) and chronic kidney disease, but epidemiological evidence on its relationship with the long-term risk of all-cause mortality and cardiovascular death is limited. Methods: A total of 20,116 adults from the United States National Health and Nutrition Examination Survey 2007-2014 were enrolled. The Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), Controlling Nutritional Status (CONUT) score, and Triglycerides (TG) × Total Cholesterol (TC) × Body Weight (BW) Index (TCBI) were calculated at baseline. Cox regression and the Kaplan-Meier analysis were conducted when participants were divided into three groups according to the tertiles of objective nutritional scores. Restricted cubic spline was performed to further explore the shape of the relationship between all-cause mortality, cardiovascular death, and nutritional scores. In addition, the area under the curve (AUC), continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were conducted to assess which nutritional scores have the greatest predictive value for all-cause death and cardiovascular death in the general population. Results: The cumulative incidence of all-cause death and cardiovascular death was significantly higher in participants with a higher CONUT score, lower GNRI, and lower PNI. TCBI showed the worst performance on grading and risk assessment. After adjusting confounding factors, the lowest PNI and GNRI tertile and highest COUNT score were independently and significantly associated with increased risk of all-cause death (all P < 0.01) and cardiovascular death (all P < 0.05) analyzed by a multivariate Cox regression model. An L-shaped association between the HR (hazard ratio) of all-cause mortality and nutritional scores (GNRI, PNI and TCBI) was observed in the overall populations. In addition, the PNI had the highest predictive value for all-cause mortality [AUC: 0.684, 95% confidence interval (CI): 0.667-0.701] and cardiovascular death (AUC: 0.710, 95% CI: 0.672-0.749) in the general population compared with other nutritional scores. Conclusion: The poorer the nutritional status of the general population, the higher the all-cause mortality and cardiovascular mortality. The PNI score may provide more useful predictive values than other nutritional scores.

Topoisomerase â ¡α Gene as a Marker for Prognostic Prediction of Hepatocellular Carcinoma: A Bioinformatics Analysis.

Objective To investigate the expression of topoisomeraseⅡα (TOP2α) in hepatocellular carcinoma (HCC) and its role in predicting prognosis of HCC patients. Methods We used HCC-related datasets in UALCAN, HCCDB, and cBioPortal databases to analyze the expression and mutation of TOP2α and its co-expressed genes in HCC tissues. GO function and KEGG pathway enrichment of TOP2α and its co-expressed genes were identified. The TIMER database was used to analyze infiltration levels of immune cells in HCC. The impacts of TOP2α and its co-expression genes and the infiltrated immune cells on the survival of HCC patients were assayed by Kaplan-Meier plotter analysis. Results TOP2α and its co-expression genes were highly expressed in HCC (P< 0.001) and detrimental to overall survival of HCC patients (P< 0.001). TOP2α and its co-expression genes were mainly involved in cell mitosis and proliferation, and cell cycle pathway (ID: hsa04110, P = 0.001945). TOP2α and its co-expression genes were mutated in HCC and the mutations were significantly detrimental to overall survival (P = 0.0247) and disease-free survival (P = 0.0265) of HCC patients. High TOP2α expression was positively correlated with the infiltration of B cell (r = 0.459, P< 0.01), CD8+ T cell (r = 0.312, P< 0.01), CD4+ T cell (r = 0.370, P< 0.01), macrophage (r = 0.459, P< 0.01), neutrophil (r = 0.405, P< 0.01), and dendritic cell (r = 0.473, P< 0.01) in HCC. The CD8+ T cell infiltration significantly prolonged the 3- and 5-year survival of HCC patients (all P< 0.05), and CD4+ T cell infiltration significantly shortened the 3-, 5-, and 10-year survival of HCC patients (all P< 0.05). ConclusionTOP2α may be an oncogene, which was associated with poor prognosis of HCC patients and could be used as a biomarker for the prognostic prediction of HCC.

Study of quality of life and its correlated factors in patients after lumbar fusion for lumbar degenerative disc disease.

