Home Life Sciences Relationship between platelet activation markers and spontaneous abortion: A meta-analysis
Article Open Access

Relationship between platelet activation markers and spontaneous abortion: A meta-analysis

  • Hua Gao EMAIL logo , Hui-Juan Ma , Ying-Jia Li , Yun Li and Ji-Rong Zhang
Published/Copyright: December 15, 2022

Abstract

Numerous studies have indicated that mean platelet volume (MPV) and platelet distribution width (PDW) were correlated with spontaneous abortion (SAB), but the results were contradictory. Hence, we performed a meta-analysis to assess the association of MPV and PDW with SAB. We systematically searched on China National Knowledge Internet, PubMed, and Embase up to May 2022 to retrieve eligible studies. The synthesized standard mean difference (SMD) with a 95% confidence interval (CI) was used to evaluate the correlation of MPV and PDW with SAB. A total of 20 studies were finally included in this meta-analysis. The pooled analysis results showed that PDW was markedly increased in patients with SAB versus women with a healthy pregnancy (SMD = 1.03; 95% CI: 0.51–1.54; p = 0.0001), while there were no significant differences in MPV between women with SAB and those with healthy pregnancy (SMD = 0.19; 95% CI: −0.26 to 0.65; p = 0.40). Therefore, PDW may serve as a potential marker for predicting SAB. However, homogeneous and multiethnic studies with larger sample sizes are warranted to validate our findings due to several limitations in this meta-analysis.

Graphical abstract

1 Introduction

Spontaneous abortion (SAB) is known to be the most frequent pregnancy complication, affecting approximately 15% of all pregnancies [1]. In particular, approximately 80% of all miscarriages occur in the first trimester. Solid evidence in the literature indicates that chromosomal anomalies, endocrine disorders, immunological causes, anatomic abnormalities, uterine anomalies, and infectious events are important causes of SAB [2,3,4,5]. However, the pathophysiology of spontaneous pregnancy loss is rather intricate and has never been fully understood [6]. Moreover, there is a lack of effective methods for predicting spontaneous miscarriage in clinical practice [7,8].

The compatible contact between the placenta and maternal circulation is a vital determinant for a successful pregnancy [9]. Conversely, thrombophilia, under which the tendency for venous thrombosis largely increases, has been considered to correlate with pregnancy loss [9,10]. Once microemboli form in the uteroplacental circulation in pregnant women with thrombophilia, a placental microenvironment conducive to fetal development is disturbed, which causes abnormal nutritional supply and inflammation, and consequently results in miscarriage [9,10,11]. Platelet activation is a pivotal event during thrombosis, which leads to the release of a mass of β-thrombo-globulin and soluble platelet P-selectin, largely increasing the risk of thrombophilia [12]. For this reason, β-thrombo-globulin and soluble platelet P-selectin have been proposed to serve as potential predictors of spontaneous miscarriage. However, the measurements of the two makers are time-consuming and expensive, thereby limiting their application in clinical practice [13]. Thus, it is imperative to identify easily accessible and cost-effective laboratory markers for predicting spontaneous pregnancy loss.

Mean platelet volume (MPV) and platelet distribution width (PDW), which are routinely detected in clinical laboratories, have been determined as parameters of platelet activation [14,15]. Intriguingly, numerous studies have investigated the association of MPV and PDW with spontaneous pregnancy loss, but the results were conflicting [7,8,13,16,17,18,19]. Therefore, herein we further evaluated the relationship of MPV and PDW to SAB through a systematic review and meta-analysis of published literature, to assess the potential of MPV and PDW as markers of predicting SAB.

2 Materials and methods

2.1 Ethical approval and informed consent

The conducted research is not related to either human or animal use, so ethical approval and informed consent are unnecessary.

2.2 Search strategy

Two researchers independently conducted the literature collection by searching PubMed, Embase, and China National Knowledge Internet up to May 2022. Search terms included “MPV, PDW or ” and “abortion or miscarriage or pregnancy loss.” In addition, the references of retrieved studies were screened to identify additional eligible studies omitted by electronic search. The detailed search strategies for each database were presented in Supplement 1.

2.3 Eligibility criteria

The studies synchronously satisfying the inclusion criteria mentioned below were eligible: (1) had a full-text organization structure; (2) investigated the association of MPV or PDW with SAB and reported the mean MPV or PDW and their corresponding SD in patients and women with healthy pregnancy; and (3) published in English or Chinese. For studies with overlapping data, the study with the larger sample size was selected. In contrast, studies were excluded if they met any of the following criteria: (1) they did not assess the association of MPV or PDW with SAB; (2) they did not provide data about the mean MPV or PDW and their corresponding SD; or (3) they were academic dissertations, review articles, editorial articles, meta-analyses, or meeting abstracts.

2.4 Quality assessment

The Newcastle-Ottawa scale (NOS) was applied to appraise study quality [20]. The NOS covers eight items for observational studies and is categorized into three dimensions: selection, comparability and exposure. The “star” rating system is utilized to grade the methodological quality. A maximum of four stars are used to rate the selection dimension, two stars are used to rate the comparability dimension, and three stars are used to rate the exposure dimension. The total score ranges from 0 (worst) to 9 stars (best), and the quality of each study is assessed as low (0–3), moderate (4–6), or high (7–9).

2.5 Data extraction

Two researchers extracted the data independently based on the inclusion criteria. Extracted data were fed into a collection table and examined by a third author. Disagreements were removed via discussion. In this meta-analysis, the extracted data included the study author, publication year, country, sample size, age of pregnant women, gestational age, type of abortion, mean MPV value, mean PDW value, and SD of MPV and PDW.

2.6 Statistical analysis

The statistical analysis was conducted using STATA version 12.0 (Stata Corporation, College Station, TX, USA) and RevMan version 5.3 software. The standard mean difference (SMD) and its 95% confidence interval (CI) were utilized to evaluate the pooled MPV and PDW values. When the SMD was above 0 and the 95% CI did not cross 0, the MPV or PDW value was considered to be increased in the SAB group versus the control group. Otherwise, the combination of SMD <0 and the 95% CI not crossing 0 indicated a decrease in the MPV or PDW value in the SAB group versus the control group. Additionally, when the 95% CI crossed 0, the MPV or PDW value was considered to be equal between the two groups. The Cochrane Q test (χ 2) and I 2 test were used to assess the statistical heterogeneity among the studies. The random-effect model was selected to calculate the SMD when there was significant heterogeneity. p < 0.05 was considered to indicate a statistically significant difference. Subgroup analyses and meta-regression analyses based on sample size, country, age of pregnant women, gestational age, and recurrent miscarriage were carried out to explore the sources of heterogeneity [21]. Sensitivity analyses were performed by excluding one study in each step. The Begg funnel plot and Egger’s test were applied to assess publication bias [20].

