Home Medicine Comparison of the ability of newly inflammatory markers to predict complicated appendicitis
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Comparison of the ability of newly inflammatory markers to predict complicated appendicitis

  • Ali Saridas ORCID logo , Nafis Vural ORCID logo EMAIL logo , Murat Duyan ORCID logo , Hasan Can Guven ORCID logo , Elif Ertas ORCID logo and Basar Cander ORCID logo
Published/Copyright: July 25, 2024

Abstract

Introduction

Acute appendicitis (AA) is the predominant condition responsible for acute abdominal pain across all age demographics. The purpose of this research is to determine if the hemoglobin, albumin, lymphocyte, and platelet (HALP) and modified HALP (m-HALP) scores differ between complicated and uncomplicated appendicitis in patients diagnosed with AA who have applied to the emergency department (ED). Additionally, this study aims to investigate whether HALP and m-HALP scores are superior to other biomarkers.

Materials and methods

The retrospective analysis included adult patients, aged eighteen or older, who were diagnosed with AA, and sought treatment at the ED of a tertiary hospital. Patients were divided into two groups: complicated appendicitis (CA) and uncomplicated appendicitis (UCA). The cut-off in diagnostic value measurements was determined using the receiver operating characteristic analysis.

Results

A total of 436 patients (CA: 126, UCA: 310) were included. Neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-albumin ratio, systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and pan-immune inflammation value (PIV) were found to have acceptable diagnostic power in CA detection (area under the curve [AUC]: 0.735–0.783). In detecting UCA, HALP and m-HALP were of fair diagnostic power (AUC: 0.64, 0.68, respectively).

Conclusions

In this study, we found that although PIV, SIRI, SII, and NLR had acceptable diagnostic values in distinguishing CA and UCA, HALP and m-HALP had fair diagnostic values.

1 Introduction

The incidence rate of acute abdominal cases in emergency admissions ranges from 5 to 10% [1]. Acute appendicitis (AA) is the predominant condition responsible for acute abdominal pain across all age demographics [2]. AA may result in complications if there are delays in diagnosis. Complications can result in higher rates of morbidity and mortality [3]. AA is categorized into two groups: complicated appendicitis (CA) and uncomplicated appendicitis (UCA). Clinical complications such as abscess, gangrenous appendicitis, perforation, and phlegm are referred to as CA [4]. It is critical to ascertain whether the administration of AA is complicated.

Complete blood count (CBC) is a commonly utilized diagnostic test for AA, alongside any physical examination findings. Additionally, white blood cell count and neutrophil count are among the early indicators of inflammatory pathologies [5]. Neutrophil-to-lymphocyte ratio (NLR), platelet (PLT)/lymphocyte ratio, and systemic immune-inflammation index (SII) are inflammatory markers that can effectively differentiate between uncomplicated and complicated AA [6].

The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is a comprehensive measure that includes hemoglobin, albumin, lymphocyte, and PLT levels. It has been recognized as a novel biomarker that can indicate both systemic inflammation and nutritional status [7]. The HALP score was identified as a dependable adverse biomarker for survival in a comprehensive meta-analysis [8]. Furthermore, HALP and modified HALP (m-HALP) scores have been identified as valuable indicators for predicting the outcome of acute cerebral ischemia and acute heart failure [9,10]. A recent study proposed that the HALP score can be utilized to forecast the severity and extent of complications associated with AA [11].

The purpose of this research is to determine whether a difference between the HALP and m-HALP exists between complicated and UCA in patients diagnosed with AA who have applied to the emergency department (ED). Additionally, this study aims to investigate whether HALP and m-HALP scores are more reliable compared to other biomarkers.

2 Materials and methods

2.1 Study design and settings

The retrospective cross-sectional study design consisted of adult patients aged 18 and over who were diagnosed with AA and sought treatment in the ED of a tertiary hospital between January 1, 2020, and January 1, 2023. The study received approval, and the requirement for informed consent was waived by the Ethics Commission (ethics committee decision number: 2023/243 date: November 20, 2023). The research was conducted in accordance with the Declaration of Helsinki.

2.2 Study protocol

After the ethics committee approval was received, the data on the hospital’s data network were retrospectively examined for patients diagnosed with AA aged 18 years and above. Demographic data (gender, age, etc.), laboratory findings, surgical operation notes, pathology reports, and abdominal CT results at the time of first admission to the ED were evaluated.

Patients who were either pregnant, had peripheral vascular disease, had previously suffered heart failure, had hematological disease, or had liver disease; were using anticoagulants, antibiotics, or steroids at time; had other acute or chronic infections; and had a pathology result revealing a tumor or whose records could not be accessed were all excluded from the study sample.

Patients who were diagnosed with AA based on a physical examination, ultrasonography, abdominal CT, and histopathology that underwent surgery were included in the study. The clinical condition of the patients, abdominal CT, surgery reports, and histopathological examinations of the appendix were evaluated en masse, and AA was classified as either complicated or uncomplicated. The clinical conditions and radiological data of the patients were not evaluated and analyzed individually. CA was defined as the presence of gangrenous or perforated appendicitis and/or diffuse peritonitis. UCA was defined as a phlegmatic inflamed appendix with no signs of necrosis or perforation [12]. Patients whose complicated or uncomplicated conditions could not be confirmed were excluded from the study sample.

