Home Medicine A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
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A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma

  • Jie Yang , Fenghai Zhou EMAIL logo , Xia Yang , Pengcheng Ma and Xiaoling Ma
Published/Copyright: September 18, 2023
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Open Medicine
From the journal Open Medicine Volume 18 Issue 1

Abstract

Bladder urothelial carcinoma (BLCA) is one of the most common cancer-related deaths in the world, along with high mortality. Due to the difficult detection of early symptoms, the treatment for this disease is still dissatisfactory. Thus, the current research hotspot is beginning to focus on the immune microenvironment in this disease, aiming to provide guidance for diagnosis and treatment. In this study, the single-cell RNA sequencing data downloaded from the gene expression omnibus database was used to classify the immune cells of BLCA. And the final seven T-cell-related cell clustering genes associated with BLCA prognosis (HSPA2, A2M, JUN, PDGFRB, GBP2, LGALS1, and GAS6) were screened out, and then used for constructing the prognostic model against BLCA based on the Cox and LASSO regression analysis. Satisfactorily, the model could efficiently evaluate the overall survival of BLCA and had the potential to be applied for the clinic treatment. Moreover, we also revealed that the difference in immune infiltration levels and gene mutation might account for the diverse prognosis in BLCA patients. In a word, our findings provided a novel insight for designing efficient immunotherapies for BLCA.

Keywords: bladder urothelial carcinoma; immune microenvironment; prognosis; single-cell RNA sequencing

1 Introduction

Bladder urothelial carcinoma (BLCA) is a common urinary system malignancy, along with a higher incidence and mortality [1,2]. It has been reported that 61,700 new cases were diagnosed in men and even 12,120 deaths occurred in 2022 in the United States [3]. More seriously, approximately 550,000 new cases, as well as 200,000 deaths, were happened each year [4]. Though the advances involved in the clinical therapies including surgery and chemo-radiotherapy have been developed, the poorer overall survival of 5-year in BLCA was also unsatisfactory [4,5]. Recently, more and more attention has been focused on this disease, hoping to reveal novel diagnostic methods and therapeutic targets.

The tumor immune microenvironment (TME) is always flooded with immunosuppressive cells and inhibitory cytokines, leading to effective immune cells being unable to infiltrate and recognize the tumor and even lose the ability to fight cancer [6]. Previous studies identified a series of immune-related key genes involved in the occurrence, development, and prognosis of human cancer including BLCA. For example, Li et al. found that CD248 was highly and specifically expressed in tumor-associated vessels in BLCA and demonstrated that the level of CD248 contributed to predict the BLCA prognosis [7]. Zhu et al. revealed that MTHFD2 was an oncogene in BLCA, and its expression level was closely correlated with the poor prognosis of patients and severe immune infiltrates [8]. In addition, several prognostic models were constructed based on different immune genes including inflammatory response-associated genes [9] and ferroptosis-related genes [10]. Although these prognostic models were demonstrated that could efficiently predict the overall survival of BLCA patients, more different models were also needed and these could be crossly validated in order to increase accuracy.

Here, we downloaded the single-cell RNA sequencing data of BLCA from the gene expression omnibus (GEO) database and screened out the differentially expressed genes in T cells. Then, a prognosis model based on the key genes was constructed. According to our results, we confirmed that the prognosis model could accurately predict the overall survival of BLCA patients and was potentially used for the clinical directed treatment. Meanwhile, the immune infiltration and gene mutation were analyzed between high- and low-risk groups, and we found that these different levels of immune infiltration and gene mutation probability might account for the diverse prognosis in BLCA patients. Our analysis might provide new insight for the clinical BLCA treatment.

2 Materials and methods

2.1 The data source

Transcriptome data, typed BLCA-FPKM, included 412 BLCA samples and clinical data from the cancer genome atlas (TCGA) database. We also downloaded GSE13507 data including BLCA samples and clinical data, and the single-cell sequencing dataset GSE145140 of BLCA from the GEO database.

2.2 Quality of single-cell sequencing

The condition was set as follows: The number of genes per cell ranged from 300 to 7,000, and the percentage of mitochondria-related genes was <10, the percentage of erythrocytes was <3, and the total gene expression copy number was less than 300,000.

2.3 Cluster analysis

Principal component analysis (PCA) was performed on the highly variable genes as previously described [11], the number of PCs was set to 6, and a total of 10 clusters were obtained. These clusters are presented in UMAP format, and the top 10 significantly different genes in each cluster are selected for mapping.

