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Acute myeloid leukaemia (AML) is a common and highly aggressive haematological malignancy in adults. Senescence-associated secretory phenotype (SASP) plays important roles in tumorigenesis and progression of tumour. However, the prognostic value of SASP in patients with AML has not been clarified. The present study aims to explore the prognostic value of SASP and develop a prognostic risk signature for AML. The RNA-sequencing data was collected from the TCGA, GTEx and TARGET databases. Subsequently, differentially expressed gene analysis, univariate Cox regression and LASSO regression were applied to identified prognostic SASP-related genes and construct a prognostic risk-scoring model. The risk score of each patient were calculated and patients were divided into high- or low-risk groups by the median risk score. This novel prognostic signature included 11 genes: G6PD, CDK4, RPS6KA1, UBC, H2BC12, KIR2DL4, HSF1, IFIT3, PIM1, RUNX3 and TRIM21. The patients with AML in the high-risk group had shorter OS, demonstrating that the risk score acted as a prognostic predictor, which was validated in the TAGET-AML dataset. Univariate and multivariate analysis revealed the risk score was an independent prognostic factor in patients with AML. Furthermore, the present study revealed that the risk score was associated with immune landscape, immune checkpoint gene expression and chemotherapeutic efficacy. In the present study, we constructed and validated a unique SASP-related prognostic model to assess therapeutic effect and prognosis in patients with AML, which might contribute to understanding the role of SASP in AML and guiding the treatment for AML., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Purpose: Health-related quality-of-life (HRQoL) data for the chronic heart failure (HF) population in Malaysia are lacking. Using EQ-5D-5L, this study intended to describe their HRQoL, identify predictors of worse HRQoL, and derive EQ-5D-5L index scores for use in economic evaluations., Methods: A cross-sectional survey was conducted between April and September 2023 to collect EQ-5D-5L, sociodemographic, and clinical data from outpatients with HF across seven public specialist hospitals in Malaysia. Multivariable logistic and linear regression models were used to identify independent predictors of reported problems in the EQ-5D-5L dimensions, and predictors of index scores and EQ-VAS, respectively., Results: EQ-5D-5L data from 424 outpatients of multi-ethnic background (mean age: 57.1 years, 23.8% female, mean left ventricular ejection fraction: 35.7%, 89.7% NYHA class I-II) were collected using either Malay, English, or Chinese, achieving a 99.8% completion rate. Nearly half of the respondents reported issues in the Mobility, Usual Activities, and Pain/Discomfort dimensions. Mean EQ-5D-5L index was 0.820, lower than the general population, and significantly lower with NYHA class III-IV (0.747) versus NYHA class I (0.846) and NYHA class II (0.805). Besides NYHA class, independent predictors of worse HRQoL included Indian ethnicity, living alone, lower education, unemployment due to ill-health, and proxy-reported HRQoL, largely aligning with existing literature., Conclusion: Community-dwelling Malaysians with HF reported poorer HRQoL compared to the general population. The observed disparities in HRQoL among HF patients may be linked to specific patient characteristics, suggesting potential areas for targeted interventions. HRQoL assessment using EQ-5D-5L proves feasible and should be considered for routine implementation in local clinics., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Alcohol addiction, or alcohol dependence, refers to a psychological state of strong craving for alcohol caused by drinking when both the drinking times and alcohol consumption reach a certain level. Alcohol addiction can cause irreversible damage, leading to mental illness or mental disorders, negative changes in their original personality, and a tendency to safety incidents such as committing suicide or violent attacks on others. Significant attention needs to be given to the mental health of alcohol addicts, which could reflect their abnormal personality traits. However, only a few papers on this issue have been reported in China., Aim: To investigate the correlation between mental health and personality in patients with alcohol addiction., Methods: In this single-center observational study, we selected 80 patients with alcohol addiction as the research subjects, according to the criteria of the K10 scale to evaluate the mental health of patients with alcohol addiction, and divided these patients into four groups based on the evaluation results: Good, average, relatively poor and bad. And then analyzed the correlation between mental health conditions and personality characteristics from these four groups of patients., Results: The average score of the K10 scale (Kessler 10 Simple Psychological Status Assessment Scale) in 80 patients with alcohol addiction was 25.45 points, the median score was 25 points, the highest score was 50 points, and the lowest score was 11 points. Pearson 's analysis showed that the K10 score was positively correlated with the scores of these two subscales, such as the P-subscale and the N-subscale ( P < 0.05). In contrast, the K10 score had no significant correlation with the scores from the E-subscale and the L-subscale ( P > 0.05)., Conclusion: The mental health conditions of patients with alcohol addiction are positively correlated with their personality characteristics., Competing Interests: Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Epithelioid angiomyolipoma (EAML) is a rare type of mesenchymal angiomyolipoma with potential malignancy in the kidney that can cause lymph node metastases, local recurrence, and distant metastases. Herein, we describe a case of EAML in the right kidney of a 51-year-old man who was admitted to the hospital with a right abdominal mass. Computed tomography revealed a heterogeneously enhanced mass with blurred margins, which was considered a malignant tumor. A radical nephrectomy was then performed. Two years later, the patient developed liver metastases from EAML and was administered sintilimab combined with bevacizumab. The patient survived after 6 months of follow-up. Histologically, the tumors showed clear boundaries and no obvious capsules. The tumor tissue mainly consisted of epithelioid tumor cells, thick-walled blood vessels, and a small amount of adipose tissue. Tumor cells with lipid vacuoles and acinar areas were large, round, polygonal, eosinophilic, or transparent in the cytoplasm. The enlarged and hyperchromatic nuclei were accompanied by distinct nucleoli and pathological mitosis. These histopathological findings resembled those of renal cell carcinoma, and immunohistochemical analysis was performed. The tumor cells were diffusely positive for HMB45, Melan-A, CK20, vimentin antibodies, and TFE3, suggesting that the tumor originated from perivascular epithelioid cells, excluding renal cell carcinoma. The Ki-67 index was 10%. These histopathological features were observed in liver mass puncture tissues. We also summarized 46 cases of EAML with distant metastasis and explored the clinicopathological features of EAML to improve the treatment of the disease. EAML is often ignored in the clinical setting, leading to metastasis and recurrence. Therefore, EAMLs require long-term follow-up, and timely detection of recurrent disease can improve the prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Wang, Chen, Wang, Wang, Liu, Pang, Jiang and Qi.)

Objective: To investigate the effect of interaction between polygenic risk score (PRS) and intestinal fungal microbiota on the risk of Schizophrenia (SCH). Methods: A case-control study was carried out. Drug-naïve, first-episode SCH patients were selected from the Psychiatric Department of the First Affiliated Hospital of Zhengzhou University between October 2017 and October 2019. Meanwhile, healthy controls (HCs) were recruited from local communities through online advertisement or physical examination center. Intestinal fungal microbiota was characterized by the 18S rRNA sequencing platform. The association of fungal microbial dysbiosis (F&#95;MD) index, α-diversity indices and PRS with SCH was detected by logistic regression analysis. Results: A total of 137 SCH patients (62 males and 75 females) and 76 HCs (31 males and 45 females) were included in the study. The age of SCH patients and HCs was (22.5±7.5) years and (22.8±2.3) years, respectively. The results of logistic regression analysis revealed that PRS ( OR =1.111, 95% CI : 1.036-1.178, P =0.002) and the increase of F&#95;MD index ( OR =1.200, 95% CI : 1.124-1.281, P <0.001) were risk factors for developing SCH. The increase of fungal α-diversity Shannon ( OR =0.813, 95% CI : 0.755-0.874, P <0.001) index, Simpson index ( OR =0.218, 95% CI : 0.091-0.523, P <0.001) and abundance of key Aspergillus ( OR =0.928, 95% CI : 0.864-0.996, P =0.040) decreased the risk of SCH. Aspergillus abundance was positively correlated with cognitive domains including working memory ( r =0.280, P =0.001), verbal learning ( r =0.253, P =0.003), reasoning and problem solving ( r =0.191, P =0.028). Conclusion: The increase of PRS may increase the risk of SCH. The increase of fungal α-diversity indices and Aspergillus abundance may decrease the risk of SCH. The interaction between PRS and intestinal fungi (Shannon index, Simpson index and Aspergillus) is a related factor for the risk of SCH.

Objective: To construct a diagnostic model of schizophrenia (SCZ) based on biomarkers such as serum neurotrophic factor. Methods: Patients of schizophrenia (SCZ group) and healthy controls (HC group) who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2019 were prospectively selected. In the SCZ group, the mental symptoms were assessed by the positive and negative symptom scale (PANSS), cognitive function was assessed by the MATRICS consensus cognitive battery (MCCB), brain-derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), fasting glucose (FGB) and fasting insulin (FINS) levels were detected, and insulin resistance (HOMA-IR) was calculated. The same methods were used to evaluate cognitive function, measure BDNF, GDNF, FGB and FINS levels, and calculate HOMA-IR in HC group. The indexes with statistically significant differences between the two groups were selected to be included in the model. The diagnostic model was constructed by machine learning and verified by cross-validation method, the receiver operating curve (ROC) was plotted, and the area under the curve (AUC), sensitivity and specificity were calculated. Results: (1) A total of 142 patients (70 males and 72 females) with schizophrenia were finally included, and aged (25±4) years. Meanwhile, 140 healthy controls (72 males and 68 females) were also enrolled, and aged (26±4) years. In SCZ group, scores in all areas of cognitive function were lower than those in HC group (all P <0.001), the levels of serum BDNF and GDNF [(6.7±1.8) ng/ml and (405±93) pg/ml] were also lower than those in HC group [(12.3±3.2) ng/ml and (574±139) pg/ml] (both P <0.001), but the levels of FINS and HOMA-IR [(8.4±0.8) μU/ml and 1.7±0.3] were higher than those in HC group [(6.7±0.9) μU/ml and 1.4±0.3] (both P <0.001). (2) Correlation analysis showed that the level of serum BDNF had a negative correlation with negative symptom scores and total scores ( r =-0.31, P <0.001; r =-0.17, P =0.040), but had a positive correlation with attention/alertness (CPT-IP) T scores, working memory (WSM-Ⅲ) T scores and visual learning (BVMT) T scores in SCZ group ( r =0.39, 0.37 and 0.29, all P <0.001). The level of serum GDNF also had a positive correlation with CPT-IP T scores, WSM-Ⅲ T scores and BVMT T scores ( r =0.32, P <0.001; r =0.23, P =0.007; r =0.40, P <0.001). The values of HOMA-IR had a positive correlation with social cognition (MSCEIT) T scores in SCZ group ( r =0.18, P =0.033). (3) AUC of the early diagnosis model constructed by combining BDNF, GDNF and HOMA-IR was 0.890 (95% CI : 0.832-0.940), the accuracy was 0.89, the sensitivity and specificity was 0.94 and 0.82, respectively. Conclusion: The final diagnostic model based on biomarkers of serum neurotrophic factor has good diagnostic efficiency for SCZ, but large-scale independent sample verification is still needed.