3 Results

3.1 Study characteristics

Through electronic and manual searches, we first obtained 77 articles. Then, academic dissertations, duplicate articles, studies with unmatched themes, studies lacking data about MPV or PDW, and articles without full text were excluded; thus, 57 studies were excluded, and 20 studies were finally included in this meta-analysis [7,8,13,16,17,18,19,22,23,24,25,26,27,28,29,30,31,32,33,34]. The flowchart of the study search and selection process is presented in Figure 1. The publication years of the included studies ranged from 2013 to 2022. Most of the studies (n = 14) came from Turkey, and the others were conducted in China. The sample size of the included studies ranged from 80 to 2192. A total of 13 studies focused on recurrent miscarriage. Among the included studies, 18 studies reported MPV measurements, while 14 studies reported PDW. The methodological quality of the studies was evaluated by NOS, and the scores ranged from 6 to 7, implying that the included studies had a relatively acceptable quality. The detailed information about study characteristics is summarized in Table 1.

Figure 1 
                  Flowchart of study search and identification.
Figure 1

Flowchart of study search and identification.

Table 1

The main characteristics of included studies

Author/year Country Case number Age (year) Recurrent abortion Gestational age Mean platelet volume (fl) Platelet distribution width (%) Quality score
Spontaneous abortion Heathy pregnancy Spontaneous abortion Heathy pregnancy Spontaneous abortion Heathy pregnancy Spontaneous abortion Heathy pregnancy
Mean SD Mean SD Mean SD Mean SD
Akdemir et al., 2013 Turkey 51 64 32.1 ± 3.5 29.4 ± 4.0 Yes <13 week 8.1 1.1 8.2 1.5 17.8 1 18 1.2 7
Akin et al., 2016 Turkey 78 91 30.3 ± 6.8 28.1 ± 5.4 NR <13 week 9.5 1.1 8.8 1 16.3 2.6 16.5 1.6 7
Ata et al., 2020 Turkey 100 100 28.1 ± 4.0 27.1 ± 5.2 NR <13 week 10.01 1.25 10.6 0.85 NR NR NR NR 6
Aynıoglu et al., 2016 Turkey 208 95 31 ± 3.8 34 ± 5.5 Yes <20 week 8.1 2.37 8.9 0.97 NR NR NR NR 7
Bas et al., 2018 Turkey 173 245 31.88 ± 6.43 30.15 ± 5.62 NR <13 week 6.72 2.41 8.67 0.94 NR NR NR NR 6
Biyik et al., 2020 Turkey 40 40 29.27 ± 6.84 28.37 ± 5.13 NR <13 week 9.07 1.48 9.72 1.33 16.65 0.79 16.3 0.73 6
Dundar et al., 2015 Turkey 60 60 27.0 ± 5.2 27.6 ± 5.3 Yes NR 10.9 1.1 10.5 0.9 17.5 3.8 15.9 0.7 7
Erdem et al., 2020 Turkey 50 60 29.8 ± 5.8 28.7 ± 5.2 Yes <20 week 9.8 1.7 8.3 1.8 15.7 1.8 14.9 2.5 6
Kaplanoglu et al., 2015 Turkey 305 168 27.16 ± 4.59 27.62 ± 4.41 NR <20 week 8.99 1.47 9.66 1.64 17.31 2.99 17.78 3.28 6
Li and Ma, 2017 China 28 40 30 ± 2.75 28 ± 3.75 Yes <20 week 10.86 2.07 9.52 1.83 15.65 2.32 13.56 2.04 6
Li et al., 2020 China 80 80 32 ± 5 30 ± 4 Yes <28 week 11.04 1.48 10.49 1.28 16.55 0.46 16.36 0.4 6
Lu et al., 2022 China 215 160 26.7 ± 3.8 26.5 ± 3.9 Yes NR 12.12 1.32 10.35 1.31 17.57 0.45 16.34 0.37 7
Oğlak and Aydın, 2020 Turkey 137 148 23 ± 2.83 26 ± 2.67 NR <13 week 8.8 0.68 8.6 0.67 15.8 0.37 15.2 0.77 7
Qian et al., 2020 China 202 90 29.2 ± 4.5 28.8 ± 5.1 Yes <28 week NR NR NR NR 16.39 3.9 11.28 2.03 7
Uysal et al., 2015 Turkey 50 50 26.18 ± 3.63 26.57 ± 3.74 Yes NR 8.06 1.56 7.72 1.1 17.85 1.75 17.96 2.27 7
Mete Ural, 2014 Turkey 74 208 31 ± 2.7 32 ± 1.9 Yes <13 week 7.99 1.02 7.98 1.24 19.89 1.21 18.59 1.77 7
Yakıştıran et al., 2021 Turkey 193 164 30.6 ± 6.8 27.8 ± 5.6 NR <13 week 8.4 6.5 8.3 1.0 NR NR NR NR 6
Yilmaz et al., 2013 Turkey 120 120 29.07 ± 2.81 28.53 ± 3.5 Yes NR 9.45 1.09 7.63 0.52 NR NR NR NR 6
Yu et al., 2020 China 206 92 32.36 ± 4.55 32.87 ± 3.82 Yes <28 week 8.53 0.92 8.8 0.61 NR NR NR NR 7
Zhang et al., 2018 China 780 1412 31 ± 5 31 ± 7 Yes <28 week NR NR NR NR 15.5 2.5 12.8 2.5 6

NR: not reported; SD: standard deviation.

3.2 Meta-analysis of the association between PDW and SAB

Fourteen studies involving 2,076 patients and 2,303 subjects with healthy pregnancy explored the relationship of PDW with spontaneous miscarriage [13,16,17,18,19,22,25,26,27,28,29,30,31,32]. Mean PDW values and SD between patients with miscarriage and healthy counterparts were subjected to meta-analysis. In view of the significant heterogeneity (I 2 = 98.0; p < 0.00001), we used random-effect models to perform the meta-analysis for PDW. The result of the overall pooled analysis showed that the PDW level was markedly increased in the SAB group versus the healthy pregnancy group (SMD = 1.03; 95% CI: 0.51–1.54 [Figure 2]). Then, subgroup analyses and meta-regression analyses by sample size, country, age of pregnant women, gestational age, and recurrent miscarriage were conducted to the sources of heterogeneity (Table 2). We found a positive correlation between PDW level and SAB in the subgroups of sample size (N > 200 and N ≤ 200), China, age of pregnant women (≤30 years), gestational age (<28 weeks), and recurrent abortion, but not in the other subgroups. Meanwhile, significant heterogeneity was still observed in all the subgroup analyses. However, the results of meta-regression analyses suggested that the study country may be one of the major sources of heterogeneity for the pooled estimation of the correlation between PDW and SAB.

