Home Medicine 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
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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

  • Qing-Qing Yang ORCID logo EMAIL logo , Yun-Gang Hu , Chao-Hua Hu , Yun-Tao Han and Hao-Yuan Shen
Published/Copyright: October 30, 2023

Abstract

This meta-analysis aimed to evaluate the diagnostic accuracy of touch imprint cytology (TIC) for sentinel lymph node (SLN) metastases of patients with clinical node-negative early breast cancer. The PubMed, Web of Science, Embase, and the Cochrane Library databases were meticulously searched to retrieve literature published from January 2005 to September 2022 by two independent reviewers. The meta-analysis was performed using STATA16.0, Meta-Disc 1.4, and RevMan 5.4.9. According to the inclusion criteria, 4,073 patients from 13 studies were included in this meta-analysis. The pooled sensitivity and specificity of TIC for detecting SLN metastases were 0.77 (95% CI 0.66–0.85) and 0.99 (95% CI 0.97–1.00), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 76.15 (95% CI 29.16–198.84) and 0.23 (95% CI 0.15–0.36), respectively. The pooled diagnostic odds ratio was 326.82 (95% CI 132.76–804.56) and the area under the sROC curve was 0.97 (95% CI 0.95–0.98), respectively. This meta-analysis revealed that TIC with high sensitivity and specificity is a feasibility and accuracy diagnosis technique for intraoperative detection of SLN metastases in breast cancer.

1 Introduction

Sentinel lymph node biopsy (SLNB) is a standard procedure for assessing axillary lymph node status in patients with clinically node-negative breast cancer [1,2]. Surgeons usually do not perform axillary lymph node dissection (ALND) in patients with pathologically-negative SLNs, which may avoid many potential and unnecessary complications including lymphedema, paresthesias, limitation of shoulder range of motion, and decline in quality of life [35]. However, when intraoperative SLNB demonstrates the detection of SLN metastases, ALND can be completed in a single operation. It can effectively prevent the patients suffering from a second surgical operation, additional pain, and financial burden.

Previous studies have indicated that the intraoperative techniques for evaluation of SLN status contain touch imprint cytology (TIC), frozen section (FS), one-step nucleic acid amplification (OSNA) assay, and immunohistochemistry [69]. FS and TIC are the two most commonly used methods for intraoperative evaluation of SLN in the world [10]. In recent years, OSNA and immunohistochemistry technologies have been gradually carried out in some hospitals. In China, FS is the most common method of intraoperative SLN diagnosis in many authoritative medical centers due to its advantage of high sensitivity of detecting macrometastases and micrometastases, and the proportion is surprisingly more than 90%. However, the FS technique is obviously accompanied with many disadvantages such as requirement of more time, tissue loss, and cost. Similarly, these drawbacks also exist in OSNA and immunohistochemistry, which might affect the subsequent histopathological examination [8].

TIC has several limitations such as lack of standardized procedure, minimal node sampling, difficulty in detecting micrometastases and macrometastases from lobular carcinoma, and the requirement of an experienced cytopathologist to interpret the imprints. However, TIC is a rapid, cost-effective, and more tissue conserving technique [11]. Not only that, several studies have demonstrated that TIC has sensitivity equivalent to or better than that of FS [1215]. Thus, we performed an updated meta-analysis to collect data to evaluate the diagnostic feasibility and accuracy of TIC for detecting SLN metastases in patients with breast cancer.

2 Materials and methods

2.1 Search strategy

Four databases including PubMed, Embase, Cochrane Library, and Web of Science were systematically searched for articles published from January 2005 to September 2022 by two independent and experienced reviewers. The medical subject heading (Mesh) terms were defined as follows: “breast cancer,” “imprint cytology,” and “sentinel lymph node.” Furthermore, we used combinations of “breast cancer,” “imprint cytology,” and “sentinel lymph node” as free text terms. Meanwhile, the references of selected articles were also carefully screened to identify additional relevant articles.