Objective: The overexpression of polo-like kinase 1 (PLK-1) has been found in a broad spectrum of human tumors, making it an attractive prognostic tumor biomarker. Nowadays, PLK-1 is considered a cancer therapeutic target with clinical therapeutic value. The aim of the present study was to systematically review the prognostic and therapeutic value of PLK-1 in different malignant neoplasms., Methods: A systematic literature search of the Cochrane Library, PubMed, Web of Science, and China National Knowledge Internet (CNKI) databases was conducted between December 2018 and September 2022. In total, 41 published studies were screened, comprising 5,301 patients. We calculated the pooled odds ratios (ORs) and corresponding 95%CIs for the clinical parameters of patients included in these studies, as well as the pooled hazard ratios (HRs) and corresponding 95% CIs for 5-year overall survival (OS)., Results: Our analysis included 41 eligible studies, representing a total of 5,301 patients. The results showed that overexpression of PLK-1 was significantly associated with poor OS (HR, 1.57; 95% CI, 1.18-2.08) and inferior 5-year disease-free survival/relapse-free survival ((HR, 1.89; 95% CI, 1.47-2.44). The pooled analysis showed that PLK-1 overexpression was significantly associated with lymph node metastasis, histological grade, clinical stages ( p < 0.001 respectively), and tumor grade ( p < 0.001). In digestive system neoplasms, PLK-1 overexpression was significantly associated with histopathological classification, primary tumor grade, histological grade, and clinical stages ( p = 0.002, p = 0.001, p < 0.0001, respectively). In breast cancer, PLK-1 was significantly associated with 5-year overall survival, histological grade, and lymph node metastasis ( p < 0.001, p = 0.003, p < 0.001, respectively). In the female reproductive system, PLK-1 was significantly associated with clinical stage ( p = 0.011). In the respiratory system, PLK-1 was significantly associated with clinical stage ( p = 0.021)., Conclusion: Our analysis indicates that high PLK-1 expression is associated with aggressiveness and poor prognosis in malignant neoplasms. Therefore, PLK-1 may be a clinically valuable target for cancer treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Li, Chen, Wang, Hu, Du, Pang and Qi.)

Molecular targeting and immunotherapy provide durable responses for advanced lung cancer clinical therapy in many patients. However, the mechanisms of occurrence of progressive disease and resistance to targeted therapy and immunotherapy have not been elucidated. Herein, we report two cases of small cell transformation of non-small cell lung cancer (NSCLC) after targeted therapy or immunotherapy. The first case was a 63-year-old female patient presenting with cough and expectoration. Left lung invasive adenocarcinoma was diagnosed after left lung tumor biopsy. After epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) targeted therapy for almost 2 years, disease progression and symptom aggravation were observed. Pathological and immunohistochemical staining results after biopsy revealed small cell lung cancer (SCLC). The second case was a 75-year-old male patient diagnosed with stage IV squamous cell carcinoma of the lung, who received carboplatin/paclitaxel adjuvant chemotherapy and pembrolizumab treatment with partial response. Disease progression and metastasis occurred within 15 cycles of immunotherapy. Computed tomography revealed a lower left lung tumor. Cytological examination of lung lavage fluid and biopsy under thoracoscope revealed SCLC. In conclusion, histological transformation to SCLC is a potential mechanism of NSCLC resistance to targeted therapy or immunotherapy. During treatment, clinicians should monitor serum tumor markers or genome sequencing, particularly in patients with disease progression, as this may be beneficial for early detection of SCLC transformation. Repeated biopsy can be performed if necessary, and the therapeutic regimen can be adjusted in a timely manner according to the results of molecular pathological tests for personalization and whole-process management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Chen, Zhang, Wang, Zhuang, Chen, Du, Pang and Qi.)

Immunotherapy has developed rapidly and has gradually become one of the important methods for treatment of gastric cancer (GC). The research on tumor infiltrating immune cells (TIICs) and immune-related genes in the tumor microenvironment (TME) greatly encourages the development of immunotherapy. The devolution algorithm (CIBERSORT) was applied to infer the proportion of 22 TIICs based on gene expression profiles of GC tissues, which were downloaded from TCGA and GEO. TCGA was utilized to analyze the differential expression of immune-related genes, and explore the potential molecular functions of these genes. We have observed the enrichment of multiple TIICs in microenvironment of GC. Some of these cells were closely related to tumor mutational burden (TMB), microsatellite instability (MSI), Fuhrman grade, and TNM staging. Survival analysis showed that the infiltration level of CD8 + T cells, activated CD4 + memory T cells and M2 macrophages were significantly related to the prognosis of GC patients. The functional enrichment analysis of immune-related genes revealed that these genes were mainly associated with cytokine activation and response. Four significant modules were screened by PPI network and 20 key genes were screened from the modules. The expression levels of CALCR and PTH1R are strikingly related to the expression of immune checkpoint and the prognosis of GC patients. The type and number of TIICs in microenvironment of GC, as well as immune-related genes are closely related to tumor progression, and can be used as important indicators for patient prognosis assessment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Yuan, Liang, Zhang, Li, Xie, Li, Jiang, Li, Shen, Pang, Zou, Zhou, Li and Hu.)

Background: Synovial sarcoma (SS) is a type of soft tissue sarcoma (STS) of undetermined tissue origin, which is characterized by the recurrent pathognomonic chromosomal translocation t (X;18)(p11.2; q11.2). Studies have shown that SS is a malignant tumor originating from cancer stem cells or pluripotent mesenchymal stem cells and may be related to fusion genes. In addition, some studies have indicated that the induction of epithelial-mesenchymal transition (EMT) via the TGF-β1/Smad signaling pathway leads to SS metastasis., Methods: We analyzed the effects of SYT-SSX1 on the stemness of SS cells via TGF-β1/Smad signaling in vitro. The SYT-SSX1 fusion gene high expression cell was constructed by lentiviral stable transfer technology. SYT-SSX1 and SW982 cells were cultured and tested for sphere-forming ability. The transwell migration assay and flow cytometry were used to assess the migration ability of the sphere cells as well as the expression of CSC-related markers. We treated SYT-SSX1 cells with rhTGF-β1 (a recombinant agent of the TGF-β1 signaling pathway) and SB431542 and observed morphological changes. A CCK-8 experiment and a western blot (WB) experiment were conducted to detect the expression of TGF-β1 signaling pathway- and EMT-related proteins after treatment. The SYT-SSX1 cells were then cultured and their ability to form spheres was tested. Flow cytometry, WB, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of CSC surface markers on SYT-SSX1 sphere cells., Results: It was found that SYT-SSX1 has stronger sphere-forming ability, migration ability, and higher expression of CSC-related molecules than SW982 cells. Through treating SYT-SSX1 and SW982 cells with rhTGF-β1 and SB431542, we found that TGF-β1 enhanced the proliferation of cells, induced EMT, and that TGF-β1 enhanced the characteristics of tumor stem cells., Conclusions: Our results suggest that SYT-SSX1 enhances invasiveness and maintains stemness in SS cells via TGF-β1/Smad signaling. These findings reveal an effective way to potentially improve the prognosis of patients with SS by eliminating the characteristics of cancer stem cells (CSCs) during treatment., (© 2022. The Author(s).)

Objectives: High-risk human papillomavirus (HR-HPV) is an important risk factor for esophageal cancer. Macrophages constitute a crucial immune medium for regulating HPV-related tumors; however, the specific regulatory mechanisms remain unknown. Therefore, the purpose of our current study was to investigate the mechanism by which HPV16E6 regulates macrophages to promote the invasion and metastasis of esophageal cancer., Methods: HPV16E6 infection was detected by polymerase chain reaction. Immunohistochemistry was used to verify the distribution of tumor-associated macrophages (TAMs) and MMP-9 expression in esophageal squamous cell carcinoma tissues (ESCCs), and cancer adjacent normal tissues (CANs) from Kazakh patients. ESCC cells were transfected with a plasmid over-expressing HPV16E6 and non-contact cocultured with macrophages., Results: The infection rate of HPV16E6 in Kazakh ESCCs was clearly higher than that in CANs (P < 0.05). The density of CD163-positive TAMs was significantly positively correlated with HPV16E6 infection in ESCCs (P < 0.05). After coculturing macrophages and EC9706 cells transfected with the HPV16E6 plasmid, the phenotype of macrophages transformed into M2 macrophages. The migration and invasion ability of ESCC cells were higher in the HPV16E6-transfected and coculture group than in the HPV16E6 empty vector-transfected and non-cocultured HPV16E6-transfected groups (all P < 0.05). The density of M2-like TAMs in ESCCs was positively correlated with the level of MMP-9 expression. MMP-9 expression in the HPV16E6-ESCC coculture macrophages group was substantially higher than that in controls (all P < 0.05)., Conclusions: HPV16 infection mediates tumor-associated macrophages to promote ESCC invasion and migration., (© 2021. Federación de Sociedades Españolas de Oncología (FESEO).)