Figure 2 
                  Meta-analysis of the association between PDW and spontaneous abortion.
Figure 2

Meta-analysis of the association between PDW and spontaneous abortion.

Table 2

Subgroup and meta-regression analyses for the correlation of PDW with spontaneous abortion

Stratified study No. of studies Pooled SMD (95% CI) p-value Heterogeneity Regression
I 2 (%) p-Value I 2 (%) Adj R 2 p-value
1 Sample size 96.97 8.99 0.16
N ≤ 165 7 0.352 (0.086–0.619) 0.01 69.6 <0.01
N > 165 7 1.003 (0.375–1.631) <0.01 98.4 <0.01
2 Country 95.23 38.75 0.012
 China 5 1.388 (0.661–2.116) <0.01 97.6 <0.01
 Turkey 9 0.302 (−0.027 to 0.631) 0.072 90.4 <0.01
3 Age 97.35 −1.29 0.374
 >30 years 5 0.42 (−0.112 to 0.953) 0.122 95.9 <0.01
 ≤30 years 9 0.845 (0.155 to 1.535) 0.016 97.7 <0.01
4 Gestational age 96.23 13.17 0.119
 <13 weeks 4 0.296 (−0.313 to 0.906) 0.34 92.7 <0.01
 <20 weeks 4 0.472 (−0.092 to 1.036) 0.101 92.6 <0.01
 <28 weeks 3 1.012 (0.562 to 1.461) <0.01 91.8 <0.01
 NA 3 1.162 (−0.731 to 3.055) 0.229 98.9 <0.01
5 Recurrent abortion 96.43 2.52 0.279
 Yes 10 0.85 (0.37–1.329) <0.01 96.8 <0.01
 NR 4 0.295 (−0.301 to –0.891) 0.332 94.7 <0.01

NR: not report.

3.3 Meta-analysis of the association between MPV and SAB

A total of 18 studies involving 1,953 women with SAB and 1,825 subjects with healthy pregnancy investigated the association between MPV and SAB [7,8,13,16,17,18,19,22,23,24,25,27,28,29,30,31,33,34]. The mean values of MPV and SD between patients with spontaneous miscarriage and women with healthy pregnancy were subjected to meta-analysis. Considering the significant heterogeneity, the random-effect models (I 2 = 97.0%; p < 0.00001) were applied in the meta-analysis for MPV. The pooled result showed that there were no significant differences in MPV levels between patients with SAB and control subjects (SMD = 0.19; 95% CI: −0.26 to 0.65 [Figure 3]). To minimize the effect of confounding factors on the pooled result and to investigate the potential sources of heterogeneity, we conducted subgroup analyses and meta-regression analyses based on sample size, country, age of pregnant women, gestational age, and recurrent miscarriage (Table 3). In general, no significant differences in MPV between women with SAB and subjects with healthy pregnancies were found in all the subgroup analyses, except the subgroup of gestational age (NR). Additionally, significant heterogeneity still existed in all the subgroup analyses, indicating that those confounding factors above may not the major sources of the heterogeneity. Nevertheless, the results of meta-regression analyses supported that the gestational age of SAB may partly explain the heterogeneity for the pooled estimation of the correlation between MPV and SAB.

Figure 3 
                  Meta-analysis of the association between MPV and spontaneous abortion.
Figure 3

Meta-analysis of the association between MPV and spontaneous abortion.

Table 3

Subgroup and meta-regression analyses for the correlation of MPV with spontaneous abortion

Stratified study No. of studies Pooled SMD (95% CI) p-Value Heterogeneity Regression
I 2 (%) p-Value I 2 (%) Adj R 2 p-value
1 Sample size 96.98 −6.14 0.839
N>200 9 0.164 (−0.427 to 0.755) 0.586 98.3 <0.01
N ≤ 200 9 0.238 (−0.104 to 0.579) 0.173 97.8 <0.01
2 Country 96.66 −0.48 0.354
 China 4 0.527 (−0.31 to 1.364) 0.217 96.9 <0.01
 Turkey 14 0.108 (−0.293 to 0.509) 0.598 96.6 <0.01
3 Age 96.47 8.94 0.128
 >30 years 8 −0.111 (−0.51 to 0.288) 0.586 94.7 <0.01
 ≤30 years 10 0.452 (−0.114 to 1.018) 0.117 97.2 <0.01
4 Gestational age 95.23 30.17 0.013
 <13 weeks 7 −0.178 (−0.668 to 0.312) 0.476 95.6 <0.01
 <20 weeks 5 0.111 (−0.342 to 0.564) 0.631 92 <0.01
 <28 weeks 2 0.031 (−0.675 to 0.736) 0.932 92 <0.01
 NR 4 1.039 (0.246–1.833) 0.01 96 <0.01
5 Recurrent abortion 96.14 16.87 0.054
 Yes 11 0.479 (−0.009 to 0.967) 0.054 96.4 <0.01
 NR 7 −0.231 (−0.68 to 0.219) 0.315 95.7 <0.01

NR: not report.

3.4 Sensitivity analyses and publication bias

To assess the robustness of meta-analysis, sensitivity analysis was performed by omitting eligible studies one by one and then pooling the data of the remaining studies. The results showed that the overall effect size of PDW and MPV exhibited no significant alterations with the exclusion of any study (Figure 4a and b). Additionally, we applied Begg’s funnel plot and Egger’s test to evaluate the publication bias. As shown in Figure 4c and d, Begg’s funnel plots for PDW and MPV were symmetric, indicating the absence of substantial publication bias. Furthermore, the p values of Egger’s test for PDW and MPV were 0.413 and 0.181, respectively, which further confirmed that no significant publication bias existed in this meta-analysis.

Figure 4 
                  Sensitivity analysis for (a) PDW and (b) MPV; funnel plot describing publication bias of (c) PDW and (d) MPV.
Figure 4

Sensitivity analysis for (a) PDW and (b) MPV; funnel plot describing publication bias of (c) PDW and (d) MPV.

