Preeclampsia is one of the leading causes of maternal and fetal morbidity and mortality worldwide. Preeclampsia is linked to mitochondrial dysfunction as a contributing factor in its progression. This study aimed to develop a novel diagnostic model based on mitochondria-related genes(MRGs) for preeclampsia using machine learning and further investigate the association of the MRGs and immune infiltration landscape in preeclampsia. In this research, we analyzed GSE75010 database and screened 552 DE-MRGs between preeclampsia samples and normal samples. Enrichment assays indicated that 552 DE-MRGs were mainly related to energy metabolism pathway and several different diseases. Then, we performed LASSO and SVM-RFE and identified three critical diagnostic genes for preeclampsia, including CPOX, DEGS1 and SH3BP5. In addition, we developed a novel diagnostic model using the above three genes and its diagnostic value was confirmed in GSE44711, GSE75010 datasets and our cohorts. Importantly, the results of RT-PCR confirmed the expressions of CPOX, DEGS1 and SH3BP5 were distinctly increased in preeclampsia samples compared with normal samples. The results of the CIBERSORT algorithm revealed a striking dissimilarity between the immune cells found in preeclampsia samples and those found in normal samples. In addition, we found that the levels of SH3BP5 were closely associated with several immune cells, highlighting its potential involved in immune microenvironment of preeclampsia. Overall, this study has provided a novel diagnostic model and diagnostic genes for preeclampsia while also revealing the association between MRGs and immune infiltration. These findings offer valuable insights for further research and treatment of preeclampsia.

The efficiency of strategic outsourcing in reverse logistics (RL) depends on stakeholder requirements (SRs) directing organization development and experts’ knowledge decomposing and reconstructing strategic decision, which urges the adoption of hierarchical and interactive quality function deployment (QFD). Considering the uncertainty within a QFD, single valued neutrosophic number (SVNN) is introduced to capture both indeterminacy and inconsistency hidden in quantitive votes and qualitative judgments of stakeholders and experts. With unknown weight assignments, two maximum deviation models are constructed to obtain the priority of SRs and Shapley weights of experts. An SVNN-enabled grey relational analysis is extended to identify the interdependence priority of engineer characterizers (ECs). Due to the interactions among components such as experts in a group or ECs in QFD, two information aggregation tools under neutrosophic environments are presented based on fuzzy integral delineating the positive or negative effect. Built on these, we propose an integrated neutrosophic approach composed of a transformation module, weight module, integration module and QFD analysis module to support the outsourcing decision. Finally, an illustration example is used to confirm the practicality of the proposed approach. Sensitivity analysis and comparative analysis with multiple views have been conducted to show the flexibility and superiority of the given decision.

β-endorphin (β-EP) is involved in the regulation of male germ cells; however, little is known about the effect of β-EP on primary germ cells via opioid receptors. In this study, we first revealed significant cell apoptosis in the testis of male rats after β-EP intervention. Subsequently, the expression of the mu opioid receptor (MOR) was detected in both Leydig cells (LCs) and spermatogonia (SGs) by fluorescence colocalization; overlapping signals were also detected in apoptotic cells. In addition, LCs and SGs were separated from the testis of male rats and primary cells were treated with β-EP; this increased the mRNA levels of MOR and was accompanied by acute cell apoptosis. Our findings provide a foundation for the further study of apoptosis in reproductive cells regulated by β-EP and the MOR receptor.

Patients with stage III lung adenocarcinoma (LUAD) have significant survival heterogeneity, meanwhile, CD8+ T cell has a remarkable function in immunotherapy. Therefore, developing novel biomarkers based on CD8+ T cell can help evaluate the prognosis and guide the strategy of immunotherapy for patients with stage III LUAD. Thus, we abstracted twelve datasets from multiple online databases and grouped the stage III LUAD patients into training and validation sets. We then used WGCNA and CIBERSORT, while univariate Cox analysis, LASSO analysis, and multivariate Cox analysis were performed. Subsequently, a novel CD8+ T cell-related classifier including HDFRP3, ARIH1, SMAD2, and UPB1 was developed, which could divide stage III LUAD patients into high- and low-risk groups with distinct survival probability in multiple cohorts (all P < 0.05). Moreover, a robust nomogram including the traditional clinical parameters and risk signature was constructed, and t-ROC, C-index, and calibration curves confirmed its powerful predictive capacity. Besides, we detected the difference in immune cell subpopulations and evaluated the potential benefits of immunotherapy between the two risk subsets. Finally, we verified the correlation between the gene expression and CD8+ T cells included in the model by immunohistochemistry and validated the validity of the model in a real-world cohort. Overall, we constructed a robust CD8+ T cell-related risk model originally which could predict the survival rates in stage III LUAD. What's more, this model suggested that patients in the high-risk group could benefit from immunotherapy, which has significant implications for accurately predicting the effect of immunotherapy and evaluating the prognosis for patients with stage III LUAD.