Objective: To explore the effects of gut microbiota and the serum level of folicacid on psychiatric symptoms in first-episode, drug-free schizophrenic (SCZ) patients. Methods: A total of 100 first-episode, drug-free SCZ patients (SCZ group) from the First Affiliated Hospital of Zhengzhou University and 90 demographically matched healthy individuals (healthy control group) were enrolled. The serum level of folic acid was measured by the electrochemical luminescence method.Positive and Negative Syndrome Scale (PANSS) was used to assess the psychiatric symptoms and Matrics Consensus Cognitive Battery (MCCB) was used to evaluate cognitive function. Bacterial DNA was extracted from the fecal samples for high-through put sequencing of the 16S rRNA.The effects of gut microbiota and folic acid on the psychiatric symptoms and cognitive function in SCZ patients were explored. Results: A total of 41 males and 59 females, with an age of (22.6±8.2) years were included in the patient group, and 32 males and 58 females with an age of (23.0±3.0) years were included in the healthy control group. The fasting folic acid level inserum of the SCZ group was lower than that of healthy control group [6.92(4.98, 8.49) μg/L vs 8.93(7.13, 13.37) μg/L, P <0.001]. The relative abundance of genus Bifidobacterium [0.005(0.003, 0.013) vs 0.014(0.004, 0.031)] and genus Bacteroides [0.015(0.001, 0.091) vs 0.083(0.029, 0.193)]was lower in the SCZ group than that of the healthy control group (both P <0.001). In comparison with the healthy control group, scores of cognitive function in the seven domains were significantly lower in the SCZ group (all P <0.05). In the patient group, the serum level of folic acid was negatively related to the negative symptom score( r =-0.378, P <0.001), but had a positive correlation with the score of speed of processing ( r =0.310, P =0.011).In the SCZ group, the relative abundance of the genus Bifidobacterium was positively correlated with the serum level of folic acid ( r =0.374, P <0.001) and the score of speed of processing( r =0.330, P =0.003) respectively, but was negatively correlated with the general psychopathology score ( r =-0.326, P =0.001). The results of multiple linear regression analysis showed that the interaction term between folic acid and genus Bifidobacterium in in SCZ patients were correlated with the general psychopathology score, with a regression coefficient of -29.240 ( F =8.655, P =0.007). There was no statistical correlation between the aforementioned interaction term and cognitive function (both P >0.05). Conclusion: In first-episode, drug-free SCZ patients, there were decreases in the serum folic acid level and the relative abundance of genus Bifidobacterium , which were related to the psychiatric symptoms, suggesting that these two substances can be used as potential objective indicators for evaluating psychiatric symptoms.

About 45% of the world's fruit and vegetables are wasted, resulting in postharvest losses and contributing to economic losses ranging from $10 billion to $100 billion worldwide. Soft rot disease caused by Rhizopus stolonifer leads to postharvest storage losses of sweet potatoes. Nanoscience stands as a new tool in our arsenal against these mounting challenges that will restrict efforts to achieve and maintain global food security. In this study, three nanomaterials (NMs) namely C 60 , CuO, and TiO 2 were evaluated for their potential application in the restriction of Rhizopus soft rot disease in two cultivars of sweet potato (Y25, J26). CuO NM exhibited a better antifungal effect than C 60 and TiO 2 NMs. The contents of three important hormones, indolepropionic acid (IPA), gibberellic acid 3 (GA-3), and indole-3-acetic acid (IAA) in the infected J26 sweet potato treated with 50 mg/L CuO NM were significantly higher than those of the control by 14.5%, 10.8%, and 24.1%. CuO and C 60 NMs promoted antioxidants in both cultivars of sweet potato. Overall, CuO NM at 50 mg/L exhibited the best antifungal properties, followed by TiO 2 NM and C 60 NM, and these results were further confirmed through scanning electron microscope (SEM) analysis. The use of CuO NMs as an antifungal agent in the prevention of Rhizopus stolonifer infections in sweet potatoes could greatly reduce postharvest storage and delivery losses.

Introduction: Synovial sarcoma (SS) is one of the most invasive soft tissue sarcomas, prone to recurrence and metastasis, and the efficacy of surgical treatment and chemotherapy for SS remains poor. Therefore, the diagnosis and treatment of SS remain a significant challenge. This study aimed to analyze the mutated genes of primary SS (PSS) and recurrent SS (RSS), discover whether these sarcomas exhibit some potential mutated genes, and then predict associated microRNAs (miRNA) and circular RNAs (circRNA) by analyzing the mutated genes. We focused on the regulation mechanism of the circRNA-miRNA-mutated hub gene in PSS and RSS. Methods: We performed a comprehensive genomic analysis of four pairs of formalin-fixed paraffin-embedded samples of PSS and RSS, using Illumina human exon microarrays. The gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) function, and pathway enrichment of the mutated genes were analyzed, and the protein-protein interaction (PPI) network was forecast using String software 11.0. The hub genes were then obtained using the Molecular Complex Detection (MCODE) plug-in for Cytoscape 3.7.2 and were used to analyze overall survival (OS) using the Gene Expression Profiling Interactive Analysis (GEPIA) database. The corresponding miRNAs were obtained from the miRDB 5.0 and TargetScan 7.2 databases. The corresponding circRNAs of the hub genes were found through the miRNAs from these databases: Circbank, CircInteractome, and StarBase v2.0. Thereafter we set up a competing endogenous RNA (ceRNA) network with circRNA-miRNA and miRNA-messenger RNA (mRNA) pairs. Results: Using the chi-squared test, 391 mutated genes were screened using a significance level of p -values < 0.01 from the four pairs of PSS and RSS samples. A GO pathway analysis of 391 mutated genes demonstrated that differential expression mRNAs (DEmRNAs) might be bound up with the "positive regulation of neurogenesis," "cell growth," "axon part," "cell-substrate junction," or "protein phosphatase binding" of SS. The PPI network was constructed using 391 mutated genes, and 53 hub genes were identified ( p < 0.05). Eight variant hub genes were discovered to be statistically significant using the OS analysis ( p < 0.05). The circRNA-miRNA-mRNA (ceRNA) network was constructed, and it identified two circRNAs (hsa&#95;circ&#95;0070557 and hsa&#95;circ&#95;0070558), 10 miRNAs (hsa-let-7a-3p, hsa-let-7b-3p, hsa-let-7f-1-3p, hsa-let-7f-2-3p, hsa-mir-1244, hsa-mir-1197, hsa-mir-124-3p, hsa-mir-1249-5p, hsa-mir-1253, and hsa-mir-1271-5p) and five hub genes (CENPE, ENPP3, GPR18, MDC1, and PLOD2). Conclusion: This study screened novel biological markers and investigated the differentiated circRNA-miRNA-mutated hub gene axis, which may play a pivotal role in the nosogenesis of PSS and RSS. Some circRNAs may be deemed new diagnostic or therapeutic targets that could be conducive to the future clinical treatment of SS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yao, He, Wang, Dong, Tu He Ta Mi Shi, Feng, Chen, Pang, Zou, Zhou, Li and Qi.)

Synovial sarcoma (SS) is an aggressive malignancy of an unknown tissue origin that is characterized by biphasic differentiation. A possible basis of the pathogenesis of SS is pathognomonic t(X;18) (p11.2; q11.2) translocation, leading to the formation and expression of the SYT-SSX fusion gene. More than a quarter of the patients die of SS metastasis within 5 years after the diagnosis, but the pathogenic factors are unknown. Therefore, there is an urgent need to explore the pathogenesis, invasion, metastasis, and clinical treatment options for SS, especially molecular-targeted drug therapy. Recent studies have shown that the SYT-SSX fusion gene associated with SS may be regulated by different signaling pathways, microRNAs, and other molecules, which may produce stem cell characteristics or promote epithelial-mesenchymal transition, resulting in SS invasion and metastasis. This review article aims to show the relationship between the SYT-SSX fusion gene and the related pathway molecules as well as other molecules involved from different perspectives, which may provide a deeper and clearer understanding of the SYT-SSX fusion gene function. Therefore, this review may provide a more innovative and broader perspective of the current research, treatment options, and prognosis assessment of SS., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Background: Acute exacerbation is a primary cause of repeated hospitalization and death in chronic obstructive pulmonary disease (COPD) patients. Therefore, how to control the symptoms of COPD at stable stage and reduce the number of acute exacerbation is a hot spot of medical research. Acupoint application (AA) is a significant part of external treatment of traditional Chinese medicine (TCM), Previous researches have reported that AA can be applied to the treatment of COPD. Nevertheless, its effectiveness is still inconclusive. This systematic review (SR) and meta-analysis is designed to appraise its effectiveness and safety for the treatment of patients with COPD., Methods: Eight databases will be systematically retrieved from their inceptions to February 2021. Inclusion criteria are randomized control trials of AA combined with routine western medicine interventions in the treatment of COPD at stable stage. The primary outcomes we focus on comprise clinical effective rate, TCM symptom score, quality of life, dyspnea, exercise capacity, lung function, frequency of acute exacerbation, adverse events. The research screening, data extraction, and risk of bias assessment will be conducted by 2 individuals independently, and divergence will be adjudicated by a third senior investigator. The Stata 13.1 software will be used for meta-analysis. The confidence of evidence will be classified adopting grading of recommendations assessment, development and evaluation (GRADE) algorithm and methodological quality of this SR will be assessed using assessment of multiple systematic reviews-2 (AMSTAR-2) tool., Results: This SR will provide evidence-based medical proof for the treatment of COPD at stable stage by AA combined with conventional western medicine interventions. The findings of this SR will be presented at relevant conferences and submitted for peer-review publication., Conclusions: The findings of this SR will provide up-todated summary proof for evaluating the effectiveness and safety of AA for COPD., Registration Number: INPLASY 202140080., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Macrophages are a double-edged sword with potential cancer-promoting and anticancer effects. Controversy remains regarding the effect of macrophages, especially M1 macrophages, on tumor promotion and suppression. We aimed to investigate the role of M1 macrophages in the occurrence and progression of esophageal squamous cell carcinoma (ESCC). Analyzing the data in Gene Expression Omnibus database by the CIBERSORT algorithm found that M1 macrophages were one of the important components of many immune cells in ESCCs, and the increase in their number was obviously negatively correlated with tumor T staging. This result was verified by our experimental data: the density of CD68/HLA-DR double-stained M1 macrophages in ESCC tumor nest and tumor stroma was significantly higher than that in cancer-adjacent normal (CAN) tissues. The density of M1 macrophages in ESCC tumor nest was negatively correlated with the patient's lymph node metastasis and clinical stage (P < 0.05), and the negative tendency was more obvious for M1 macrophages in ESCC tumor stroma (P < 0.001). Exposure to M1 macrophage-conditioned medium inhibited ESCC cell migration and invasion ability significantly (P < 0.05). Moreover, the increased M1 macrophage density in ESCC tumor stroma correlated positively with good prognosis of ESCC. M1 macrophages were involved in inhibiting ESCC cell migration and invasion, which could serve as a good prognostic factor in patients with ESCC., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: This meta-analysis was designed to systematically evaluate whether autologous cytokine-induced killer cells (CIK) or dendritic cells and cytokine-induced killer cells (DC-CIK) immunotherapy combined with chemotherapy can improve the therapeutic effect and safety of chemotherapy in esophageal cancer (EC)., Materials and Methods: Randomized controlled trials (RCTs) were electronically searched databases including CNKI, WanFang, WeiPu, CBMDisc, PubMed, Web of Science, EMbase, the Cochrane Library, and Clinical Trials. The databases were searched for articles published until June 2019. Two researchers independently screened the literature, extracted data, and evaluated the quality of the included literature. Meta-analysis was performed using RevMan5.3., Results: Seventeen studies (1416 participants) were included. The differences between CIK/DC-CIK combination chemotherapy and chemotherapy alone were significant. The results displayed that the number of CD3+, CD4+, CD4+/CD8+, and NK cells was significantly increased after 1 to 2 weeks of treatment with CIK/DC-CIK cells in the treatment group (all P < .05). In addition, the results shown that 1-year overall survival was significantly prolonged (P < .0001) and quality of life was improved (P = .001) in EC chemotherapy combined with immunotherapy groups compared with conventional treatment. Furthermore, cytokine expression levels of interleukin 2 (IL-2), tumor necrosis factor α (TNF-α), and interleukin 12 (IL-12) were significantly increased (P = .0003) as well as the levels of immunoglobulins were elevated (P < .00001). Serum levels of tumor marker molecules, carcinoembryonic antigen (CEA), carbohydrate antigen (CA)-199, and CA-125 were lower in treatment groups than that of control groups (P < .00001). No fatal adverse reactions were noted (P = .04)., Conclusions: It is safe and effective for patients to use chemotherapy combined with CIK/DC-CIK immunotherapy. Immunotherapy can simultaneously improve the antitumor immune response. Specifically, DC-CIK cells can increase T lymphocyte subsets, CIK cells, NK cells, and immunoglobulins in peripheral blood to enhance antitumor immunity. Therefore, combination therapy enhances the immune function and improves the therapeutic efficacy of patients with EC., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