Background: In the present work, we aimed to explore the correlated factors of quality of life in patients receiving lumbar fusion for lumbar degenerative disc disease (DDD) in China. Methods: A total of 180 patients treated with lumbar fusion were included in the present study. Their general demographic characteristics, Visual Analog Scale (VAS) scores, Japanese Orthopedic Association (JOA) scores, Simplified Coping Style Questionnaire (SCSQ), Social Support Questionnaire (SSQ), and Medical Outcomes Study Short Form 36 (MOS SF-36) were collected and evaluated preoperatively and at 1 year postoperatively. Results: There were significant improvements in scores of VAS, JOA, and quality of life of patients from preoperation to 1-year postoperation after lumbar fusion. Marital status, with or without children, education level, economic pressure, and social support had significant predictive effects on the physical health of patients undergoing lumbar fusion. Marital status, education level, and economic pressure had significant predictive effects on the mental health of patients undergoing lumbar fusion. Conclusions: Factors correlated with the physical health of patients after lumbar fusion included positive coping style, negative coping style, social support, age, education level (high school college), disease duration (5-10), suffering from other diseases (combined with two or more other disease) and the number of surgical segments (double and three or more). Factors correlated with the mental health included negative coping style, social support, age, education level (middle school and high school college) and the number of surgical segments (double and three or more). The results verify that these factors were correlated to the patient's quality of life after lumbar fusion. Emphasizing and selectively intervening these correlated factors can further improve the quality of life in patients receiving lumbar fusion for lumbar degenerative disc disease.

[Immunocyte infiltration characteristics of gene expression profile in nasopharyngeal carcinoma and clinical significance].

Objective To analyze the immunocyte infiltration characteristics and clinical significance of gene expression profile in nasopharyngeal carcinoma (NPC). Methods Firstly, the gene expression profile data of NPC were downloaded from Gene Expression Omnibus (GEO), and the infiltration of 22 kinds of immune cells in NPC was analyzed by CIBERSORT's R software package. Secondly, differential genes were obtained by GEO2R and analyzed by R Studio regarding gene ontology (GO) function and Kyoto Encyclopedia of Genes and Gnomes (KEGG). Then, the network diagram of protein-protein interaction (PPI) was drawn by STRING database and the Degree algorithm of Cytoscape software was used to screen for key genes. Finally, the expression and clinical significance of key genes in NPC and the relationship between the key genes and immune cells were analyzed. Results The expression levels of M0 macrophages, M1 macrophages and γδ T cells in NPC increased, but the differences were not significant, while the expression levels of memory B cells and resting memory CD4+T cells decreased, and the difference was significant. There were positive correlations between monocytes and eosinophils (r=0.99), plasma cells and regulatory T cells (r=0.88), activated mast cells and dendritic cells (r=0.75) in NPC, while M1 macrophages were negatively correlated with memory B cells (r=-0.71) and activated memory CD4+T cells (r=-0.63). In addition, GO of differential genes in NPC was mainly enriched in the function related to ciliary movement, and KEGG was mainly enriched in the pathway related to cytochrome P450. CCDC39 was a key gene in NPC, which was highly expressed in NPC and beneficial to the prognosis of patients, but the low expression of memory B cells was not conducive to the prognosis of patients. Conclusion A large number of immune cells are distributed in the microenvironment of NPC, and the expression of different types of immune cells is different, but memory B cells have the most obvious effect on the prognosis of patients.

[Chloroquine enhances cisplatin-induced apoptosis of nasopharyngeal carcinoma cells by inhibiting autophagy via upregulating miR129].

