The upregulation and transcriptional regulatory mechanisms of Extra spindle pole bodies like 1 in bladder cancer: An immunohistochemistry and high-throughput screening Evaluation.

Background: This study aimed to explore the expression level and transcriptional regulation mechanism of Extra Spindle Pole Bodies Like 1 (ESPL1) in bladder cancer (BC). Methods: A multicentre database of samples (n = 1391) was assayed for ESPL1 mRNA expression in BC and validated at the protein level by immunohistochemical (IHC) staining of in-house samples (n = 202). Single-cell sequencing (scRNA-seq) analysis and enrichment analysis explored ESPL1 distribution and their accompanying molecular mechanisms. ATAC-seq, ChIP-seq and Hi-C data from multiple platforms were used to investigate ESPL1 upstream transcription factors (TFs) and potential epigenetic regulatory mechanisms. Immune-related analysis, drug sensitivity and molecular docking of ESPL1 were also calculated. Furthermore, upstream microRNAs and the binding sites of ESPL1 were predicted. The expression level and early screening efficacy of miR-299-5p in blood (n = 6625) and tissues (n = 537) were examined. Results: ESPL1 was significantly overexpressed at the mRNA level (p < 0.05, SMD = 0.75; 95 % CI = 0.09, 1.40), and IHC staining of in-house samples verified this finding (p < 0.0001). ESPL1 was predominantly distributed in BC epithelial cells. Coexpressed genes of ESPL1 were enriched in cell cycle-related signalling pathways, and ESPL1 might be involved in the communication between epithelial and residual cells in the Hippo, ErbB, PI3K-Akt and Ras signalling pathways. Three TFs (H2AZ, IRF5 and HIF1A) were detected upstream of ESPL1 and presence of promoter-super enhancer and promoter-typical enhancer loops. ESPL1 expression was correlated with various immune cell infiltration levels. ESPL1 expression might promote BC growth and affect the sensitivity and therapeutic efficacy of paclitaxel and gemcitabine in BC patients. As an upstream regulator of ESPL1, miR-299-5p expression was downregulated in both the blood and tissues, possessing great potential for early screening. Conclusions: ESPL1 expression was upregulated in BC and was mainly distributed in epithelial cells. Elevated ESPL1 expression was associated with TFs at the upstream transcription start site (TSS) and distant chromatin loops of regulatory elements. ESPL1 might be an immune-related predictive and diagnostic marker for BC, and the overexpression of ESPL1 played a cancer-promoting role and affected BC patients' sensitivity to drug therapy. miR-299-5p was downregulated in BC blood and tissues and was also expected to be a novel marker for early screening.

[Research progress on mechanism of traditional Chinese medicine intervention in angiogenesis in prevention and treatment of nontraumatic avascular necrosis of femoral head].

Nontraumatic avascular necrosis of the femoral head(NANFH) is a common and refractory femoral head disease that causes bone death due to interruption of blood supply. Early clinical symptoms are atypical, such as hip pain and limited joint function. In the late stage, severe pain, shortening of the affected limb, claudication, and other serious symptoms are common, which se-riously affects the quality of life of patients. Therefore, it is of great significance to actively improve the clinical symptoms of NANFH to enhance the quality of life of patients. The pathogenesis of NANFH is complex, such as traumatic vascular circulatory disorders, the use of hormones or other drugs, alcoholism, and diabetes mellitus. These factors directly or indirectly lead to femoral head vascular damage, thrombosis, and coagulation system disorders, which reduce the blood supply to the acetabulum and femoral head, thus causing ischaemic death of the femoral head or even femoral head collapse. NANFH is mainly categorized as "bone impotence" and "bone paralysis" in traditional Chinese medicine(TCM). The treatment of NANFH with TCM has the characteristics and advantages of a long history, stable and reliable therapeutic effect, fewer adverse reactions, good patient tolerance, and high acceptance. Previous studies have shown that the promotion of angiogenesis is a key initiative in the prevention and treatment of NANFH, and TCM can promote fe-moral head angiogenesis by interfering with the expression of angiogenesis-related factors, which in turn can help to restore the blood supply of the femoral head and thus improve clinical symptoms of NANFH and prevent and treat NANFH. This article described the roles of blood supply interruption and angiogenesis in NANFH and the accumulated knowledge and experience of TCM in NANFH and summarized the role of angiogenesis-related factors in NANFH and the research progress on TCM intervention, so as to provide an idea for the subsequent research and a new basis for the clinical application of TCM in the treatment of NANFH.

TM9SF1 promotes bladder cancer cell growth and infiltration.