Objective: This study intends to identify potential prognostic marker genes associated with the prognosis of patients suffering from hepatocellular carcinoma (HCC) based on TCGA and GEO analysis. Methods: TCGA-LIHC cohort was downloaded and the data related to HCC were extracted from The Cancer Genome Atlas (TCGA) database and subjected to differential analysis. HCC-related gene expression datasets were retrieved from the GEO database, followed by differential analysis. After intersection of the results of TCGA and GEO databases, gene interaction analysis was performed to obtain the core genes. To identify the genes related to the prognosis of HCC patients, we conducted univariate and multivariate Cox analyses. Results: Based on differential analysis of TCGA database, 854 genes were differentially expressed in HCC, any of which might link to the occurrence and progression of HCC. Meanwhile, joint analysis of HCC-related gene expression datasets in the GEO database screened 214 genes. Five core genes CDC20, TOP2A, RRM2, UBE2C and AOX1 were significantly associated with the prognosis of HCC patients and the risk model based on these five genes effectively predicted the prognosis of HCC patients. Conclusion: Collectively, our data suggest that CDC20, TOP2A, RRM2, UBE2C and AOX1 may be the key genes affecting the prognosis of patients with HCC. The five-gene signature could accurately predict the prognosis of HCC patients.

To analyze the association between glutathione S-transferases polymorphisms and the risk of cervical lesions. Case-control studies focusing on the association between glutathione S-transferase polymorphisms and the risk of cervical lesions were collected from the PubMed, Web of Science, Cochrane Library, Embase, Medline, CNKI, VIP and Wanfang databases from inception to August 2018. Pooled odds ratios and 95% confidence intervals were employed to evaluate the strength of the association. Subgroup analysis and sensitivity analysis were used to test the potential discrepancy and robustness, respectively. A total of 30 studies comprising 3961 patients and 4726 healthy controls satisfied the inclusion criteria. Of these, 6 studies contained information about GSTP1, 27 studies contained information about GSTM1, and 22 studies contained information about GSTT1. Our results supported that there was no statistical association between GSTP1 polymorphism and the risk of cervical lesions (odds ratio [OR]= 1.08, P=.40). The GSTM1 null variant showed increased susceptibility to cervical lesions (OR= 1.45, P<.001). Subgroup analysis revealed that the GSTM1 null variant caused cervical lesions among HPV infection cases (OR= 1.69, P=.02) and among the Chinese and Indian populations (OR= 2.24 and OR= 1.87, respectively, P<.001). The GSTT1 null variant increased the risk of cervical lesions in smokers (OR= 1.52, P=.03). The GSTT1 null genotype was also related to high-grade intraepithelial neoplasia (HSIL) and cervical cancer risk (OR= 1.30 and OR= 1.78, respectively, P<.05). TheGSTM1 null variant causedcervical lesions, especially amongHPVinfection cases andamong theChinese andIndianpopulations. The GSTT1 null variant increased the risk of cervical lesions in smokers and was also related to HISL and cervical cancer risk.

Bone tissue regeneration was closely associated with osteogenesis and angiogenesis. The harmonious regulation of osteogenetic and angiogenic growth factors would enhance bone regeneration, while the imbalance of that would lead to local excessive bone formation or vascular mass due to exogenous delivery. Therefore, microRNA is believed to regulate multiple metabolism progress through endogenous signaling pathways on the gene level. In this work, we identified microRNA 378 as a positive regulator of osteogenesis and angiogenesis simultaneously and also observed an increase of microRNA 378 than control in human bone marrow mesenchymal stem cells (hBMMSCs) after osteoblast induction. Besides, osteogenetic and angiogenic gene expression increased simultaneously after overexpression of microRNA 378. Moreover, alizarin red staining and alkaline phosphatase (ALP) staining enhanced, and secretion of vascular endothelial growth factor (VEGF) increased. In this way, we believed miR378 was an ideal target to osteogenesis-angiogenesis coupling for bone regeneration, which provides a potential tool for the gene therapy of bone regeneration.