The immune response facilitated by tumor-associated macrophages is a vital determinant of tumor progression. We identified differentially expressed genes between various macrophage phenotypes in the Gene Expression Omnibus, and used Kaplan-Meier Plotter to determine which of them altered the prognosis of esophageal carcinoma patients. Fibrinogen-like protein 2 ( FGL2 ), an immunosuppressive factor in the tumor microenvironment of various cancers, was upregulated in M2 macrophages, and higher FGL2 expression was associated with poorer survival in esophageal carcinoma patients. Using the TIMER database, we found that FGL2 expression correlated positively with the levels of immune markers of infiltrating B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells in esophageal carcinoma samples. Correlation analyses in cBioPortal revealed that the mRNA levels of FGL2 correlated strongly with those of interleukin 10, matrix metalloproteinase 9, C-C motif chemokine ligand 5, T-cell immunoglobulin mucin 3, interleukin 13, vascular cell adhesion molecule 1, macrophage colony-stimulating factor and fibroblast growth factor 7 in esophageal carcinoma tissues. The same cytokines were upregulated when esophageal squamous cell carcinoma cells were co-cultured with M2-like tumor-associated macrophages. Thus, by secreting FGL2, M2-like tumor-associated macrophages may create an immunosuppressive tumor microenvironment that induces the occurrence and progression of esophageal carcinoma.

Background: The therapeutic strategies of idiopathic pulmonary fibrosis (IPF) tend to be comprehensive. Improving the major symptoms and quality of life (QoL) is as important as postponing the process of fibrosis. However, only pirfenidone and nintedanib conditionally recommended by guidelines and no definite proof indicate that they can significantly ameliorate the main symptoms and QoL of IPF sufferers. At present, multiple types of Traditional Chinese Medicine (TCM) interventions alone or in combination with conventional western medicine managements are widespreadly applied in IPF treatment, which seemingly have a promising clinical effect, especially in ameliorating the main symptoms and improving QoL. Subsequently, the number of relevant studies in systematic reviews(SRs) and meta-analyses of randomized controlled trials(RCTs) increased significantly. Hence, we plan to implement an overview to collect, evaluate, and summarize the results of these SRs., Methods: An all-round literature retrieval will be conducted in 9 electronic databases, including PubMed, EMBASE, CINAHL, Cochrane Library, Epistemonikos, CNKI, CBM, Wanfang, and VIP. We will focus on the systematic review and meta-analysis of RCTs for multiple TCM interventions alone or in combination with routine western medicine measures in IPF treatment. The main outcomes we follow with interest include the improvement of major symptoms (cough, dyspnea) and QoL. Secondary outcomes will consist of minor symptoms improvement, clinical total effective rate, lung function, blood gas analysis, 6-minute walk text, adverse events, acute exacerbation, all-cause mortality, and IPF-related mortality. Two reviewers will independently select the SRs satisfactory with the enrolling criteria, extract key characteristics, and datas on predefined form, evaluate methodological quality by AMSTAR-2, ROBIS and PRISMA tools, and the quality of evidences adopting GRADE method. In case of any divergence will be reached an agreement by discussion or adjudicated by a third senior reviewer. We will perform a narrative synthesis of the proofs from SRs included., Results: The findings of this overvew will be presented at relevant conferences and submitted for peer-review publication., Conclusions: We expect to obtain comprehensive and reliable evidence of IPF treated by diversified TCM interventions from the potential standard SRs, which may provide suggestions for future RCTs and SRs., Registration Number: INPLASY 202080110.

Introduction: Androgen deprivation therapy (ADT) remains the mainstay of treatment for metastatic prostate cancer (mPCa) but is associated with significant morbidities. Comparisons of medical castration (MC) and surgical orchidectomy (SO) have yielded varied results. We aimed to evaluate the oncological outcomes, adverse effect (AE) profiles and costs of MC and SO in patients with mPCa., Methods and Materials: We reviewed 523 patients who presented with de novo mPCa from a prospectively maintained prostate cancer database over 15 years (2001-2015). All patients received ADT (either MC or SO) within 3 months of diagnosis. The data were analyzed with chi-square, binary and logistics regression models., Results: One hundred and fifty one (28.9%) patients received SO while 372 (71.1%) patients had MC. The median age of presentation was 73 [67 -79] years old. The median prostate-specific antigen (PSA) was 280ng/ml [82.4-958]. Three hundred and thirty one patients (66.3%) had high volume bone metastasis and 57 patients (10.9%) had visceral metastasis. Clinical demographics and clinicopathological were similar across both groups. Similar oncological outcomes were observed in both groups. The proportion of PSA response (PSA <1ng/ml) was 65.6% for SO and 67.2% for MC (P = 0.212). Both therapies achieve >95% of effective androgen suppression (testosterone <50ng/dL). Time to castrate-resistance was similar (18 vs 16 months, P = 0.097), with comparative overall survival (42 vs. 38.5 months, P = 0.058) and prostate cancer mortality (80.1 vs. 75.9%, P = 0.328). Similarly, no difference was observed for the 4 AE profiles between SO and MC respectively; change in Haemoglobin (-0.75 vs. -1.0g/dL, P = 0.302), newly diagnosed Diabetes mellitus (4.6 vs. 2.9%, P = 0.281), control measured by HbA1c (0.2 vs. 0.25%, P = 0.769), coronary artery disease events (9.9 vs. 12.9%, P = 0.376) and skeletal-related fractures (9.3 vs. 7.3%, P = 0.476). After adjusting for varying governmental subsidies and inflation rates, the median cost of SO was $5275, compared to MC of $9185.80., Conclusion: Both SO and MC have similar oncological outcomes and AE profiles. However, SO remains a much more cost-effective form of ADT for the long-term treatment of mPCa patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The goal of this study was to determine whether the plasma leptin, nesfatin-1, cortisol, brain-derived neurotrophic factor (BDNF), and inflammatory cytokines could be used as potential biomarkers for the degree of craving in the alcohol-dependent patients after 1 month of abstinence. A total of 83 patients with alcohol use disorder (AUD) and 61 healthy subjects were assessed. Patients with AUD were selected from Department of Material Dependence, Anhui Mental Health Center, and subjects in the control group were selected from healthy volunteers. The Alcohol Urge questionnaire Scale (AUQ) was used to evaluate the extent of craving for alcohol, and the Michigan Alcoholism Screening Test (MAST), the Fagerstrom Test for Nicotine Dependence (FTND), the Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS) were also assessed in patients with AUD. Enzyme-Linked Immunosorbent Assay (ELISA) was used for the measurement of plasma leptin, nesfatin-1, cortisol, BDNF, Interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) levels. Compare with healthy controls, the average leptin, leptin/BMI, IL-6, CRP, and TNF-α levels in patients with AUD were significantly increased, while the BDNF levels were significantly decreased. Moreover, the partial correlational analysis showed that the AUQ scores of the alcohol-dependent patients were positively correlated with the plasma leptin levels ( r = 0.613, P < 0.001), rather than nesfatin-1 ( r = 0.066, P = 0.569) after controlling for age as covariate. Furthermore, plasma nesfatin-1 levels were found to be correlated with the SDS scores ( r = 0.366, P = 0.001) in the AUD group. In addition, plasma leptin levels were positively associated with the plasma IL-6 ( r = 0.257, P = 0.033), CRP ( r = 0.305, P = 0.011), and TNF-α ( r = 0.311, P = 0.009) levels, and negatively associated with the BDNF levels ( r = -0.245, P = 0.042) in patients with AUD. These results suggest that plasma leptin, but not nesfatin-1, might be a potential biomarker for the degree of craving in alcohol-dependent patients after 1 month of abstinence, the mechanism of which might be related to the dysfunction of the inflammatory cytokines and BDNF levels., (Copyright © 2020 Xu, Ge, Chen, Liang, Pang, Gao, Cao, Shan, Liu, Yan and Xia.)