4 Discussion

Pregnancy loss represents a serious reproductive health problem, which brings huge emotional and physical damage to thousands of families [35]. The etiology of spontaneous pregnancy loss is multifactorial and remains largely unknown, and there is a lack of an effective method of predicting miscarriage in clinical practice [35]. A growing number of studies have found that PDW and MPV, two simple, easily measurable, and cost-effective parameters, were markedly increased in women with SAB versus in counterparts with healthy pregnancies, suggesting that they may serve as tools to predict spontaneous miscarriage [13,17,22]. However, some conflicting results on this topic were also reported [7,8,16,25,31]. Therefore, the association of PDW and MPV with spontaneous pregnancy loss should be further assessed. To our best knowledge, this study is the first systematic review and meta-analysis to comprehensively evaluate the relationship of PDW and MPV to spontaneous miscarriage. We found that PDW value was much higher in patients with SAB than that in women with normal pregnancy (SMD = 1.03; 95% CI: 0.51–1.54; p = 0.0001), whereas there were no significant differences in MPV value (SMD = 0.19; 95% CI: −0.26 to 0.65; p = 0.40).

The concentrations of coagulation factors are often altered during pregnancy, leading to a state of hypercoagulation [36]. Moreover, platelet activity is also increased in pregnant women, and activated platelets are capable of producing a rich number of prothrombotic meditators, such as thromboxane A2, serotonin, P-selectin, and glycoprotein, thereby contributing to hypercoagulatory state [37]. This prothrombotic state will bring about uteroplacental vascular thrombosis, which is a major cause of pregnancy loss [38]. PDW, a parameter for describing the variation in platelet size, has been determined as a specific marker of platelet activation [25]. For these reasons, many studies have been performed to explore the association of PDW with spontaneous miscarriage. Some studies showed that the PDW value was much higher in women with SAB than in subjects with healthy pregnancies, indicating the potential of PDW as a marker of predicting pregnancy loss [13,26,28,31,32]. However, other studies reported no significant relationship between PDW and spontaneous miscarriage [19,22,25,27]. The conflicting results may be partly caused by the limited sample size of those individual studies. To remove this influence, we carried out a meta-analysis of the literature studies on this topic. Consistent with some previous research articles [13,26,28,31,32], our overall pooled analysis found a higher PDW value in women with spontaneous miscarriage compared to those with healthy pregnancies. There was significant heterogeneity across the included studies referring to PDW, which may challenge the validity of our meta-analysis. Hence, to account for the heterogeneity, we performed the subgroup analyses based on sample size, country, biological age, gestational age, and miscarriage type. However, substantial heterogeneity still existed in each subgroup, suggesting that these factors might not be the major sources of heterogeneity. Additionally, PDW values were significantly higher in patients with spontaneous miscarriage versus in women with healthy pregnancy in subgroups of sample size (N > 200 and N ≤ 200), China, biological age (≤30 year), gestational age (<28 week), but not in the other subgroups. The limitation of case numbers in individual subgroups may be partly responsible for these contradictory results. Of note, our sensitivity analysis showed that the overall estimation of PDW did not substantially alter with a single study sequentially excluded, and no evident publication bias for studies referring to PDW was identified, which suggested the validity of our meta-analysis to a degree. In addition to the hypercoagulation state, an excessive maternal inflammatory response is another crucial cause of spontaneous pregnancy loss [17]. The platelets in activated form can also promote inflammatory response through releasing small molecular meditators that activate other immune cells, notwithstanding their major functions are hemostasis and coagulation [39]. Remarkably, PDW has been identified as a systemic inflammatory marker, and its value is positively correlated with the activity of many inflammatory diseases [25,39]. Hence, the correlation between PDW and systematic inflammation may also explain the finding of our meta-analysis at least partly.

MPV is a parameter of evaluating platelet size and has also been identified as a marker of platelet activation [40] and systematic inflammation [39]. A large number of studies have demonstrated that incremental MPV level was associated with a higher risk of venous thromboembolism in the context of multiple diseases [41,42]. Meanwhile, MPV level was found to be elevated in various inflammatory disorders and positively correlate with the activity and severity of diseases [43,44,45,46]. Furthermore, many research studies have also been conducted to investigate the relationship between MPV and spontaneous miscarriage. However, the results on this topic were conflicting. For example, Akin et al. [22] suggested that a higher MPV value was correlated with spontaneous pregnancy loss, whereas Uysal et al. [19] found no significant association between MPV and SAB, and Bas et al. [24] and Ata et al. [7] even reported that there was an inverse link between MPV value and pregnancy loss. In this study, our overall pooled analysis demonstrated that there were no significant differences in MPV between women with spontaneous miscarriage and subjects with healthy pregnancies. To minimize the influence of confounding factors on the pooled estimation and interpret the heterogeneity, we further conducted subgroup analyses by sample size, country, biological age, gestational age, and miscarriage type. In accordance with the overall pooled estimation, all the subgroup analyses showed that MPV values were similar in patients with SAB and women with healthy pregnancies. In addition, sensitivity analysis by omitting a single study in each step showed that the combined analysis of the correlation between MPV and spontaneous miscarriage was stable. Moreover, Begg’s and Egger’s tests detected no significant publication bias across included studies reporting MPV. Overall, these results supported that our meta-analysis of the association between MPV and spontaneous pregnancy loss was reliable and robust. Superficially, the results contradicted the potential of MPV as a marker of platelet activation and systematic inflammation. In fact, MPV values may be influenced by multiple factors in women with pregnancy loss. MPV can be directly affected by platelet distension [47], under which condition an increment in MPV value may be detected, though platelet activation does not exist. Meanwhile, it has been revealed that activated platelets with larger volumes can migrate to the region in early gestational periods [7,13], consequently leading to a decreased MPV level in the circulation of women with pregnancy loss. When these factors that can influence MPV value coexist in pregnant women, the measured value of MPV may depend on which factor plays the major role and fail to truly reflect the platelet activity. Therefore, MPV alone may not be reliable for predicting pregnancy loss, although it correlates with platelet activation. Of note, it has been proposed that the combination of PDW and MPV could reflect the activation of coagulation more accurately. In the future, it will be of interest to explore the potential of the combination of PDW and MPV in predicting spontaneous pregnancy loss.