2.2 Inclusion and exclusion criteria

The inclusion criteria were as follows: (1) patients included in the studies were finally diagnosed as breast cancer by postoperative pathology, (2) patients did not receive any neoadjuvant therapy or radiotherapy, (3) the purpose of diagnosis was to detect SLN metastases, (4) all specimens were fresh SLNs, (5) all specimens were evaluated by intraoperative TIC and postoperative histopathology, (6) postoperative hematoxylin–eosin staining technique was used as the reference standard in SLNs assessment, (7) detailed data analysis of all the studies was based on per-patient, and (8) providing sufficient information for calculating false-positive (Fp), false-negative (Fn), true-positive (Tp), and true-negative (Tn) values.

The exclusion criteria were as follows: (1) non-English literature; (2) data analysis of study was based on per-node but not on per-patient; (3) non-clinical research literature including reviews, letters, conference abstracts, basic experiments, case reports, and comments; and (4) published data were insufficient to form a 2 × 2 table.

2.3 Data extraction and quality assessment

Data extraction for each included study was performed independently by two reviewers, and then verified for accuracy by another reviewer. Any disagreement was resolved by team consensus through discussion. The following information was extracted: first author, publication year, country, number of patients, number of SLNs, mean age of patients, reference standard method, thickness of slices and interval of serial slices detected by pathological examination, number of Tp, Fp, Fn, and Tn.

Two reviewers independently assessed the quality of included studies using a standardized tool named Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2), which comprises four key domains: patient selection, a reference standard, index testing, and flow and timing. We classified the risk of bias as “low,” “high,” or “unclear.” When the answers are “yes” to all signaling questions for a domain, the risk of bias can be considered low. But if any question is answered “no,” the risk of bias should be judged as high. We used similar criteria to judge the applicability concerns.

2.4 Statistical analysis

First, Spearman’s correlation coefficient was used to measure the threshold effect which is an important source of heterogeneity; when P > 0.05, there was no threshold effect. Heterogeneity caused by non-threshold effect between the studies was assessed by Cochran Q-test and expressed as an “I-square” value. I 2 values <25, 25–50, and >50% indicate mild, moderate, and significant heterogeneity, respectively [16]. If P < 0.05 or I 2 > 50%, which was considered as significant statistical heterogeneity, the combined sensitivity, specificity, negative likelihood ratio (NLR), positive likelihood ratio (PLR), and diagnostic odds ratio (DOR) with the corresponding 95% CIs were calculated by a random-effect model. But if we obtained an insignificant heterogeneity, a fixed effects model was performed [17]. Similarly, Cochran Q-test and I 2 statistics were adopted to evaluate the heterogeneity of the pooled results. We constructed a summary receiver operating characteristic (sROC) curve to evaluate diagnostic accuracy for TIC, the area under the sROC curve (AUC) value is proportional to the diagnostic value. Deek’s funnel plot asymmetry test was performed to assess publication bias.

The statistical analysis was carried out with STATA16.0 (StataCorp, College Station, TX, USA), Meta-Disc 1.4 (Unit of Clinical Biostatistics, Ramo e Cajal Hospital, Madrid, Spain), and RevMan 5.4 (Revman, the Cochrane Collaboration).

3 Results

3.1 Study selection

As shown in Figure 1, a total of 529 studies from PubMed, Embase, Cochrane Library, and Web of Science databases were retrieved according to the search strategy. We did not find eligible articles after screening the references. The publication dates of these articles ranged from January 2005 to September 2022. Of these, 32 duplicate studies were excluded and 37 studies were removed (e.g., review, letters, meeting abstracts, and proceeding articles). And 447 articles were excluded after screening the titles and abstracts since they did not meet the inclusion criteria: 215 articles were not related to the topic, 13 articles included patients who underwent neoadjuvant therapy or radiotherapy, 55 articles focused on non-sentinel lymph nodes rather than sentinel lymph nodes, 135 articles were non-clinical research literature, data analysis of 8 articles were not based on per-patient, and 21 articles had no sufficient data to form 2 × 2 tables. Finally, 13 articles satisfied the eligibility criteria (Table 1).