2.3 Laboratory analyses

An automated hematology analyzer (Coulter Gen-S Hematology Analyzer; Beckman Coulter Corp, Hialeah, FL, USA) was used to determine the CBC. Hematological parameters, such as total leucocyte counts and differential, hemoglobin, hematocrit, PLT levels, NLR, neutrophil-to-albumin ratio (NAR), SII, systemic inflammation response index (SIRI), and pan-immune inflammation value (PIV), were recorded.

Serum sodium, potassium, glucose, urea, creatinine, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels were recorded.

The NLR, NAR, PIV, SII, and SIRI were defined as “neutrophil count/lymphocyte count,” “neutrophil count/albumin level,” “neutrophil count × platelet count × monocyte count/lymphocyte count,” “neutrophil count × platelet count/lymphocyte count,” and “neutrophil × monocyte/lymphocyte count,” respectively. The HALP score was calculated by using the hemoglobin (g/L) × albumin (g/L) × lymphocyte count (1/L)/PLT count (1/L) method. The modified HALP score was calculated by using the hemoglobin (g/L) × albumin (g/L) × lymphocyte count (1/L) × PLT count (1/L) method.

2.4 Data analysis

Parametric tests were used without the normality test due to the compatibility of the central limit theorem [13]. In the analysis of the data, the mean, standard deviation, and minimum and maximum values of the features were used while performing the statistics of continuous data. Categorical variables were defined using frequency and percentage values. Student’s t-test statistics were used to compare the CA and UCA patients. Chi-square test statistics were used to evaluate the relationship between the two independent categorical variables. The receiver operating characteristic (ROC) analysis was used to determine the cut-off value of NLR, NAR, SII, SIRI, PIV, HALP, and m-HALP in predicting CA and UCA. Cut-off accuracy was evaluated with sensitivity and specificity statistics. The area under the curve (AUC) of 0.5–0.6 was interpreted as poor, 0.6–0.7 as fair, 0.7–0.8 as acceptable, 0.8–0.9 as excellent, and >0.9 as outstanding. The level of statistical significance of the data is considered p < 0.05. New York software (e-picos, New York, NY, USA, www.e-picos.com) and the MedCalc statistical package program (MedCalc Software Ltd., Ostend, Belgium) were used for data evaluation.

3 Results

A total of 436 patients (CA: 126, UCA: 310) were included in the study. Table 1 shows the average and standard deviation values of age, gender, and biomarkers. There is a significant relationship between the study groups and gender (p < 0.05). While 64% of the CA patients were male, only 51% of the UCA patient group were male. There is also a significant relationship between the study groups and age of the patients. The mean age of CA patients was lower compared to UCA patients.

Table 1

Comparison of basic and laboratory characteristics of complicated acute appendicitis and uncomplicated acute appendicitis groups

CA (n = 126) UCA (n = 310) p-value
± SD ± SD
Age (years) 35.14 ± 13.81 39.21 ± 31.09 <0.028*
n (%) n (%)
Sex
Female 45 (36) 152 (49) 0.02**
Male 81 (64) 158 (51)
Features
Glucose (mg/dL) 115.46 ± 31.09 109.37 ± 29.80 0.36*
Serum sodium (mEq/L) 138.41 ± 2.8 139.48 ± 3.02 0.65*
Serum potassium (mEq/L) 4.22 ± 0.35 4.21 ± 0.37 0.007*
Urea (mg/dL) 31.32 ± 12.93 28.37 ± 9.89 0.004*
Creatinine (mg/dL) 0.87 ± 0.31 0.75 ± 0.29 0.14*
AST (U/L) 22.32 ± 8.71 19.17 ± 7.49 0.06*
ALT (U/L) 29.92 ± 16.06 19.15 ± 10.05 0.001*
CRP (mg/L) 65.71 ± 43.64 18.48 ± 16.26 <0.001*
Albumin 39.74 ± 2.57 40.98 ± 3.23 0.003*
Hemoglobin 14.74 ± 1.79 14.11 ± 1.53 0.23*
HTC 43.01 ± 4.61 41.25 ± 4.51 0.72*
PLT (103 μL) 263.91 ± 56.57 259.45 ± 58.16 0.021*
NEU (103 μL) 11.73 ± 3.54 9.16 ± 2.81 0.008*
LYM (103 μL) 1.73 ± 0.55 2.38 ± 0.86 <0.001*
MON (103 μL) 1.01 ± 0.21 0.98 ± 0.26 <0.001*
NLR 7.31 ± 2.75 4.54 ± 2.68 <0.001*
NAR 0.31 ± 0.09 0.23 ± 0.07 <0.001*
SII 1886.54 ± 850.62 1218.21 ± 634.21 <0.001*
SIRI 7.19 ± 3.26 4.25 ± 3.03 <0.001*
PIV 1915.02 ± 973.79 1133.27 ± 741.13 <0.001*
HALP 4.18 ± 1.81 5.18 ± 2.39 0.001*
m-HALP 2776,941.82 ± 115867.7 394267.1 ± 189061.5 0.001*

*Student’s t test, **Chi-square test (p < 0.05 significance).

