Home Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
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Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery

  • Qingqing Wei , Jing Sun , Yusuo Bai , Chang Meng , Guobin Miao EMAIL logo , Peng Liu EMAIL logo and Haijun Wang EMAIL logo
Published/Copyright: August 26, 2023

Abstract

Low molecular weight heparin (LMWH) is often used to prevent perioperative venous thrombosis after surgery, but aspirin is also recommended by academics. Studies were searched in electronic databases until February 24, 2023. We performed a meta-analysis to evaluate the safety and efficacy of aspirin and LMWH for venous thromboembolism (VTE) prophylaxis in patients after orthopedic surgery. The outcomes were death from any causes, deep vein thrombosis (DVT), pulmonary embolism (PE), etc. This study was registered with INPLASY, number 202320117. Six randomized controlled trials enrolled 13,851 patients with postoperative joint surgery. The risk of DVT was comparable between the two groups when aspirin was combined with mechanical devices (RR 0.61 [95% CI 0.27–1.39], I² = 62%, P = 0.24). No significant differences in all cause death, PE, wound infection, and wound complication were found between the aspirin and LMWH groups. In this meta-analysis, the mortality rate was comparable between the aspirin and LMWH groups. However, aspirin alone had a higher risk of DVT than LMWH. Based on the results of this meta-analysis, we suggest aspirin combined with mechanical devices for VTE prophylaxis in patients after orthopedic surgery.

1 Introduction

Venous thromboembolism (VTE) is a serious consequence in patients with orthopedic trauma [1]. Some clinical guidelines recommend the use of thromboprophylaxis after orthopedic surgery to reduce the risk of VTE after orthopedic surgery and to reduce the associated risk of death and complications [2,3].

Previous studies have analyzed the efficacy and safety of aspirin and low molecular weight heparin (LMWH) in different orthopedic patients [4]. Recent large randomized clinical trials (RCTs) [5] have filled a gap in antithrombotic therapy in patients with surgically treated fractures. The results of most studies indicate that aspirin and low molecular weight have similar outcome markers, but the sample sizes of most studies are relatively small. Some studies have also analyzed the advantages of aspirin combined with mechanical devices to prevent venous thrombosis. After all, aspirin as an oral drug has irreplaceable convenience compared with LMWH, but LMWH as a clotting pathway inhibitor also plays a very important role in thrombosis.

O’Toole et al. [5] included patients who had had surgery for a broken limb or had any pelvic or acetabular fractures at multiple centers, and the results showed that aspirin’s thromboprophylaxis was no less effective at preventing death than LMWH. Anderson et al. [6] included total hip arthroplasty patients, and by extending the application time of aspirin to 28 days, compared with the LMWH group, the incidence of deep vein thrombosis (DVT) was similar between the two groups. The author mentioned that considering economic factors, aspirin could also be considered for clinical application.

Several subsequent studies [710] have looked at similar issues in patients undergoing joint replacement surgery, but with different drug timings and follow-up times. Recent studies [11] have analyzed the effect of other anticoagulant drugs on the prevention of DVT, which is also the direction of future research. Three studies [810] combined with mechanical devices, also offer new solutions for future treatment. In this meta-analysis, we summarized previously published RCTs to investigate the efficacy and safety of aspirin and LMWH in antithrombotic therapy for patients after orthopedic surgery.

2 Methods

We carried out the meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines [12]. Our protocol has been registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols database (Inplasy protocol: INPLASY202320117), and is available in full on inplasy.com (https://inplasy.com/inplasy-2023-2-0117). Ethics approval was not required for our work.

2.1 Search strategy

Three independent researchers conducted extensive electronic searches for relevant articles published until February 24, 2023. The database includes PubMed, Embase, and the Cochrane database. Manually select relevant randomized controlled trial. The search strategy of the literature is shown in Table A1.

