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Ultrasound-guided unilateral versus bilateral erector spinae plane block for postoperative analgesia of patients undergoing laparoscopic cholecystectomy

  • Ayça Tuba Dumanlı Özcan EMAIL logo , Yusuf Yılmaz , Mustafa Turan , Erdal Özcan , Ezgi Erkılıç and Handan Güleç
Published/Copyright: October 13, 2025

Abstract

Introduction

Ultrasound-guided erector spinae plane block (ESPB) was originally developed for the treatment of neuropathic chest pain and has since been used in various thoracic, lumbar, and sacral surgeries.

Objective

This study aimed to establish whether unilateral or bilateral ESPB is more effective for pain management in laparoscopic cholecystectomy.

Materials and methods

A total of 54 adult patients undergoing laparoscopic cholecystectomy were divided into three groups: unilateral ESPB, bilateral ESPB, and a control group (no ESPB). The unilateral ESPB group received 20 mL of 0.25% bupivacaine preoperatively at the T8 vertebral level. The bilateral ESPB group received 20 mL of 0.25% bupivacaine to both sides of the vertebra. The control group received no intervention, and all three groups received general anesthesia. Intraoperatively, all patients received 50 mg of dexketoprofen and 1 mg/kg of tramadol. Postoperative tramadol use and visual analog scale (VAS) scores were recorded at 0 min, 30 min, 2 h, 6 h, 12 h, and 24 h.

Results

Demographic characteristics did not differ significantly between the groups. At the 6 h post-surgery, the VAS scores in the bilateral ESPB group were significantly lower than the control group (p < 0.001). Total tramadol use in 24 h was significantly lower in the bilateral ESPB group compared with the control group (p = 0.003).

Conclusions

Bilateral ESPB could be a valuable component of multimodal analgesia strategies in laparoscopic cholecystectomies.

1 Introduction

Forero et al. developed an ultrasound-guided erector spinae plane block (ESPB) for the treatment of neuropathic chest pain, which has since been used in various thoracic, lumbar, and sacral surgeries [1]. ESPB is a regional anesthetic technique that involves the ultrasound-guided injection of local anesthetic into the paraspinal region, aimed at reducing both visceral and somatic pain. Pain following laparoscopic cholecystectomy is associated with both trocar entry incisions in the abdominal wall and distention caused by pneumoperitoneum, along with somatic pain originating from the T6–L2 nerves. Laparoscopic cholecystectomy is a routine surgical procedure in adults and can result in various types of pain, including visceral (e.g., intra-abdominal pain), incisional (e.g., somatic pain), and referred somatic pain (e.g., shoulder pain), due to factors, such as tissue damage, diaphragmatic irritation, and residual pneumoperitoneum [2]. Therefore, analgesic options that effectively address all sources of pain should be prioritized [3]. ESPB provides both somatic and visceral analgesia and can be beneficial for this procedure [4].

There have been cases in the literature where unexpected bilateral effects were observed, even when unilateral ESPB was performed. A cadaveric study concluded that the reason for bilateral ESPB was increased pressure from insufflation, which affected the spread of the local anesthetic [5]. Additionally, the local anesthetic could have dispersed depending on the patient’s position due to gravitational effects. Previous studies have shown that the spread of local anesthetic is influenced by the patient’s position during an epidural block [6]. Unilateral ESPB can offer advantages, such as shorter procedure time, reduced local anesthetic use, fewer risks of complications, and effective analgesia with a single injection. As such, the aim of this study was to compare unilateral and bilateral blocks to establish whether unilateral ESPB is sufficient for this type of surgery.

2 Materials and methods

2.1 Study design

For this prospective randomized study, the adult case, who underwent laparoscopic cholecystectomy surgery in the American Society of Anesthesiologists (ASA) I–II group under general anesthesia, was informed and included in the study after written consent was given. The inclusion criteria were that the participants were aged 18–65 years, had ASA status I–II, and had a body mass index (BMI) of 23–35. Those with an ASA physical status III and higher; renal failure requiring hemodialysis; liver cirrhosis leading to liver dysfunction (e.g., prolonged international normalized ratio and increased basal bilirubin); known dementia, stroke, or other central nerve system disease; a history of severe psychiatric illness, alcohol consumption, or patients with drug abuse; multiple trauma and head trauma; and patients with a BMI of greater than 35 were excluded from the study.