BACKGROUND: Bladder cancer (BC) is the most common urological tumor. It has a high recurrence rate, displays tutor heterogeneity, and resists chemotherapy. Furthermore, the long-term survival rate of BC patients has remained unchanged for decades, which seriously affects the quality of patient survival. To improve the survival rate and prognosis of BC patients, it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention. Transmembrane 9 superfamily member 1 (TM9SF1), also known as MP70 and HMP70, is a member of a family of nine transmembrane superfamily proteins, which was first identified in 1997. TM9SF1 can be expressed in BC, but its biological function and mechanism in BC are not clear. AIM: To investigate the biological function and mechanism of TM9SF1 in BC. METHODS: Cells at 60%-80% confluence were transfected with lentiviral vectors for 48-72 h to achieve stable TM9SF1 overexpression or silencing in three BC cell lines (5637, T24, and UM-UC-3). The effect of TM9SF1 on the biological behavior of BC cells was then investigated through CCK8, wound-healing assay, transwell assay, and flow cytometry. RESULTS: Overexpression of TM9SF1 increased the in vitro proliferation, migration, and invasion of BC cells by promoting the entry of BC cells into the G2/M phase. Silencing of TM9SF1 inhibited in vitro proliferation, migration, and invasion of BC cells and blocked BC cells in the G1 phase. CONCLUSION: TM9SF1 may be an oncogene in BC.

What should be the future direction of development in the field of prostate cancer with lung metastasis?

BACKGROUND: Since the start of the 21st century, prostate cancer with lung metastasis (PCLM) has accumulated significant scientific research output. However, a systematic knowledge framework for PCLM is still lacking. AIM: To reconstruct the global knowledge system in the field of PCLM, sort out hot research directions, and provide reference for the clinical and mechanism research of PCLM. METHODS: We retrieved 280 high-quality papers from the Web of Science Core Collection and conducted a bibliometric analysis of keywords, publication volume, and citation frequency. Additionally, we selected differentially expressed genes from global high-throughput datasets and performed enrichment analysis and protein-protein interaction analysis to further summarize and explore the mechanisms of PCLM. RESULTS: PCLM has received extensive attention over the past 22 years, but there is an uneven spatial distribution in PCLM research. In the clinical aspect, the treatment of PCLM is mainly based on chemotherapy and immunotherapy, while diagnosis relies on methods such as prostate-specific membrane antigen positron emission tomography/computed tomography. In the basic research aspect, the focus is on cell adhesion molecules and signal transducer and activator of transcription 3, among others. Traditional treatments, such as chemotherapy, remain the mainstay of PCLM treatment, while novel approaches such as immunotherapy have limited effectiveness in PCLM. This study reveals for the first time that pathways related to coronavirus disease 2019, cytokine-cytokine receptor interaction, and ribosome are closely associated with PCLM. CONCLUSION: Future research should focus on exploring and enhancing mechanisms such as cytokine-cytokine receptor interaction and ribosome and improve existing mechanisms like cadherin binding and cell adhesion molecules.

Effects of surgical treatment modalities on postoperative cognitive function and delirium in elderly patients with extremely unstable hip fractures.

BACKGROUND: As the perioperative risk of elderly patients with extremely unstable hip fractures (EUHFs) is relatively high and therapeutic effect is not satisfactory, new thera-peutic strategies need to be proposed urgently to improve the efficacy and clinical outcomes of such patients. AIM: To determine the influence of two surgical treatment modalities on postoperative cognitive function (CF) and delirium in elderly patients with EUHFs. METHODS: A total of 60 elderly patients consecutively diagnosed with EUHF between September 2020 and January 2022 in the Chongqing University Three Gorges Hospital were included. Of them, 30 patients received conventional treatment (control group; general consultation + fracture type-guided internal fixation), and the other 30 received novel treatment (research group; perioperative multidisciplinary treatment diagnosis and treatment + individualized surgical plan + risk prediction). Information on hip function [Harris hip score (HHS)], perioperative risk of orthopedic surgery [Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM)], CF [Montreal cognitive assessment scale (MoCA)], postoperative delirium [mini-cognitive (Mini-Cog)], adverse events (AEs; internal fixation failure, infection, nonunion, malunion, and postoperative delirium), and clinical indicators [operation time (OT), postoperative hospital length of stay (HLOS), ambulation time, and intraoperative blood loss (IBL)] were collected from both groups for comparative analyses. RESULTS: The HHS scores were similar between both groups. The POSSUM score at 6 mo after surgery was significantly lower in the research group compared with the control group, and MoCA and Mini-Cog scores were statistically higher. In addition, the overall postoperative complication rate was significantly lower in the research than in the control group, including reduced OT, postoperative HLOS, ambulation time, and IBL. CONCLUSION: The new treatment modality has more clinical advantages over the conventional treatment, such as less IBL, faster functional recovery, more effectively optimized perioperative quality control, improved postoperative CF, mitigated postoperative delirium, and reduced operation-related AEs.