2.4 The construction of prognostic model

Univariate Cox proportional hazard regression analysis was performed to screen out key genes that were associated with BLCA prognosis in the last section, with p < 0.001 as the set. The prognostic model (Risk score) was constructed as follows:

Risk core = ∑ i = 1 n coefi × id

Then patients were divided into high- and low-risk groups according to the median-risk score.

2.5 Evaluation of the prognosis model

Kaplan–Meier survival was used to analyze the overall survival of patients in two groups in the TCGA and the GEO datasets. The time ROC package was used to draw time-dependent ROC curves for 1 and 3 years. In addition, the heat maps were used to compare the expression of the model genes between two risk groups in two datasets. The distribution of patients between two risk groups was explored with the Rtsen package.

2.6 Evaluation of immune infiltration level between two risk groups

As previously described [12], the CIBERSORT web portal (http://CIBERSORT.stanford.edu/) was used to assess the immune cell subsets distribution, which was an algorithm that transformed the normalized expression matrix into infiltrating immune cell components [13].

2.7 Evaluation of gene mutation

MafTools package was used to evaluate the mutations in patients between two risk groups in two datasets as previously described [14].

2.8 Statistical analysis

R V4.1.0 (http://www.Rproject.org) was used to perform the statistical evaluation, with p < 0.05 as the significant threshold.

3 Results

3.1 The acquisition of important genes correlated to immune subtypes

First, we performed quality control on single-cell RNA sequencing data, and the number of genes expressed in all cells obtained by quality control will be 300–7,000. The distribution was relatively uniform. Meanwhile, mitochondrial genes were expressed in less than 5% of the cells, and cells expressing less than 1% of the hemoglobin gene (Figure 1a). From Figure 1b, we found that cells are evenly distributed in the four samples. The gene number is negatively correlated with their percent. HB level (−0.09), percent. MT (−0.64), and percent. Ribosome (−0.88). Hence, we selected the 2,000 high variable genes in red in Figure 1c, with the first top 10 genes flagged.

Figure 1 Quality control of single-cell RNA sequencing data. (a) Gene expression levels in each cell among four samples. (b) Scatter plot showing the distribution of count number (nCount_RNA) with gene number (nFeature_RNA), percentage of hemoglobin genes (percent.HB), percentage of mitochondrial genes (percent.MT), and percentage of ribosome genes (percent.Ribosome). (c) Scatter plots showing the 2000 high variable genes in red, and the top 10 genes were flagged.
Figure 1

Quality control of single-cell RNA sequencing data. (a) Gene expression levels in each cell among four samples. (b) Scatter plot showing the distribution of count number (nCount_RNA) with gene number (nFeature_RNA), percentage of hemoglobin genes (percent.HB), percentage of mitochondrial genes (percent.MT), and percentage of ribosome genes (percent.Ribosome). (c) Scatter plots showing the 2000 high variable genes in red, and the top 10 genes were flagged.

Then, through performing the PCA analysis, our analysis yielded the top ten genes with expression differences between the clusters (Figure 2a). The expression levels of the 10 genes were significantly higher than others in each cluster (Figure 2a). The expression of important biomarker genes is shown in Figure 2b. T cells or NK cells (markers: MS4A1 and CD3E), B cells (MS4A1), and myeloid cells (LYZ) were clustered according to immune cell markers (FCER1A and FCGR3A are Macrophage markers; GNLY are Neutrophils marker; CD8A and NKG7 are T-cell and NK-cell markers). The label colors according to separate clusters are shown in Figure 2c. Hence, T-cell-related genes were selected for the subsequent analysis.

Figure 2 The acquisition of T-cell-related genes. (a) Heatmap showing the expression level of the top five marker genes of each cluster. (b) Umap plots showing the expression level of important marker genes in nine clusters. (c) Umap plots showing the cell-type identification of each cluster.
Figure 2

The acquisition of T-cell-related genes. (a) Heatmap showing the expression level of the top five marker genes of each cluster. (b) Umap plots showing the expression level of important marker genes in nine clusters. (c) Umap plots showing the cell-type identification of each cluster.

3.2 Analysis of T-cell-related genes

To investigate which function and signaling pathways were enriched, KEGG and GO analyses were performed using these T-cell-related genes. As shown in Figure 3a and b for GO analysis, we found that these genes were significantly correlated to cytokine-mediated signaling pathway, regulation of T-cell activation, mononuclear cell differentiation, and positive regulation of cell activation. As shown in Figure 3c and d, these genes were significantly enriched in focal adhesion, Rap1 signaling pathway, and PI3K-Akt signaling pathway.