Background: Hepatocellular carcinoma (HCC) is the most common type of liver tumour, and is closely related to liver cirrhosis. Previous studies have focussed on the pathogenesis of liver cirrhosis developing into HCC, but the molecular mechanism remains unclear. The aims of the present study were to identify key genes related to the transformation of cirrhosis into HCC, and explore the associated molecular mechanisms., Methods: GSE89377, GSE17548, GSE63898 and GSE54236 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analysed to obtain differentially expressed genes (DEGs) between HCC and liver cirrhosis tissues, and network analysis of protein-protein interactions (PPIs) was carried out. String and Cytoscape were used to analyse modules and identify hub genes, Kaplan-Meier Plotter and Oncomine databases were used to explore relationships between hub genes and disease occurrence, development and prognosis of HCC, and the molecular mechanism of the main hub gene was probed using Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis., Results: In total, 58 DEGs were obtained, of which 12 and 46 were up- and down-regulated, respectively. Three hub genes (CDKN3, CYP2C9 and LCAT) were identified and associated prognostic information was obtained. CDKN3 may be correlated with the occurrence, invasion, and recurrence of HCC. Genes closely related to changes in the CDKN3 hub gene were screened, and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway analysis identified numerous cell cycle-related genes., Conclusion: CDKN3 may affect the transformation of liver cirrhosis into HCC, and represents a new candidate molecular marker of the occurrence and progression of HCC.

Background: Gallbladder squamous cell carcinoma (GBSCC) is a rare subtype of malignancy and accounts for only 2%-3% of gallbladder malignancies. Due to its rapid development, most patients with GBSCC initially present with an advanced stage of the disease and hence a poor prognosis. The clinicopathological and biological features of SCC remain to be fully elucidated, owing to its uncommon occurrence. The majority of currently available data only described individual case reports or series analyses of trivial cases., Case Summary: A 64-year-old man was admitted for progressively poor abdominal distension and pain. Liver computed tomography (CT) showed infiltration of gallbladder carcinoma into the adjacent liver, and enlarged retroperitoneal lymph nodes. The patient underwent radical cholecystectomy. Part of the mass was grey and soft, and the neoplastic section showed a purulent-necrotic lesion. Hematoxylin and eosin staining revealed a moderately differentiated SCC. Immunohistochemical studies showed strong staining of the tumor for AE1/3 and CK5/6. Staining for CK19, CK7, and CAM5.2 was positive in the cytoplasm. Systemic chemotherapy was not administered because of the patient's poor physical condition. After five months, CT and magnetic resonance cholangiopancreatography showed multiple metastases in the liver and abdominal cavity., Conclusion: Squamous components of GBSCC may explain the complex biological behavior, and CD109 may be involved in the pathogenesis., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: The morbidity of idiopathic pulmonary fibrosis (IPF) was found in an increasing trend, progressive worsening of symptoms and deterioration in lung function tend to trigger off a lower quality of life (QoL). Only pirfenidone and nintedanib have been recommended in the guidelines, which can modify the disease process. However, no evidence was verified to significantly alleviate the main clinical manifestations of IPF. At present, Chinese herbal formula (CHF) is widely prescribed as an adjunct to western medicine to treat the disease, and have shown promising benefits on clinical symptoms and QoL. There are mainly 3 Traditional Chinese Medicine (TCM) treatment methods guiding the composition of CHFs, which are devoting to comfort the common symptoms of IPF. Nevertheless, the paucity of direct comparative evidence of them posed a challenge for clinicians to determine the relative merits options. Therefore, we formulate this protocol, which is described for a systematic review to investigate relative advantages among different TCM treatment method and provide more reliable evidence for clinical decision-making., Methods and Analysis: A systematic literature search will be employed in 10 electronic databases. Inclusion criteria are randomized control trials of CHFs composed based on the 3 TCM treatment methods, which act as an adjuvant treatment with routine drugs, compared with routine drugs alone. The primary outcomes we focus on include St George's Hospital Respiratory Questionnaire (SGRQ) scores, TCM symptom (dyspnea, cough) scores. The research screening, data extraction, and methodological quality assessment will be conducted by 2 individuals separately, and dispute will be adjudicated by a third senior reviewer. We will employ network meta-analysis (NMA) in a Bayesian framework with vague priors and the surface under the cumulative ranking curve (SUCRA) to obtain the comprehensive rank for the 3 TCM treatment methods., Results: This systematic review will provide an evidence of CHFs composed under the guidance by 3 TCM treatment methods with routine drugs, compared with routine drugs alone for IPF, and will submit to a peer-reviewed journal for publication., Conclusion: The conclusion of this systematic review will provide evidence for relative advantages among the 3 TCM treatment methods.

Objective: To investigate whether craving and demographic factors to predict relapse in alcohol dependence., Methods: This study was a prospective cohort study. From August 2017 to August 2018, 158 Han male inpatients who met the diagnositic and statistical manual disorders-fourth version(DSM-IV) alcohol dependence diagnostic criteria were recruited from three mental hospitals in China. The participants were interviewed at baseline and followed up by telephone after 3 months for assessment. The baseline assessment after the acute withdrawal period included demographic data and alcohol-related data, clinical institute withdrawal assessment-advanced revised (CIWA-Ar), withdrawal and cue-induced craving on visual analog scale (VAS), Michigan alcoholism screening test (MAST), self-rating anxiety scale (SAS), self-rating depression scale (SDS) and alcohol urge questionnaire (AUQ). According to the follow-up results, "relapse" was defined as the consumption of beverages containing ethanol at any time during the follow-up study, and "time to relapse" was defined as the number of days from the first drinking to the baseline. Whether relapse occurred and the time to relapse were the primary endpoints. Cox proportional hazard regression model was used to analyze the factors affecting the relapse of alcohol dependence., Results: In the study, 158 alcohol dependence patients were finally included, age from 21 to 60 years, with the mean age of (40.31±9.14) years. The relapse rate was 63.7% three months after baseline assessment. According to Cox univariate analysis and multivariate analysis, the age (OR=0.975, P=0.030) and CIWA-Ar scores (OR=1.126, P=0.010) significantly predicted relapse. And there was no significant difference in education level, marital status, withdrawal and cue-induced craving on VAS, SAS and SDS between the relapse group and the non-relapse group (P>0.05)., Conclusion: Age and severity of alcohol-dependent withdrawal symptoms during hospitalization are significantly related to relapse for alcohol in alcohol-dependent patients. To be exact, the older age is a protective factor, that is to say, the younger patients are prone to relapse, while the risk of relapse is raised by the higher severity of withdrawal symptoms. However, neither cue-induced nor withdrawal craving can predict relapse of alcohol-dependent patients.

Mitogen-activated protein kinase kinase kinase 3 (MAP3K3), a member of the serine/threonine protein kinase family, is ubiquitously expressed and acts as an oncogene. However, the expression and exact molecular mechanism of MAP3K3 in ovarian carcinoma (OC) remain unclear. Here, we found that MAP3K3 protein was highly expressed in 70.5% of high-grade serous ovarian carcinoma (HGSOC) samples. MAP3K3 overexpression was significantly associated with the FIGO stage and chemotherapy response. Additionally, MAP3K3 overexpression was associated with reduced disease-free survival and overall survival. In vitro experiments showed that MAP3K3 overexpression promoted cell proliferation, inhibited apoptosis, and enhanced the migration and invasion of OC cells. Moreover, in vivo tumourigenesis experiments confirmed that silencing MAP3K3 significantly reduced the growth rate and volume of transplanted tumours in nude mice. Drug sensitivity experiments demonstrated that differential expression of MAP3K3 in OC cell lines correlates with chemotherapy resistance. Functionally, the MAP3K3 gene regulated the malignant biological behaviour of OC cells by mediating NF-κB signalling pathways, affecting the downstream epithelial-mesenchymal transition and cytoskeletal protein expression. Our results unveiled the role of MAP3K3 in mediating NF-κB signalling to promote the proliferation, invasion, migration, and chemotherapeutic resistance of OC cells, highlighting a potential new therapeutic and prognostic target.

Esophageal squamous cell carcinoma (ESCC) is a highly invasive disease with a poor long-term survival rate. Although there has been progress in understanding the pathogenesis of ESCC, there are currently no molecular biomarkers that are used in routine clinical practices to determine prognosis. Therefore, the aim of this study was to determine a small immunohistochemical panel that could predict the prognosis of patients with ESCC. Phospholipase C epsilon-1 (PLCE1), IKKα, IKBα, p65, and p53 were highly expressed in ESCC tissues. The high expression level of PLCE1, IKBα, and p53 showed a significant positive correlation with a short overall survival (P = .022, .009, and .024, respectively). This 3-biomarker panel (ie, PLCE1, IKBα, and p53) was found to be a predictor of ESCC, with a worse overall survival as each positive marker was added (hazard ratio, 1.553; 95% confidence interval, 1.166-2.067; P = .003). In another cohort (including 1922 esophageal endoscopic biopsy tissues), the lesions of 28 patients were aggravated. Three proteins (PLCE1, 12/28 [42.86%]; IKBα, 16/28 [57.14%]; p53, 16/28 [57.14%]) were immunoreactive in patients with progressive disease. Our study identified and validated that this immunohistochemical biomarker panel of 3 proteins, consisting of PLCE1, IKBα, and p53, is not only independently associated with an unfavorable outcome for ESCC patients but also able to predict disease progression to precancerous lesions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Renal cancer represents about 3% of all human cancers. Clear cell renal cell carcinoma (ccRCC) is the main type of renal cancer. MicroRNAs (miRNAs) have been reported to play crucial roles in the carcinogenesis of human cancers. This study was aimed to investigate the expression of miR-1294 and the mechanisms underlying miR-1294-mediated ccRCC progression., Materials and Methods: The miR-1294 expression levels in ccRCC cell lines were analyzed by quantified real time-PCR (qRT-PCR). The effect of the miR-1294 expression on the overall survival of ccRCC patients was analyzed by the Kaplan-Meier Plotter. Cell proliferation, colony growth, and cell invasion were examined by cell counting kit-8 assay, colony formation assay, and transwell invasion assay, respectively. The luciferase activity reporter assay and Western blot assay were conducted to validate the connection between miR-1294 and homeobox A6 (HOXA6)., Results: MiR-1294 was downregulated in ccRCC cell lines and correlated with the poor overall survival of ccRCC patients. The overexpression of miR-1294 inhibits ccRCC cell proliferation, colony growth, and cell invasion. HOXA6 was validated as a target of miR-1294 and negatively regulated by miR-1294. The overexpression of HOXA6 attenuated the miR-1294-mediated effects on ccRCC cellular functions., Conclusions: Our results indicated that miR-1294 functions as a tumor suppressor in ccRCC. MiR-1294 suppressed cell proliferation, colony formation, and invasion in ccRCC partially via targeting HOXA6.