There are several limitations in our meta-analysis, so the results should be interpreted cautiously. First of all, the clinical heterogeneity among the included studies exists in this meta-analysis, such as definitions of spontaneous miscarriage, age of patients and control subjects, gestational age, thromboembolism-precipitating risk, methods of measuring PDW and MPV, and testing time. Thus, it is hard to exclude the possibility that the pooled results could be biased by heterogenic factors. Second, all of the included studies collected data with the retrospective method, which may be accompanied by a high risk of selection bias. Third, this study only compared the levels of PDW between women with pregnancy loss and healthy subjects, while the cut-off values of high PDW levels were not determined due to the unavailability of relevant data in the included studies. This drawback makes it difficult to use PDW as a clinical tool to predict spontaneous pregnancy loss. Fourth, publication bias might exist since only studies published in English and Chinese were considered in this meta-analysis, notwithstanding the funnel plot and Egger’s test indicating no evident publication bias. Fifth, all the included studies only enrolled Chinese or Turks, so it is arbitrary to generalize our conclusion to other ethnicities. Last but not least, trial sequential analysis (TSA) can help to evaluate whether the least sample size required for obtaining a stable and robust conclusion is enough [48]. Of note, TSA is just suitable for the meta-analysis of studies that assesses the causal correlation of the risk factors with outcomes using relative risk (RR) and odds risk (OR) with 95% CIs. However, in this meta-analysis, we only compared the values of PDW and MPV between patients with SAB and subjects with a healthy pregnancy, and the OR and RR for evaluating the correlation of PDW and MPV with spontaneous miscarriage between PDW were not reported in the included studies. Therefore, TSA could not be performed in the present study.

5 Conclusion

In summary, PDW was markedly increased in patients with SAB versus women with healthy pregnancies, while there were no significant differences in MPV between patients with SAB and women with healthy pregnancies. Therefore, PDW may be used as a potential marker for predicting SAB. However, homogeneous and multiethnic studies with larger sample sizes are warranted to validate our findings due to several limitations in this meta-analysis.

Acknowledgments

We would like to thank A. E. J. company for providing service of editing our manuscript.

  1. Funding information: Authors state no funding is involved.

  2. Author contributions: H. G. and H. J. M. conceived and designed this work. H. G., Y. J. L., Y. L., and J. R. Z. carried out the literature search. H. G., H. J. M., and Y. L. contributed to the data analyses. All authors participated in writing and reviewing the manuscript.

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

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

References

[1] Ghazanfarpour M, Kashani ZA, Pakzad R, Abdi F, Rahnemaei FA, Akbari PA, et al. Effect of electromagnetic field on abortion: a systematic review and meta-analysis. Open Med (Wars). 2021;16(1):1628–41.10.1515/med-2021-0384Search in Google Scholar PubMed PubMed Central

[2] Yifu P, Lei Y, Shaoming L, Yujin G, Xingwang Z. Sperm DNA fragmentation index with unexplained recurrent spontaneous abortion: A systematic review and meta-analysis. J Gynecol Obstet Hum Reprod. 2020;49(10):101740.10.1016/j.jogoh.2020.101740Search in Google Scholar PubMed

[3] Zhu W, Zheng H, Liu J, Cai J, Wang G, Li Y, et al. The correlation between chronic exposure to particulate matter and spontaneous abortion: a meta-analysis. Chemosphere. 2022;286(Pt 2):131802.10.1016/j.chemosphere.2021.131802Search in Google Scholar PubMed

[4] Fu YY, Ren CE, Qiao PY, Meng YH. Uterine natural killer cells and recurrent spontaneous abortion. Am J Reprod Immunol. 2021;86(2):e13433.10.1111/aji.13433Search in Google Scholar PubMed

[5] Li D, Zheng L, Zhao D, Xu Y, Wang Y. The role of immune cells in recurrent spontaneous abortion. Reprod Sci. 2021;28(12):3303–15.10.1007/s43032-021-00599-ySearch in Google Scholar PubMed PubMed Central

[6] Lou C, Goodier JL, Qiang R. A potential new mechanism for pregnancy loss: considering the role of LINE-1 retrotransposons in early spontaneous miscarriage. Reprod Biol Endocrinol. 2020;18(1):6.10.1186/s12958-020-0564-xSearch in Google Scholar PubMed PubMed Central

[7] Ata N, Kulhan M, Kulhan NG, Turkler C. Can neutrophil-lymphocyte and platelet-lymphocyte ratios predict threatened abortion and early pregnancy loss? Ginekol Pol. 2020;91(4):210–5.10.5603/GP.2020.0042Search in Google Scholar PubMed

[8] Yakıştıran B, Tanacan A, Altınboğa O, Yücel A. Can derived neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and delta neutrophil index predict spontaneous abortion? Z Geburtshilfe Neonatol. 2021;225(5):418–22.10.1055/a-1363-2855Search in Google Scholar PubMed

[9] Kaymaz E, Gun BD, Genc GC, Kokturk F, Ozmen KG. May the morphological findings in the first-trimester abortion materials be indicative of inherited thrombophilia? J Obstet Gynaecol Res. 2020;46(11):2261–71.10.1111/jog.14419Search in Google Scholar PubMed

[10] Bagot CN, Pavord S, Hunt BJ. Managing venous thromboembolic risk in women undergoing spontaneous or induced early pregnancy loss: a consensus statement from the British Society of Haematology Obstetric Haematology Special Interest Group. Br J Haematol. 2020;190(1):115–8.10.1111/bjh.16496Search in Google Scholar PubMed

[11] Bianco M, Mantovani S, D’Agostino FG, Bassi M, Amore D, Cagnetti S, et al. Deep venous thrombosis and abortion: an unusual clinical manifestation of severe form of pectus excavatum. Gen Thorac Cardiovasc Surg. 2021;69(5):897–901.10.1007/s11748-020-01583-0Search in Google Scholar PubMed PubMed Central

[12] Kaur S, Singh A, Kaur J, Verma N, Pandey AK, Das S, et al. Upregulation of cytokine signalling in platelets increases risk of thrombophilia in severe COVID-19 patients. Blood Cells Mol Dis. 2022;94:102653.10.1016/j.bcmd.2022.102653Search in Google Scholar PubMed PubMed Central

[13] Dundar O, Pektas MK, Bodur S, Bakir LV, Cetin A. Recurrent pregnancy loss is associated with increased red cell distribution width and platelet distribution width. J Obstet Gynaecol Res. 2015;41(4):551–8.10.1111/jog.12600Search in Google Scholar PubMed

[14] Cai N, Chen ZQ, Tao M, Fan WT, Liao W. Mean platelet volume and red blood cell distribution width is associated with prognosis in premature neonates with sepsis. Open Med (Wars). 2021;16(1):1175–81.10.1515/med-2021-0323Search in Google Scholar PubMed PubMed Central