Hub genes, diagnostic model, and predicted drugs in systemic sclerosis by integrated bioinformatics analysis.

Background: Systemic sclerosis (scleroderma; SSc), a rare and heterogeneous connective tissue disease, remains unclear in terms of its underlying causative genes and effective therapeutic approaches. The purpose of the present study was to identify hub genes, diagnostic markers and explore potential small-molecule drugs of SSc. Methods: The cohorts of data used in this study were downloaded from the Gene Expression Complex (GEO) database. Integrated bioinformatic tools were utilized for exploration, including Weighted Gene Co-Expression Network Analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, gene set enrichment analysis (GSEA), Connectivity Map (CMap) analysis, molecular docking, and pharmacokinetic/toxicity properties exploration. Results: Seven hub genes (THY1, SULF1, PRSS23, COL5A2, NNMT, SLCO2B1, and TIMP1) were obtained in the merged gene expression profiles of GSE45485 and GSE76885. GSEA results have shown that they are associated with autoimmune diseases, microorganism infections, inflammatory related pathways, immune responses, and fibrosis process. Among them, THY1 and SULF1 were identified as diagnostic markers and validated in skin samples from GSE32413, GSE95065, GSE58095 and GSE125362. Finally, ten small-molecule drugs with potential therapeutic effects were identified, mainly including phosphodiesterase (PDE) inhibitors (BRL-50481, dipyridamole), TGF-ß receptor inhibitor (SB-525334), and so on. Conclusion: This study provides new sights into a deeper understanding the molecular mechanisms in the pathogenesis of SSc. More importantly, the results may offer promising clues for further experimental studies and novel treatment strategies.

CCNB1 is involved in bladder cancer pathogenesis and silencing CCNB1 decelerates tumor growth and improves prognosis of bladder cancer.

In search of an effective therapeutic target for bladder urothelial carcinoma (BLCA), the present study aimed to investigate the expression of cyclin B1 (CCNB1) and its putative mechanism in BLCA. BLCA sequencing data from Gene Expression Omnibus and The Cancer Genome Atlas were used to analyze expression of CCNB1 mRNA and high CCNB1 expression had a poorer prognosis compared with those with low expression. Immunohistochemistry (IHC) samples collected from the Human Protein Atlas database were analyzed for CCNB1 protein expression. Short hairpin (sh) CCNB1-transfected BLCA T24 and 5637 cells were used to investigate the effects of CCNB1 and inhibit the proliferation, migration and invasion of BLCA cells, affect the cell cycle distribution and promote apoptosis of 5637 cells. A sh-CCNB1 BLCA chicken embryo chorioallantoic membrane (CAM) transplantation model was established to observe the impacts of sh-CCNB1 on the tumorigenesis of BLCA in vivo. Analysis of sequencing data showed that CCNB1 mRNA was significantly elevated in tumor and BLCA compared with normal tissues [standardized mean difference (SMD)=1.21; 95% CI: 0.26-2.15; I²=95.9%]. IHC indicated that CCNB1 protein was localized in the nucleus and cytoplasm and was significantly increased in BLCA tumor tissues. The in vitro tests demonstrated that proliferation of T24 and 5637 cells transfected with sh-CCNB1 was significantly inhibited and cell migration and invasion ability were significantly decreased. sh-CCNB1 decreased the percentage of T24 cells in G0/G1, 5637 cells in the G0/G1 phase and S phase and increased percentage of 5637 cells in the G2/M phase and increased early apoptosis of 5637 cells. The in vivo experiments demonstrated that the mass of transplanted tumors was significantly decreased compared with the control group following silencing of CCNB1. The present results suggested that CCNB1 was involve in the development and prognosis of BLCA and silencing of CCNB1 may be a promising targeted therapy for BLCA.

High expression of centromere protein A and its molecular mechanism and clinical significance in prostate cancer: A study based on data mining and immunohistochemistry.