2.2 Material and methods

A total of 54 patients were randomly assigned to either group 1 (control, n = 17), group 2 (unilateral ESPB, n = 20), or group 3 (bilateral ESPB, n = 17) (Figure 2). Random assignment of the patients was performed using the closed envelope method. The patients were taken to the operating room and a non-invasive blood pressure cuff, pulse oximetry probe for peripheral oxygen saturation (SpO2), and precordial ECG electrode in the standard D2 lead were placed. Vascular access was established with an 18–20 G intravenous cannula on the back of the hand, and the calculated maintenance was given as a crystalloid. After preoxygenation with 100% oxygen for 3 min, induction was performed with lidocaine (1–1.5 mg/kg), propofol (2–3 mg/kg), remifentanil (1 µg/kg), and rocuronium (0.6–1.2 mg/kg) were administered intravenously. After waiting for sufficient time, the patients were intubated endotracheally. Basal ventilation tidal volume was set to 6–8 mL/kg, frequency to 12, and fraction of inspired oxygen (FiO2) to 50%, but then the ETCO2 was kept at 30–36, and changes were made so that the peak pressure remained below 38 cm H2O. For maintenance, a 50:50 ratio of O2 to air was maintained, and 3% sevoflurane was administered. All patients received 50 mg dexketoprofen intraoperatively. The patients’ systolic arterial pressure (SAB), diastolic arterial pressure, mean arterial pressure, peak heart rate, oxygen saturation (SO2), and end-tidal CO2 (ETCO2) values were followed throughout the operation and recorded at 5 min intervals. The group I patients (control) were not treated with ESPB. For group 2, a unilateral block was performed with 0.25% 20 mL bupivacaine under ultrasound guidance, and group 3 received a bilateral ESP block. The ESP block was applied immediately before the induction of general anesthesia. ESP was performed after skin preparation and under ultrasonographic guidance using a linear 3–13 MHz ultrasound probe (SonoSite S-Nerve, Bothell, WA98021, USA). The ultrasonographic probe was placed longitudinally and parasagittally 3 cm lateral to the T8 spinous process of the thoracic vertebra. The T8 transverse process of the erector spinae muscles was defined as superficial. A 22-G 8 cm needle (sonoPlex STIM, PAJUNK, Germany) was used.

The tip of the needle was inserted into the plane of the fascia from the deep face of the erector spina muscle, and its position was confirmed by ultrasonography of the elevating view of the erector spina muscle of the needle tip and of fluid dissemination in the bony body of the transverse process. In total, 20 mL of 0.25% bupivacaine was injected on one side of the T8 spinous process for group 2 and both sides for group 3. No additional local anesthetic was applied to the trocar entry sites.

Tramadol dose as postoperative rescue analgesia and the visual analog scale (VAS) values at 0 min, 30 min, 2 h, 6 h, 12 h, and 24 h were recorded. T0 is defined as the first postoperative minute immediately after extubation at the end of surgery. Pain intensity was compared between groups using a VAS. VAS is a subjective scale that is graded 0–10 and was used to measure the level of pain. The anesthesiologist who randomly assigned the patients also performed the blocks for all participants but was not involved in the collection of postoperative data or its analyses.

2.3 Outcome measures

The primary outcome measures of the study were the VAS pain scores that were recorded at 0 min, 30 min, 2 h, 6 h, 12 h, and 24 h. The secondary outcomes were additional rescue analgesic requirement and total amount of tramadol used in 24 h. Rescue analgesia (intravenous tramadol 50 mg) was given if the pain score was 4 or higher on VAS during 1–24 h. If the pain remained the same in the following 1-h period, further intravenous tramadol (50 mg) was given. Furthermore, shoulder pain, nausea, vomiting during the first 24 h, and duration of discharge were noted.

2.4 Sample size

Based on a prospective, single-blind, randomized clinical study (J Clin Anesth. 2018; 50:65-68. doi: 10.1016/j.jclinane.2018.06.033) evaluating the effectiveness of the ESPB for postoperative analgesia management in laparoscopic cholecystectomy, the effect size calculated with the mean and standard deviation values of tramadol use in the first 24 h after surgery (effect size f = 0.48), alpha error (p value) was 0.05, and 1-beta error (power) was 0.80, assuming that the null hypothesis is tested. A total of 45 people (15 per group) would be enough to complete the study. G Power Statistical Program version 3.1.9.4 (Universität Düsseldorf, Germany) was used for analyses.

2.5 Statistical analyses

Data analyses were performed with IBM SPSS Statistics 25.0 software (IBM Corporation, Armonk, NY, USA). The near-normality of the distribution of continuous numerical variables was examined using the Shapiro–Wilk test. The Levene test was used to test the homogeneity of variances. Descriptive statistics were expressed as mean ± standard deviation or median (25th percentile–75th percentile) for continuous numerical variables and as number of cases (%) and for categorical variables. The significance of differences between groups with respect to the mean was assessed using one-way analysis of variance (ANOVA), whereas the significance of differences with respect to continuous numeric and sortable variables where the assumptions of the parametric test statistic were not met were examined by the Kruskal–Wallis test. If the Kruskal–Wallis test results were significant, Dunn–Bonferroni multiple comparison tests were used to identify the group(s) causing the said difference. Categorical variables were assessed using the Pearson χ test or the Fisher–Freeman–Halton test. The Friedman test was used to determine whether there were statistically significant differences in VAS scores between groups for the follow-up timepoints. If the statistical results of the Friedman test were significant, the Dunn–Bonferroni multiple comparison test was used to establish the follow-up period causing the difference. Unless otherwise stated, results with p < 0.05 were statistically significant. However, the Bonferroni correction was used to control for type I error in all possible multiple comparisons.

  1. Informed consent: All patients were informed and enrolled after obtaining written consent.

  2. Ethics approval: The study was approved by the T.C. Ministry of Health Ankara Bilkent City Hospital 2nd Ethics Committee, numbered E2-21-228 (clinical trial approval no. NCT05152602, start date 01/10/2022, and last update posted on 01/10/2023).

3 Results

There was no significant difference between the groups in terms of demographics, including mean age, female to male distribution, BMI averages, concomitant disease, and median operation time (p > 0.05; Table 1).