Figure 3 Enrichment analysis of T-cell-related genes. (a) Bar plot showing the GO analysis of T-cell-related genes. (b) Circos plot showing the log2 fold change of the main GO terms between BLCA samples and healthy samples. (c) Bar plot showing the KEGG enrichment analysis of T-cell-related genes. (d) Circos plot showing the log2 fold change of the main KEGG enrichment terms between BLCA samples and healthy samples.
Figure 3

Enrichment analysis of T-cell-related genes. (a) Bar plot showing the GO analysis of T-cell-related genes. (b) Circos plot showing the log2 fold change of the main GO terms between BLCA samples and healthy samples. (c) Bar plot showing the KEGG enrichment analysis of T-cell-related genes. (d) Circos plot showing the log2 fold change of the main KEGG enrichment terms between BLCA samples and healthy samples.

3.3 Construction of the prognostic model

Next, Cox analysis was done in conjunction with clinical follow-up data and identified 12 genes that were associated with T cells and correlated with survival time and status (Figure 4a). LASSO regression analysis was then operated based on these 12 genes (Figure 4b and c). We finally generated seven modeling genes, which were HSPA2, A2M, JUN, PDGFRB, GBP2, LGALS1, and GAS6 for constructing the prognosis model, and then, the Risk score = HSPA2 × 0.016 + A2M × 0.020 + JUN × 0.102 + PDGFRB × 0.103 + GBP2 × (−0.243) + LGALS1 × 0.045 + GAS6 × 0.030 was established. To better evaluate the value of our prognosis model, we divide the BLCA patients into high- and low-risk groups based on the median-risk score. HSPA2 gene silencing could affect the motility and invasiveness of urothelial and cervical cancer cell lines (PMID: 19914824). Extracellular vesicle-derived A2M has been regarded as a novel diagnostic biomarker for bladder cancer (PMID: 36176383); here, we verified it as a target gene in the BLCA prognosis model. The oncogenic transcription factor JUN affects transcriptome regulation and cellular function, especially extracellular stimulation and energy metabolism in BLCA. The expression of T-cell-related PDGFRB was associated with tumor microenvironment, which significantly downregulated after chemotherapy treatment. GBP2 is a member of the GBP family, which plays an essential role in the inflammatory process and might be a prognostic protective factor for BLCA (PMID: 17980030). Highly consistent with our single-cell data analysis, a previous study reported that bladder cancer cells with LGALS1 silencing and GAS6 depletion could reduce cell proliferation, lower invasive capability, and lower clonogenicity (PMID: 27440446 and PMID: 32547108).

Figure 4 Construction of the prognostic model. (a) Scatter plot showing the univariate COX analysis for screening those genes related to T immune cells with prognostic values. (b) and (c) Line chart showing the LASSO regression analysis of the 12 genes.
Figure 4

Construction of the prognostic model. (a) Scatter plot showing the univariate COX analysis for screening those genes related to T immune cells with prognostic values. (b) and (c) Line chart showing the LASSO regression analysis of the 12 genes.

3.4 The evaluation of the prognostic model

Kaplan–Meier survival curves were plotted based on the database from TCGA and GEO datasets, and we found that the patients showed a poorer prognosis in the high-risk group both in the TCGA (Figure 5a) and in the GEO data sets (Figure 5b). The area under the ROC curve of 1 year and 3 years in both data sets was approximately 0.65, and that of 5 years was approximately 0.68 (Figure 5c and d), suggesting that the prognostic model has good stability and accuracy.

Figure 5 Evaluation of the value of the prognostic model. (a) and (b) The Kaplan–Meier survival curve analysis showing the significant difference between the high-risk and the low-risk groups in TCGA and GEO data sets. (c) and (d) Time-dependent ROC analysis showing the significant prognostic value in TCGA and GEO data sets.
Figure 5

Evaluation of the value of the prognostic model. (a) and (b) The Kaplan–Meier survival curve analysis showing the significant difference between the high-risk and the low-risk groups in TCGA and GEO data sets. (c) and (d) Time-dependent ROC analysis showing the significant prognostic value in TCGA and GEO data sets.

Subsequently, the BLCA patients in the TCGA and GEO datasets were then divided into the low-risk group and high-risk group according to the median risk score in the two data sets (Figure 6a and b). The distribution of survival status between two risk groups in two data sets is shown in Figure 6c and d. As shown in Figure 6e and f by clinical clustering heat-map, we found that the risk score was significantly correlated to TNM stage and grade. Meanwhile, we also found that BLCA patients could be well divided into two categories in both data sets (Figure 6g and h).