[15] Awad A, Elnemr S, Hodeib H, El Amrousy D. Platelet activation markers in children with pulmonary arterial hypertension associated with congenital heart disease. Pediatr Cardiol. 2022;43(6):1264–70.10.1007/s00246-022-02847-7Search in Google Scholar PubMed PubMed Central

[16] Akdemira N, Cevrioglua AS, Ozdena S, Kurua B, Bilira F, Bilirb C. Platelet indices and blood groups in early recurrent miscarriage: a study in pregnant women. J Clin Gynecol Obstet. 2013;2(1):27–30.10.4021/jcgo90eSearch in Google Scholar

[17] Erdem ZS, Cayir Y, Kosan Z, Erdem HB. Is there any relation between recurrent miscarriage and complete blood count values? A case-control study. Konuralp Tip Dergisi. 2020;12(1):39–43.10.18521/ktd.518494Search in Google Scholar

[18] Mete Ural U, Bayoğlu Tekin Y, Balik G, Kir Şahin F, Colak S. Could platelet distribution width be a predictive marker for unexplained recurrent miscarriage? Arch Gynecol Obstet. 2014;290(2):233–6.10.1007/s00404-014-3192-xSearch in Google Scholar PubMed

[19] Uysal A, İncebıyık A, Hacıvelioğlu S, Gencer M, Güngör A, Coşar E. Is there any relationship between platelet functions, red cell distribution width and recurrent pregnancy loss? J Clin Anal Med. 2015;6(2):149–51.Search in Google Scholar

[20] Zhang YL, Chen P, Guo Y, Zhang YJ. Clinical value of SIRT1 as a prognostic biomarker in esophageal squamous cell carcinoma, a systematic meta-analysis. Open Med (Wars). 2022;17(1):527–35.10.1515/med-2022-0454Search in Google Scholar PubMed PubMed Central

[21] Rahnemaei FA, Pakzad R, Amirian A, Pakzad I, Abdi F. Effect of gestational diabetes mellitus on lipid profile: A systematic review and meta-analysis. Open Med (Wars). 2022;17(1):70–86.10.1515/med-2021-0408Search in Google Scholar PubMed PubMed Central

[22] Akin MN, Kasap B, Yuvaci HU, Turhan N. Association between platelet indices and first trimester miscarriage. Blood Coagul Fibrinolysis. 2016;27(5):526–30.10.1097/MBC.0000000000000445Search in Google Scholar PubMed

[23] Aynıoglu O, Isık H, Sahbaz A, Harma MI, Isık M, Kokturk F. Can plateletcrit be a marker for recurrent pregnancy loss? Clin Appl Thromb Hemost. 2016;22(5):447–52.10.1177/1076029614565882Search in Google Scholar PubMed

[24] Bas FY, Tola EN, Sak S, Cankaya BA. The role of complete blood inflammation markers in the prediction of spontaneous abortion. Pak J Med Sci. 2018;34(6):1381–5.10.12669/pjms.346.15939Search in Google Scholar PubMed PubMed Central

[25] Biyik I, Albayrak M, Keskin F. Platelet to lymphocyte ratio and neutrophil to lymphocyte ratio in missed abortion. Rev Bras Ginecol Obstet. 2020;42(5):235–9.10.1055/s-0040-1709693Search in Google Scholar PubMed

[26] Zhang L, Ma Y, Zhu YN, Shen YF, Li S, Zhu B. Association of RDW-CV, PDW and NLR with recurrent spontaneous abortion. Chin J Clin Lab Sci. 2018;36(6):432–4.Search in Google Scholar

[27] Kaplanoglu M, Yuce T, Bulbul M. Decreased mean platelet volume is associated with the developing stage of fetoplacental unit in spontaneous abortion. Int J Clin Exp Med. 2015;8(7):11301–6.Search in Google Scholar

[28] Li Q, MA C. Significance of Hcy, folic acid, PLT, MPV and PDW detection in patients with recurrent spontaneous abortion. Int J Lab Med. 2017;38(5):613–4.Search in Google Scholar

[29] Li XJ, Yi H, Huang YL, Liu ZY. The correlation of thromboela-stogram and platelet parameters with recurrent miscarriage. Chin J Clin Obstet Gynecol. 2020;21(6):634–5.Search in Google Scholar

[30] Lu XJ, Liang JM, Seng LL, Bai YQ, Gao JX, Qin LX, et al. Analyze the diagnostic value of different detection methods for recurrent miscarriage. Chin J Lab Diag. 2022;26(4):0480.Search in Google Scholar

[31] Oğlak SC, Aydın MF. Are neutrophil to lymphocyte ratio and platelet to lymphocyte ratio clinically useful for the prediction of early pregnancy loss? Ginekol Pol. 2020;91(9):524–7.10.5603/GP.a2020.0082Search in Google Scholar PubMed

[32] Qian SJ, Li J, Shen XH. Diagnostic value and clinical significance of combined detection of PDW and NLR in patients with recurrent spotaneous abortion. Int J Lab Med. 2020;41(9):1101–4.Search in Google Scholar

[33] Yilmaz M, Delibas IB, Isaoglu U, Ingec M, Borekci B, Ulug P. Relationship between mean platelet volume and recurrent miscarriage: a preliminary study. Arch Med Sci. 2015;11(5):989–93.Search in Google Scholar

[34] Yu PY, Zhao FL, Zhang XH, Zhao LJ, Zhao LY. Predtive values of thromboelastograph, mean platelet volume/platelet count ratio and fibrinogen level in recurrent spontaneous abortion. JJU-ME. 2020;46(1):127–31.Search in Google Scholar

[35] Qin XY, Shen HH, Zhou WJ, Mei J, Lu H, Tan XF, et al. Insight of autophagy in spontaneous miscarriage. Int J Biol Sci. 2022;18(3):1150–70.10.7150/ijbs.68335Search in Google Scholar PubMed PubMed Central

[36] Bitsadze V, Khizroeva J, Alexander M, Elalamy I. Venous thrombosis risk factors in pregnant women. J Perinat Med. 2022;50(5):505–18.10.1515/jpm-2022-0008Search in Google Scholar PubMed

[37] Peshkova AD, Safiullina SI, Evtugina NG, Baras YS, Ataullakhanov FI, Weisel JW, et al. Premorbid hemostasis in women with a history of pregnancy loss. Thromb Haemost. 2019;119(12):1994–2004.10.1055/s-0039-1696972Search in Google Scholar PubMed

[38] Middeldorp S, Naue C, Köhler C. Thrombophilia, thrombosis and thromboprophylaxis in pregnancy: for what and in whom? Hamostaseologie. 2022;42(1):54–64.10.1055/a-1717-7663Search in Google Scholar PubMed