Table 1

Socio-demographic and clinical characteristics

Control group (n = 17) Right ESP block group (n = 20) Bilateral ESP block group (n = 17) p-value
Age (years) (mean ± SD) 48.70 ± 12.02 47.90 ± 13.98 46.41 ± 12.64 0.872*
BMI (kg/m 2 ) (mean ± SD) 27.97 ± 5.71 27.39 ± 5.64 29.00 ± 5.21 0.677*
Operation duration (min) (mean ± SD) 82.41 ± 19.43 77.30 ± 25.56 72.70 ± 18.57 0.432*
Gender ( n , %) 0.732**
Female 8 (47.1) 12 (60.0) 9 (52.9)
Male 9 (52.9) 8 (40.0) 8 (47.1)
ASA ( n , %) 0.104**
1 5 (29.4) 3 (15.0) 8 (47.1)
2 12(70.6) 17 (85.0) 9 (52.9)
Additional disease ( n , %) 0.286**
No 9 (52.9) 9 (45.0) 12 (70.6)
Yes 8 (47.1) 11 (55.0) 5 (29.4)
Total 71 (100.0) 67 (100.0) 66 (100.0)

*One-way ANOVA test.

**Chi-square test.

At 6 h post-surgery, the VAS scores of the bilateral ESPB group were significantly lower than the control group (p < 0.001; Table 2). There was no significant difference between the control and unilateral ESPB groups (p = 0.019) and unilateral ESPB and bilateral ESPB groups (p = 0.836) in terms of VAS levels at 6 h post-surgery (Figure 1). There was no significant difference between the groups in terms of VAS values at 24 h post-surgery (p = 0.096; Table 2).

Table 2

VAS scores according to groups and follow-up times

Control (n = 17) Unilateral (n = 20) Bilateral (n = 17) p-value
Post-extubation 2 (0–3.5)a 0 (0–2)e 1 (0–3) 0.412
Post-op 0 min 3 (1–4.5) 2 (0–3) 2 (0–3) 0.267
Post-op 2 h 2 (1–3)b 1 (0–2.75) 1 (0.5–2)f 0.156
Post-op 6 h 4 (3–5)A,a,b,c 2 (2–3.75) 2 (1–3)A <0.001
Post-op 12 h 3 (3–4)d 3 (2–3)d,e 3 (2–3.5)f 0.043
Post-op 24 h 2 (1.5–2)c,d 2 (0.25–2)d 2 (1–3) 0.101
p-value <0.001 <0.001 <0.001

Data; displayed as median (25th percentile–75th percentile). Bold indicates the difference between the control group and the bilateral ESPB group was statistically significant (p < 0.001).

Comparisons between groups at each follow-up time, according to Kruskal–Wallis test, Bonferroni correction, results for p < 0.0071 were considered statistically significant.

Comparisons between the follow-up times within the groups, Friedman test, Bonferroni correction for p < 0.0167 were considered statistically significant.

AThe difference between the control group and the bilateral ESPB group was statistically significant (p < 0.001).

aStatistically significant difference between post-extubation and post-op 6th hour (p < 0.001).

bPost-op 2nd hour, the difference between the post-op 6th hour and the 6th hour was statistically significant (p = 0.007).

cDifference between post-op 6th hour and post-op 24th hour statistically significant (p < 0.001).

dThe difference between post-op 12 h and post-op 24 h was statistically significant (p < 0.0167).

eThe difference between post-extubation and post-op 12th hour was statistically significant (p = 0.005).

fPost-op 2nd hour to post-op 12th hour, the difference between the two is statistically significant (p < 0.001).

Figure 1 
               Box-plot graph for VAS scores in terms of study groups according to the follow-up times. The horizontal orange lines in the middle of each box indicate the median, while the top and bottom borders of the box mark the 25th and 75th percentiles, respectively. The whiskers above and below the box mark the maximum and minimum values for VAS scores.
Figure 1

Box-plot graph for VAS scores in terms of study groups according to the follow-up times. The horizontal orange lines in the middle of each box indicate the median, while the top and bottom borders of the box mark the 25th and 75th percentiles, respectively. The whiskers above and below the box mark the maximum and minimum values for VAS scores.

Figure 2 
               Flow chart of the study.
Figure 2

Flow chart of the study.

There was no significant difference between the groups regarding additional analgesic requirement, incidence of nausea and vomiting, shoulder pain, or discharge time in days (p > 0.05; Table 3). Tramadol use in the bilateral ESPB group was lower than in the control group (p = 0.003). Although the 24 h total tramadol use was lower in the unilateral group compared with the control group; however, the difference was not significant (p = 0.081; Table 3). In addition, there was no significant difference between the unilateral ESPB and bilateral ESPB groups (p = 0.924).

Table 3

Groups in terms of tramadol consumption amount in the first 24 h, shoulder pain, nausea, vomiting, and duration of discharge

Control (n = 17) Unilateral (n = 20) Bilateral (n = 17) p-value
Additional analgesic requirement 8 (47.1%) 10 (50%) 7 (35.0%) 0.531
Discharge time (days) (n, %)
1 10 (58.8) 12 (60.0) 9 (52.9) 0.634**
2 6 (35.3) 8 (40.0) 8 (47.1)
3 1 (5.9) 0 (0.0) 0 (0.0)
Nausea and vomiting 7 (41.2%) 3 (15.0%) 4 (23.5%) 0.197
Shoulder pain 0 (0.0%) 2 (10.0%) 0 (0.0%) 0.323
Total amount of 24 h tramadol 300 (200–300)a 200 (100–200) 100 (50–272.5)a 0.003

Bold indicates the difference between the control group and the bilateral group was statistically significant (p = 0.003).

Pearson’s χ 2 test.

Kruskal–Wallis test.

Fisher–Freeman–Halton test.