The progression of prostate cancer (PCa) leads to poor prognosis. However, the molecular mechanism of PCa is still not completely clear. This study aimed to elucidate the important role of centromere protein A (CENPA) in PCa. Large numbers of bulk RNA sequencing (RNA-seq) data and in-house immunohistochemistry data were used in analysing the expression level of CENPA in PCa and metastatic PCa (MPCa). Single-cell RNA-seq data was used to explore the expression status of CENPA in different prostate subpopulations. Enrichment analysis was employed to detect the function of CENPA in PCa. Clinicopathological parameters analysis was utilised in analysing the clinical value of CENPA. The results showed that CENPA was upregulated in PCa (standardised mean difference [SMD] = 0.83, p = 0.001) and MPCa (SMD = 0.61, p = 0.029). CENPA was overexpressed in prostate cancer stem cells (CSCs) with androgen receptor (AR) negative compared to epithelial cells with AR positive. CENPA may influence the development of PCa through affecting cell cycle. Patients with nodal metastasis had higher expression level of CENPA. And patients with high CENPA expression had poor disease-free survival. Taken together, Overexpression of CENPA may influence the development of PCa by regulating cell cycle and promoting metastasis.

Macrocycle Self-Assembly Hydrogel for High-Efficient Oil-Water Separation.

Supramolecular hydrogels involved macrocycles have been explored widely in recent years, but it remains challenging to develop hydrogel based on solitary macrocycle with super gelation capability. Here, the construction of lantern[33 ]arene-based hydrogel with low critical gelation concentration (0.05 wt%), which can be used for efficient oil-water separation, is reported. The lantern[33 ]arenes self-assemble into hydrogen-bonded organic nanoribbons, which intertwine into entangled fibers to form hydrogel. This hydrogel which exhibits reversible pH-responsiveness characteristics can be coated on stainless-steel mesh by in situ sol-gel transformation. The resultant mesh exhibits excellent oil-water separation efficiency (>99%) and flux (>6 × 104 L m-2 h-1 ). This lantern[33 ]arene-based hydrogel not only sheds additional light on the gelation mechanisms for supramolecular hydrogels, but also extends the application of macrocycle-based hydrogels as functional interfacial materials.

Nitidine chloride regulates cell function of bladder cancer in vitro through downregulating Lymphocyte antigen 75.

Nitidine chloride (NC) is effective on cancer in many tumors, but its effect on bladder cancer (BC) is unknown. We conducted cell function experiments to verify the antineoplastic effect of NC on BC cell lines (5637, T24, and UM-UC-3) in vitro. Then, mRNAs of NC-treated and NC-untreated BC cells were extracted for mRNA sequencing. Differentially expressed genes (DEGs), expression analysis, and drug molecular docking were conducted to discover the target gene of NC. Finally, functional enrichment was analyzed to explore the underlying mechanisms. NC dramatically inhibited proliferation, migration, and invasion, and it induced apoptosis and arrested the S and G2/M phases of BC cell lines. Lymphocyte antigen 75 (LY75) appeared to be the target of NC. LY75 was highly expressed and had the ability to distinguish BC tissue from non-cancerous tissue. Then, drug molecular docking confirmed the targeting relationship between NC and LY75. Gene enrichment analysis showed that the downregulated genes, after being treated with NC, were mainly enriched in pathways relevant to cell pathophysiological processes. NC inhibits BC cell proliferation, migration, and invasion, induces apoptosis, and arrests cell cycles by downregulating the expression of LY75. This study provides molecular and theoretical bases for NC treatment of BC.

Down-regulation and clinical significance of Sorbin and SH3 domain-containing protein 1 in bladder cancer tissues.

Bladder cancer (BC) is a common cancer worldwide with a high prevalence. This study was conducted to elucidate the expression and clinical significance of Sorbin and SH3 domain-containing protein 1 (SORBS1) in BC as well as to explore its molecular mechanism in BC tumourigenesis. RNA-sequencing data, microarray, and Immunohistochemistry (IHC) were applied to elucidated the SORBS1 expression at multiple levels. After that, the relationship between tumour-immune infiltration and SORBS1 was also explored. Finally, SORBS1-related genes in BC were identified to perform functional enrichment analyses. The expression integration revealed that the comprehensive expression of SORBS1 at the mRNA level was -1.02 and that at the protein level was -3.73, based on 12 platforms, including 1221 BC and 187 non-BC samples. SORBS1 was negatively correlated with tumour purity (correlation = -0.342, p < 0.001) and positively correlated with macrophage (correlation = 0.358, p < 0.001). The results of enrichment analyses revealed that the most significant biological pathways of SORBS1-related genes were epithelial-mesenchymal transition. SORBS1 was significantly down-regulated in BC and may play a role as tumour suppressor. This study provides new directions and biomarkers for future BC diagnosis.

Metadherin Promotes the Development of Bladder Cancer by Enhancing Cell Division.