AST: aspartate aminotransferase, ALT: alanine aminotransferase, CRP: C-reactive protein, INR: international normalized ratio, PLT: platelets, NEU: neutrophil, LYM: lymphocyte, MON: monocyte, NLR: neutrophil-to-lymphocyte ratio, SII: systemic immune inflammation index, SIRI: systemic inflammation response index, PIV: pan-immune inflammation value, HALP: hemoglobin × albumin levels × lymphocyte count/platelet count, m-HALP: modified HALP.

There was no significant difference between the group mean values of glucose, serum sodium, creatinine, AST, hemoglobin, and hematocrit (p > 0.05).

There was a significant difference between the group means of serum potassium, urea, ALT, CRP, albumin, PLT, neutrophil count (NEU), lymphocyte count (LYM), monocyte count (MON), NLR, NAR, SII, SIRI, PIV, HALP, and m-HALP values (p < 0.05) (Table 1).

Table 2 presents in detail the diagnostic accuracy of biomarkers important for the differential diagnosis of CA and UCA in ROC analysis (Tables 2 and 3, Figures 1 and 2).

Table 2

Diagnostic accuracy of inflammatory parameters to predicting complicated acute appendicitis

CA: 126 AUC Cut-off Sensitivity % Specificity % AUC 95% CI p-value
UCA: 310
NLR 0.778 >5.43 68.3 76.1 0.74–0.82 <0.001
NAR 0.735 >0.23 68.7 68.4 0.69–0.78 <0.001
SII 0.742 >1647.01 82.6 56.3 0.70–0.79 <0.001
SIRI 0.783 >4.45 78.6 65.5 0.74–0.82 <0.001
PIV 0.761 >1179.81 75.4 66.1 0.71–0.79 <0.001

AUC, area under curve; SE, standard error; PPV, positive predictive value; NPV, negative predictive value; CI, confidence interval; NLR, neutrophil-to-lymphocyte ratio; NAR, neutrophil-to-albumin ratio; NPR, neutrophil-to-platelet ratio, SII: systemic immune inflammation index, SIRI: systemic inflammation response index, PIV: pan-immune inflammation value.

Table 3

Diagnostic accuracy of inflammatory parameters to predicting uncomplicated acute appendicitis

CA: 126 AUC Cut-off Sensitivity % Specificity % AUC 95% CI p-value
UCA: 310
HALP 0.64 >4.69 77.2 51.8 0.59–0.68 <0.001
m-HALP 0.68 >348,737.98 83.3 56.8 0.64–0.73 <0.001

HALP: hemoglobin × albumin levels × lymphocyte count/platelet count m-HALP: The modified HALP.

Figure 1 
               The ROC curves of biomarkers for predicting complicated acute appendicitis. NLR: neutrophil-to-lymphocyte ratio, NAR: neutrophil-to-albumin ratio, NPR: neutrophil-to-platelet ratio, SII: systemic immune inflammation index, SIRI: systemic inflammation response index, PIV: pan-immune inflammation value.
Figure 1

The ROC curves of biomarkers for predicting complicated acute appendicitis. NLR: neutrophil-to-lymphocyte ratio, NAR: neutrophil-to-albumin ratio, NPR: neutrophil-to-platelet ratio, SII: systemic immune inflammation index, SIRI: systemic inflammation response index, PIV: pan-immune inflammation value.

Figure 2 
               The ROC curves of biomarkers for predicting uncomplicated acute appendicitis. HALP: hemoglobin × albumin levels × lymphocyte count/platelet count, m-HALP: modified HALP.
Figure 2

The ROC curves of biomarkers for predicting uncomplicated acute appendicitis. HALP: hemoglobin × albumin levels × lymphocyte count/platelet count, m-HALP: modified HALP.

NLR, NAR, SII, SIRI, and PIV were found to have acceptable diagnostic power in CA detection (AUC: 0.735–0.783).

In detecting UCA, HALP and m-HALP were of fair diagnostic power (AUC: 0.64, 0.68, respectively).

4 Discussion

It is critical to distinguish whether AA is complicated or not, as well as to diagnose it correctly. While clinical studies analyze the diagnosis of AA itself, few have attempted to distinguish between CA and UCA [12]. However, the guidelines currently do not contain explicit instructions on how to differentiate between uncomplicated and complicated cases of appendicitis [14,15]. The same guidelines recommend that CA should be treated more urgently and that UCA can only be treated with antibiotics [14,15]. Therefore, it is important to make a differential diagnosis of complications or UCA in a patient diagnosed with AA.

The constituent elements of the HALP score can offer crucial insights into the immunological nutritional state of the patient. Assessing hemoglobin levels is an important procedure because hemoglobin levels are an indicator of anemia, which is a prevalent illness worsened by many inflammatory processes. Albumin, which is a protein produced by the liver, is classified as a negative acute phase reactant. Low levels of albumin in the blood are indicative of an inflammatory condition. Lymphocytes and PLTs play critical roles in the immunological function of the body, decreased lymphocyte count, and elevated PLT count may suggest a compromised immune system with a heightened susceptibility to infection [16]. According to this data, low HALP and m-HALP scores are indicative of the intensity of inflammation. Therefore, low scores can be seen as an indirect indication of CA.