**Chi-square test.

aThe difference between the control group and the bilateral group was statistically significant (p = 0.003).

4 Discussion

In this study, bilateral ESPB provided significant advantages over the control group and had lower pain scores and less tramadol use. Although unilateral ESPB also provided some advantages over the control group, no significant difference was observed. VAS scores were lower in the bilateral ESPB group compared with the control group at 6 h post-surgery. The recruitment of additional analgesics in the bilateral ESPB group was lower than the control group.

Reducing the side effects of postoperative analgesia has been a key goal in pain management. Opioids cause nausea, vomiting, and delayed recovery and discharge [7]. Multimodal analgesics with peripheral blocks reduce opioid use and side effects, and also reduce opioid requirements [4]. Nevertheless, paracetamol and non-steroidal anti-inflammatory drugs are the preferred pharmacological agents for laparoscopic cholecystectomy as stated in the recently updated PROSPECT guidelines. It was recommended that transversus abdominis, subcostal blocks, and peritoneal local anesthetic infiltrations are added when basic analgesia was not an option. It is possible that, despite its absence from the current discussion, the ESPB will eventually become an essential element in the management of somatic and visceral pain [8]. In a meta-analysis by Park et al., which included 6 randomized controlled trials and 314 patients, subcostal transversus abdominis plane (TAP) block and wound infiltration with local anesthetics were compared in terms of postoperative analgesia. More effective analgesia was provided in the patient group who underwent subcostal TAP block compared with the wound local anesthetic infiltration group [9].

The analgesic mechanism of ESPB is not fully understood but might involve paravertebral, epidural, or intercostal spread of local anesthetic. It is suggested that local anesthetic could spread to the paravertebral, epidural, or intercostal spaces, potentially providing both somatic and visceral analgesia, which might explain the analgesic effects observed in our study.

Ivanusic et al. suggest that when a local anesthetic is injected into the erector spinae muscle, the muscle undergoes craniocaudal elongation. Furthermore, the local anesthetic penetrates the costotransverse foramen and exerts its effects on both the dorsal and ventral branches via paravertebral and epidural spread [10]. Schwartzman et al. established the contralateral distribution of local anesthetic by examining the circumferential spread of local anesthetic into the epidural space with unilateral ESPB using magnetic resonance imaging [11]. Tulgar et al. [12] reported the unexpected spread of bilateral sensation as detected by an examiner masked to the test results, followed by a contralateral anesthesia using a local anesthetic, which clarified the results by examining the epidural space and including the dorsal rami via an alternative, posterior vertebral structure route. A previous investigation suggested that adequate analgesia could be achieved with unilateral ESPB [13].

Similar to our findings, Cesur et al. [14] showed that a bilateral ESPB is more efficacious than a unilateral ESPB in patients undergoing elective laparoscopic cholecystectomy. Additionally, the bilateral ESPB reportedly results in a reduction in the amount of opioids used and a decrease in the incidence of postoperative shoulder pain; however, this study did not identify any significant difference in the incidence of shoulder pain.

Similarly, a meta-analysis indicates that bilateral ultrasound-guided ESPB might be a suitable option for reducing the use of opioids and the time to the first administration of analgesia in adults undergoing laparoscopic cholecystectomy [15]. Vrsajkov et al. reported that the bilateral ESP block has been shown to provide superior postoperative analgesia and a reduction in the requirement for opioids following laparoscopic cholecystectomy [16].

These results were associated with better local anesthetic distribution and higher total amount of local analgesic in the bilateral ESPB group compared with unilateral ESPB. Our findings are in line with previous reports of the analgesic benefits of ESPB in abdominal surgeries. However, conflicting results in the literature underline the need for larger, multicenter trials. Clinicians should consider both the anatomical characteristics of the patient and the expertise of the practitioner when selecting ESPB as a component of multimodal analgesia. Future research should explore different volumes, concentrations, and techniques to optimize the block. On the one hand, the optimal concentration and type of local anesthetic are also not well established, although the doses of these blockers effectively influence the distribution of sensory blockers. Tulgar et al. [12] were performed with 0.25% bupivacaine 20cc. Aksu and Gürkan [17] injected 0.5 mL/kg 0.25% bupivacaine into the erector spinae plane (maximum dose was 4 mL per side). Gürkan et al. [18] administered 30 mL of 0.25% bupivacaine for breast surgery unilaterally at the T4 level. Altıparmak et al. [19] injected 20 mL of 0.25% bupivacaine as ESPB bilaterally at the T7 level. Unilateral injections of 30–40 mL of 0.25% bupivacaine have been observed to produce bilateral ESPB.

Enhanced recovery programs that aim to reduce opioid requirements and potential opioid-related side effects during the perioperative period are very important. The ESPB, which is part of a multimodal analgesia approach, is reportedly more effective than standard analgesia protocols in patients undergoing laparoscopic cholecystectomy and could, therefore, improve the quality of perioperative analgesia [20].