Background: Bladder cancer (BLCA) is a malignant tumor occurring in bladder mucosa. Metadherin (MTDH) has been implicated in tumor progression; however, its molecular biological mechanisms in BLCA remain unclear. Materials and Methods: Cell functions were tested after BLCA cells were transfected by both short hairpin RNAs and small interfering RNAs to silence MTDH. Furthermore, in-house RNA sequencing (RNA-seq) was performed with T24 cells after the knockdown of MTDH. In addition, MTDH-related pathways were explored. Finally, MTDH mRNA and protein expression levels were examined using multiple detection methods in BLCA tissues. Results: MTDH knockdown could largely inhibit cell proliferation, viability, and migration and induce apoptosis of BLCA cells. In-house RNA-seq showed that MTDH knockdown led to extracellular matrix organization and cell division. The integrated analysis showed that the comprehensive expression of MTDH at the mRNA level was 0.47 and that at the protein level was 0.54, based on 11 platforms, including 1485 BLCA and 180 non-BLCA samples. Conclusions: MTDH promotes the growth of BLCA cells through the pathway of cell division. This study provides new directions and biomarkers for future treatment.

The expression characteristics and clinical significance of ACP6, a potential target of nitidine chloride, in hepatocellular carcinoma.

BACKGROUND: Acid phosphatase type 6 (ACP6) is a mitochondrial lipid phosphate phosphatase that played a role in regulating lipid metabolism and there is still blank in the clinico-pathological significance and functional roles of ACP6 in human cancers. No investigations have been conducted on ACP6 in hepatocellular carcinoma (HCC) up to date. METHODS: Herein, we appraised the clinico-pathological significance of ACP6 in HCC via organizing expression profiles from globally multi-center microarrays and RNA-seq datasets. The molecular basis of ACP6 in HCC was explored through multidimensional analysis. We also carried out in vitro and in vivo experiment on nude mice to investigate the effect of knocking down ACP6 expression on biological functions of HCC cells, and to evaluate the expression variance of ACP6 in xenograft of HCC tissues before and after the treatment of NC. RESULTS: ACP6 displayed significant overexpression in HCC samples (standard mean difference (SMD) = 0.69, 95% confidence interval (CI) = 0.56-0.83) and up-regulated ACP6 performed well in screening HCC samples from non-cancer liver samples. ACP6 expression was also remarkably correlated with clinical progression and worse overall survival of HCC patients. There were close links between ACP6 expression and immune cells including B cells, CD8 + T cells and naive CD4 + T cells. Co-expressed genes of ACP6 mainly participated in pathways including cytokine-cytokine receptor interaction, glucocorticoid receptor pathway and NABA proteoglycans. The proliferation and migration rate of HCC cells transfected with ACP6 siRNA was significantly suppressed compared with those transfected with negative control siRNA. ACP6 expression was significantly inhibited by nitidine chloride (NC) in xenograft HCC tissues. CONCLUSIONS: ACP6 expression may serve as novel clinical biomarker indicating the clinical development of HCC and ACP6 might be potential target of anti-cancer effect by NC in HCC.

Clinical significance and potential regulatory mechanism of overexpression of pituitary tumor-transforming gene transcription factor in bladder cancer.

BACKGROUND: Pituitary tumor transforming gene-1 (PTTG1) transcription factor is identified as carcinogenic and associated with tumor invasiveness, but its role in bladder cancer (BLCA) remains obscure. This research is intended to analyze the aberrant expression and clinical significance of PTTG1 in BLCA, explore the relationship between PTTG1 and tumor microenvironment characteristics and predict its potential transcriptional activity in BLCA tissue. METHODS: We compared the expression discrepancy of PTTG1 mRNA in BLCA and normal bladder tissue, using the BLCA transcriptomic datasets from GEO, ArrayExpress, TCGA, and GTEx. In-house immunohistochemical staining was implemented to determine the PTTG1 protein intensity. The prognostic value of PTTG1 was evaluated using the Kaplan-Meier Plotter. CRISPR screen data was utilized to estimate the effect PTTG1 interference has on BLCA cell lines. We predicted the abundance of the immune cells in the BLCA tumor microenvironment using the microenvironment cell populations-counter and ESTIMATE algorithms. Single-cell RNA sequencing data was applied to identify the major cell types in BLCA, and the dynamics of BLCA progression were revealed using pseudotime analysis. PTTG1 target genes were predicted by CistromeDB. RESULTS: The elevated expression level of PTTG1 was confirmed in 1037 BLCA samples compared with 127 non-BLCA samples, with a standardized mean difference value of 1.04. Higher PTTG1 expression status exhibited a poorer BLCA prognosis. Moreover, the PTTG1 Chronos genetic effect scores were negative, indicating that PTTG1 silence may inhibit the proliferation and survival of BLCA cells. With PTTG1 mRNA expression level increasing, higher natural killer, cytotoxic lymphocyte, and monocyte lineage cell infiltration levels were observed. A total of four candidate targets containing CHEK2, OCIAD2, UBE2L3, and ZNF367 were determined ultimately. CONCLUSIONS: PTTG1 mRNA over-expression may become a potential biomarker for BLCA prognosis. Additionally, PTTG1 may correlate with the BLCA tumor microenvironment and exert transcriptional activity by targeting CHEK2, OCIAD2, UBE2L3, and ZNF367 in BLCA tissue.