A study conducted after surgery found that a low HALP score was linked to complications and postoperative morbidity in patients of AA [11]. Patients diagnosed with metastatic stomach cancer exhibited significantly lower survival rates compared to individuals with high HALP scores [17]. A separate study demonstrated that a low HALP score can differentiate between malignant origins in patients experiencing extrahepatic biliary obstruction [18]. A meta-analysis conducted on cancer patients has determined that a low HALP score can serve as a negative biomarker for survival [8]. Since inflammation is more severe in patients with CA, albumin and lymphocyte levels are expected to decrease. Therefore, unlike other inflammatory biomarkers, the HALP and m-HALP scores are expected to be negative biomarkers. Inflammatory biomarkers such as PIV, SIRI, SII, and NLR are expected to be positive biomarkers in distinguishing complicated and uncomplicated patients with AA. Thus, when evaluating HALP and m-HALP scores, it is expected to be higher in UCA. In this study, HALP and m-HALP scores had a fair diagnostic value in distinguishing uncomplicated and complicated patients with AA.

Elevated NLR levels are associated with an increase in neutrophils or a decrease in lymphocytes during inflammation of the appendix [19]. Increased NLR levels are associated with an increase in neutrophils or a decrease in lymphocytes during inflammation of the appendix [20]. A recent similar study showed that NLR predicted CA with an AUC of 0.730 [21]. In this study, we found that NLR can predict CA with a higher diagnostic value.

SIRI and SII, which are usually assessed based on peripheral blood-based parameters (e.g., lymphocytes, CRP, monocytes, neutrophils, or PLT count), have been shown to be associated with several types of cancer [22,23]. A study undertaken throughout the COVID-19 pandemic revealed a correlation between SII and SIRI and the occurrence of AA complications [24]. In the study conducted by Tekeli et al., SII was found to be useful in determining CA. In this study, it was concluded that SII and SIRI could be useful in detecting complicated AA. This conclusion supports the existing literature.

PIV is a novel composite biomarker utilized to assess inflammatory conditions. Unlike current biomarkers, PIV incorporates all four primary cell types seen in peripheral blood [25]. A study conducted in patients with rheumatoid arthritis determined that PIV is an effective tool for differentiating between periods of active disease and times of remission [26]. Additionally, it has been discovered to be a promising biomarker in individuals diagnosed with colorectal cancer [27]. Nevertheless, the connection between AA and PIV remained ambiguous. This study demonstrated that the diagnostic efficacy of PIV in differentiating between difficult and UCA was comparable to that of previously used inflammatory indicators.

There is still no parameter with a high diagnostic value in distinguishing between complicated and uncomplicated AA patients. According to the results of our study, when compared to HALP and m-HALP scores, inflammatory biomarkers such as PIV, SIRI, SII, and NLR had a higher diagnostic value in making this distinction.

5 Study limitations

As our study was planned to be single-centered and retrospective, examination findings could not be obtained. The assessment of AA solely focused on determining whether it was complicated or not, without considering the surgical intervention or the length of hospitalization post-surgery. Since most of the patients diagnosed with AA were operated on in the hospital where the study was conducted, the number of those who were not operated on was low. These patients were not included in the study as they did not have a definitive histopathological diagnosis. The clinical condition of the patients, abdominal CT, surgery reports, and histopathological examinations of the appendix were evaluated collectively, and AA was classified as complicated or uncomplicated. The clinical conditions and radiological data of the patients were not evaluated and analyzed individually. These are the important limitations of our study. Large-scale prospective studies are needed for more reliable results.

6 Conclusions

The utilization of inflammatory biomarkers, derived from routine blood tests commonly employed in the diagnostic protocol within the ED, is more prevalent due to its ease of calculation and cost-effectiveness. In this study, we found that, although PIV, SIRI, SII, and NLR had acceptable diagnostic values in distinguishing complicated and uncomplicated AA, HALP and m-HALP also had a fair diagnostic value.

  1. Funding information: Not applicable.

  2. Author contributions: (1) Conception and design: Ali Saridas, Nafis Vural, and Murat Duyan; (2) administrative support: Ali Saridas, Nafis Vural, Murat Duyan, Hasan Can Guven, Elif Ertas, and Basar Cander; (3) provision of study materials or patients: Ali Saridas, Nafis Vural, Murat Duyan, Hasan Can Guven, Elif Ertas, and Basar Cander; (4) collection and assembly of data: Ali Saridas and Basar Cander; (5) data analysis and interpretation: Ali Saridas, Nafis Vural, Murat Duyan, Hasan Can Guven, Elif Ertas, and Basar Cander; (6) manuscript writing: Ali Saridas, Nafis Vural, Murat Duyan, Hasan Can Guven, Elif Ertas, and Basar Cander; and (7) final approval of manuscript: all authors.

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

  4. Data availability statement: The data in this study are available from the corresponding author on reasonable request.