[39] Chen Y, Zhong H, Zhao Y, Luo X, Gao W. Role of platelet biomarkers in inflammatory response. Biomark Res. 2020;8:28.10.1186/s40364-020-00207-2Search in Google Scholar PubMed PubMed Central

[40] Pala AA, Urcun YS. Is the mean platelet volume a predictive factor for atrial fibrillation developing after coronary artery bypass grafting in elderly patients? Heart Surg Forum. 2020;23(6):E809–14.10.1532/hsf.3201Search in Google Scholar PubMed

[41] Braester A, Stemer G, Khouri S, Raviv B, Barhoum M. Is there a predictive value of high mean platelet volume in early diagnosis of venous thromboembolism? Isr Med Assoc J. 2021;23(10):635–8.Search in Google Scholar

[42] Edvardsen MS, Hansen ES, Hindberg K, Morelli VM, Ueland T, Aukrust P, et al. Combined effects of plasma von Willebrand factor and platelet measures on the risk of incident venous thromboembolism. Blood. 2021;138(22):2269–77.10.1182/blood.2021011494Search in Google Scholar PubMed

[43] Dechanuwong P, Phuan-Udom R. Hematological parameters as a predictor of disease remission in patients with rheumatoid arthritis. Ann Med Surg (Lond). 2021;72:103085.10.1016/j.amsu.2021.103085Search in Google Scholar PubMed PubMed Central

[44] Masoumi M, Shadmanfar S, Davatchi F, Shahram F, Akhlagi M, Faezi T, et al. Correlation of clinical signs and symptoms of Behçet’s disease with mean platelet volume (MPV) and red cell distribution width (RDW). Orphanet J Rare Dis. 2020;15(1):297.10.1186/s13023-020-01588-1Search in Google Scholar PubMed PubMed Central

[45] Taha SI, Samaan SF, Ibrahim RA, Moustafa NM, El-Sehsah EM, Youssef MK. Can complete blood count picture tell us more about the activity of rheumatological diseases? Clin Med Insights Arthritis Musculoskelet Disord. 2022;15:11795441221089182.10.1177/11795441221089182Search in Google Scholar PubMed PubMed Central

[46] Uzkeser H, Keskin H, Haliloglu S, Cayir Y, Karaaslan Y, Kosar A, et al. Is mean platelet volume related to disease activity in systemic lupus erythematosus? Int J Clin Pract. 2021;75(11):e14676.10.1111/ijcp.14676Search in Google Scholar PubMed

[47] Vagdatli E, Gounari E, Lazaridou E, Katsibourlia E, Tsikopoulou F, Labrianou I. Platelet distribution width: a simple, practical and specific marker of activation of coagulation. Hippokratia. 2010;14(1):28–32.Search in Google Scholar

[48] Meng J, Wang S, Zhang M, Fan S, Zhang L, Liang C. TP73 G4C14-A4T14 polymorphism and cancer susceptibility: evidence from 36 case-control studies. Biosci Rep. 2018;38(6):BSR20181452.10.1042/BSR20181452Search in Google Scholar PubMed PubMed Central

Received: 2022-04-04
Revised: 2022-05-25
Accepted: 2022-07-28
Published Online: 2022-12-15

