Home The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
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The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer

  • Xinyu Cheng , Jianguo Xia , Qi Xu EMAIL logo and Huawei Gui
Published/Copyright: November 14, 2023

Abstract

This study aimed to explore the value of color Doppler ultrasonography combined with carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in differential diagnosis of gastric stromal tumor (GST) and gastric cancer (GC). An analysis of the clinical data of 180 patients with clinically suspected gastric space occupying lesions. According to the postoperative pathological results, 180 suspected gastric space-occupying lesion patients were divided into GST group (n = 83) and GC group (n = 97). Color Doppler ultrasonography, serum tumor markers CEA and CA19-9 were compared. The research results showed that serum CEA and CA19-9 levels were lower in patients with GST group than those with GC group (both P < 0.001). With postoperative pathology as the gold standard, detection rates of GST and GC by combination of color Doppler ultrasound (CDUS), serum CEA, and CA19-9 were higher than those of each index alone (both P < 0.001). There was no difference between detection rates of GST and GC by combination of CDUS, serum CEA, and CA19-9 (P = 0.058). Color Doppler ultrasonography combined with serum tumor markers CEA and CA19-9 tests has a certain differential diagnostic value for GST and GC, which may provide a reliable reference basis for clinical diagnosis and treatment.

1 Introduction

Gastric stromal tumor (GST), which is aggressive and potentially malignant, refers to a group of non-epithelial tumors of the stomach without immunohistochemical features of Schwann cells or ultrastructure of smooth muscle cells [1]. Gastric cancer (GC) is a common malignant tumor of the digestive system [2]. Differentiating between GST and GC is crucial as both conditions have distinct pathological features, different prognoses, and require different treatment approaches. Misdiagnosis or delayed diagnosis of either condition can lead to inadequate treatment, affecting patient outcomes. Moreover, GSTs, although relatively rare, have an increasing incidence and prevalence globally, necessitating greater awareness and understanding of the disease. Differentiation helps to ensure appropriate management and treatment decisions, preventing unnecessary surgical interventions, and improving long-term outcomes. Therefore, understanding the differences between GST and GC is essential for accurate diagnosis, timely treatment, and improving patient outcomes. Furthermore, accurate diagnosis and differentiation between GST and GC are crucial for treatment decision-making and determining patient prognosis. In contrast to GC, surgical resection is generally the first-line treatment option for GST. However, if misdiagnosed or if the tumor regresses or metastasizes, the prognosis can be significantly worse. Therefore, improving understanding of the differences between GST and GC and increasing awareness of the increased incidence of GST may help to improve early detection and appropriate management, ultimately leading to improved patient outcomes.

Both GST and GC feature epigastric discomfort, abdominal pain, upper gastrointestinal bleeding, and abdominal mass, hence the difficulty in their clinical distinguishing. GST and GC are often detected clinically by ultrasound endoscopy or CT and MR enhancement scan, but ultrasound endoscopy is invasive and CT and MR enhancement scan are highly expensive [3,4].

Transabdominal color Doppler ultrasound (CDUS) is a simple imaging tool to differentiate GST from GC, but missed diagnosis may occur [5]. Its efficacy in differential diagnosis of GST remains controversial. Some studies have shown that transabdominal CDUS has a better differential diagnosis of GST [6]. In contrast, it was also found that only 16 lesions were detected by abdominal ultrasound in 88 GST patients. Abdominal ultrasound was believed to be of little value as it can only detect extraluminal, metastatic lesions and a small number of intraluminal lesions [7].

Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are important serum tumor markers. CEA levels in human serum increase significantly in the presence of tumors, so it is associated with tumor diagnosis and prognosis [8]. CA19-9, in the form of salivary mucin, exists in human serum. It is a mucin-like tumor marker and has demonstrated some value in the diagnosis of tumors [9].

CEA and CA19-9 have been reported to be used in the diagnosis of gastrointestinal cancers, but there are also misdiagnoses and missed diagnoses [10]. The known information is that CEA and CA19-9 are both tumor markers that have been used in the diagnosis and monitoring of cancer, including GC. Color Doppler ultrasonography is a non-invasive imaging technique that can provide detailed information on blood flow in and around tumors. However, the combination of these methods in the differential diagnosis of GST and GC is not well-established.

The purpose of this study was to investigate the value of color Doppler ultrasonography combined with CEA and CA19-9 in differential diagnosis of GST and GC.