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Received: 2024-03-12
Revised: 2024-06-20
Accepted: 2024-06-22
Published Online: 2024-07-25

© 2024 the author(s), published by De Gruyter

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

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  28. Circ_0051428 targeting miR-885-3p/MMP2 axis enhances the malignancy of cervical cancer
  29. Effectiveness of ginkgo diterpene lactone meglumine on cognitive function in patients with acute ischemic stroke
  30. The construction of a novel prognostic prediction model for glioma based on GWAS-identified prognostic-related risk loci
  31. Evaluating the impact of childhood BMI on the risk of coronavirus disease 2019: A Mendelian randomization study
  32. Lactate dehydrogenase to albumin ratio is associated with in-hospital mortality in patients with acute heart failure: Data from the MIMIC-III database
  33. CD36-mediated podocyte lipotoxicity promotes foot process effacement
  34. Efficacy of etonogestrel subcutaneous implants versus the levonorgestrel-releasing intrauterine system in the conservative treatment of adenomyosis
  35. FLRT2 mediates chondrogenesis of nasal septal cartilage and mandibular condyle cartilage
  36. Challenges in treating primary immune thrombocytopenia patients undergoing COVID-19 vaccination: A retrospective study
  37. Let-7 family regulates HaCaT cell proliferation and apoptosis via the ΔNp63/PI3K/AKT pathway
  38. Phospholipid transfer protein ameliorates sepsis-induced cardiac dysfunction through NLRP3 inflammasome inhibition
  39. Postoperative cognitive dysfunction in elderly patients with colorectal cancer: A randomized controlled study comparing goal-directed and conventional fluid therapy
  40. Long-pulsed ultrasound-mediated microbubble thrombolysis in a rat model of microvascular obstruction
  41. High SEC61A1 expression predicts poor outcome of acute myeloid leukemia
  42. Comparison of polymerase chain reaction and next-generation sequencing with conventional urine culture for the diagnosis of urinary tract infections: A meta-analysis
  43. Secreted frizzled-related protein 5 protects against renal fibrosis by inhibiting Wnt/β-catenin pathway
  44. Pan-cancer and single-cell analysis of actin cytoskeleton genes related to disulfidptosis
  45. Overexpression of miR-532-5p restrains oxidative stress response of chondrocytes in nontraumatic osteonecrosis of the femoral head by inhibiting ABL1
  46. Autologous liver transplantation for unresectable hepatobiliary malignancies in enhanced recovery after surgery model
  47. Clinical analysis of incomplete rupture of the uterus secondary to previous cesarean section
  48. Abnormal sleep duration is associated with sarcopenia in older Chinese people: A large retrospective cross-sectional study
  49. No genetic causality between obesity and benign paroxysmal vertigo: A two-sample Mendelian randomization study
  50. Identification and validation of autophagy-related genes in SSc
  51. Long non-coding RNA SRA1 suppresses radiotherapy resistance in esophageal squamous cell carcinoma by modulating glycolytic reprogramming
  52. Evaluation of quality of life in patients with schizophrenia: An inpatient social welfare institution-based cross-sectional study
  53. The possible role of oxidative stress marker glutathione in the assessment of cognitive impairment in multiple sclerosis
  54. Compilation of a self-management assessment scale for postoperative patients with aortic dissection
  55. Left atrial appendage closure in conjunction with radiofrequency ablation: Effects on left atrial functioning in patients with paroxysmal atrial fibrillation
  56. Effect of anterior femoral cortical notch grade on postoperative function and complications during TKA surgery: A multicenter, retrospective study
  57. Clinical characteristics and assessment of risk factors in patients with influenza A-induced severe pneumonia after the prevalence of SARS-CoV-2
  58. Analgesia nociception index is an indicator of laparoscopic trocar insertion-induced transient nociceptive stimuli
  59. High STAT4 expression correlates with poor prognosis in acute myeloid leukemia and facilitates disease progression by upregulating VEGFA expression
  60. Factors influencing cardiovascular system-related post-COVID-19 sequelae: A single-center cohort study
  61. HOXD10 regulates intestinal permeability and inhibits inflammation of dextran sulfate sodium-induced ulcerative colitis through the inactivation of the Rho/ROCK/MMPs axis
  62. Mesenchymal stem cell-derived exosomal miR-26a induces ferroptosis, suppresses hepatic stellate cell activation, and ameliorates liver fibrosis by modulating SLC7A11
  63. Endovascular thrombectomy versus intravenous thrombolysis for primary distal, medium vessel occlusion in acute ischemic stroke
  64. ANO6 (TMEM16F) inhibits gastrointestinal stromal tumor growth and induces ferroptosis
  65. Prognostic value of EIF5A2 in solid tumors: A meta-analysis and bioinformatics analysis
  66. The role of enhanced expression of Cx43 in patients with ulcerative colitis
  67. Choosing a COVID-19 vaccination site might be driven by anxiety and body vigilance
  68. Role of ICAM-1 in triple-negative breast cancer
  69. Cost-effectiveness of ambroxol in the treatment of Gaucher disease type 2
  70. HLA-DRB5 promotes immune thrombocytopenia via activating CD8+ T cells
  71. Efficacy and factors of myofascial release therapy combined with electrical and magnetic stimulation in the treatment of chronic pelvic pain syndrome
  72. Efficacy of tacrolimus monotherapy in primary membranous nephropathy
  73. Mechanisms of Tripterygium wilfordii Hook F on treating rheumatoid arthritis explored by network pharmacology analysis and molecular docking