One of the limitations of this study was the lack of consideration of PCA morphine dose, which could be considered a deficiency. Also, there was a lack of data regarding postoperative PCA morphine use. Such data would have allowed a more comprehensive assessment of analgesic efficacy. Future studies should incorporate PCA morphine use as an outcome measure to better evaluate the opioid-sparing effects of ESPB. However, the adequacy of tramadol as an analgesic in laparoscopic cholecystectomies is acknowledged in the literature. The most important limitation of this study was the limited number of patients. Studies with larger samples are needed. Another important limitation was the absence of dermatome mapping to assess the extent of sensory blockade. Dermatome evaluation would provide valuable insight into the distribution and effectiveness of the ESPB. We recommend including objective sensory assessments in future studies to better understand the mechanism of action. While the mechanism of action of ESPB remains unclear and there is a possibility that even systemic absorption of the local anesthetic could have an effect, more detailed studies are required. Our study focused on the first 24 h of the postoperative period. As such, long-term outcomes related to pain control and functional recovery were not evaluated. Future studies should include long-term follow-up to assess the sustained effects of ESPB on postoperative recovery. Patients with BMI greater than 35 were excluded to maintain procedural consistency and reduce technical variability. However, this exclusion limits the generalizability of our findings. Future studies should consider broader inclusion criteria or subgroup analyses to assess the block’s efficacy in different patient populations.

The findings in this study are in line with previous reports demonstrating the analgesic benefits of ESPB in abdominal surgeries. However, conflicting results in the literature underline the need for larger, multicenter trials. Clinicians should consider both the anatomical characteristics of the patient and the expertise of the practitioner when selecting ESPB as a component of multimodal analgesia. Future research should explore different volumes, concentrations, and techniques to optimize the block.

5 Conclusions

There is currently no consensus on several key aspects of ESPBs, such as the optimal dose, infusion method, ideal local anesthetic concentration, and the required volume for single-shot or catheter applications. One of the main challenges remains the difficulty in predicting the distribution of local anesthetics. Despite these uncertainties, evidence suggests that a bilateral ESPB could be more effective than a unilateral ESPB for acute pain management. Although no statistically significant difference was observed in VAS scores between the two techniques, the bilateral approach could still offer clinical advantages, particularly in reducing postoperative opioid consumption. Therefore, bilateral ESPB should be considered a valuable component of multimodal analgesia strategies.

  1. Funding information: This research received no specific funding from any public, commercial, or non-profit agencies.

  2. Author contributions: A.T.D.Ö. and Y.Y. conceived and planned the work and interpreted the evidence it content; M.T. and E.E. wrote the paper and reviewed successive versions; E.Ö. and E.E. took part in the revision process; and H.G. and A.T.D.Ö. approved the final version.

  3. Conflict of interest: The authors declare no competing interests relevant to this study and the publication thereof.

  4. Data availability statement: All data generated in the study are available in the article.

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Received: 2024-03-29
Revised: 2025-08-01
Accepted: 2025-08-11
Published Online: 2025-10-13