2.2 Inclusion and exclusion

EndNote (X9 version) software is selected for document management; two investigators independently evaluated the eligibility of the identified items. The title and summary are filtered for the first time, and qualified articles are reserved for full-text review. Inclusion criteria for studies meeting the following requirements include: (1) patients after postoperative joint surgery, (2) treat with aspirin or LMWH, and (3) outcome indicators: all cause death, DVT, pulmonary embolism (PE), wound infection, wound complication, including one. We excluded studies enrolling patients <18 years old, and there was not enough data to extract, such as the summary of some meetings, literature materials such as review and pharmacological introduction. We contacted the authors if associated data from their studies were required.

2.3 Bias and quality assessment

The two researchers independently evaluated, preliminarily selected and checked the literature data according to the unified and standardized method, and included them in the literature in strict accordance with the admission and exclusion criteria, and then collected information. Evaluate the quality of selected articles according to the quality evaluation standard of Cochrane Reviewer Handbook 5.1.0 [13].

2.4 Data synthesis and analysis

Revman5.3 was used for meta-analysis. Data which met homogeneity (P > 0.10 and I 2 ≤ 50%) through heterogeneity test were meta-analyzed using fixed effect model. If homogeneity (P ≤ 0.10 or I 2 > 50%) was not met, and heterogeneity cannot be ruled out, random effect model can be used to combine effects [14]. While it should be noted that sensitivity analysis and subgroup analysis should be considered for this type of analysis data. For the continuous outcomes, mean differences and 95% CIs were estimated as effective. Some included RCTs reported median as the measure of treatment effect, with interquartile range. A P value <0.05 was considered statistically significant.

3 Results

The flow chart (Figure 1) summarizes the search and study selection process. A total of 289 studies were identified through the electronic searches, of which 137 were excluded due to duplication. Around 122 studies were also excluded after reading the titles and abstracts. The remaining 24 studies were assessed by reading the full texts. Data from six trails of 13,851 patients evaluating the efficacy and safety in postoperative joint surgery treated with aspirin versus LMWH were included.

Figure 1 
               The flow chart of the search and study selection process.
Figure 1

The flow chart of the search and study selection process.

The main features of the included trials are presented in Table 1. All included studies were randomized controlled trials, and the follow-up time lasted from hospitalization to 6-week or 3-month. Three of the six trials (n = 633) included patients treated with aspirin combined mobile compression device, subgroup analysis of DVT, and wound complications were performed. No differences were observed in terms of the proportion of patients lost to follow up between the aspirin and LMWH groups across trials.

Table 1

Design and outcomes of the studies included in the meta-analysis

Num. Author/Year Design Intervention assignments Participants Outcomes
Aspirin LMWH Sample size, n Mean age, years (A/L) Male% (A/L) Time of medication
1 Robert/2023 RCTs, MC 81 mg bid Enoxaparin 30 mg twice daily 12,211 44.5/44.7 62.8/61.7 About 1 month All cause deaths, PE, DVT, bleeding complication, wound complication, infection (follow 90-day)
2 Zou/2014 RCTs, SC 100 mg qd AxaIU 4,000 U qd 222 62.7/65.7 25.5/17.9 14 days DVT, wound complications, limb swelling (follow 4-week)
3 Anderson/2013 RCTs, MC 81 mg qd Dalteparin 5,000 U qd 785 57.6/57.9 60/53.3 28 days/10 days All cause deaths, PE, DVT, major bleeding, minor bleeding, wound infection (follow 90-day)
4* Jiang/2014 RCTs, SC 100 mg qd 5,000 U qd 120 65.1/63.8 8.3/6.7 14 days All cause deaths, DVT, ematoma, wound complications (follow 6-week)
5* Colwell/2010 RCTs, MC 81 mg qd 30 mg Bid until discharge and then 40 mg qd 392 63/62 45/46 10 days DVT; hematoma (follow 12-week)
6* Gelfer/2006 RCTs, SC 100 mg qd Enoxaparin 40 mg qd 121 68/67 34/38 In-hospital All cause deaths, PE, DVT, wound drainage (follow 3-month)

A/L = aspirin group/LMWH group; Bid = twice daily; DVT = deep vein thrombosis; LMWH = low molecular weight heparin; MC = multicenter; PE = pulmonary embolism; PS = prospective study; qd = Once a day; RCTs = randomized clinical trials; SC = single center; *Aspirin combined mobile compression device.