  74. FBXO45 levels regulated ferroptosis renal tubular epithelial cells in a model of diabetic nephropathy by PLK1
  75. Optimizing anesthesia strategies to NSCLC patients in VATS procedures: Insights from drug requirements and patient recovery patterns
  76. Alpha-lipoic acid upregulates the PPARγ/NRF2/GPX4 signal pathway to inhibit ferroptosis in the pathogenesis of unexplained recurrent pregnancy loss
  77. Correlation between fat-soluble vitamin levels and inflammatory factors in paediatric community-acquired pneumonia: A prospective study
  78. CD1d affects the proliferation, migration, and apoptosis of human papillary thyroid carcinoma TPC-1 cells via regulating MAPK/NF-κB signaling pathway
  79. miR-let-7a inhibits sympathetic nerve remodeling after myocardial infarction by downregulating the expression of nerve growth factor
  80. Immune response analysis of solid organ transplantation recipients inoculated with inactivated COVID-19 vaccine: A retrospective analysis
  81. The H2Valdien derivatives regulate the epithelial–mesenchymal transition of hepatoma carcinoma cells through the Hedgehog signaling pathway
  82. Clinical efficacy of dexamethasone combined with isoniazid in the treatment of tuberculous meningitis and its effect on peripheral blood T cell subsets
  83. Comparison of short-segment and long-segment fixation in treatment of degenerative scoliosis and analysis of factors associated with adjacent spondylolisthesis
  84. Lycopene inhibits pyroptosis of endothelial progenitor cells induced by ox-LDL through the AMPK/mTOR/NLRP3 pathway
  85. Methylation regulation for FUNDC1 stability in childhood leukemia was up-regulated and facilitates metastasis and reduces ferroptosis of leukemia through mitochondrial damage by FBXL2
  86. Correlation of single-fiber electromyography studies and functional status in patients with amyotrophic lateral sclerosis
  87. Risk factors of postoperative airway obstruction complications in children with oral floor mass
  88. Expression levels and clinical significance of serum miR-19a/CCL20 in patients with acute cerebral infarction
  89. Physical activity and mental health trends in Korean adolescents: Analyzing the impact of the COVID-19 pandemic from 2018 to 2022
  90. Evaluating anemia in HIV-infected patients using chest CT
  91. Ponticulus posticus and skeletal malocclusion: A pilot study in a Southern Italian pre-orthodontic court
  92. Causal association of circulating immune cells and lymphoma: A Mendelian randomization study
  93. Assessment of the renal function and fibrosis indexes of conventional western medicine with Chinese medicine for dredging collaterals on treating renal fibrosis: A systematic review and meta-analysis
  94. Comprehensive landscape of integrator complex subunits and their association with prognosis and tumor microenvironment in gastric cancer
  95. New target-HMGCR inhibitors for the treatment of primary sclerosing cholangitis: A drug Mendelian randomization study
  96. Population pharmacokinetics of meropenem in critically ill patients
  97. Comparison of the ability of newly inflammatory markers to predict complicated appendicitis
  98. Comparative morphology of the cruciate ligaments: A radiological study
  99. Immune landscape of hepatocellular carcinoma: The central role of TP53-inducible glycolysis and apoptosis regulator
  100. Serum SIRT3 levels in epilepsy patients and its association with clinical outcomes and severity: A prospective observational study
  101. SHP-1 mediates cigarette smoke extract-induced epithelial–mesenchymal transformation and inflammation in 16HBE cells
  102. Acute hyper-hypoxia accelerates the development of depression in mice via the IL-6/PGC1α/MFN2 signaling pathway
  103. The GJB3 correlates with the prognosis, immune cell infiltration, and therapeutic responses in lung adenocarcinoma
  104. Physical fitness and blood parameters outcomes of breast cancer survivor in a low-intensity circuit resistance exercise program
  105. Exploring anesthetic-induced gene expression changes and immune cell dynamics in atrial tissue post-coronary artery bypass graft surgery
  106. Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism
  107. Analysis of the risk factors of the radiation-induced encephalopathy in nasopharyngeal carcinoma: A retrospective cohort study
  108. Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review
  109. Evaluation of upper airway ultrasonographic measurements in predicting difficult intubation: A cross-section of the Turkish population
  110. Prognostic and diagnostic value of circulating IGFBP2 in pancreatic cancer
  111. Postural stability after operative reconstruction of the AFTL in chronic ankle instability comparing three different surgical techniques
  112. Research trends related to emergence agitation in the post-anaesthesia care unit from 2001 to 2023: A bibliometric analysis
  113. Frequency and clinicopathological correlation of gastrointestinal polyps: A six-year single center experience
  114. ACSL4 mediates inflammatory bowel disease and contributes to LPS-induced intestinal epithelial cell dysfunction by activating ferroptosis and inflammation
  115. Affibody-based molecular probe 99mTc-(HE)3ZHER2:V2 for non-invasive HER2 detection in ovarian and breast cancer xenografts
  116. Effectiveness of nutritional support for clinical outcomes in gastric cancer patients: A meta-analysis of randomized controlled trials
  117. The relationship between IFN-γ, IL-10, IL-6 cytokines, and severity of the condition with serum zinc and Fe in children infected with Mycoplasma pneumoniae
  118. Paraquat disrupts the blood–brain barrier by increasing IL-6 expression and oxidative stress through the activation of PI3K/AKT signaling pathway