This meta-analysis systematically reviews the association between Toll-like receptor 9 polymorphisms and the risk of cervical cancer. Case-control studies focused on the association were collected from the PubMed, Web of Science, Cochrane Library, Embase, MEDLINE, CNKI, VIP, and Wanfang databases from inception to July 2017. We screened the studies and assessed the methodological quality of the included studies and extracted data. A meta-analysis was performed using RevMan 5.3 and Stata 12.0 software. Pooled odds ratios and 95% confidence intervals were employed to evaluate the strength of the associations between Toll-like receptor 9 polymorphisms and cervical cancer risk. A total of 9 studies comprising 3331 cervical cancer patients and 4109 healthy controls met the inclusion criteria. Of these, 8 studies contained information about G2848A (rs352140) and 4 studies contained information about -1486T/C (rs187084). Our results revealed that the associations between rs187084 and cervical cancer risk in the dominant model (p = 0.002) and heterozygous model (p = 0.002) were significant, with 1.30- and 1.32-fold increases in susceptibility, respectively, compared to that in the wild-type model. However, rs352140 was not related to cervical cancer regardless of whether the subgroup analysis was conducted (p > 0.05). In conclusion, there is a significant correlation between rs187084 and cervical cancer risk with the minor C allele increasing the risk of occurrence of cervical cancer. However, rs352140 is not associated with the occurrence of cervical cancer.

BACKGROUND:The disequilibrium of local immune microenvironment is an essential element during tumorigenesis.METHOD:By conducting real-time polymerase chain reaction, we identified the mRNA level of immune factors, FoxP3 (forkhead box protein P3), CCL22/CCR4 (chemokine (C-C motif) ligand 22/CC chemokine receptor 4), OX40L/OX40 (tumor necrosis factor superfamily member 4/tumor necrosis factor receptor superfamily member 4) and Smad3 (SMAD family member 3) in neoplastic foci and its periphery tissues from 30 cases of squamous cervical carcinoma and 20 cases of normal cervix.RESULT:The FoxP3, CCL22 and CCR4 mRNA level in local immune microenvironment of normal cervix was lower than that in cervical cancer. While OX40L, OX40 and Smad3 mRNA level profile in normal cervix was higher than that in cervical cancer. Beyond individual effect, the pairwise positive correlations were demonstrated among the mRNA level of FoxP3, CCL22 and CCR4. The mRNA level of OX40 negatively correlated with CCL22, but positively correlated with Smad3. Moreover, the mRNA level of FoxP3 and CCL22 was increased while Smad3 was decreased in cervical tissue with HPV (human papilloma virus) infection.CONCLUSION:Our data yields insight into the roles of these immune factors in cervical carcinogenesis. It may therefore be that, in microenvironment of cervical squamous cell carcinoma, along with the context of HPV infection, negative immune regulators FoxP3, CCL22 and CCR4 might overwhelm positive immune factors OX40L, OX40 and Smad3, giving rise to an immunosuppressive status and promote the progression of cervical carcinogenesis.TRIAL REGISTRATION:Not applicable.