OBJECTIVE: To investigate the role of miR129 in mediating the effect of chloroquine to enhance cisplatin- induced apoptosis in nasopharyngeal carcinoma cells (HNE1). METHODS: MTT assay was used to detect the viability of HNE1 cells treated with different concentrations of cisplatin. Colony formation of HNE1 cells treated with cisplatin and chloroquine, alone or in combination, was observed using crystal violet staining. BALB/C unde mice were inoculated with HNE1 cells and randomly divided into 4 groups with 6 mice in each group. The mice received intraperitoneal injections of cisplatin and chloroquine, alone or in combination once every 3 days for 4 consecutive weeks, and the tumor growth was observed in each group. The expression of miR129 in HNE1 cells treated with chloroquine, cisplatin, or both was detected with qPCR. The effects of miR129 suppression with a miR129 inhibitor on the expressions of autophagy related proteins p62, LC3B, Beclin1 and the drug-resistant related protein P-glycoprotein (P-gp) were examined using Western blotting in HNE1 cells treated with chloroquine, cisplatin, or both; the changes in cell apoptosis were detected Annexin V/PI double staining. RESULTS: Chloroquine combined with cisplatin significantly inhibited HNE1 cell proliferation in vitro and the growth of HNE1 cell-derived tumor in nude mice as compared with cisplatin alone (P < 0.01). In cultured HNE1 cells, inhibition of the expression of miR129 significantly promoted autophagy and up-regulated P-gp expression (P < 0.01); Chloroquine obviously inhibited cisplatin-induced autophagy and up-regulated the expression of miR129 in HNE1 cells (P < 0.01). Transfection of the cells with the miR129 inhibitor abolished the inhibitory effect of chloroquine on cisplatin-induced autophagy, and significantly increased the cell survival rate (P < 0.05) and lower the cell apoptotic rate (P < 0.01) after combined treatment with chloroquine and cisplatin. CONCLUSIONS: Chloroquine enhances the pro-apoptotic effect of cisplatin by up-regulating miR129 to inhibit autophagy and drug resistance in HNE1 cells.

Application of a modified surgical position in anterior approach for total cervical artificial disc replacement.

BACKGROUND: Total cervical artificial disc replacement (TDR) has been considered a safe and effective alternative surgical treatment for cervical spondylosis and degenerative disc disease that have failed to improve with conservative methods. Positioning the surgical patient is a critical part of the procedure. Appropriate patient positioning is crucial not only for the safety of the patient but also for optimizing surgical exposure, ensuring adequate and safe anesthesia, and allowing the surgeon to operate comfortably during lengthy procedures. The surgical posture is the traditional position used in anterior cervical approach; in general, patients are in a supine position with a pad under their shoulders and a ring-shaped pillow under their head. AIM: To investigate the clinical outcomes of the use of a modified surgical position versus the traditional surgical position in anterior approach for TDR. METHODS: In the modified position group, the patients had a soft pillow under their neck, and their jaw and both shoulders were fixed with wide tape. The analyzed data included intraoperative blood loss, position setting time, total operation time, and perioperative blood pressure and heart rate. RESULTS: Blood pressure and heart rate were not significantly different before and after body positioning in both groups (P > 0.05). Compared with the traditional position group, the modified position group showed a statistically significantly longer position setting time (P < 0.05). However, the total operation time and intraoperative blood loss were significantly reduced in the modified position group compared with the traditional position group (P < 0.05). CONCLUSION: The clinical outcomes indicated that total operation time and intraoperative blood loss were relatively lower in the modified position group than in the traditional position group, thus reducing the risks of surgery while increasing the position setting time. The modified surgical position is a safe and effective method to be used in anterior approach for TDR surgery.

[miR-129-1-3p reverses cisplatin resistance of HNE1/CDDP human nasopharyngeal carcinoma cells by targeting inhibition of WEE1 kinase].