  119. Sleep quality associate with the increased prevalence of cognitive impairment in coronary artery disease patients: A retrospective case–control study
  120. Dioscin protects against chronic prostatitis through the TLR4/NF-κB pathway
  121. Association of polymorphisms in FBN1, MYH11, and TGF-β signaling-related genes with susceptibility of sporadic thoracic aortic aneurysm and dissection in the Zhejiang Han population
  122. Application value of multi-parameter magnetic resonance image-transrectal ultrasound cognitive fusion in prostate biopsy
  123. Laboratory variables‐based artificial neural network models for predicting fatty liver disease: A retrospective study
  124. Decreased BIRC5-206 promotes epithelial–mesenchymal transition in nasopharyngeal carcinoma through sponging miR-145-5p
  125. Sepsis induces the cardiomyocyte apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway
  126. Assessment of iron metabolism and iron deficiency in incident patients on incident continuous ambulatory peritoneal dialysis
  127. Tibial periosteum flap combined with autologous bone grafting in the treatment of Gustilo-IIIB/IIIC open tibial fractures
  128. The application of intravenous general anesthesia under nasopharyngeal airway assisted ventilation undergoing ureteroscopic holmium laser lithotripsy: A prospective, single-center, controlled trial
  129. Long intergenic noncoding RNA for IGF2BP2 stability suppresses gastric cancer cell apoptosis by inhibiting the maturation of microRNA-34a
  130. Role of FOXM1 and AURKB in regulating keratinocyte function in psoriasis
  131. Parental control attitudes over their pre-school children’s diet
  132. The role of auto-HSCT in extranodal natural killer/T cell lymphoma
  133. Significance of negative cervical cytology and positive HPV in the diagnosis of cervical lesions by colposcopy
  134. Echinacoside inhibits PASMCs calcium overload to prevent hypoxic pulmonary artery remodeling by regulating TRPC1/4/6 and calmodulin
  135. ADAR1 plays a protective role in proximal tubular cells under high glucose conditions by attenuating the PI3K/AKT/mTOR signaling pathway
  136. The risk of cancer among insulin glargine users in Lithuania: A retrospective population-based study
  137. The unusual location of primary hydatid cyst: A case series study
  138. Intraoperative changes in electrophysiological monitoring can be used to predict clinical outcomes in patients with spinal cavernous malformation
  139. Obesity and risk of placenta accreta spectrum: A meta-analysis
  140. Shikonin alleviates asthma phenotypes in mice via an airway epithelial STAT3-dependent mechanism
  141. NSUN6 and HTR7 disturbed the stability of carotid atherosclerotic plaques by regulating the immune responses of macrophages
  142. The effect of COVID-19 lockdown on admission rates in Maternity Hospital
  143. Temporal muscle thickness is not a prognostic predictor in patients with high-grade glioma, an experience at two centers in China
  144. Luteolin alleviates cerebral ischemia/reperfusion injury by regulating cell pyroptosis
  145. Therapeutic role of respiratory exercise in patients with tuberculous pleurisy
  146. Effects of CFTR-ENaC on spinal cord edema after spinal cord injury
  147. Irisin-regulated lncRNAs and their potential regulatory functions in chondrogenic differentiation of human mesenchymal stem cells
  148. DMD mutations in pediatric patients with phenotypes of Duchenne/Becker muscular dystrophy
  149. Combination of C-reactive protein and fibrinogen-to-albumin ratio as a novel predictor of all-cause mortality in heart failure patients
  150. Significant role and the underly mechanism of cullin-1 in chronic obstructive pulmonary disease
  151. Ferroptosis-related prognostic model of mantle cell lymphoma
  152. Observation of choking reaction and other related indexes in elderly painless fiberoptic bronchoscopy with transnasal high-flow humidification oxygen therapy
  153. A bibliometric analysis of Prader-Willi syndrome from 2002 to 2022
  154. The causal effects of childhood sunburn occasions on melanoma: A univariable and multivariable Mendelian randomization study
  155. Oxidative stress regulates glycogen synthase kinase-3 in lymphocytes of diabetes mellitus patients complicated with cerebral infarction
  156. Role of COX6C and NDUFB3 in septic shock and stroke
  157. Trends in disease burden of type 2 diabetes, stroke, and hypertensive heart disease attributable to high BMI in China: 1990–2019
  158. Purinergic P2X7 receptor mediates hyperoxia-induced injury in pulmonary microvascular endothelial cells via NLRP3-mediated pyroptotic pathway
  159. Investigating the role of oviductal mucosa–endometrial co-culture in modulating factors relevant to embryo implantation
  160. Analgesic effect of external oblique intercostal block in laparoscopic cholecystectomy: A retrospective study
  161. Elevated serum miR-142-5p correlates with ischemic lesions and both NSE and S100β in ischemic stroke patients
  162. Correlation between the mechanism of arteriopathy in IgA nephropathy and blood stasis syndrome: A cohort study
  163. Risk factors for progressive kyphosis after percutaneous kyphoplasty in osteoporotic vertebral compression fracture
  164. Predictive role of neuron-specific enolase and S100-β in early neurological deterioration and unfavorable prognosis in patients with ischemic stroke
  165. The potential risk factors of postoperative cognitive dysfunction for endovascular therapy in acute ischemic stroke with general anesthesia
  166. Fluoxetine inhibited RANKL-induced osteoclastic differentiation in vitro
  167. Detection of serum FOXM1 and IGF2 in patients with ARDS and their correlation with disease and prognosis