Figure 6 Evaluation of the value of the prognostic model. (a) and (b) Risk score distribution of the patients in TCGA and GEO data sets. (c) and (d) Survival status scatter plots showing poorer prognosis of the high-risk group compared with the low-risk group in two data sets. (e) and (f) Multifactorial heat map showing certain clinical features with a significant correlation with the risk score in two data sets. (g) and (h) PCA analysis in two data sets.
Figure 6

Evaluation of the value of the prognostic model. (a) and (b) Risk score distribution of the patients in TCGA and GEO data sets. (c) and (d) Survival status scatter plots showing poorer prognosis of the high-risk group compared with the low-risk group in two data sets. (e) and (f) Multifactorial heat map showing certain clinical features with a significant correlation with the risk score in two data sets. (g) and (h) PCA analysis in two data sets.

3.5 Analysis of immune infiltration levels between two risk groups

Through the functional analysis of GSEA, we found that most of the high-risk groups were enriched in immune related functional pathways both in TCGA and in GEO data sets (Figure 7a and b). Meanwhile, most of the immune checkpoints in the high-risk group genes were upregulated (Figure 7c), and the immune score was also higher in the high-risk group (Figure 7d), as well as the estimated score (Figure 7e). Patients in the high-risk group had lower tumor purity scores than those in the low-risk group (Figure 7f). The stromal score was higher in the high-risk group (Figure 7g).

Figure 7 Analysis of immune infiltration and immune checkpoint. (a) and (b) The GSEA enrichment analyses of function pathways between two risk groups in two data sets. (c) The expression of the immune checkpoint genes between two risk groups. (d) Boxplot showing the immune score between two risk groups. (e) Boxplot showing the estimated scores between two risk groups. (f) Boxplot showing the tumor purity scores between two risk groups. (g) Boxplot showing the stromal score between two risk groups.
Figure 7

Analysis of immune infiltration and immune checkpoint. (a) and (b) The GSEA enrichment analyses of function pathways between two risk groups in two data sets. (c) The expression of the immune checkpoint genes between two risk groups. (d) Boxplot showing the immune score between two risk groups. (e) Boxplot showing the estimated scores between two risk groups. (f) Boxplot showing the tumor purity scores between two risk groups. (g) Boxplot showing the stromal score between two risk groups.

3.6 Evaluation of gene mutation between two risk groups

Finally, we also analyzed the probability of gene mutation between two risk groups and found 89.16% mutation probability in the high-risk group (Figure 8a) and 90.26% in the low-risk group (Figure 8b). This result suggests that BLCA patients in the low-risk group had more frequent mutations, but their mutations were mostly favorable and led to a better prognosis. In addition, TTN was the most mutated gene, and the missense mutation was the main mutation type between the two risk groups. Our analysis results also revealed that the mutation types of ARID1A and ACVR2A were mainly nonsense mutation and frame mutation in the high-risk group.

Figure 8 Evaluation of gene mutations between two risk groups: (a) and (b) Heatmaps showing the mutation analysis between high- and low-risk groups in both TCGA and GEO data sets.
Figure 8

Evaluation of gene mutations between two risk groups: (a) and (b) Heatmaps showing the mutation analysis between high- and low-risk groups in both TCGA and GEO data sets.

4 Discussion

In the past decades, although several advanced methods involved in the diagnosis including molecular biology and imaging, and therapeutic methods such as surgery, chemotherapy, and radiotherapy have been developed and applied [15,16], the therapeutic effect and the 5-year survival of BLCA patients are still poor. Hence, the development of new approaches to diagnosis and treatment involved in subsets and biomarkers is urgent. On the other hand, the poor prognosis of BLCA patients and low prediction efficiency are also some of the high mortalities. Therefore, the investigation of the prognosis model could guide clinical prognostic treatment.