Objective To explore the effect of miR-129-1-3p on cisplatin sensitivity of chemo-resistant epithelial nasopharyngeal carcinoma HNE19/CDDP cells and the related mechanism. Methods Human nasopharyngeal carcinoma HNE1 cells and cisplatin-resistant HNE19/CDDP cells were cultured. Cisplatin resistance index of cisplatin-resistant HNE1/CDDP cells was tested by MTT assay. The levels of miR-129-1-3p and WEE1 mRNA in HNE1 and HNE19/CDDP cells were measured by real-time quantitative PCR. miR-129-1-3p mimics and unrelated sequence control (miR-129-1-3p NC) were transfected into HNE1/CDDP cells using LipofectamineTM 2000. The drug sensitivity (IC50) of these cells to cisplatin was determined by MTT assay. The protein expression level of WEE1 was determined by Western blot analysis. The 3'-UTR of WEE1 was cloned into luciferase reporter vector and its luciferase activity was detected to verify whether miR-129-1-3p targets WEE1. Results Resistance index of HNE1/CDDP cells to cisplatin was 5.29. The expression level of miR-129-1-3p in the HNE1 cells was significantly higher than that in the HNE1/CDDP cells. The mRNA expression level of WEE1 in the HNE1 cells was lower than that in the HNE1/CDDP cells. The level of miR-129-1-3p was negatively correlated with the level of WEE1 mRNA (r=-0.9784). The IC50 of cisplatin was significantly reduced in the HNE1/CDDP cells after transfected with miR-129-1-3p mimics. The protein expression level of WEE1 in the cells transfected with miR-129-1-3p mimics significantly decreased as compared with the control group and blank group. The miR-129-1-3p regulated the 3'-UTR of WEE1 and reduced the expression activity of luciferase. Conclusion miR-129-1-3p could reverse cisplatin resistance of HNE1/CDDP nasopharyngeal carcinoma cells via inhibiting WEE1 expression.

[Analysis of the correlation between the expression of WFDC2 in B cells of lung adenocarcinoma tissue and the survival rate of patients].

Objective To investigate the expression and clinical significance of whey acidic protein (WAP) 4-disulfide core domain 2/human epididymis protein 4 (WFDC2/HE4) in lung adenocarcinoma. Methods The expression of WFDC2 in normal lung tissues and lung adenocarcinoma tissues, the correlation between WFDC2 and the prognosis survival in patients with lung adenocarcinoma were analyzed using the BioGPS database, GEPIA database, Oncomine database and Kaplan-Meier Plotter databases. The expression of WFDC2 in cancer tissue T cells and B cells was analyzed using the Cancer Cell Line Encyclopedia (CCLE). The WFDC2-related genes and functional annotations of their gene ontology (GO), the pathway enrichment of Kyoto Gene and Genomic Encyclopedia (KEGG) were analyzed using the STRING database. The co-expression relationship, correlation and significance of WFDC2-related genes in lung adenocarcinoma were analyzed using the cBioPortal database. The expression of WFDC2 in immune infiltrates and its implication to survival prognosis in the patients with lung adenocarcinoma were analyzed using the Tumor Immune Estimation Resource (TIMER) database. Results BioGPS database analysis showed that the expression of WFDC2 was low in normal lung tissues, but none in T cells and B cells of normal human tissues. GEPIA database analysis showed that the expression of WFDC2 was higher in lung adenocarcinoma compared with normal lung tissues. Four hundred and fourteen samples of differential expression of WFDC2 were obtained from Oncomine database. Nineteen of them had increased WFDC2 expression with four in lung adenocarcinoma; fifteen of them had decreased WFDC2 expression with one in lung adenocarcinoma. Meta-analysis of 4 studies meeting the setting conditions showed that the expression level of WFDC2 was high in lung adenocarcinoma tissues. Kaplan-Meier Plotter database results showed that the overall survival (OS) time of patients with lung adenocarcinoma in the high WFDC2 expression group was significantly longer than that in the low WFDC2 expression group. CCLE analysis showed that the expression of WFDC2 in cancer tissue T cells and B cells was significantly higher than that in normal tissues. String database analysis showed that there were 30 genes associated with WFDC2, which were involved in 4 signaling pathways. The classification results from GO annotation indicated the enrichment in 4 cell components, 8 molecular functions, and 27 biological processes. The cBioPortal database showed that the correlation and difference between secretory leukocyte protease inhibitor (SLPI) and WFDC2 in lung adenocarcinoma were markedly significant (Pearson=0.26; Spearman=0.46; P=6.20E-28). TIMER database analysis showed that B cells with high expression of WFDC2 in the immune microenvironment significantly prolonged the survival prognosis of patients with lung adenocarcinoma for 1 year, 3 years, 5 years and 10 years. Conclusion WFDC2 is highly expressed in lung adenocarcinoma tissues with the anti-tumor immunosuppressive effect, which can significantly prolong OS of lung adenocarcinoma patients and be used as a candidate marker for investigating clinical prognosis of lung adenocarcinoma.