2 Materials and methods

2.1 Patients

A total of 180 patients admitted to our hospital with clinically suspected gastric space occupying lesions from January 2015 to May 2021 were selected as subjects for the study. Inclusion criteria were that patients with suspected gastric space occupying lesions; patients with clinical symptoms such as vague pain and distension in the upper abdomen.

Patients received preoperative transabdominal color Doppler ultrasonography, and the diagnosis of GST or GC in all cases was confirmed by the gold standard of postoperative pathological findings; age ≥18 years; single tumor; complete clinical data; patients and families gave informed consent and voluntarily participated in the study.

Exclusion criteria were that patients combined with other gastric diseases such as gastric polyps and gastritis; patients combined with serious primary cardiovascular and cerebrovascular diseases, liver, kidney abnormalities, etc.; patients combined with blood diseases and infectious diseases; patients who did not cooperate; patients with visual and hearing impairment; patients with GST and GC; patients with other malignant tumors; women during pregnancy and lactation; patients with mental illness; and patients having undergone radiotherapy or chemotherapy before surgery.

2.2 Transabdominal CDUS examination method

All patients received preoperative examination by transabdominal CDUS (C5-1 probe, frequency 3.5–5.0 MHz). They were asked to fast for over 8 h before the examination. The patient was placed in supine position, and a whole multi-sectional transabdominal ultrasound scan was performed to observe gastric fundus, body, and antrum. The size was measured and the location determined after detection of the tumor mass. Internal echoes, relationship between the tumor mass and the gastric wall, clarity of the gastric wall stratification, and presence of perigastric lymph node enlargement were closely observed. Distribution of blood flow within and around the tumor mass was observed by color Doppler ultrasonography. If the tumor was in close proximity to the stomach and bladder, the stomach and bladder needed to be filled before the examination. The color Doppler ultrasonography imaging appearance was compared with pathological findings (the gold standard).

2.3 Pathological detection method

GST and GC were diagnosed by routine postoperative pathological examination. Specifically, surgically resected specimens were taken from all patients, routinely prepared, HE stained, and observed under light microscopy. Cancers were classified according to the diagnostic criteria from Rosai and Ackerman’s Surgical Pathology [11]. If tumor <3 cm in diameter, no cellular heterogeneity seen, no nuclear division phase; borderline, tumor size of 3–5 cm, dense cells, mild heterogeneity, occasional focal infiltration, and nuclear division phase of 1-4/50 HPFs: the tumor was judged as benign, i.e., GST. If tumor ≥5 cm in diameter, dense cells, marked heterogeneity, infiltrative growth, and nuclear division phase ≥5/50 HPFs, the tumor was judged as malignant, namely GC.

According to the postoperative pathological results, 180 suspected gastric space-occupying lesion patients were divided into GST group (n = 83) and GC group (n = 97).

2.4 Serum tumor markers detection method

Preoperative fasting venous blood was collected from all study subjects in the early morning, and serum was extracted after centrifugation. Levels of serum tumor markers CEA and CA19-9 were measured by electrochemiluminescence. Postoperative pathological results were used as the gold standard to compare the detection rates of GST and GC by color Doppler ultrasonography, serum tumor markers CEA and CA19-9 alone, and the combination of the three.

2.5 Statistic analysis

SPSS 25.0 was used for data processing. Measurement data conforming to the normal distribution were represented by mean ± SD, and independent sample t-test was used for measurement data comparison. Count data were expressed as n (%), and chi-square test was used. P < 0.05 indicated that the difference was statistically significant.

  1. Informed consent: Informed consent has been obtained from all individuals included in this study.

  2. Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenets of the Helsinki Declaration and has been approved by the authors’ institutional review board or equivalent committee.

3 Results

3.1 Demographic characteristic of the patients

Of the 83 patients with GST group confirmed by postoperative pathology, 54 (65.06%) were male and 29 (34.94%) female, aged 35–72 years, with a mean of (52.49 ± 8.15) years; among the 97 patients with GC group, 60 (61.86%) were male and 37 (38.14%) female, aged 33–73 years, with a mean of (52.37 ± 7.96) years.

3.2 Comparison of serum marker levels

The serum CEA and CA19-9 levels were significantly lower in patients with GST group than those with GC group, and the differences were statistically significant (both P < 0.001, Table 1).