The data of all cause death were available from two trials (Figure 2). There is no significant differences between the aspirin and LMWH groups (RR 1.02 [95% CI 0.68–1.53], I² = 0%, P = 0.91). The data of PE were available from three trials (Figure 3). No significant differences were found between the aspirin and LMWH groups (RR 0.96 [95% CI 0.72–1.28], I² = 2%, P = 0.78). The data of wound infection were available from two trials (Figure 4). No significant differences were found between the aspirin and LMWH groups (RR 1.07 [95% CI 0.82–1.40], I² = 0%, P = 0.60).

Figure 2 
               The outcomes of all cause death.
Figure 2

The outcomes of all cause death.

Figure 3 
               The outcomes of PE.
Figure 3

The outcomes of PE.

Figure 4 
               The outcomes of wound infection.
Figure 4

The outcomes of wound infection.

The data of DVT were available from six trials (Figure 5). There is no significant differences between the aspirin and LMWH groups (RR 0.92 [95% CI 0.56–1.51], I² = 63%, P = 0.73). In the subgroup analysis, we saw that the risk of DVT in the aspirin alone group was higher than that in the low molecular heparin group (RR 1.43 [95% CI 1.14–1.80], I² = 0%, P = 0.002), but the risk of DVT was comparable between the two groups when aspirin was combined with mechanical devices (RR 0.61 [95% CI 0.27–1.39], I² = 62%, P = 0.24). The data of wound complication were available from five trials (Figure 6). There is no significant differences between the aspirin and LMWH groups (RR 1.13 [95% CI 0.72–1.76], I² = 35%, P = 0.60). There was no statistically significant difference between aspirin alone and aspirin combined with mechanical devices (RR 1.14 [95% CI 0.67–1.94], I² = 64%, P = 0.63; OR 1.09 [95% CI 0.48–2.47], I² = 0%, P = 0.84).

Figure 5 
               The outcomes of DVT.
Figure 5

The outcomes of DVT.

Figure 6 
               The outcomes of wound complication.
Figure 6

The outcomes of wound complication.

We used Revman to investigate the influence of a single study on the overall pooled estimate of each predefined outcome. We found that the removal of any one study would not affect the following results. The results of the risk of bias assessment with the RoB2 of randomized control trials are summarized in the Table A1.

4 Discussion

Studies have reported that approximately 1.5 million hip and knee arthroplasty procedures are performed each year in the United States [15,16]. The incidence of surgical symptomatic VTE in patients is about 2%, posing a serious threat to postoperative recovery [11,17]. The prevention of DVT has become the focus of many scholars. LMWH has traditionally been used for anticoagulant therapy. In recent years, the use of aspirin-based thromboprophylaxis has increased [18,19]. This meta-analysis discussed the efficacy and safety of aspirin and LMWH in patients after orthopedic surgery by summarizing several RCTs. Our article had a large sample size and high quality, and the results were very reliable.