Objective To explore the expressions and co-relationship of immune factors forkhead box p3 (FoxP3),chemokine (C-C motif) ligand 22 (CCL22),tumor necrosis factor receptor superfamily member 40(OX40),and SMAD family member 3 (Smad3) in cervical carcinoma and investigate their immunomodulatory roles in cervical carcinogenesis.Methods Totally 30 cases of cervical carcinoma with adjacent tissues and 20 cases of normal cervix were collected in this study. FoxP3,CCL22,OX40,and Smad3 mRNA expressions were detected by real-time polymerase chain reaction (RT-PCR). Results Compared to normal cervix,the expression levels of FoxP3 and CCL22 mRNA were elevated in neoplastic foci(P=0.000,P=0.002) and tumor periphery (P=0.048,P=0.040).The mRNAs increased modestly in high-grade squamous cell carcinoma focal(P=0.019,P=0.020) and periphery tissue (P=0.023,P=0.031) in comparison with low-grade squamous cell carcinoma. The expression levels of OX40 and Smad3 mRNA were significantly lower in neoplastic foci(P=0.000,P=0.015) than normal cervix. Compared to low-grade squamous cell carcinoma focal and periphery tissue,the mRNAs decreased moderately in high-grade squamous cell carcinoma(P=0.018,P=0.030; P=0.027,P=0.014). In both neoplastic foci and tumor periphery,the mRNA expression level of CCL22 was positively correlated with FoxP3 (r=0.353,P=0.000; r=0.307,P=0.000) but negatively correlated with OX40 (r=-0.288,P=0.031; r=-0.263,P=0.037),while OX40 was positively correlated with Smad3 (r=0.384,P=0.002;r=0.288,P=0.023). The mRNA expressions of FoxP3 and CCL22 were increased in foci and pericarcinous tissues (P=0.024,P=0.039; P=0.032,P=0.034) while Smad3 was decreased in neoplastic foci (P=0.017) in contrast to HPV negative corresponding group. Conclusion FoxP3 and CCL22 expressions increase while OX40 and Smad3 expression decrease at mRNA level in the microenvironment of cervical cancer,which may be associated with such immunological model that the immunosuppressive roles of FoxP3 and CCL22 enhance while the immunity-boosting roles of OX40 and Smad3 are impeded,contributing to the deterioration of immune disequilibrium in local site and cervical cancer carcinogenesis.

Objective To screen and identify heterogeneous phenotype-associated genes of human bladder transitional cell carcinoma.Methods Subtractive cDNA libraries was established by means of suppression subtractive hybridization(SSH) on the basis of two human bladder transitional cell carcinoma cell lines(BLZ-211 and BLS-211) derived from the same patient,which had similar changes in chromosomes but different cell phenotypes(in terms of cell shape,susceptibility to 5-Fu and tumorigenic capacity).The positive clones in the library were selected for screening differentially expressed gene fragments by sequence analysis and blasting,and Northern blotting was performed to confirm the differentially expressed genes.Results The subtractive forward and reverse cDNA libraries consisted of 168 and 206 white clones containing 200-700 bp inserts.After differential screening,55 cDNA clones containing 35 different transcripts were obtained,among which 15 were identified by homology analysis as known genes(such as those coding for vimentin,keratin 7,dihydrodiol dehydrogenase and thioredoxin reductase),11 as unknown genes,and 9 as new ESTs(GenBank dbEST database accession number DY505708,DY230447-8,DR008207).Conclusion SSH is a powerful method for identifying differentialy expressed genes between different cell lines or clones,and characterization of the identified genes may provide useful information for understanding the genes responsible for different cell phenotypes.

A novel active backstepping control method is presented for synchronizing two identical Rossler hyperchaotic systems with each other, and extended to achieve the generalized synchronization of the Chua chaotic system with the Rossler hyperchaotic system. It is a systematic design approach and consists of a recursive procedure interlacing the choice of a Lyapunov function with the design of active control. In particular, this technique gives flexibility in constructing a control law. Numerical experiments verify the feasibility and effectiveness of the proposed control technique.

Objective To explore the mechanisms of the acute leukemia escape and the clinical significance of assay of IFN-γ, IL- 10 in the acute leukemia patients. Methods Plasma concentrations of IFN-γ, IL-10 were measured in the first visit patients by ELISA. Results ①Compared with healthy controls, the IFN-γ concentrations decreased significantly in first visit acute leukemia patients, and the IL -10 concentrations increased significantly in first visit acute leukemia patients. ②IFN-γ concentrations before intensive chemotherapy in CR,PR, death patients on whom the chemotherapy had failed to take effect decreased successively, but IL-10 increased successively. Compared with death patients, there was a significant increase of lFN-γ concentrations in CR and PR patients, IL-10 concentrations in three groups differed significantly. Conclusion Th_2 type cytokines were dominant in the first visit acute leukemia patients, and contributed to the immunosuppressive state at the tumor site, which was probably one of important mechanisms of the acute leukemia escape. In the tumor microenvironment of the acute leukemia, the serious lack of Th_1 type cytokines and the increase of Th_2 type cytokine were correlated with fatal outcome. Therefore we could estimate immune function of the acute leukemia patients and prognosis by assaying Th_1, Th_2 type cytokine.