Table 1

Comparison of serum marker levels between GST group and GC group

Parameter GST group (n = 83) GC group (n = 97) P value
Serum CEA (μg/L) 9.10 ± 0.84 13.48 ± 1.39 <0.001
Serum CA19-9 (U/mL) 35.81 ± 3.33 75.63 ± 5.76 <0.001

3.3 Preoperative color Doppler ultrasonography and postoperative pathological findings

CDUS imaging appearance of GST group: round-like and elliptical in shape, mainly found in gastric fundus and body. Ultrasonography showed most masses were well encapsulated and hypoechoic with expansive growth pattern and regular morphology. Liquefaction necrosis appeared in some lesions in which the blood flow was abundant and no lymphadenectasis was found (Figure 1a and b for typical case pictures of the same GST patient; Figure 2a and b for typical pictures of healthy person).

Figure 1 
                  (a) Preoperative color Doppler ultrasonography in a GST patient: solid lesion in the right mid-upper abdomen (below the lower pole of the right kidney and above the right side of the inferior vena cava). (b) Postoperative pathological findings of a GST patient: high-risk gastrointestinal stromal tumor (multiple masses with visible necrosis and vascular invasion).
Figure 1

(a) Preoperative color Doppler ultrasonography in a GST patient: solid lesion in the right mid-upper abdomen (below the lower pole of the right kidney and above the right side of the inferior vena cava). (b) Postoperative pathological findings of a GST patient: high-risk gastrointestinal stromal tumor (multiple masses with visible necrosis and vascular invasion).

Figure 2 
                  (a) Ultrasonogram of a normal stomach (an ultrasound image of the stomach in a filling state in a healthy person, where the gastric cavity is filled and enlarged, showing liquid echoes with small bubbles floating, and the layered structure of the gastric wall is clearly displayed). (b) Pathological picture of a normal stomach (in a healthy person, the stomach has a normal gastric mucosal layer and gastric glands, and the complete glandular structure can be seen).
Figure 2

(a) Ultrasonogram of a normal stomach (an ultrasound image of the stomach in a filling state in a healthy person, where the gastric cavity is filled and enlarged, showing liquid echoes with small bubbles floating, and the layered structure of the gastric wall is clearly displayed). (b) Pathological picture of a normal stomach (in a healthy person, the stomach has a normal gastric mucosal layer and gastric glands, and the complete glandular structure can be seen).

CDUS imaging appearance of GC group: mainly found in gastric antrum, mostly presented as ill-defined margin irregular hypoechoic lesions with invasive growth pattern and pseudokidney sign was observed because of the lesions growing around the gastric cavity. Blood flow was not abundant and lymphadenectasis was found in some lesions.

3.4 Comparison of the detection rates of each index alone and in combination for GST and GC

With postoperative pathology as the gold standard, the detection rates of GST by the combination of CDUS, serum CEA, and CA19-9 were significantly higher than those of each index alone, and the difference was statistically significant (P < 0.001, Table 2).

Table 2

Comparison of the detection rates of each index alone and in combination for GST and GC (n[%])

Parameter CDUS Serum CEA (cutoff value = 10 μg/L) Serum CA19-9 (cutoff value = 39 U/mL) Combined examinations of CDUS, serum CEA, and CA19-9 P value
GST group (n = 83) 66 (79.52) 15 (18.07) 10 (12.05) 77 (92.77)* <0.001
GC group (n = 97) 70 (72.16) 39 (40.21) 45 (46.39) 81 (83.51) <0.001

*Note: Compared with the detection rate of combined examinations of CDUS, serum CEA, and CA19-9 for GC, P = 0.058.

With postoperative pathology as the gold standard, the detection rates of GC by the combination of CDUS, serum CEA, and CA19-9 were significantly higher than those of each index alone, and the difference was statistically significant (P < 0.001, Table 2).

There was no statistically significant difference between the detection rates of GST and GC by the combination of CDUS, serum CEA, and CA19-9 (P = 0.058, Table 2).