Figure 1 
                  Flow diagram of the study selection process.
Figure 1

Flow diagram of the study selection process.

Table 1

Summary of patient characteristics of included studies

Author Year Country No. of patients No. of nodes Mean age Tp Fp Fn Tn Thicknesses (μm) Interval (μm) Reference method
Cotarelo [18] 2021 Germany 1,072 2,276 61.3 191 0 78 803 2,000 250 H&E
Hashmi [19] 2021 PAK 114 53.41 ± 12.46 41 1 8 64 2,000 H&E
Pétursson [20] 2018 Sweden 1,227 1,974 60 192 2 88 945 2,000 200 H&E and IHC
Sun [21] 2017 China 79 342 50 12 10 1 56 2,000 200 H&E
Bell [22] 2010 Ireland 102 58.8 33 0 8 61 2,000 H&E and IHC
Hamidian Jahromi [23] 2009 London 74 146 49.59 ± 13.6 11 1 6 56 H&E
Upender [24] 2009 India 40 49.80 ± 11.19 22 0 2 16 H&E and IHC
Tamiolakis [25] 2006 Greece 87 128 53.6 24 5 0 58 H&E and IHC
Clarke [11] 2009 UK 166 239 61.2 29 0 18 119 2,000 H&E
Van Eetvelde [26] 2011 Belgium 45 83 60 13 1 9 22 2,000 300 H&E and IHC
Motomura [27] 2008 Japan 631 54 110 17 20 484 2,000 200 H&E and IHC
Seenu [28] 2021 India 81 176 49.88 10 1 6 64 2,000 H&E
Lorand [29] 2010 France 355 56.9 32 2 56 265 2,000 250 H&E and IHC

3.2 Study characteristics

The 13 eligible articles (Cotarelo et al., 2021; Hashmi et al., 2021; Pétursson et al., 2018; Sun et al., 2017; Bell et al., 2010; Hamidian Jahromi et al., 2009; Upender et al., 2009; Tamiolakis et al., 2006; Motomura et al., 2008; Seenu et al., 2021; Clarke et al., 2009; Lorand et al., 2010; Van Eetvelde et al., 2011) containing a total of 4,073 patients were included in this meta-analysis [11,1829]. There were two approaches of pathological examinations in different studies: six studies adopted H&E staining and seven studies combined detection of H&E and IHC.

3.3 Quality assessment

The QUADAS-2 was used to assess the quality of each study. Each question was evaluated separately by two independent reviewers, and the disputed issues were evaluated again by a third party to reach a consensus. The results are shown in Figure 2, which indicate that the risk of bias was low and the quality was moderate to high.

Figure 2 
                  Forest plots of pooled sensitivity and specificity.
Figure 2

Forest plots of pooled sensitivity and specificity.

3.4 Diagnostic performance

In the threshold analysis, Spearman’s correlation coefficient was 0.45 and P-value was 0.12, which indicated that there was no evidence of a threshold effect. We adopted a random effect model since the significant heterogeneity caused by non-threshold effects to perform the follow-up meta-analysis. According to Figure 2, we figured out that the values of I 2 for sensitivity and specificity were 86.62 and 93.02%, respectively. The pooled sensitivity and specificity (Figure 2) of TIC for detecting SLN metastases were 0.77 (95% CI 0.66–0.85) and 0.99 (95% CI 0.97–1.00), respectively. The pooled PLR and NLR (Figure 3) were 76.15 (95% CI 29.16–198.84) and 0.23 (95% CI 0.15–0.36), respectively. The pooled DOR (Figure 4) was 326.82 (95% CI 132.76–804.56) and AUC (Figure 5) was 0.97 (95% CI 0.95–0.98), respectively.

Figure 3 
                  Forest plots of pooled PLR and NLR.
Figure 3

Forest plots of pooled PLR and NLR.