© 2025 the author(s), published by De Gruyter

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

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  2. Network pharmacological analysis and in vitro testing of the rutin effects on triple-negative breast cancer
  3. Impact of diabetes on long-term survival in elderly liver cancer patients: A retrospective study
  4. Knockdown of CCNB1 alleviates high glucose-triggered trophoblast dysfunction during gestational diabetes via Wnt/β-catenin signaling pathway
  5. Risk factors for severe adverse drug reactions in hospitalized patients
  6. Analysis of the effect of ALA-PDT on macrophages in footpad model of mice infected with Fonsecaea monophora based on single-cell sequencing
  7. Development and validation of headspace gas chromatography with a flame ionization detector method for the determination of ethanol in the vitreous humor
  8. CMSP exerts anti-tumor effects on small cell lung cancer cells by inducing mitochondrial dysfunction and ferroptosis
  9. Predictive value of plasma sB7-H3 and YKL-40 in pediatric refractory Mycoplasma pneumoniae pneumonia
  10. Antiangiogenic potential of Elaeagnus umbellata extracts and molecular docking study by targeting VEGFR-2 pathway
  11. Comparison of the effectiveness of nurse-led preoperative counseling and postoperative follow-up care vs standard care for patients with gastric cancer
  12. Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis
  13. Adhered macrophages as an additional marker of cardiomyocyte injury in biopsies of patients with dilated cardiomyopathy
  14. Association between statin administration and outcome in patients with sepsis: A retrospective study
  15. Exploration of the association between estimated glucose disposal rate and osteoarthritis in middle-aged and older adults: An analysis of NHANES data from 2011 to 2018
  16. A comparative analysis of the binary and multiclass classified chest X-ray images of pneumonia and COVID-19 with ML and DL models
  17. Lysophosphatidic acid 2 alleviates deep vein thrombosis via protective endothelial barrier function
  18. Transcription factor A, mitochondrial promotes lymph node metastasis and lymphangiogenesis in epithelial ovarian carcinoma
  19. Serum PM20D1 levels are associated with nutritional status and inflammatory factors in gastric cancer patients undergoing early enteral nutrition
  20. Hydromorphone reduced the incidence of emergence agitation after adenotonsillectomy in children with obstructive sleep apnea: A randomized, double-blind study
  21. Vitamin D replacement therapy may regulate sleep habits in patients with restless leg syndrome
  22. The first-line antihypertensive nitrendipine potentiated the therapeutic effect of oxaliplatin by downregulating CACNA1D in colorectal cancer
  23. Health literacy and health-related quality of life: The mediating role of irrational happiness
  24. Modulatory effects of Lycium barbarum polysaccharide on bone cell dynamics in osteoporosis
  25. Mechanism research on inhibition of gastric cancer in vitro by the extract of Pinellia ternata based on network pharmacology and cellular metabolomics
  26. Examination of the causal role of immune cells in non-alcoholic fatty liver disease by a bidirectional Mendelian randomization study
  27. Clinical analysis of ten cases of HIV infection combined with acute leukemia
  28. Investigating the cardioprotective potential of quercetin against tacrolimus-induced cardiotoxicity in Wistar rats: A mechanistic insights
  29. Clinical observation of probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema in treating mild-to-moderate ulcerative colitis
  30. Diagnostic value of ratio of blood inflammation to coagulation markers in periprosthetic joint infection
  31. Sex-specific associations of sex hormone binding globulin and risk of bladder cancer
  32. Core muscle strength and stability-oriented breathing training reduces inter-recti distance in postpartum women
  33. The ERAS nursing care strategy for patients undergoing transsphenoidal endoscopic pituitary tumor resection: A randomized blinded controlled trial
  34. The serum IL-17A levels in patients with traumatic bowel rupture post-surgery and its predictive value for patient prognosis
  35. Impact of Kolb’s experiential learning theory-based nursing on caregiver burden and psychological state of caregivers of dementia patients
  36. Analysis of serum NLR combined with intraoperative margin condition to predict the prognosis of cervical HSIL patients undergoing LEEP surgery
  37. Commiphora gileadensis ameliorate infertility and erectile dysfunction in diabetic male mice
  38. The correlation between epithelial–mesenchymal transition classification and MMP2 expression of circulating tumor cells and prognosis of advanced or metastatic nasopharyngeal carcinoma
  39. Tetrahydropalmatine improves mitochondrial function in vascular smooth muscle cells of atherosclerosis in vitro by inhibiting Ras homolog gene family A/Rho-associated protein kinase-1 signaling pathway
  40. A cross-sectional study: Relationship between serum oxidative stress levels and arteriovenous fistula maturation in maintenance dialysis patients
  41. A comparative analysis of the impact of repeated administration of flavan 3-ol on brown, subcutaneous, and visceral adipose tissue
  42. Identifying early screening factors for depression in middle-aged and older adults: A cohort study
  43. Perform tumor-specific survival analysis for Merkel cell carcinoma patients undergoing surgical resection based on the SEER database by constructing a nomogram chart
  44. Unveiling the role of CXCL10 in pancreatic cancer progression: A novel prognostic indicator
  45. High-dose preoperative intraperitoneal erythropoietin and intravenous methylprednisolone in acute traumatic spinal cord injuries following decompression surgeries
  46. RAB39B: A novel biomarker for acute myeloid leukemia identified via multi-omics and functional validation
  47. Impact of peripheral conditioning on reperfusion injury following primary percutaneous coronary intervention in diabetic and non-diabetic STEMI patients
  48. Clinical efficacy of azacitidine in the treatment of middle- and high-risk myelodysplastic syndrome in middle-aged and elderly patients: A retrospective study
  49. The effect of ambulatory blood pressure load on mitral regurgitation in continuous ambulatory peritoneal dialysis patients
  50. Expression and clinical significance of ITGA3 in breast cancer
  51. Single-nucleus RNA sequencing reveals ARHGAP28 expression of podocytes as a biomarker in human diabetic nephropathy
  52. rSIG combined with NLR in the prognostic assessment of patients with multiple injuries
  53. Toxic metals and metalloids in collagen supplements of fish and jellyfish origin: Risk assessment for daily intake
  54. Exploring causal relationship between 41 inflammatory cytokines and marginal zone lymphoma: A bidirectional Mendelian randomization study
  55. Gender beliefs and legitimization of dating violence in adolescents
  56. Effect of serum IL-6, CRP, and MMP-9 levels on the efficacy of modified preperitoneal Kugel repair in patients with inguinal hernia
  57. Effect of smoking and smoking cessation on hematological parameters in polycythemic patients
  58. Pathogen surveillance and risk factors for pulmonary infection in patients with lung cancer: A retrospective single-center study
  59. Necroptosis of hippocampal neurons in paclitaxel chemotherapy-induced cognitive impairment mediates microglial activation via TLR4/MyD88 signaling pathway
  60. Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway
  61. Cord-lamina angle and foraminal diameter as key predictors of C5 palsy after anterior cervical decompression and fusion surgery
  62. GATA1: A key biomarker for predicting the prognosis of patients with diffuse large B-cell lymphoma
  63. Influencing factors of false lumen thrombosis in type B aortic dissection: A single-center retrospective study