Objective: To explore the possible role of Irisin in antipsychotic drug-induced insulin resistance and abdominal obesity in patients with schizophrenia and to provide a theoretical basis for the prevention of antipsychotic drug-induced obesity. Methods: Fifty-five patients with first-episode schizophrenia, from the First Affiliated Hospital of Zhengzhou University, between January 2016 and December 2017, were admitted as well as fifty healthy controls during the same period. Serum Irisin levels were measured by enzyme-linked immunosorbent assay (ELISA). Fasting blood glucose (FBG), fasting insulin (INS), homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride (TG), total cholesterol (TCHO), highdensity lipoprotein (HDL), low density lipoprotein (LDL) were detected. Results: The average Irisin level ((233±228) mmol/L) was higher than that in the normal control group ((124±89) mmol/L) ( P <0.05).Repeated measurement analysis of variance showed that the average levels of the height, waist, FBG, INS, TCHO, TG, HDL, LDL, BMI, HOMA-IR and Irisin at the end of the 12(th) and 24(th) week's treatment were higher than baseline ( P <0.05). After correlation analysis, the level of Irisinat baseline was positively correlated with HOMA-IR ( r =0.383, P <0.05). At the 12(th) week, the level of Irisin was positively correlated with waist circumference, and HOMA-IR ( r =0.360, r =0.475, all P <0.05). Multiple linear regression analysis showed that at the 12(th) week's treatment, compared with the baseline period, changes of Irisin was positively correlated with waist circumference and HOMA-IR, respectively ( β =0.453, β =0.420, both P <0.05). Conclusion: Irisin may be involved in the process of metabolic regulation and bean early predictor of antipsychotic drug-induced insulin resistance and abdominal obesity.

Objective: To observe the relationship between serum oxidative stress as well as brain-derived neurotrophic factor (BDNF) and cognitive function in first-episode drug-free schizophrenics, and to explore the possible effect of oxidative stress in cognitive impairment of first-episode schizophrenia. Methods: A total of 125 first-episode drug-free schizophrenics (schizophrenia group) from the First Affiliated Hospital of Zhengzhou University and 80 healthy individuals (control group) were enrolled. The serum concentration of oxidized glutathione (GSSG) was measured by the Microenzyme method the serum concentration of nitric oxide (NO) was measured by one-step method, the BDNF level was measured by enzyme linked immunosorbent assay and Matrics Consensus Cognitive Battery(MCCB) was used to evaluate the cognitive function. Results: (1)The serum level of BDNF in schizophrenia group (2 763±1 728 pg/ml) was significantly lower than that in control group (4 165±1 299 pg/ml)( P< 0.001). And the serum levels of GSSG and NO in schizophrenia group ((36±9), (81±65) μmol/L) were significantly higher than that in control group ((27±11), (24±16) μmol/L) ( P< 0.001). In comparison with the control group scores were significantly lower in the seven domains of cognitive function in the schizophrenia group (all P< 0.001). (2)After controlling the confounding factors like age, gender, cultural differences and course of disease by partial correlation analysis, the correlation analysis showed that: serum level of BDNF in schizophrenia group had positive correlation with Information processing rate T points, attentional facilitating T points, working memory T points and Reasoning and problem solving T points ( r= 0.417, 0.206, 0.247, 0.318, all P< 0.05). In schizophrenia group the serum level of GSSG had a negative correlation with information processing rate T points and reasoning and problem solving T points ( r= -0.321, -0.231, all P< 0.05). The serum level of NO was negatively related to Information processing rate T points working memory T points Verbal learning T points( r= -0.201, -0.193, -0.237, all P< 0.05). Conclusions: Oxidative stress may be involved in the cognitive impairment of schizophrenia Oxidation products are risk factors for cognitive impairment of schizophrenia and BDNF is a protective factor of cognitive function.

Increasing evidence indicates that tumor-initiating cells (TICs) are responsible for the occurrence, development, recurrence, and development of the drug resistance of cancer. MicroRNA (miRNA) plays a significant functional role by directly regulating targets of TIC-triggered non-small-cell lung cancer (NSCLC), but little is known about the function of the miR-30 family in TICs. In this study, we found the miR-30 family to be downregulated during the spheroid formation of NSCLC cells, and patients with lower miR-30a/c expression had shorter overall survival (OS) and progression-free survival (PFS). Moreover, transmembrane 4 super family member 1 (TM4SF1) was confirmed to be a direct target of miR-30a/c. Concomitant low expression of miR-30a/c and high expression of TM4SF1 correlated with a shorter median OS and PFS in NSCLC patients. miR-30a/c significantly inhibited stem-like characteristics in vitro and in vivo via suppression of its target gene TM4SF1, and then it inhibited the activity of the mTOR/AKT-signaling pathway. Thus, our data provide the first evidence that TM4SF1 is a direct target of miR-30a/c and miR-30a/c inhibits the stemness and proliferation of NSCLC cells by targeting TM4SF1, suggesting that miR-30a/c and TM4SF1 may be useful as tumor biomarkers for the diagnosis and treatment of NSCLC patients., (Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Hsa-MicroRNA-124a-3p (hsa-miR-124-3p) is involved in tumor progression in certain malignant tumors. However, its function and clinical implication in hepatocellular carcinoma (HCC) have not yet been illustrated. In this study, we explored the expression and prognostic value of hsa-miR-124-3p in patients with HCC. Hsa-miR-124-3p expression in HCC was analyzed in silico, which was subsequently confirmed by quantitative PCR in 155 HCC biopsy samples. Overall survival (OS) and disease-free survival in HCC patients was evaluated by Kaplan-Meier survival analysis, and univariate and multivariate Cox proportional hazard models were used. The in silico results demonstrated that hsa-miR-124-3p was reduced in cell lines and tissues of HCC, and hsa-miR-124-3p expression was lower in HCC tumor samples than in normal liver tissues. Moreover, a decrease in hsa-miR-124-3p expression was closely correlated with tumor diameter (≥ 5 cm) and number of lesions (multiple). Lower hsa-miR-124-3p expression was shown to be correlated with a shorter OS and poor prognosis in HCC. Our findings demonstrate that hsa-miR-124-3p might be a potential target for the diagnosis and prognosis of HCC.

Objective: To develop an effective, low-cost, single-visit cervical screening strategy incorporating a modified Pap test and visual inspection with acetic acid and Lugol's iodine for low-income settings., Methods: We conducted a prospective cohort trial. Two low-income Muslim Uyghur communities in China's far western Kashi Prefecture served as pilot and validation study sites, respectively, and 4,049 women (aged 30-59 years) were screened. The conventional Pap test was modified using a cotton swab to collect cervical cells without scraping the cervix using an Ayre spatula, allowing visual inspection with acetic acid (and visual inspection with Lugol's iodine if visual inspection with acetic acid was negative) to be performed in a single visit. Results from both tests were available within 1-2 hours. Women positive for either or both underwent same-day biopsy that was shipped by a courier service to a central pathology laboratory., Results: Single-visit screening incorporating both a modified Pap test and visual inspection achieved a sensitivity of 96.0% (95% CI 91.6-100), which was superior to Pap testing (76%, 95% CI 66.3-85.7; P<.001) or visual inspection with acetic acid-visual inspection with Lugol's iodine (48%, 95% CI 36.7-59.3; P<.001) alone in detecting cervical intraepithelial neoplasia (CIN) 2 or worse lesions. Rapid interpretation of both diagnostic procedures facilitated efficient same-day biopsy that achieved a negative predictive value of 98.2% in detecting CIN 2 or worse lesions. The increased sensitivity and minimized loss of follow-up allowed this approach to identify an extremely high prevalence of CIN 1 (2,741/100,000, 95% CI 2,238-3,245/100,000), CIN 2 or 3 (1,457/100,000, 95% CI 1,088-1,826/100,000), and cervical cancer (395/100,000, 95% CI 202-589/100,000) among these underscreened, at-risk women., Conclusion: Single-visit cervical screening with both a modified Pap test and visual inspection has greater sensitivity to detect high-grade CINs, reduces loss of follow-up, and could be an efficient low-cost strategy for low-resource settings.

Background: Postoperative delirium is a prevalent and disabling mental disorder in patients undergoing on-pump cardiac surgery. There is some evidence that the use of pharmacological interventions may reduce the risk of developing of postoperative delirium. Therefore, the aim of this meta-analysis was to determine the effect of pharmacologic agents for the prevention postoperative delirium after cardiac surgery., Methods: Randomized controlled trials (RCTs) were identified through a systematic literature search of electronic databases and article references up to October 2016. End points included incidence of postoperative delirium, severity of postoperative delirium, cognitive disturbances of postoperative delirium, duration of postoperative delirium, length of stay in intensive care unit (ICU) and hospital, and short-term mortality., Results: A total of 14 RCTs with an aggregate of 14,139 patients were included. The results of the present meta-analysis show that pharmacologic agents significantly decrease postoperative delirium [relative risk (RR), 0.83; 95% confidence interval (95% CI), 0.75-0.91, P < .00001] and duration of postoperative delirium (RR = -0.37, 95% CI = -0.47 to -0.27, P < .00001) after on-pump cardiac surgery. In addition, subgroup analysis shows that dexamethasone and dexamethasone were associated with a trend toward a reduction in postoperative delirium (RR, 0.45; 95% CI, 0.30-0.66, P < .0001; RR, 0.80; 95% CI, 0.68-0.93, P = .003, respectively). However, our results fail to support the assumption that pharmacologic prophylaxis is associated with a positively reduction in short-term mortality, length of ICU, or hospital stay., Conclusion: This meta-analysis suggests that the perioperative use of pharmacologic agents can prevent postoperative delirium development in patients undergoing cardiac surgery. However, there remain important gaps in the evidence base on a few small studies with multiple limitations. Further large-scale, high-quality RCTs are needed in this area.