Decreased expression of transcription factor Homeobox A11 and its potential target genes in bladder cancer.

Bladder cancer (BC) ranks as the ninth most commonly diagnosed cancer worldwide. The presence of a transcription factor (TF) has been uncovered as a significant contributor to the pathophysiological changes of cancers. In present study, we elucidated the expression and clinical significance of Homeobox A11 (HOXA11) in BC for the first time, and originally investigated HOXA11 as a TF. Employing in-house immunohistochemistry (IHC), we incorporated 137 BC and 34 non-BC cases to detect the expression of HOXA11 protein in BC tissues. HOXA11-related RNA-sequencing (RNA-seq) expression and RNA microarrays were collected from public databases, the "sva" and "limma" R packages were implemented to integrate and normalize the RNA-seq data and microarrays separately. Integration expression was carried out to further evaluate the HOXA11 expression by utilizing the standard mean difference (SMD). The expression level of HOXA11 in various BC cell lines was also evaluated. We further systematically analyzed the downstream target genes of HOXA11 in BC by utilizing Chromatin Immunoprecipitation Sequencing (ChIP-seq) profiles, differentially expressed genes (DEGs), and HOXA11-related genes. Modification of histone marks on the promoter region of target genes were also discovered by histone ChIP-seq data. Results of the IHC and RNA-seq revealed the protein and mRNA expression of HOXA11 was significantly decreased in BC tissues compared to non-BC tissues (2.98 ± 1.48 vs. 8.23 ± 2.64; 6.87 ± 1.54 vs. 8.38 ± 1.42). Five platforms significantly revealed the down-regulation of HOXA11 expression in BC (GPL96, GPL570, GPL6102, GPL6884, and GPL13497). A similar decreased trend was discovered in BC tissues in expression integration with the incorporated SMD reaching -0.843 (-1.362 ~ -0.325, p = 0.001) and -1.051 (-1.674 ~ -0.428, p = 0.001). Expression of HOXA11 was down-regulated in most of the BC cell lines. COL1A1 was considered as a final HOXA11 target gene and positively related to HOXA11 with the correlation coefficient as 0.584 (95% CI: 0.371-0.739, p < 0.001). HOXA11 regulates COL1A1 expression in BC via H3K27ac modification. The expression of COL1A1 was down-regulated with the SMD reached -0.312 (p < 0.001). In conclusion, HOXA11 expression is markedly decreased and might promote the transcription of COL1A1 to inhibit BC.

UiO-66 Selective Enrichment Integrated with Thermal Desorption GC-MS for Detection of Benzene Homologues in Ambient Air.

In this study, UiO-66 was selected as sorbent media packed in the tube to selectively enrich trace levels of benzene homologues such as benzene, toluene, and xylene (BTX) in ambient air prior to thermal desorption (TD)-GC-MS determination. A series of experiments were conducted to obtain the optimal TD conditions. The results indicated that the optimal TD parameters were as follows: desorption temperature of 180°C, desorption flow rate of 50 mL min-1, and desorption time of 30 min. Furthermore, the method based on UiO-66 enrichment integrated with TD-GC-MS for trace levels of BTX was successfully developed. It exhibited a good linearity (R 2 > 0.99) in the range of 50-1000 ng, except for p, m-xylene in the range of 100-2000 ng, and achieved the recovery of 69.4-101.3%, and the relative standard deviation of 3.8-6.4%. The detection limits of BTX were 1.6-4.0 ng; according to 10 L of sampling volume, the method detection limits would be in the range of 0.16-0.40 µg m-3. Additionally, the method was successfully applied to determine BTX in indoor air and showed good selectivity and sensitivity. In summary, the findings in this work revealed that UiO-66 was an attractive adsorbent for selective enrichment trace levels of BTX compounds in ambient air, which was favorable for the subsequent detection by TD-GC-MS.

Conductive One-Dimensional Coordination Polymers with Tunable Selectivity for the Oxygen Reduction Reaction.