  168. Rhein promotes skin wound healing by activating the PI3K/AKT signaling pathway
  169. Differences in mortality risk by levels of physical activity among persons with disabilities in South Korea
  170. Review Articles
  171. Cutaneous signs of selected cardiovascular disorders: A narrative review
  172. XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis
  173. A narrative review on adverse drug reactions of COVID-19 treatments on the kidney
  174. Emerging role and function of SPDL1 in human health and diseases
  175. Adverse reactions of piperacillin: A literature review of case reports
  176. Molecular mechanism and intervention measures of microvascular complications in diabetes
  177. Regulation of mesenchymal stem cell differentiation by autophagy
  178. Molecular landscape of borderline ovarian tumours: A systematic review
  179. Advances in synthetic lethality modalities for glioblastoma multiforme
  180. Investigating hormesis, aging, and neurodegeneration: From bench to clinics
  181. Frankincense: A neuronutrient to approach Parkinson’s disease treatment
  182. Sox9: A potential regulator of cancer stem cells in osteosarcoma
  183. Early detection of cardiovascular risk markers through non-invasive ultrasound methodologies in periodontitis patients
  184. Advanced neuroimaging and criminal interrogation in lie detection
  185. Maternal factors for neural tube defects in offspring: An umbrella review
  186. The chemoprotective hormetic effects of rosmarinic acid
  187. CBD’s potential impact on Parkinson’s disease: An updated overview
  188. Progress in cytokine research for ARDS: A comprehensive review
  189. Utilizing reactive oxygen species-scavenging nanoparticles for targeting oxidative stress in the treatment of ischemic stroke: A review
  190. NRXN1-related disorders, attempt to better define clinical assessment
  191. Lidocaine infusion for the treatment of complex regional pain syndrome: Case series and literature review
  192. Trends and future directions of autophagy in osteosarcoma: A bibliometric analysis
  193. Iron in ventricular remodeling and aneurysms post-myocardial infarction
  194. Case Reports
  195. Sirolimus potentiated angioedema: A case report and review of the literature
  196. Identification of mixed anaerobic infections after inguinal hernia repair based on metagenomic next-generation sequencing: A case report
  197. Successful treatment with bortezomib in combination with dexamethasone in a middle-aged male with idiopathic multicentric Castleman’s disease: A case report
  198. Complete heart block associated with hepatitis A infection in a female child with fatal outcome
  199. Elevation of D-dimer in eosinophilic gastrointestinal diseases in the absence of venous thrombosis: A case series and literature review
  200. Four years of natural progressive course: A rare case report of juvenile Xp11.2 translocations renal cell carcinoma with TFE3 gene fusion
  201. Advancing prenatal diagnosis: Echocardiographic detection of Scimitar syndrome in China – A case series
  202. Outcomes and complications of hemodialysis in patients with renal cancer following bilateral nephrectomy
  203. Anti-HMGCR myopathy mimicking facioscapulohumeral muscular dystrophy
  204. Recurrent opportunistic infections in a HIV-negative patient with combined C6 and NFKB1 mutations: A case report, pedigree analysis, and literature review
  205. Letter to the Editor
  206. Letter to the Editor: Total parenteral nutrition-induced Wernicke’s encephalopathy after oncologic gastrointestinal surgery
  207. Erratum
  208. Erratum to “Bladder-embedded ectopic intrauterine device with calculus”
  209. Retraction
  210. Retraction of “XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis”
  211. Corrigendum
  212. Corrigendum to “Investigating hormesis, aging, and neurodegeneration: From bench to clinics”
  213. Corrigendum to “Frankincense: A neuronutrient to approach Parkinson’s disease treatment”
  214. Special Issue The evolving saga of RNAs from bench to bedside - Part II
  215. Machine-learning-based prediction of a diagnostic model using autophagy-related genes based on RNA sequencing for patients with papillary thyroid carcinoma
  216. Unlocking the future of hepatocellular carcinoma treatment: A comprehensive analysis of disulfidptosis-related lncRNAs for prognosis and drug screening
  217. Elevated mRNA level indicates FSIP1 promotes EMT and gastric cancer progression by regulating fibroblasts in tumor microenvironment
  218. Special Issue Advancements in oncology: bridging clinical and experimental research - Part I
  219. Ultrasound-guided transperineal vs transrectal prostate biopsy: A meta-analysis of diagnostic accuracy and complication rates
  220. Assessment of diagnostic value of unilateral systematic biopsy combined with targeted biopsy in detecting clinically significant prostate cancer
  221. SENP7 inhibits glioblastoma metastasis and invasion by dissociating SUMO2/3 binding to specific target proteins
  222. MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE
  223. Analysis of postoperative complications in bladder cancer patients
  224. Carboplatin combined with arsenic trioxide versus carboplatin combined with docetaxel treatment for LACC: A randomized, open-label, phase II clinical study
  225. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part I
  226. Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma
  227. Identification of signatures associated with microsatellite instability and immune characteristics to predict the prognostic risk of colon cancer
  228. Single-cell analysis identified key macrophage subpopulations associated with atherosclerosis
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