In this study, through analyzing the single cell sequencing data, we obtained seven modeling genes (HSPA2, A2M, JUN, PDGFRB, GBP2, LGALS1, and GAS6), which were finally used for constructing a prognosis model. Despite this study, the diagnostic and prognostic values of these relevant genes in BLCA and also other human cancers have been partially studied. HSPA2, one DNA methylation biomarker, was identified to be a reliable, noninvasive, and cost-effective diagnostic tool in bladder carcinoma [17]. Lee et al. found that downregulated ADAMTS1 incorporating A2M could contribute to the lung adenocarcinoma progression and change TME, and was also associated with the prognosis of lung adenocarcinoma patients [18]. JUN is an inflammation-related gene and participates in the development of different human cancers such as breast cancer [19], non-small cell lung cancer [20], colorectal cancer [21], and recent studies revealed that JUN was also significantly correlated to overall survival of cancer patients. Liu et al. found that PDGFRB played a crucial role in angiogenesis and tumor cell proliferation development, and this gene was considered as a potential prognostic marker in gastric cancer [22]. GBP2 was also identified as a prognosis-related biomarker and immunotherapeutic target in several human cancers including colorectal cancer and breast cancer [23,24]. A previous study demonstrated that an increased mRNA level of LGALS1 was linked to BLCA cell invasiveness and also significantly associated with BLCA prognosis [25]. A recent study revealed that inhibition of GAS6-AS1 axis could efficiently prevent cell propagation and disease development of acute myeloid leukemia [26], suggesting that GAS6 might be a potential diagnostic and therapeutic target. Although the prognostic values of the several key genes in BLCA have been explored, the significance of a whole based on seven genes joined together in BLCA prognosis remains unclear. In this study, we revealed that these seven genes were most significantly correlated to BLCA overall survival, and we finally constructed the prognostic model using these seven genes and meanwhile confirmed that our prognostic model could accurately predict the patient prognosis of BLCA patients. Our model provided insight into personalized prognostic treatment.

Immune infiltration by T cells admittedly and profoundly influences cancer progression and also in response to immunotherapy [27]. To investigate the impact of immune infiltration on patient prognosis, we analyzed the immune infiltration levels between high- and low-risk groups, and found that most of the high-risk groups were enriched in immune-related functional pathways, and most of the immune checkpoint genes were upregulated in the high-risk group. It suggested that high immune infiltration levels might lead to a better prognosis. In addition, we also analyzed the gene mutations between two risk groups and revealed that patients in the low-risk group have more frequent mutations, suggesting that higher frequent mutations might contribute to a better prognosis. Our findings in the level of immune might account for the diverse prognosis in BLCA patients.

In conclusion, our study constructed a prognostic model using the seven T-cell-related key genes and confirmed that this model could efficiently predict the prognosis of BLCA patients. Meanwhile, we also suggested that diverse levels of immune infiltration and gene mutation probability might be the reason for different prognoses in BLCA. Our results provided novel insight for immunotherapy in BLCA clinically.

5 Limitations of study

In order to predict the prognosis of the BLCA, we constructed a prognostic model using the seven T-cell-related key genes. Although this model has been verified in silico, future efforts might be needed to directly observe these genes in patient samples.

Acknowledgments

Not applicable.

  1. Funding information: This study was not supported by any funders.

  2. Author contributions: This work was performed by JY. The manuscript was written by JY and edited by FZ. XM made the literature research; XY and PM helped with data analysis.

  3. Conflict of interest: The authors declare they have no conflict of interest.

  4. Data availability statement: The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2022-10-09
Revised: 2023-07-10
Accepted: 2023-07-25
Published Online: 2023-09-18

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  38. Genetic polymorphisms of MRPS30-DT and NINJ2 may influence lung cancer risk
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  41. Upregulation of lncRNA LANCL1-AS1 inhibits the progression of non-small-cell lung cancer via the miR-3680-3p/GMFG axis
  42. CircRANBP17 modulated KDM1A to regulate neuroblastoma progression by sponging miR-27b-3p
  43. Exosomal miR-93-5p regulated the progression of osteoarthritis by targeting ADAMTS9
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  45. HDAC5-mediated PRAME regulates the proliferation, migration, invasion, and EMT of laryngeal squamous cell carcinoma via the PI3K/AKT/mTOR signaling pathway
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  58. Silencing of long noncoding RNA MIAT inhibits the viability and proliferation of breast cancer cells by promoting miR-378a-5p expression
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  68. Long noncoding RNA Mhrt alleviates angiotensin II-induced cardiac hypertrophy phenotypes by mediating the miR-765/Wnt family member 7B pathway
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  74. miR-2053 inhibits the growth of ovarian cancer cells by downregulating SOX4
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  80. Outcomes of low-risk birth care during the Covid-19 pandemic: A cohort study from a tertiary care center in Lithuania
  81. Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
  82. Integrated transcriptome analysis identifies APPL1/RPS6KB2/GALK1 as immune-related metastasis factors in breast cancer
  83. Genomic analysis of immunogenic cell death-related subtypes for predicting prognosis and immunotherapy outcomes in glioblastoma multiforme
  84. Circular RNA Circ_0038467 promotes the maturation of miRNA-203 to increase lipopolysaccharide-induced apoptosis of chondrocytes
  85. An economic evaluation of fine-needle cytology as the primary diagnostic tool in the diagnosis of lymphadenopathy
  86. Midazolam impedes lung carcinoma cell proliferation and migration via EGFR/MEK/ERK signaling pathway
  87. Network pharmacology combined with molecular docking and experimental validation to reveal the pharmacological mechanism of naringin against renal fibrosis
  88. PTPN12 down-regulated by miR-146b-3p gene affects the malignant progression of laryngeal squamous cell carcinoma
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  117. Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice
  118. Analysis of somatic mutations and key driving factors of cervical cancer progression
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  131. Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU
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  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
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  144. Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase
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  149. A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
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  154. AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
  155. Establishment of two oxaliplatin-resistant gallbladder cancer cell lines and comprehensive analysis of dysregulated genes
  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
  159. Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
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  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
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  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
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  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
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  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
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  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
  197. Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study
  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
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  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
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  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
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  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
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  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
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  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
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  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
https://doi.org/10.1515/med-2023-0773
Keywords for this article
bladder urothelial carcinoma; immune microenvironment; prognosis; single-cell RNA sequencing
Creative Commons
BY 4.0