Conductive materials involving nonprecious metal coordination complexes as electrocatalysts for the oxygen reduction reaction (ORR) have received increasing attention in recent years. Herein, we reported efficient ORR electrocatalysts containing M-S2N2 sites with tunable selectivity based on simple one-dimensional (1D) coordination polymers (CPs). The 1D CPs were synthesized from M(OAc)2 and 2,5-diamino-1,4-benzenedithiol (DABDT) by a solvent thermal method. Due to their good electrical conductivities (10-6-10-2 S cm-1), the 1D CPs could be used as ORR catalysts in low catalytic amounts without the addition of carbon materials. Cobalt-based CPs showed a well-organized structure of nanosheets with Co-S2N2 sites exposed and exhibited remarkable electrocatalytic ORR activity (Eonset = 0.93 V vs reversible hydrogen electrode (RHE), E1/2 = 0.82 V, n = 3.85, JL = 5.22 mA cm-2, Tafel slope of 63 mV dec-1) in alkaline media. However, nickel-based CPs favored a 2e- ORR process with ∼87% H2O2 selectivity and an Eonset of 0.78 V. This work provides new opportunities for the construction of ORR catalysts based on conductive nonprecious metal CPs.

[Expression of Ras-Associated Protein 1 in the Vascular Endothelium of Bone Tissue with Non-Traumatic Osteonecrosis of Femoral Head].

Objective: To investigate the difference in the expression of Ras-associated protein 1 (Rap1) in necrotic and healthy areas of non-traumatic osteonecrosis of femoral head (NONFH) patients. Methods: Femoral head tissue samples from 30 cases of NONFH and 30 cases of traumatic osteonecrosis of the femoral head (TONFH) were collected after hip replacement surgery, respectively. No significant difference of Association Research Circulation Osseous (ARCO) staging was found between the NONFH and the TONFH groups ( Z=-0.769, P=0.442). In the NONFH group, 8 patients were ARCO stage IIIb, 10 were stage IV, and 12 were stage V, while in the TONFH ground, 11 patients were ARCO stage IIIb, 9 were stage IV, and 10 were stage V. There were 19 males and 11 females in the NONFH group, with an average age of 49.6 yr. (26-69 yr.), and 16 males and 14 females in the TONFH group, with an average age of 54.2 yr. (37-68 yr.). There was no significant difference in gender or age between the two groups ( P>0.05). Specimens were collected from different bone areas, including those from the necrotic areas (area A) and the healthy areas (area B) of the NONFH group, and those from the healthy areas (area B') of the TONFH group, i.e., the control group. Western blot and quantitative real-time reverse transcription PCR (qRT-PCR) were used to analyze the different expression of Rap1, vascular endothelial growth factor (VEGF) protein, phosphoinositide 3-kinase (PI3K), and Akt protein and their corresponding mRNA in the three areas of bone tissue. HE staining and immunohistochemisty staining were done in order to observe the morphological changes of each area. Results: Western blot results indicated that there was no statistical difference in the relative expression of Rap1, VEGF, PI3K, and Akt proteins ( P>0.05). The relative expressions of Rap1, VEGF, PI3K, and Akt proteins in the area A were lower than those in the area B and the difference was statistically significant ( P<0.05). qRT-PCR results showed that the relative expressions of Rap1, VEGF, PI3 K and Akt mRNA in area A were lower than those of area B, and a statistical difference was found ( P<0.05). The relative expression of the mRNA of Rap1, VEGF , PI3 K and Akt in area B and area B' were not significantly different ( P>0.05). HE staining and immunohistochemisty staining showed that chondrocytes decreased in the necrotic area (area A) of NONFH, chondrocytes nucleus disappeared, subchondral bone trabeculae were broken, bone trabeculae thickened, and empty bone lacunae appeared. Granulation tissues composed of new capillaries and fibrous cells have proliferated and crawled around the necrotic area. Positive expressions of the Rap1, VEGF, PI3K and Akt proteins in area A were weaker than those of the normal area. In addition, there were positive expressions of Rap1, PI3K and Akt on the trabecular bone of both area A and area B at similar intensity of expression. There were strong positive expressions of Rap1, VEGF, PI3K and Akt on the intima of arterioles and venules, and on the peripheral stromal cell membrane, but the positive expression in area A was significantly lower than that in area B. However, the positive expression positions and intensity of all indicators were similar in area B and area B'. Conclusion: The necrosis in NONFH may be related to vascular endothelial damages caused by the inhibition of the Rap1-PI3K/Akt signaling pathways and the subsequent decline in the protein expression.

[Treatment of senile lumbar spinal stenosis by unilateral approach and bilateral decompression with large channel endoscopy].