  64. MZB1 regulates the immune microenvironment and inhibits ovarian cancer cell migration
  65. Integrating experimental and network pharmacology to explore the pharmacological mechanisms of Dioscin against glioblastoma
  66. Trends in research on preterm birth in twin pregnancy based on bibliometrics
  67. Four-week IgE/baseline IgE ratio combined with tryptase predicts clinical outcome in omalizumab-treated children with moderate-to-severe asthma
  68. Single-cell transcriptomic analysis identifies a stress response Schwann cell subtype
  69. Acute pancreatitis risk in the diagnosis and management of inflammatory bowel disease: A critical focus
  70. Effect of subclinical esketamine on NLRP3 and cognitive dysfunction in elderly ischemic stroke patients
  71. Interleukin-37 mediates the anti-oral tumor activity in oral cancer through STAT3
  72. CA199 and CEA expression levels, and minimally invasive postoperative prognosis analysis in esophageal squamous carcinoma patients
  73. Efficacy of a novel drainage catheter in the treatment of CSF leak after posterior spine surgery: A retrospective cohort study
  74. Comprehensive biomedicine assessment of Apteranthes tuberculata extracts: Phytochemical analysis and multifaceted pharmacological evaluation in animal models
  75. Relation of time in range to severity of coronary artery disease in patients with type 2 diabetes: A cross-sectional study
  76. Dopamine attenuates ethanol-induced neuronal apoptosis by stimulating electrical activity in the developing rat retina
  77. Correlation between albumin levels during the third trimester and the risk of postpartum levator ani muscle rupture
  78. Factors associated with maternal attention and distraction during breastfeeding and childcare: A cross-sectional study in the west of Iran
  79. Mechanisms of hesperetin in treating metabolic dysfunction-associated steatosis liver disease via network pharmacology and in vitro experiments
  80. The law on oncological oblivion in the Italian and European context: How to best uphold the cancer patients’ rights to privacy and self-determination?
  81. The prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutritional index for survival in patients with colorectal cancer
  82. Factors affecting the measurements of peripheral oxygen saturation values in healthy young adults
  83. Comparison and correlations between findings of hysteroscopy and vaginal color Doppler ultrasonography for detection of uterine abnormalities in patients with recurrent implantation failure
  84. The effects of different types of RAGT on balance function in stroke patients with low levels of independent walking in a convalescent rehabilitation hospital
  85. Causal relationship between asthma and ankylosing spondylitis: A bidirectional two-sample univariable and multivariable Mendelian randomization study
  86. Correlations of health literacy with individuals’ understanding and use of medications in Southern Taiwan
  87. Correlation of serum calprotectin with outcome of acute cerebral infarction
  88. Comparison of computed tomography and guided bronchoscopy in the diagnosis of pulmonary nodules: A systematic review and meta-analysis
  89. Curdione protects vascular endothelial cells and atherosclerosis via the regulation of DNMT1-mediated ERBB4 promoter methylation
  90. The identification of novel missense variant in ChAT gene in a patient with gestational diabetes denotes plausible genetic association
  91. Molecular genotyping of multi-system rare blood types in foreign blood donors based on DNA sequencing and its clinical significance
  92. Exploring the role of succinyl carnitine in the association between CD39⁺ CD4⁺ T cell and ulcerative colitis: A Mendelian randomization study
  93. Dexmedetomidine suppresses microglial activation in postoperative cognitive dysfunction via the mmu-miRNA-125/TRAF6 signaling axis
  94. Analysis of serum metabolomics in patients with different types of chronic heart failure
  95. Diagnostic value of hematological parameters in the early diagnosis of acute cholecystitis
  96. Pachymaran alleviates fat accumulation, hepatocyte degeneration, and injury in mice with nonalcoholic fatty liver disease
  97. Decrease in CD4 and CD8 lymphocytes are predictors of severe clinical picture and unfavorable outcome of the disease in patients with COVID-19
  98. METTL3 blocked the progression of diabetic retinopathy through m6A-modified SOX2
  99. The predictive significance of anti-RO-52 antibody in patients with interstitial pneumonia after treatment of malignant tumors
  100. Exploring cerebrospinal fluid metabolites, cognitive function, and brain atrophy: Insights from Mendelian randomization
  101. Development and validation of potential molecular subtypes and signatures of ocular sarcoidosis based on autophagy-related gene analysis
  102. Widespread venous thrombosis: Unveiling a complex case of Behçet’s disease with a literature perspective
  103. Uterine fibroid embolization: An analysis of clinical outcomes and impact on patients’ quality of life
  104. Discovery of lipid metabolism-related diagnostic biomarkers and construction of diagnostic model in steroid-induced osteonecrosis of femoral head
  105. Serum-derived exomiR-188-3p is a promising novel biomarker for early-stage ovarian cancer
  106. Enhancing chronic back pain management: A comparative study of ultrasound–MRI fusion guidance for paravertebral nerve block
  107. Peptide CCAT1-70aa promotes hepatocellular carcinoma proliferation and invasion via the MAPK/ERK pathway
  108. Electroacupuncture-induced reduction of myocardial ischemia–reperfusion injury via FTO-dependent m6A methylation modulation
  109. Hemorrhoids and cardiovascular disease: A bidirectional Mendelian randomization study
  110. Cell-free adipose extract inhibits hypertrophic scar formation through collagen remodeling and antiangiogenesis
  111. HALP score in Demodex blepharitis: A case–control study
  112. Assessment of SOX2 performance as a marker for circulating cancer stem-like cells (CCSCs) identification in advanced breast cancer patients using CytoTrack system
  113. Risk and prognosis for brain metastasis in primary metastatic cervical cancer patients: A population-based study
  114. Comparison of the two intestinal anastomosis methods in pediatric patients
  115. Factors influencing hematological toxicity and adverse effects of perioperative hyperthermic intraperitoneal vs intraperitoneal chemotherapy in gastrointestinal cancer
  116. Endotoxin tolerance inhibits NLRP3 inflammasome activation in macrophages of septic mice by restoring autophagic flux through TRIM26
  117. Lateral transperitoneal laparoscopic adrenalectomy: A single-centre experience of 21 procedures
  118. Petunidin attenuates lipopolysaccharide-induced retinal microglia inflammatory response in diabetic retinopathy by targeting OGT/NF-κB/LCN2 axis
  119. Procalcitonin and C-reactive protein as biomarkers for diagnosing and assessing the severity of acute cholecystitis
  120. Factors determining the number of sessions in successful extracorporeal shock wave lithotripsy patients
  121. Development of a nomogram for predicting cancer-specific survival in patients with renal pelvic cancer following surgery
  122. Inhibition of ATG7 promotes orthodontic tooth movement by regulating the RANKL/OPG ratio under compression force
  123. A machine learning-based prognostic model integrating mRNA stemness index, hypoxia, and glycolysis‑related biomarkers for colorectal cancer
  124. Glutathione attenuates sepsis-associated encephalopathy via dual modulation of NF-κB and PKA/CREB pathways
  125. FAHD1 prevents neuronal ferroptosis by modulating R-loop and the cGAS–STING pathway
  126. Association of placenta weight and morphology with term low birth weight: A case–control study
  127. Investigation of the pathogenic variants induced Sjogren’s syndrome in Turkish population