However, regarding aspirin in the prevention of DVT in patients after orthopedic surgery, the efficacy of aspirin as the only prophylactic drug is also questioned [20], which is consistent with the results of this study. In this meta-analysis, we could see that there was no statistical difference between the aspirin group and the LMWH group in the prevalence of PE and wound complications. In terms of the incidence of DVT, we can see that aspirin alone is worse than LMWH, and aspirin combined with mechanical device changes this outcome. This may seem different from the conclusions of individual studies, but it is probably the most realistic conclusion because our analysis included a large sample size and relied on standardized statistical analysis, after all, aspirin is more commonly used as an antiplatelet agent for the prevention of arterial embolization events. Therefore, we suggest that aspirin combined with mechanical auxiliary devices can be considered in the prevention of DVT after orthopedic surgery. On the one hand, aspirin can reduce the pain of patients, and it is easy to operate and implement. Future research can further explore the advantages and disadvantages of different mechanical devices, and provide a more simple and feasible program for patients after fracture surgery. Recent studies compared the risk of thromboembolic events under different routes of administration, which also provides some inspiration for this study [21]. There are also studies that female patients have a low risk of gynecological surgery embolization events, and gender classification is also one of the future research directions [22]. The metabolic pathways of embolic events have also been studied, which may also be one of the future research directions [23].

There are several limitations to be mentioned. First, we included several RCTs, in which different populations had different oral aspirin doses, medication cycles, and follow-up times, which may have increased the heterogeneity of the findings. Second, the number of patients was relatively small and some follow-up outcomes could not be obtained. For example, the cerebral function in different oxygen supply strategies could not be evaluated for cardiac arrest patients.

5 Conclusion

Death rates were comparable between the aspirin group and the LMWH group. Based on the results of this meta-analysis, we recommend the use of aspirin in combination with mechanical devices for the prevention of VTE in patients after orthopedic surgery.


# These authors have contributed equally to this work.


  1. Funding information: Study of Clinical Prediction Model and Related Metabolomics Analysis of Atrial High-rate Episode (Natural Science Foundation project of Inner Mongolia Autonomous Region No. 2023QN08004).

  2. Author contributions: Q.-Q.W., J.S., and G.-B.M. searched the scientific literature and drafted the manuscript. Y.-S.B. and C.M. contributed to data abstract. H.-J.W. and P.L. contributed to conception, design, data interpretation, manuscript revision for critical intellectual content, and supervision of the study. The authors read and approved the final manuscript.

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

  4. Data availability statement: Datasets are available on request from the corresponding author.

Appendix

Figure A1 
                  Risk of bias graph.
Figure A1

Risk of bias graph.

Table A1

Search strategy

Electronic database Search strategy
PubMed (NCBI) (“aspirin”[Title/Abstract] OR “acetylsalicylic acid”[Title/Abstract] AND (“Low molecular weight heparin”[Title/Abstract] OR “lmwh”[Title/Abstract] OR “nadroparin”[Title/Abstract] OR “Lovenox”[Title/Abstract] OR “heparin”[Title/Abstract]) AND (“cataclasis”[Title/Abstract] OR “fracture”[Title/Abstract] OR “joint”[Title/Abstract] OR “articulation”[Title/Abstract] OR “arthroplasty”[Title/Abstract]) AND (“randomized controlled trial” OR “randomized” OR “placebo” OR “randomly” OR “trial”)
Embase #1 (‘aspirin’:ab,ti OR ‘acetylsalicylic acid’:ab,ti)
#2 (‘Low molecular weight heparin’:ab,ti OR ‘lmwh’:ab,ti OR ‘nadroparin’:ab,ti OR ‘Lovenox’:ab,ti OR ‘heparin’:ab,ti)
#3 (‘cataclasis’:ab,ti OR ‘fracture’:ab,ti OR ‘joint’:ab,ti OR ‘articulation’:ab,ti OR ‘arthroplasty’:ab,ti)
#4 (‘randomized controlled trial’:ab,ti OR ‘randomized’:ab,ti OR ‘placebo’:ab,ti OR ‘randomly’:ab,ti OR ‘trial’:ab,ti)
#5 #1 AND #2 AND #3 AND #4
Cochrane (aspirin OR acetylsalicylic acid) AND (lmwh OR Low molecular weight heparin OR nadroparin OR Lovenox OR heparin) AND (cataclasis OR fracture OR joint OR articulation OR arthroplasty)

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Received: 2023-03-01
Revised: 2023-06-19
Accepted: 2023-06-27
Published Online: 2023-08-26

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

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

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