[Role of miR-144-3p and its target gene in regulating osteogenic differentiation of rat bone marrow mesenchymal stem cells in vitro].

OBJECTIVE: To investigate the role of miR-144-3p in regulating osteogenic differentiation of bone marrow mesenchymal stem cells and predict its target genes. METHODS: Rat bone marrow mesenchymal stem cells (BMSCs) with induced osteogenic differentiation were examined for the expressions of Runx2, OCN and miR-144-3p. The effects of transfection with a miR-144-3p mimic or a miR-144-3p inhibitor were tested on the osteogenic differentiation of the BMSCs. The changes in the expressions of the predicted target of miR-144-3p in the BMSCs during induced osteogenic differentiation were examined using Western blotting and qRT-PCR. RESULTS: Rat BMSCs with induced differentiation into osteoblasts exhibited a progressive increase in the expressions of Runx2 and OCN (two markers of osteogenic differentiation), while the expression of miR-144-3p gradually decreased during the differentiation till reaching the lowest level at 21 days of induction. In rat BMSCs, transfection with the miR-144-3p mimic significantly decreased ALP activity (P < 0.05) wile transfection with the miR-144-3p inhibitor significantly increased ALP activity (P < 0.05) in rat BMSCs. Analysis based on miRanda, microRNA.org database and TargetScan suggested that Smad4 was the most likely target gene of miR-144-3p. The results of qRT-PCR showed no significant differences in expression levels of Smad4 among the cells with different treatments (P > 0.05), while Western blotting revealed a significantly decreased expression of Smad4 in the cells transfected with miR-144-3p mimics and an increased Smad4 expression in the cells transfected with the miR-144-3p inhibitor as compared with the control cells (P < 0.05). CONCLUSIONS: miR-144-3p participates in the regulation of osteogenic differentiation of rat BMSCs, and its inhibitory effect on osteogenic differentiation is achieved probably by decreasing the expression level of Smad4.

[Expression and significance of WFDC2 in ovarian cancer based on multiple gene databases].

Objective To investigate the expression and clinical significance of whey acidic protein (WAP) 4-disulfide core domain 2 (WFDC2) in ovarian cancer. Methods The expression of WFDC2 gene in normal human tissues, ovarian cancer tissues and ovarian cancer cell lines and the correlation with the prognosis survival in patients with ovarian cancer were analyzed using the BioGPS database, Oncomine database, Cancer Cell Encyclopedia (CCLE) and Kaplan-Meier Plotter databases. Results BioGPS database analysis showed that the expression of WFDC2 was not found in normal ovarian tissues. Four hundred and seventeen samples were searched from Oncomine database, and the different expression of WFDC2 in 34 studies were statistically significant, which included the WFDC2 expression increasing in 19 studies, and WFDC2 expression decreasing in 15 studies. Meta-analysis of 7 studies meeting the setting conditions showed that the expression level of WFDC2 was high in ovarian cancer tissues. CCLE analysis showed that the expression level of WFDC2 was also high in ovarian cancer cell lines; Kaplan-Meier Plotter database results showed the overall survival time of patients with ovarian cancer in the high WFDC2 expression group was significantly longer than that in the low WFDC2 expression group. Conclusion The expression of WFDC2 in ovarian cancer tissues is high, and which is significantly associated with the prognosis survival in patients with ovarian cancer.