Figure 4 
                  Forest plots of pooled DOR.
Figure 4

Forest plots of pooled DOR.

Figure 5 
                  ROC curve for the diagnostic accuracy of TIC in detecting SLN metastasis in breast cancer.
Figure 5

ROC curve for the diagnostic accuracy of TIC in detecting SLN metastasis in breast cancer.

3.5 Publication bias

The evaluation of the publication bias among the included studies was carried out by performing Deek’s funnel chart asymmetry test using STATA software. There was no evidence of significant publication bias since the shape of Deek’s funnel chart was symmetrical and P value was 0.12 (Figure 6).

Figure 6 
                  Deek’s funnel chart asymmetry test of publication bias.
Figure 6

Deek’s funnel chart asymmetry test of publication bias.

4 Discussion

There is no doubt that axillary lymph node status is a very important prognostic factor of invasive breast cancer. SLNB has become a routine method to predict lymph node status [30]. Since it not only enables patients with SLN metastases to complete ALND in one operation, but also enables patients with negative SLN to avoid suffering from long-term complications, such as upper limb lymph node edema, pain, numbness, etc. [35].

It is known that more than 90% of breast centers in China only use FS as a technique for intraoperative evaluation of SLN metastases in breast cancer. However, given the disadvantages of FS such as expensive, loss of tissue, time-consuming, and requirement of experienced and trained technologists and pathologists [8], some authoritative hospitals at home and abroad focused on TIC in view of its main advantages such as simple, rapid, cost-effective, and leaving more tissues for final postoperative pathological analyses [11].

Although some studies have reported the specificity and sensitivity of TIC for the SLN intraoperative diagnosis in breast cancer, the sample sizes of these studies are relatively moderate and the results vary to some extent. Therefore, we conducted the comprehensive meta-analysis to comprehensively analyze the accuracy of TIC in the intraoperative diagnosis of SLN in breast cancer, in the hope that both doctors and patients could benefit from it. In this study, we meta-analyzed 13 studies based on per-patient to evaluate the diagnosis value of TIC. We figured out that the pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of TIC were 0.77 (95% CI 0.66–0.85), 0.99 (95% CI 0.97–1.00), 76.15 (95% CI 29.16–198.84), 0.23 (95% CI 0.15–0.36), 326.82 (95% CI 132.76–804.56), and 0.97 (95% CI 0.95–0.98), respectively. As reported by Kim et al., higher PLR values forecast a stronger association between a test result and a disease, but lower NLR values indicate a stronger association between a test result and the absence of a disease. Thus, given the PLR and NLR values obtained for TIC, this technique is reliable for the intraoperative evaluation of SLN metastases in breast cancer. Furthermore, the sROC value was 0.97, which proved a high degree of overall diagnostic accuracy [31].

Numerous studies have shown that the sensitivity of TIC for the diagnosis of macrometastasis is comparable to FS. However, TIC has a low sensitivity in the diagnosis of micrometastasis. Studies indicated that pathologists with proper technique and experience are more likely to detect micrometastasis. Moreover, even if the micrometastasis is detected in postoperative pathology, there is no necessity to perform ALND. This view has been recognized by the expert consensus [32]. Previous studies have shown that TIC is more accurate than FS in diagnosis of negative SLNs, which means that TIC has a better negative predictive value than FS [21]. The SLN metastasis in invasive lobular carcinoma is difficult to be diagnosed because of the different subtypes of lobular carcinoma with features of diverse cytological morphology. For instance, rosette-like pattern is usually detected in alveolar type; large cell is more common in the polymorphic type. Unfortunately, these subtypes are difficult to be identified except for some very experienced pathologists by TIC [33]. Although the sensitivity of TIC technique in detecting micrometastasis and metastatic sentinel nodes in invasive lobular carcinoma is not satisfactory, it has many obvious advantages such as simplicity, leaving more tissue for postoperative histopathological examination, and saving operative time and cost for some patients as compensation. More encouragingly, it has been reported that the sensitivity of TIC is increasing over time [34].