Aim: To explore the association between the determinant factors including HLA-DQB1*03, DRB1-*07, -*13 and high-risk HPV infection, the cervical squamous cell carcinoma (CSCC) pathogenesis among Chinese Uighur and Han population., Materials & Methods: HLA alleles were genotyped by PCR sequence-specific primers., Results: HPV16 infection rate was significantly higher among the Uighurs and Hans with CSCC as compared with healthy controls, respectively. HLA-DQB1*03 significantly increased among Uighurs with CSCC, while HLA-DRB1*07 significantly increased among Hans with CSCC. Similar tendencies were observed for DQB1*03 with HPV16-positive Uighurs CSCC and DRB1*07 with HPV16-positive Hans CSCC., Conclusion: This study suggests that HLA-DQB1*03 and DRB1*07 alleles may influence the immune response to HPV16 infection and increase the risk of CSCC among the Uighurs and Hans in China.

Synovial sarcoma (SS) is a mesenchymal malignant neoplasm showing characteristics of epithelial-mesenchymal biphasic differentiation. SS is of uncertain cellular origin; however, studies have suggested that SS originates from a somatic stem cell population. In this study, we aim to determine whether differential morphological features of the epithelial-mesenchymal transition (EMT) contributed to the tumourigenesis of SS invasion and metastasis. Twelve paraffin-embedded formalin-fixed tissue (FFPE) SS tissue specimens were obtained, and laser capture microdissection (LCM) with the ArcturusXT system and small chip method (SCM) were used to isolate and purify spindle and epithelial cells from SS specimens. The TRIzol method was used to extract RNA, and the mRNA levels of EMT-related genes in epithelial and spindle cells of SS specimens were measured using real-time fluorescent quantitative reverse transcription polymerase chain reaction (qRT-PCR). The results show that collection of about 2 × 10 4 cells from FFPE samples using LCM was sufficient for qRT-PCR, with an efficiency of 75%. Compared with LCM, 72.2% (13 of 18) RNA samples were successfully extracted using SCM to isolate cells from FFPE SS tissues. In the 16 samples (11 spindle cell samples and 5 epithelial cell samples), Snail mRNA was significantly upregulated in spindle cell areas compared with that in epithelial cell areas (P = .001). Expression levels of the epithelial marker E-cadherin and the mesenchymal marker N-cadherin were not significantly different between epithelial and spindle cell areas. In spindle cells of recurrent SS samples, the mRNA levels of E-cadherin, N-cadherin, Snail, and Slug were higher in primary SS samples than in recurrent samples. Taken together, our results indicated that in SS samples, Snail mRNA was upregulated in spindle cell areas compared with that in epithelial cell areas and that the expression of EMT-related genes was increased in primary SS. LCM could be used to isolate and purify RNA from FFPE samples., (© 2018 John Wiley & Sons Australia, Ltd.)

The present study was to investigate the role of the interaction between canonical transient receptor potential channel 1 (TRPC1) and calcium release-activated calcium modulator 1 (Orai1) in extracellular Ca 2+ -sensing receptor (CaR)-induced extracellular Ca 2+ influx and nitric oxide (NO) production. Human umbilical vein endothelial cells (HUVECs) were incubated with CaR agonist Spermine [activating store-operated calcium channels (SOC) and receptor-operated calcium channels (ROC)] alone or in combination with the following reagents: CaR negative allosteric modulator Calhex231 plus ROC analogue TPA (activating ROC and blocking SOC), Ro31-8220 (PKC inhibitor that activates SOC and blocks ROC) or Go6967 (PKCs and PKCµ inhibitor that activates SOC and blocks ROC). The protein expressions and co-localization of TRPC1 and Orai1 were determined using immunofluorescent staining. The interaction between TRPC1 and Orai1 was examined by co-immunoprecipitation. We silenced the expressions of their genes in the HUVECs by transfection of constructed TRPC1 and Orai1 shRNA plasmids. Intracellular Ca 2+ concentration ([Ca 2+ ] i ) was detected using Ca 2+ indicator Fura-2/AM, and NO production was determined by DAF-FM staining. The results showed that TRPC1 and Orai1 protein expressions were co-located on the cell membrane of the HUVECs. Compared with Spermine+Ca 2+ group, Calhex231+ TPA+Spermine+Ca 2+ , Ro31-8220+Spermine+Ca 2+ and Go6976+Spermine+Ca 2+ groups exhibited down-regulated protein expressions of TRPC1 and Orai1 in cytoplasm and decreased co-localization on the cell membrane. Co-immunoprecipitation results showed that the interaction between TRPC1 and Orai1 was reduced by Calhex231 plus TPA, Ro31-8220 or Go6976 addition in the Spermine-stimulated HUVECs. Double knockdown of Trpc1 and Orai1 genes significantly decreased [Ca 2+ ] i level and NO production in all of the Spermine+Ca 2+ , Calhex231+TPA+Spermine+Ca 2+ , Ro31-8220+Spermine+Ca 2+ and Go6976+Spermine+Ca 2+ groups. These results suggest that TRPC1/Orai1 may form a complex that mediates Ca 2+ influx and No production via SOC and ROC activation.

A novel quaternary ammonium polyethylene nonwoven fabric for removing chromium ions from water was prepared via radiation-induced grafting of glycidyl methacrylate and further modification with N,N'-dimethylethylenediamine. The structural and morphological characteristics of the adsorbent were analyzed using Fourier transform infrared spectroscopy (FTIR), thermogravimetry and differential thermogravimetry (TG/DTG), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). The influences of several principal factors, including pH value, initial Cr(VI) concentration, contact time, and coexisting anions (including SO 4 2- , CO 3 2- , NO 3 - , PO 4 3- , and Cl - ), on adsorption performance were investigated via batch tests. The results showed that the optimum removal efficiency was 99.2% at pH 3 and the maximum adsorption quantity for Cr(VI) at 25 °C was 336 mg/g. The adsorption kinetic parameters were better fitted with the pseudo-second-order kinetic model, and the equilibrium data were described very well by the Freundlich isotherm model. Furthermore, the as-synthesized adsorbent exhibited excellent regeneration and recyclability while maintaining high adsorption performance after five adsorption/desorption cycles.

Objective: To explore the relationship of serum level of homocysteine (Hcy) and insulin resistance with cognitive function in first-episode drug-free schizophrenics. Methods: A total of 80 first-episode drug-free schizophrenics (schizophrenia group) from the First Affiliated Hospital of Zhengzhou University and 70 healthy individuals (control group) were enrolled.The serum concentration of Hcy was measured by the enzymatic cycling assay, the concentration of serum fast blood-glucose(FPG) by glucose oxidase method and fast insulin (FINS) by electrical chemiluminescence immunoassay.Then insulin resistance index was calculated in the form of HOMA-IR.Positive and Negative Syndrome Scale (PANSS) was used to evaluate the mental symptoms and Matrics Consensus Cognitive Battery (MCCB) was used to evaluate the cognitive function. Results: (1) The serum level of Hcy in schizophrenia group [(24±6) μmoL/L]was significantly higher than that in control group[(16±4) μmoL/L] ( P <0.001). And the serum level of FINS in schizophrenia group [(8.0±2.1) mU/L] was significantly higher than that in control group[(6.0±1.3) mU/L] ( P <0.001). The HOMA-IR of schizophrenia group (1.6±0.5) was higher than that of control group (1.3±0.4) ( P <0.001). The serum level of Hcy in schizophrenia group had positive correlations with serum FINS level, HOMA-IR and negative symptoms ( r =0.365, 0.354 and 0.233, all P <0.05). In comparison with the control group , scores were significantly lower in the seven domains of cognitive function in the schizophrenia group (all P <0.05). (2) In schizophrenia group, the serum level of Hcy had a negative correlation with Information processing rate P points, Attentional facilitating P points , and Verbal learning P points ( r =-0.231, -0.339, -0.255, all P <0.05); the serum level of FINS was negatively related to Attentional facilitating P points, Working memory P pointsand Visual memory P points ( r =-0.317, -0.309, -0.318, all P <0.05); HOMA-IR had a negative correlation with Attentional facilitating P points, Working memory P points, and Visual memory P points ( r =-0.286, -0.224, -0.266, all P <0.05). After the influencing factors were adjusted by multiple regression, the associations of serum Hcy level with Information processing rate P points, Attentional facilitating P points and Verbal learning P points were still evident, and HOMA-IR was still related with Attentional facilitating P points and Visual memory P points (all P <0.05). Conclusion: The increase of serum Hcy and insulin resistance in first-episode schizophrenics, both have some relevance with cognitive dysfunction.