  128. Nucleotide metabolic abnormalities in post-COVID-19 condition and type 2 diabetes mellitus patients and their association with endocrine dysfunction
  129. TGF-β–Smad2/3 signaling in high-altitude pulmonary hypertension in rats: Role and mechanisms via macrophage M2 polarization
  130. Ultrasound-guided unilateral versus bilateral erector spinae plane block for postoperative analgesia of patients undergoing laparoscopic cholecystectomy
  131. Profiling gut microbiome dynamics in subacute thyroiditis: Implications for pathogenesis, diagnosis, and treatment
  132. Delta neutrophil index, CRP/albumin ratio, procalcitonin, immature granulocytes, and HALP score in acute appendicitis: Best performing biomarker?
  133. Anticancer activity mechanism of novelly synthesized and characterized benzofuran ring-linked 3-nitrophenyl chalcone derivative on colon cancer cells
  134. H2valdien3 arrests the cell cycle and induces apoptosis of gastric cancer
  135. Prognostic relevance of PRSS2 and its immune correlates in papillary thyroid carcinoma
  136. Association of SGLT2 inhibition with psychiatric disorders: A Mendelian randomization study
  137. Motivational interviewing for alcohol use reduction in Thai patients
  138. Luteolin alleviates oxygen-glucose deprivation/reoxygenation-induced neuron injury by regulating NLRP3/IL-1β signaling
  139. Polyphyllin II inhibits thyroid cancer cell growth by simultaneously inhibiting glycolysis and oxidative phosphorylation
  140. Relationship between the expression of copper death promoting factor SLC31A1 in papillary thyroid carcinoma and clinicopathological indicators and prognosis
  141. CSF2 polarized neutrophils and invaded renal cancer cells in vitro influence
  142. Proton pump inhibitors-induced thrombocytopenia: A systematic literature analysis of case reports
  143. The current status and influence factors of research ability among community nurses: A sequential qualitative–quantitative study
  144. OKAIN: A comprehensive oncology knowledge base for the interpretation of clinically actionable alterations
  145. The relationship between serum CA50, CA242, and SAA levels and clinical pathological characteristics and prognosis in patients with pancreatic cancer
  146. Identification and external validation of a prognostic signature based on hypoxia–glycolysis-related genes for kidney renal clear cell carcinoma
  147. Engineered RBC-derived nanovesicles functionalized with tumor-targeting ligands: A comparative study on breast cancer targeting efficiency and biocompatibility
  148. Relationship of resting echocardiography combined with serum micronutrients to the severity of low-gradient severe aortic stenosis
  149. Effect of vibration on pain during subcutaneous heparin injection: A randomized, single-blind, placebo-controlled trial
  150. The diagnostic performance of machine learning-based FFRCT for coronary artery disease: A meta-analysis
  151. Comparing biofeedback device vs diaphragmatic breathing for bloating relief: A randomized controlled trial
  152. Serum uric acid to albumin ratio and C-reactive protein as predictive biomarkers for chronic total occlusion and coronary collateral circulation quality
  153. Multiple organ scoring systems for predicting in-hospital mortality of sepsis patients in the intensive care unit
  154. Single-cell RNA sequencing data analysis of the inner ear in gentamicin-treated mice via intraperitoneal injection
  155. Suppression of cathepsin B attenuates myocardial injury via limiting cardiomyocyte apoptosis
  156. Review Articles
  157. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  158. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  159. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  160. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  161. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  162. The safety and efficacy of BCG combined with mitomycin C compared with BCG monotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis
  163. The application of augmented reality in robotic general surgery: A mini-review
  164. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  165. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  166. Plant polyphenols, terpenes, and terpenoids in oral health
  167. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  168. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  169. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  170. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  171. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  172. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  173. Giant borderline ovarian tumours – review of the literature
  174. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  175. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  176. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  177. Supplement strategies for infertility in overweight women: Evidence and legal insights
  178. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  179. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  180. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  181. Strategies for hyperkalemia management in dialysis patients: A systematic review
  182. C-reactive protein-to-albumin ratio in peripheral artery disease
  183. Case Reports
  184. Delayed graft function after renal transplantation
  185. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  186. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  187. Giant right atrial hemangioma presenting with ascites: A case report
  188. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  189. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  190. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  191. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  192. Rapid Communication
  193. Biological properties of valve materials using RGD and EC
  194. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  195. Letter to the Editor
  196. Role of enhanced external counterpulsation in long COVID
  197. Expression of Concern
  198. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  199. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  200. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  201. Corrigendum
  202. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  203. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  204. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  205. Retraction
  206. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  207. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  208. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  209. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  210. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  211. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  212. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  213. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  214. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  215. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  216. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  217. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  218. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  219. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  220. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  221. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  222. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  223. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  224. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  225. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  226. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  227. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  228. A review of brain research on T2DM-related cognitive dysfunction
  229. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  230. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  231. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
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