OBJECTIVE: To evaluate clinical effect of unilateral approach and bilateral decompression via large channel endoscopic system for the treatment of lumbar spinal stenosis. METHODS: The clinical data of 32 patients with lumbar spinal tenosis treated by unilateral approach and bilateral decompression via large channel endoscopy from February 2018 to February 2019 were retrospectively analyzed. There were 18 males and 14 females, aged 65 to 84 years old with an average of (70.6± 8.4) years. The course of disease was from 1 to 12 years. All 32 cases were accompanied by numbness or pain in the lower limbs, of which 28 cases were accompanied by intermittent claudication. Narrow segments were L3, 4 of 2 cases, L4, 5 of 19 cases, L5S1 of 13 cases, including double segments of 2 cases. Preoperative imaging showed 3 cases of central canal stenosis, 21 cases of bilateral lateral recess stenosis and 8 cases of mixed stenosis. Operation time and complications were recorded. X-ray, CT and MRI were analyzed at 3 days, 3 months and 1 year after operation. Visual analogue scale(VAS), Oswestry Disability Index (ODI), single continuous walking distance(SCWD) were observed before and after operation. Modified Macnab standard were used to evaluate the clinical effect at 1 year after operation. RESULTS: All the patients were followed up for 12-24 (17.68±2.43) months and all operations were successfully completed with the operation time of 70-160(85.64±11.94) min. Spinal dural tear occurred in 1 case during the operation, and sensory disturbance in the other side of lower limb in a short period of time occurred in 2 cases, all improved after corresponding treatment. Postoperative imaging showed that the spinal canal was significantly enlarged and the nerve root was fully released. Before operation and 3 days, 3 months, 1 year after operation, VAS scores of low back pain were 4.62 ±1.41, 2.73 ±1.35, 1.21 ±1.17, 1.11 ±0.34, respectively;VAS scores of leg pain were 6.83 ± 1.71, 3.10±1.50, 1.08±0.19, 0.89±0.24, respectively. VAS scores of low back pain and leg pain each time point after operation were obvious improved (P<0.05); there was significant difference between 3 months and 3 days after operation(P<0.05), and there was no significant difference between 3 months and 1 year after operation (P>0.05). Before operation and 3 days, 3 months, 1 year after operation, ODI scores were 38.40 ±6.48, 18.42 ±2.40, 5.48 ±0.77, 3.05 ±0.28, respectively; SCWD was (47.48±5.32) m, (52.89±11.23) m, (245.43±18.94) m, (468.97±55.87) m, respectively. The differences in ODI score and SCWD postoperative time points were statistically significant compared with those before operation (P<0.05). The difference between 3 months and 3 days after operation was statistically significant (P<0.05). The difference between 1 year and 3 months after operation was statistically significant (P<0.05). According to Macnab standard to evaluate clinical effect at 1 year after operation, 15 cases got excellent results, 14 good, 3 fair. CONCLUSION: It is a safe and effective way to treat lumbar spinal stenosis with unilateral approach and bilateral decompression via large channel endoscopic system. It has the advantages of sufficient decompression, less trauma, fast recovery, high safety and low incidence of postoperative complications. It can minimize the damage to the stable structure of the lumbar spine and is an ideal minimally invasive operation for the treatment of lumbar spinal stenosis.

MiRNA-145-5p expression and prospective molecular mechanisms in the metastasis of prostate cancer.

The clinicopathological implication and prospective molecular mechanisms of miRNA-145-5p in the metastasis of prostate cancer (PCa) stand unclear. Herein, it is found that miRNA-145-5p expression was remarkably reduced in 131 cases of metastatic PCa than 1371 cases of localised ones, as the standardised mean differences (SMD) was -1.26 and the area under the curve (AUC) was 0.86, based on miRNA-chip and miRNA-sequencing datasets. The potential targets of miRNA-145-5p in metastatic PCa (n = 414) was achieved from the intersection of miRNA-145-5p transfected metastatic PCa cell line data, differential expression of metastatic PCa upregulated genes and online prediction databases. TOP2A was screened as one of the target hub genes by PPI network analysis, which was adversely related to miRNA-145-5p expression in both metastatic PCa (r = -0.504) and primary PCa (r = -0.281). Gene-chip and RNA-sequencing datasets, as well as IHC performed on clinical PCa samples, showed consistent upregulated expression of TOP2A mRNA and protein in PCa compared with non-PCa. The expression of TOP2A mRNA was also significantly higher in metastatic than localised PCa with the SMD being 1.72 and the AUC of sROC being 0.91. In summary, miRNA-145-5p may participate in PCa metastasis by binding TOP2A and be useful as a biomarker for the detection of metastatic PCa.