Although we have conducted a comprehensive and rigorous analysis, there are still several limitations in our present study. First, we only adopted the literature published in English and excluded potential studies published in other languages. Second, our meta-analysis only incorporated published research. However, studies with meaningful positive results are much more likely to be published than those with negative results, which can lead to potential publication bias. Third, there were several factors contributing to clinical and methodological heterogeneity in our analysis, such as the populations of the study samples, proportions of patients with different age, tumor size, molecular subtype and histological grade, and reagent manufacturer selected. Unfortunately, when we tried to perform subgroup analysis, we found some data deficiencies.

5 Conclusions

Intraoperative evaluation of SLN in patients with clinically node-negative breast carcinoma by TIC is proved to be a reliable and feasible technique. TIC and FS showed similar low sensitivity in the diagnosis of micrometastasis. However, TIC retains more tissue for subsequent histological evaluation as compensation. As a result, we believe that the TIC technique for diagnosis of SLN metastasis in breast cancer deserves to be widely applied in clinical practice.

Abbreviations

ALND

axillary lymph node dissection

AUC

area under the sROC curve

DOR

diagnostic odds ratio

FS

frozen section

NLR

negative likelihood ratio

OSNA

one-step nucleic acid amplification

PLR

positive likelihood ratio

QUADAS

Quality Assessment of Diagnostic Accuracy Studies

SLNB

sentinel lymph node biopsy

SROC

Summary receiver operating characteristic

TIC

touch imprint cytology


# Equal contributors and co-first authors.


  1. Funding information: None.

  2. Author contributions: Conceptualization: Qing-Qing Yang; data curation: Yun-Gang Hu and Qing-Qing Yang; formal analysis: Hao-Yuan Shen; methodology: Chao-Hua Hu and Yun-Tao Han; writing the article: Qing-Qing Yang and Yun-Gang Hu.

  3. Conflict of interest: The authors have no conflicts of interests to disclose.

  4. Data availability statement: All data included in this study are available upon request by contact with the corresponding author.

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Received: 2022-11-19
Revised: 2023-05-09
Accepted: 2023-10-03
Published Online: 2023-10-30

© 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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  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
  31. Monitoring of sirolimus in the whole blood samples from pediatric patients with lymphatic anomalies
  32. Effects of osteogenic growth peptide C-terminal pentapeptide and its analogue on bone remodeling in an osteoporosis rat model
  33. A novel autophagy-related long non-coding RNAs signature predicting progression-free interval and I-131 therapy benefits in papillary thyroid carcinoma
  34. WGCNA-based identification of potential targets and pathways in response to treatment in locally advanced breast cancer patients
  35. Radiomics model using preoperative computed tomography angiography images to differentiate new from old emboli of acute lower limb arterial embolism
  36. Dysregulated lncRNAs are involved in the progress of myocardial infarction by constructing regulatory networks
  37. Single-arm trial to evaluate the efficacy and safety of baclofen in treatment of intractable hiccup caused by malignant tumor chemotherapy
  38. Genetic polymorphisms of MRPS30-DT and NINJ2 may influence lung cancer risk
  39. Efficacy of immune checkpoint inhibitors in patients with KRAS-mutant advanced non-small cell lung cancer: A retrospective analysis
  40. Pyroptosis-based risk score predicts prognosis and drug sensitivity in lung adenocarcinoma
  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
  44. Downregulation of RBM17 enhances cisplatin sensitivity and inhibits cell invasion in human hypopharyngeal cancer cells
  45. HDAC5-mediated PRAME regulates the proliferation, migration, invasion, and EMT of laryngeal squamous cell carcinoma via the PI3K/AKT/mTOR signaling pathway
  46. The association between sleep duration, quality, and nonalcoholic fatty liver disease: A cross-sectional study
  47. Myostatin silencing inhibits podocyte apoptosis in membranous nephropathy through Smad3/PKA/NOX4 signaling pathway
  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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