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  3. Current situation of acute ST-segment elevation myocardial infarction in a county hospital chest pain center during an epidemic of novel coronavirus pneumonia
  4. circ-IARS depletion inhibits the progression of non-small-cell lung cancer by circ-IARS/miR-1252-5p/HDGF ceRNA pathway
  5. circRNA ITGA7 restrains growth and enhances radiosensitivity by up-regulating SMAD4 in colorectal carcinoma
  6. WDR79 promotes aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) by the suppression of SIRT4
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  8. Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
  9. 3D-printed polyether-ether-ketone/n-TiO2 composite enhances the cytocompatibility and osteogenic differentiation of MC3T3-E1 cells by downregulating miR-154-5p
  10. Propofol-mediated circ_0000735 downregulation restrains tumor growth by decreasing integrin-β1 expression in non-small cell lung cancer
  11. PVT1/miR-16/CCND1 axis regulates gastric cancer progression
  12. Silencing of circ_002136 sensitizes gastric cancer to paclitaxel by targeting the miR-16-5p/HMGA1 axis
  13. Short-term outcomes after simultaneous gastrectomy plus cholecystectomy in gastric cancer: A pooling up analysis
  14. SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways
  15. Molecular mechanism by which the Notch signaling pathway regulates autophagy in a rat model of pulmonary fibrosis in pigeon breeder’s lung
  16. lncRNA TPT1-AS1 promotes cell migration and invasion in esophageal squamous-cell carcinomas by regulating the miR-26a/HMGA1 axis
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  21. circ_0000376 knockdown suppresses non-small cell lung cancer cell tumor properties by the miR-545-3p/PDPK1 pathway
  22. Delivery in a vertical birth chair supported by freedom of movement during labor: A randomized control trial
  23. UBE2J1 knockdown promotes cell apoptosis in endometrial cancer via regulating PI3K/AKT and MDM2/p53 signaling
  24. Metabolic resuscitation therapy in critically ill patients with sepsis and septic shock: A pilot prospective randomized controlled trial
  25. Lycopene ameliorates locomotor activity and urinary frequency induced by pelvic venous congestion in rats
  26. UHRF1-induced connexin26 methylation is involved in hearing damage triggered by intermittent hypoxia in neonatal rats
  27. LINC00511 promotes melanoma progression by targeting miR-610/NUCB2
  28. Ultra-high-performance liquid chromatography-tandem mass spectrometry analysis of serum metabolomic characteristics in people with different vitamin D levels
  29. Role of Jumonji domain-containing protein D3 and its inhibitor GSK-J4 in Hashimoto’s thyroiditis
  30. circ_0014736 induces GPR4 to regulate the biological behaviors of human placental trophoblast cells through miR-942-5p in preeclampsia
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  34. WGCNA-based identification of potential targets and pathways in response to treatment in locally advanced breast cancer patients
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  41. Upregulation of lncRNA LANCL1-AS1 inhibits the progression of non-small-cell lung cancer via the miR-3680-3p/GMFG axis
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  48. A novel long noncoding RNA AC125257.1 facilitates colorectal cancer progression by targeting miR-133a-3p/CASC5 axis
  49. Impact of omicron wave and associated control measures in Shanghai on health management and psychosocial well-being of patients with chronic conditions
  50. Clinicopathological characteristics and prognosis of young patients aged ≤45 years old with non-small cell lung cancer
  51. TMT-based comprehensive proteomic profiling identifies serum prognostic signatures of acute myeloid leukemia
  52. The dose limits of teeth protection for patients with nasopharyngeal carcinoma undergoing radiotherapy based on the early oral health-related quality of life
  53. miR-30b-5p targeting GRIN2A inhibits hippocampal damage in epilepsy
  54. Long non-coding RNA AL137789.1 promoted malignant biological behaviors and immune escape of pancreatic carcinoma cells
  55. IRF6 and FGF1 polymorphisms in non-syndromic cleft lip with or without cleft palate in the Polish population
  56. Comprehensive analysis of the role of SFXN family in breast cancer
  57. Efficacy of bronchoscopic intratumoral injection of endostar and cisplatin in lung squamous cell carcinoma patients underwent conventional chemoradiotherapy
  58. Silencing of long noncoding RNA MIAT inhibits the viability and proliferation of breast cancer cells by promoting miR-378a-5p expression
  59. AG1024, an IGF-1 receptor inhibitor, ameliorates renal injury in rats with diabetic nephropathy via the SOCS/JAK2/STAT pathway
  60. Downregulation of KIAA1199 alleviated the activation, proliferation, and migration of hepatic stellate cells by the inhibition of epithelial–mesenchymal transition
  61. Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment
  62. Inhibition of glycolysis represses the growth and alleviates the endoplasmic reticulum stress of breast cancer cells by regulating TMTC3
  63. The function of lncRNA EMX2OS/miR-653-5p and its regulatory mechanism in lung adenocarcinoma
  64. Tectorigenin alleviates the apoptosis and inflammation in spinal cord injury cell model through inhibiting insulin-like growth factor-binding protein 6
  65. Ultrasound examination supporting CT or MRI in the evaluation of cervical lymphadenopathy in patients with irradiation-treated head and neck cancer
  66. F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway
  67. Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis
  68. Long noncoding RNA Mhrt alleviates angiotensin II-induced cardiac hypertrophy phenotypes by mediating the miR-765/Wnt family member 7B pathway
  69. Effect of miR-499-5p/SOX6 axis on atrial fibrosis in rats with atrial fibrillation
  70. Cholesterol induces inflammation and reduces glucose utilization
  71. circ_0004904 regulates the trophoblast cell in preeclampsia via miR-19b-3p/ARRDC3 axis
  72. NECAB3 promotes the migration and invasion of liver cancer cells through HIF-1α/RIT1 signaling pathway
  73. The poor performance of cardiovascular risk scores in identifying patients with idiopathic inflammatory myopathies at high cardiovascular risk
  74. miR-2053 inhibits the growth of ovarian cancer cells by downregulating SOX4
  75. Nucleophosmin 1 associating with engulfment and cell motility protein 1 regulates hepatocellular carcinoma cell chemotaxis and metastasis
  76. α-Hederin regulates macrophage polarization to relieve sepsis-induced lung and liver injuries in mice
  77. Changes of microbiota level in urinary tract infections: A meta-analysis
  78. Identification of key enzalutamide-resistance-related genes in castration-resistant prostate cancer and verification of RAD51 functions
  79. Falls during oxaliplatin-based chemotherapy for gastrointestinal malignancies – (lessons learned from) a prospective study
  80. Outcomes of low-risk birth care during the Covid-19 pandemic: A cohort study from a tertiary care center in Lithuania
  81. Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
  82. Integrated transcriptome analysis identifies APPL1/RPS6KB2/GALK1 as immune-related metastasis factors in breast cancer
  83. Genomic analysis of immunogenic cell death-related subtypes for predicting prognosis and immunotherapy outcomes in glioblastoma multiforme
  84. Circular RNA Circ_0038467 promotes the maturation of miRNA-203 to increase lipopolysaccharide-induced apoptosis of chondrocytes
  85. An economic evaluation of fine-needle cytology as the primary diagnostic tool in the diagnosis of lymphadenopathy
  86. Midazolam impedes lung carcinoma cell proliferation and migration via EGFR/MEK/ERK signaling pathway
  87. Network pharmacology combined with molecular docking and experimental validation to reveal the pharmacological mechanism of naringin against renal fibrosis
  88. PTPN12 down-regulated by miR-146b-3p gene affects the malignant progression of laryngeal squamous cell carcinoma
  89. miR-141-3p accelerates ovarian cancer progression and promotes M2-like macrophage polarization by targeting the Keap1-Nrf2 pathway
  90. lncRNA OIP5-AS1 attenuates the osteoarthritis progression in IL-1β-stimulated chondrocytes
  91. Overexpression of LINC00607 inhibits cell growth and aggressiveness by regulating the miR-1289/EFNA5 axis in non-small-cell lung cancer
  92. Subjective well-being in informal caregivers during the COVID-19 pandemic
  93. Nrf2 protects against myocardial ischemia-reperfusion injury in diabetic rats by inhibiting Drp1-mediated mitochondrial fission
  94. Unfolded protein response inhibits KAT2B/MLKL-mediated necroptosis of hepatocytes by promoting BMI1 level to ubiquitinate KAT2B
  95. Bladder cancer screening: The new selection and prediction model
  96. circNFATC3 facilitated the progression of oral squamous cell carcinoma via the miR-520h/LDHA axis
  97. Prone position effect in intensive care patients with SARS-COV-2 pneumonia
  98. Clinical observation on the efficacy of Tongdu Tuina manipulation in the treatment of primary enuresis in children
  99. Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway
  100. Knockdown of circ_0113656 assuages oxidized low-density lipoprotein-induced vascular smooth muscle cell injury through the miR-188-3p/IGF2 pathway
  101. Low Ang-(1–7) and high des-Arg9 bradykinin serum levels are correlated with cardiovascular risk factors in patients with COVID-19
  102. Effect of maternal age and body mass index on induction of labor with oral misoprostol for premature rupture of membrane at term: A retrospective cross-sectional study
  103. Potential protective effects of Huanglian Jiedu Decoction against COVID-19-associated acute kidney injury: A network-based pharmacological and molecular docking study
  104. Clinical significance of serum MBD3 detection in girls with central precocious puberty
  105. Clinical features of varicella-zoster virus caused neurological diseases detected by metagenomic next-generation sequencing