Objective: To investigate the interaction of Ca(2+) protein TRPC1 and STIM1 in extracellular Ca(2+) -sensing receptor (CaR)-induced extracellular Ca(2+) influx and the production of nitric oxide (NO). Methods: Human umbilical vein endothelial cells (HUVECs) were cultured and incubated with CaR agonist spermine (activating store-operates cation channels (SOC) and receptor-operated channels (ROC)), CaR negative allosteric modulator Calhex231 (blocking SOC, activating ROC) and ROC analogue TPA (activating ROC, blocking SOC), protein kinase C (PKC) inhibitor Ro31-8220, PKCs and PKCμ inhibitor Go6967(activate SOC, blocking ROC), respectively. The interaction of TRPC1 and STIM1 was determined using the immunofluorescence methods. The interaction between TRPC1 and STIM1 were examined by Co-immuno precipitation. The HUVECs were divided into: TRPC1 and STIM1 short hairpin RNA group (shTRPC1+ shSTIM1 group), vehicle-TRPC1+ vehicle-STIM1 group and control group. The cells were incubated with four different treatments under the action of above mentioned interventions, intracellular Ca(2+) concentration ([Ca(2+) ](i)) was detected using the fluorescence Ca(2+) indicator Fura-2/AM, the production of NO was determined by DAF-FM. Results: (1) The expression of TRPC1 and STIM1 proteins levels in HUVECs: Under the confocal microscope, TRPC1 and STIM1 protein expression showed masculine gender, both located in cytoplasm in the normal control group. Post incubation with Calhex231+ TPA, Ro31-8220 and Go6967, TRPC1 and STIM1 positioned in cytoplasm was significantly reduced, and the combined TRPC1 and STIM1 was also significantly reduced. (2) The interaction of TRPC1 and STIM1 in HUVECs: The relative ratios of Calhex231+ TPA+ Spermine+ Ca(2+) group, Ro31-8220+ Spermine+ Ca(2+) group and Go6976+ Spermine+ Ca(2+) group STIM1/TRPC1 and TRPC1/STIM1 were as follows: (25.98±2.17)% and (44.10±4.01)%, (20.85±1.01)% and (46.31±3.47)%, (23.88±2.05)% and (39.65±2.91)%, which were significantly lower than those in the control group (100.00±4.66)% and (100.00±6.40)% and in the Spermine+ Ca(2+) group (106.04±2.45)% and (107.78±2.66)% (all P <0.05). (3) The influence of joint TRPC1 and STIM1 transfection to four different drugs treated HUVECs on [Ca(2+) ](i) and NO generation: The changes of two excitation fluorescence intensity ratio and NO net fluorescence intensity values were consistent, [Ca(2+) ](i) and NO net fluorescence intensity values were significantly lower in the experimental group than the control group and the vehicle group (all P <0.05), while which were similar between the vehicle group and control group (all P >0.05). Conclusions: Our results indicate that TRPC1 and STIM1 jointly regulate CaR-mediated Ca(2+) influx and nitric oxide generation in HUVECs in the form of binary complex.

Tumor-associated macrophages (TAMs), the most important immune cells in tumor microenvironment, were reported to play a key role in cancer progression, but the correlation of TAMs and Kazakh esophageal squamous cell carcinoma (ESCC) was still not clear, so we sought to identify the function of TAMs in Kazakh ESCC clinicopathological and prognostic evaluation. CD68 as the TAMs marker, and immunohistochemistry (IHC) was used to quantify the TAMs infiltrated in tumor nest and stroma, the IHC staining was also used to evaluate the expression of MMP-9 in Kazakh ESCCs. The density of CD68-TAMs in ESCCs tumor nest and stromal, were significantly higher than those of CANs (P<0.05). The increasing number of CD68-positive TAMs in tumor nest and stromal were positively associated with tumors lymph node metastasis and clinical stage (P<0.05). The expression of MMP-9 in Kazakh ESCCs was higher than that of CAN tissues (P<0.05). Increased MMP-9 expression in ESCCs was significantly associated with lymph node metastasis and tumor clinical stage (P<0.05). Importantly, the number of CD68-positive TAMs in ESCCs was significantly correlated with the expression of MMP-9 (P<0.05). Furthermore, the survival analyses demonstrated that high-density of CD68-TAMs in tumor nest was positively related to the shorter overall survival time of patients (P<0.05). Increasing numbers of CD68-TAMs promote higher expression of MMP-9 and may play an important role in the occurrence and progression of Kazakh ESCCs, and which could be used as important prognostic markers for Kazakh ESCCs., Competing Interests: None., (IJCEP Copyright © 2017.)

M2 macrophages was domesticated by tumor microenvironment to produce some angiogenic molecules and protease, facilitating angiogenesis and matrix breakdown, promoting tumor invasive and metastasis. However, The function of M2 macrophages to progression of eophageal carcinoma, especially Kazakh esophageal carcinoma is still dimness. This study aims to investigate M2 macrophages correlated with matrix metalloproteinase-9 (MMP9) and microvessel density, and the role in the progression of Kazakh esophageal squamous cell carcinoma. CD163 and CD34 as the marker of M2 macrophages and endothelial cells, were used to identify the M2 macrophages density and microvessel density, respectively. Immunohistochemistry staining was evaluated the expression of MMP9. The number of infiltrated CD163-positive M2 macrophages in tumor islets and stroma was significantly higher than in cancer adjacent normal tissues. The increased of M2 macrophages and microvessel density were significantly correlated with more malignant phenotypes including lymph node metastasis and clinical stage progression. Meanwhile, the expression of MMP9 showed much higher level in esophageal squamous cell carcinoma than that in cancer adjacent normal tissues, and high expression of MMP9 in Kazakh esophageal squamous cell carcinoma was significantly associated with age, depth of tumor invasion, lymph node metastasis, and tumor clinical stage. The quantity of M2 macrophages in tumor stroma was positively associated with microvessel density and the expression of MMP9, and as an independent poorly prognostic factor for overall survival time of Kazakh esophageal squamous cell carcinoma. These findings suggest the increased number of M2 macrophages correlated with high expression of MMP9 and high microvessel density may contribute to the tumor aggressiveness and angiogenesis, promoting the progression of Kazakh esophageal squamous cell carcinoma.

Tumor associated macrophages (TAMs) play an important role in the growth, progression, and metastasis of tumors. The distribution of TAMs in Kazakh esophageal squamous cell carcinoma (ESCC) is not determined. We aimed to investigate the role of TAMs in the occurrence and progression of Kazakh ESCC. CD163 was used as the TAM marker, and immunohistochemistry (IHC) counts were used to quantify the density of TAMs in tumor nest and surrounding stroma. IHC staining was used to evaluate the expression of vascular endothelial growth factor C (VEGF-C) in Kazakh ESCC and cancer adjacent normal (CAN) tissues. The density of TAMs in Kazakh ESCCs tumor nest and stromal was significantly higher than that in CAN tissues. The increased number of CD163-positive TAMs in tumor nest and tumor stromal was positively associated with Kazakh ESCC lymph node metastasis and clinical stage progression. Meanwhile, the expression of VEGF-C in Kazakh ESCCs was significantly higher than that in CAN tissues. Overexpression of VEGF-C in Kazakh ESCCs was significantly associated with gender, depth of tumor invasion, lymph node metastasis and tumor clinical stage. The increased number of TAMs, either in the tumor nests or tumor stroma was positively correlated with the overexpression of VEGF-C, which may promote lymphangiogenesis and play an important role in the invasion and metastasis of Kazakh ESCC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To explore hormone such as follicle-stimulating hormone (FSH), luteinizing (LH), prolactin (PRL), estradiol (E2), progesterone (PROG) and testosterone (TESTO) levels in first-episode drug-free schizophrenics, and the relationship between clinical symptoms and sex hormones, in order to further study the pathogenesis of schizophrenia., Methods: Eighty-one first-episode drug-free schizophrenics including thirty-nine male and forty-two female from First Affiliated Hospital of Zhengzhou University and seventy healthy subjects (thirty male and forty female) were enrolled.Serum levels of hormone were measured using electrical chemiluminescence immunoassay, and Positive and Negative Syndrome Scale (PANSS) was used to evaluate the mental symptoms and Matrics Consensus Cognitive Battery (MCCB) was used to evaluate cognitive function., Results: (1) The serum levels of PRL in male patients group ((24±9) ng/ml) was higher than that of control group ((10±3) ng/ml) (P<0.05), the serum levels of E2, TESTO of male patients group ((29±10) ng/ml), ((3.2±1.7) ng/ml) was lower than that of control group ((35±11) ng/ml), ((4.4±1.6) ng/ml) (P<0.05); The serum levels of PRL, TESTO of female patients group ((29±16) ng/ml), ((0.5±0.4) ng/ml) were dramatically higher than that of control group ((13±5) ng/ml), ((0.3±0.1) ng/ml) (P<0.05), the serum levels of E2 of female patients group ((51±40) ng/ml) was lower than that of control group ((63±66) ng/ml) (P=0.05). (2) The serum levels of PRL, E2, TESTO in male patients group were negatively associated with negative symptoms (r=-0.478,-0.443,-0.576, P<0.05), PRL were negatively related to positive symptoms (r=-0.542, P<0.05); In female patients group, the serum levels of PRL were negatively associated with negative symptoms (r=-0.343, P<0.05), the serum levels of E2 was negatively related to positive symptoms, general psychopathology grade, total PANSS grade (r=-0.351,-0.487,-0.405, P<0.05), TESTO had a positive correlation with positive symptoms (r=0.445, P<0.05). (3) In male patients group, PRL had an negative correlation with working memory P point, reasoning and problem solving P points (r=-0.384,-0.374, P<0.05), the serum levels of E2 was positively related to Information processing rate P points, Visual memory P points, Reasoning and problem solving P points (r=0.379, 0.336, 0.407, P<0.05), TESTO had a positive correlation with Information processing rate P points, Visual memory P points, Reasoning and problem solving P points (r=0.564, 0.513, 0.552, P<0.05). In female patients group, PRL had an negative correlation with working memory P point, Reasoning and problem solving P points and social cognition P points (r=-0.303,-0.358,-0.368, P<0.05), the serum levels of E2 was positively related to working memory, Reasoning and problem solving P points, social cognition P points (r=0.376, 0.453, 0.355, P<0.05)., Conclusions: Our study shows that first-episode drug-free schizophrenics have hormone secretion abnormal, which suggests that hypothalamus-hypophysis-gonad axis may probably involve in physiopathologic mechanism of first-episode medicine-free schizophrenics.Slightly elevated serum PRL level may be the reaction of stress response in first-episode medicine-free schizophrenics.Endogenous testosterone and estradiol may protect cognitive function against recession, and declining of testosterone and estradiol in blood is the hazards of cognitive dysfunction in first-episode drug-free male schizophrenics. PRL, E2, TESTO may be one of the measurements of the severity of clinical symptoms.