4 Discussion

Distinguishing between GC and GST beforehand by using different combinations can have significant value in deciding the most appropriate treatment plan for the patient post-surgery. While surgical resection is the first-line treatment for both types of cancer, patients diagnosed with GC or GST may require different treatments, such as chemotherapy or radiation therapy, depending on their specific diagnosis. By accurately distinguishing between GC and GST beforehand through the use of multiple combinations, doctors can tailor a treatment plan specific to the patient’s individual needs, improving their chances of successful recovery. Additionally, distinguishing between GC and GST beforehand can help doctors better understand the characteristics and behaviors of each type of cancer, leading to the development of more effective treatment options in the future.

This study found that Color Doppler ultrasonography combined with serum tumor markers CEA and CA19-9 tests has a certain differential diagnostic value for GST and GC. Transabdominal CDUS has been shown to be effective in differential diagnosis of intestinal stromal tumor and intestinal cancer [12]. However, GST and GC each show characteristic presentations on CDUS, and the effectiveness of differential diagnosis between the two remains unclear. Their difference in the origin and growth pattern is the pathological basis for CDUS differentiation.

Originating in the submucosa and growing swollen in the myocardium of the gastric wall, GSTs are mostly convex to the subplasma or submucosa, and they are encapsulated tumors with regular margins at an early stage [13]. CDUS imaging appearance of GST showed characteristics of round-like or elliptical shape, hypoechoic mass with clear margins, and uniform internal echogenicity [14].

GC starts from the mucosal epithelium and grows as infiltrative thickening of the gastric wall [15]. CDUS imaging appearance of GC showed characteristics like ill-defined margin irregular hypoechoic lesions, pseudokidney sign, shallower and wider mucosal ulceration surface compared with stomal tumors [16].

Serum tumor marker detection is convenient, non-invasive, and widely applied in clinical practice. This approach contributes to improving the diagnostic accuracy of tumor patients, which provides a basis for formulating effective treatment plans and evaluating the prognostic quality of patients. However, there is a lack of effective diagnostic markers for GST. One study showed that serum CEA and CA19-9 levels were elevated in GST patients, suggesting that they may be potential markers [17].

The results of this study showed that serum CEA and CA19-9 levels were significantly lower in GST patients compared with patients with GC, suggesting that serum CEA and CA19-9 are of more significant value in the diagnosis of GC. However, it should be noted that in the GC group, clinical features of different patients such as age and tumor, node, metastasis may affect the serum CEA and CA19-9 levels of GC patients. Previous studies also showed that the preoperative serum CA19-9 levels were significantly higher in patients with GC, and the preoperative serum CA19-9 can be detected to identify the staging in patients with GC [18].

The positive rate of CEA and CA19-9 in early GC has been shown to be low in previous studies [19].The detection rates of GST and GC by combined CDUS and serum CEA and CA19-9 were significantly higher than those by each index alone, but the difference was not statistically significant when comparing the detection rates of GST and GC by combining CDUS and serum CEA and CA19-9. It should be noted that there were many similar studies discussing the increased detection rate of the combination of CDUS and serum tumor markers in different tumors [20,21].

The novelty of this study is that it aims to provide evidence of the usefulness of combining color Doppler ultrasonography with CEA and CA19-9 in the differential diagnosis of GST and GC. This study will contribute to the development of a more accurate, non-invasive, and cost-effective diagnostic approach for these two conditions.

This study did not design a normal control group, which is a limitation. The author did not perform receiver operator characteristic (ROC) analysis in this study due to limited sample size. The author will take into consideration the possibility of performing ROC analysis in future studies with a larger sample size. The relationship between GST and GC is important to consider when analyzing the diagnostic accuracy of a tool used to distinguish between the two conditions. If GST and GC are simply different stages of the same disease process, it could impact the interpretation of the results. For example, a tool that accurately diagnoses GC may also diagnose GST, but may not accurately differentiate between the two. This could lead to false positives or negatives, affecting the tool’s sensitivity and specificity. In addition, the 180 patients seem to be diagnosed to have either GST or GC. Many of other patients are excluded. For next research the author needs to have some people without either of the two conditions to test sensitivity and specificity.

5 Conclusion

Color Doppler ultrasonography combined with serum tumor markers CEA and CA19-9 tests has a certain differential diagnostic value for GST and GC, which can provide a reliable reference basis for clinical diagnosis and treatment.

Acknowledgements

Not applicable.

  1. Funding information: Not applicable.

  2. Conflict of interest: Authors state no conflict of interest.

  3. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2022-09-21
Revised: 2023-08-17
Accepted: 2023-09-01
Published Online: 2023-11-14

© 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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  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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