  106. Collagen treatment of complex anorectal fistula: 3 years follow-up
  107. LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through down-regulating SP-A by sponging to miR-424
  108. Efficacy analysis of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy as a first-line Helicobacter pylori eradication regimen – An open-label, randomized trial
  109. SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy
  110. A prospective cohort study of the impact of chronic disease on fall injuries in middle-aged and older adults
  111. circRNA THBS1 silencing inhibits the malignant biological behavior of cervical cancer cells via the regulation of miR-543/HMGB2 axis
  112. hsa_circ_0000285 sponging miR-582-3p promotes neuroblastoma progression by regulating the Wnt/β-catenin signaling pathway
  113. Long non-coding RNA GNAS-AS1 knockdown inhibits proliferation and epithelial–mesenchymal transition of lung adenocarcinoma cells via the microRNA-433-3p/Rab3A axis
  114. lncRNA UCA1 regulates miR-132/Lrrfip1 axis to promote vascular smooth muscle cell proliferation
  115. Twenty-four-color full spectrum flow cytometry panel for minimal residual disease detection in acute myeloid leukemia
  116. Hsa-miR-223-3p participates in the process of anthracycline-induced cardiomyocyte damage by regulating NFIA gene
  117. Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice
  118. Analysis of somatic mutations and key driving factors of cervical cancer progression
  119. Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis
  120. Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases
  121. Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats
  122. Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics
  123. Risk factors of recurrent bacterial vaginosis among women of reproductive age: A cross-sectional study
  124. Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
  125. Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients
  126. Correlation between microvessel maturity and ISUP grades assessed using contrast-enhanced transrectal ultrasonography in prostate cancer
  127. The protective effect of caffeic acid phenethyl ester in the nephrotoxicity induced by α-cypermethrin
  128. Norepinephrine alleviates cyclosporin A-induced nephrotoxicity by enhancing the expression of SFRP1
  129. Effect of RUNX1/FOXP3 axis on apoptosis of T and B lymphocytes and immunosuppression in sepsis
  130. The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity
  131. Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU
  132. Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway
  133. Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
  134. The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
  135. Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
  137. Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling
  138. miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
  139. The application of iliac fascia space block combined with esketamine intravenous general anesthesia in PFNA surgery of the elderly: A prospective, single-center, controlled trial
  140. Elevated blood acetoacetate levels reduce major adverse cardiac and cerebrovascular events risk in acute myocardial infarction
  141. The effects of progesterone on the healing of obstetric anal sphincter damage in female rats
  142. Identification of cuproptosis-related genes for predicting the development of prostate cancer
  143. Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
  144. Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase
  145. A single center prospective study: Influences of different hip flexion angles on the measurement of lumbar spine bone mineral density by dual energy X-ray absorptiometry
  146. Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis
  147. Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis
  148. Construction of a ceRNA network to reveal a vascular invasion associated prognostic model in hepatocellular carcinoma
  149. A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
  150. A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
  151. Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter
  152. The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
  153. Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
  154. AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
  155. Establishment of two oxaliplatin-resistant gallbladder cancer cell lines and comprehensive analysis of dysregulated genes
  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
  159. Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
  161. Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
  168. Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway
  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
  181. A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage
  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
  197. Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study
  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
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