© 2022 Hua Gao et al., published by De Gruyter

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

Articles in the same Issue

  1. Biomedical Sciences
  2. Effects of direct oral anticoagulants dabigatran and rivaroxaban on the blood coagulation function in rabbits
  3. The mother of all battles: Viruses vs humans. Can humans avoid extinction in 50–100 years?
  4. Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia
  5. LINC00665 regulates hepatocellular carcinoma by modulating mRNA via the m6A enzyme
  6. Association study of CLDN14 variations in patients with kidney stones
  7. Concanavalin A-induced autoimmune hepatitis model in mice: Mechanisms and future outlook
  8. Regulation of miR-30b in cancer development, apoptosis, and drug resistance
  9. Informatic analysis of the pulmonary microecology in non-cystic fibrosis bronchiectasis at three different stages
  10. Swimming attenuates tumor growth in CT-26 tumor-bearing mice and suppresses angiogenesis by mediating the HIF-1α/VEGFA pathway
  11. Characterization of intestinal microbiota and serum metabolites in patients with mild hepatic encephalopathy
  12. Functional conservation and divergence in plant-specific GRF gene family revealed by sequences and expression analysis
  13. Application of the FLP/LoxP-FRT recombination system to switch the eGFP expression in a model prokaryote
  14. Biomedical evaluation of antioxidant properties of lamb meat enriched with iodine and selenium
  15. Intravenous infusion of the exosomes derived from human umbilical cord mesenchymal stem cells enhance neurological recovery after traumatic brain injury via suppressing the NF-κB pathway
  16. Effect of dietary pattern on pregnant women with gestational diabetes mellitus and its clinical significance
  17. Potential regulatory mechanism of TNF-α/TNFR1/ANXA1 in glioma cells and its role in glioma cell proliferation
  18. Effect of the genetic mutant G71R in uridine diphosphate-glucuronosyltransferase 1A1 on the conjugation of bilirubin
  19. Quercetin inhibits cytotoxicity of PC12 cells induced by amyloid-beta 25–35 via stimulating estrogen receptor α, activating ERK1/2, and inhibiting apoptosis
  20. Nutrition intervention in the management of novel coronavirus pneumonia patients
  21. circ-CFH promotes the development of HCC by regulating cell proliferation, apoptosis, migration, invasion, and glycolysis through the miR-377-3p/RNF38 axis
  22. Bmi-1 directly upregulates glucose transporter 1 in human gastric adenocarcinoma
  23. Lacunar infarction aggravates the cognitive deficit in the elderly with white matter lesion
  24. Hydroxysafflor yellow A improved retinopathy via Nrf2/HO-1 pathway in rats
  25. Comparison of axon extension: PTFE versus PLA formed by a 3D printer
  26. Elevated IL-35 level and iTr35 subset increase the bacterial burden and lung lesions in Mycobacterium tuberculosis-infected mice
  27. A case report of CAT gene and HNF1β gene variations in a patient with early-onset diabetes
  28. Study on the mechanism of inhibiting patulin production by fengycin
  29. SOX4 promotes high-glucose-induced inflammation and angiogenesis of retinal endothelial cells by activating NF-κB signaling pathway
  30. Relationship between blood clots and COVID-19 vaccines: A literature review
  31. Analysis of genetic characteristics of 436 children with dysplasia and detailed analysis of rare karyotype
  32. Bioinformatics network analyses of growth differentiation factor 11
  33. NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling
  34. Expression of Zeb1 in the differentiation of mouse embryonic stem cell
  35. Study on the genetic damage caused by cadmium sulfide quantum dots in human lymphocytes
  36. Association between single-nucleotide polymorphisms of NKX2.5 and congenital heart disease in Chinese population: A meta-analysis
  37. Assessment of the anesthetic effect of modified pentothal sodium solution on Sprague-Dawley rats
  38. Genetic susceptibility to high myopia in Han Chinese population
  39. Potential biomarkers and molecular mechanisms in preeclampsia progression
  40. Silencing circular RNA-friend leukemia virus integration 1 restrained malignancy of CC cells and oxaliplatin resistance by disturbing dyskeratosis congenita 1
  41. Endostar plus pembrolizumab combined with a platinum-based dual chemotherapy regime for advanced pulmonary large-cell neuroendocrine carcinoma as a first-line treatment: A case report
  42. The significance of PAK4 in signaling and clinicopathology: A review
  43. Sorafenib inhibits ovarian cancer cell proliferation and mobility and induces radiosensitivity by targeting the tumor cell epithelial–mesenchymal transition
  44. Characterization of rabbit polyclonal antibody against camel recombinant nanobodies
  45. Active legumain promotes invasion and migration of neuroblastoma by regulating epithelial-mesenchymal transition
  46. Effect of cell receptors in the pathogenesis of osteoarthritis: Current insights
  47. MT-12 inhibits the proliferation of bladder cells in vitro and in vivo by enhancing autophagy through mitochondrial dysfunction
  48. Study of hsa_circRNA_000121 and hsa_circRNA_004183 in papillary thyroid microcarcinoma
  49. BuyangHuanwu Decoction attenuates cerebral vasospasm caused by subarachnoid hemorrhage in rats via PI3K/AKT/eNOS axis
  50. Effects of the interaction of Notch and TLR4 pathways on inflammation and heart function in septic heart
  51. Monosodium iodoacetate-induced subchondral bone microstructure and inflammatory changes in an animal model of osteoarthritis
  52. A rare presentation of type II Abernethy malformation and nephrotic syndrome: Case report and review
  53. Rapid death due to pulmonary epithelioid haemangioendothelioma in several weeks: A case report
  54. Hepatoprotective role of peroxisome proliferator-activated receptor-α in non-cancerous hepatic tissues following transcatheter arterial embolization
  55. Correlation between peripheral blood lymphocyte subpopulations and primary systemic lupus erythematosus
  56. A novel SLC8A1-ALK fusion in lung adenocarcinoma confers sensitivity to alectinib: A case report
  57. β-Hydroxybutyrate upregulates FGF21 expression through inhibition of histone deacetylases in hepatocytes
  58. Identification of metabolic genes for the prediction of prognosis and tumor microenvironment infiltration in early-stage non-small cell lung cancer
  59. BTBD10 inhibits glioma tumorigenesis by downregulating cyclin D1 and p-Akt
  60. Mucormycosis co-infection in COVID-19 patients: An update
  61. Metagenomic next-generation sequencing in diagnosing Pneumocystis jirovecii pneumonia: A case report
  62. Long non-coding RNA HOXB-AS1 is a prognostic marker and promotes hepatocellular carcinoma cells’ proliferation and invasion
  63. Preparation and evaluation of LA-PEG-SPION, a targeted MRI contrast agent for liver cancer
  64. Proteomic analysis of the liver regulating lipid metabolism in Chaohu ducks using two-dimensional electrophoresis
  65. Nasopharyngeal tuberculosis: A case report
  66. Characterization and evaluation of anti-Salmonella enteritidis activity of indigenous probiotic lactobacilli in mice
  67. Aberrant pulmonary immune response of obese mice to periodontal infection
  68. Bacteriospermia – A formidable player in male subfertility
  69. In silico and in vivo analysis of TIPE1 expression in diffuse large B cell lymphoma
  70. Effects of KCa channels on biological behavior of trophoblasts
  71. Interleukin-17A influences the vulnerability rather than the size of established atherosclerotic plaques in apolipoprotein E-deficient mice
  72. Multiple organ failure and death caused by Staphylococcus aureus hip infection: A case report
  73. Prognostic signature related to the immune environment of oral squamous cell carcinoma
  74. Primary and metastatic squamous cell carcinoma of the thyroid gland: Two case reports
  75. Neuroprotective effects of crocin and crocin-loaded niosomes against the paraquat-induced oxidative brain damage in rats
  76. Role of MMP-2 and CD147 in kidney fibrosis
  77. Geometric basis of action potential of skeletal muscle cells and neurons
  78. Babesia microti-induced fulminant sepsis in an immunocompromised host: A case report and the case-specific literature review
  79. Role of cerebellar cortex in associative learning and memory in guinea pigs
  80. Application of metagenomic next-generation sequencing technique for diagnosing a specific case of necrotizing meningoencephalitis caused by human herpesvirus 2
  81. Case report: Quadruple primary malignant neoplasms including esophageal, ureteral, and lung in an elderly male
  82. Long non-coding RNA NEAT1 promotes angiogenesis in hepatoma carcinoma via the miR-125a-5p/VEGF pathway
  83. Osteogenic differentiation of periodontal membrane stem cells in inflammatory environments
  84. Knockdown of SHMT2 enhances the sensitivity of gastric cancer cells to radiotherapy through the Wnt/β-catenin pathway
  85. Continuous renal replacement therapy combined with double filtration plasmapheresis in the treatment of severe lupus complicated by serious bacterial infections in children: A case report
  86. Simultaneous triple primary malignancies, including bladder cancer, lymphoma, and lung cancer, in an elderly male: A case report
  87. Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine
  88. One case of iodine-125 therapy – A new minimally invasive treatment of intrahepatic cholangiocarcinoma
  89. S1P promotes corneal trigeminal neuron differentiation and corneal nerve repair via upregulating nerve growth factor expression in a mouse model
  90. Early cancer detection by a targeted methylation assay of circulating tumor DNA in plasma
  91. Calcifying nanoparticles initiate the calcification process of mesenchymal stem cells in vitro through the activation of the TGF-β1/Smad signaling pathway and promote the decay of echinococcosis
  92. Evaluation of prognostic markers in patients infected with SARS-CoV-2
  93. N6-Methyladenosine-related alternative splicing events play a role in bladder cancer
  94. Characterization of the structural, oxidative, and immunological features of testis tissue from Zucker diabetic fatty rats
  95. Effects of glucose and osmotic pressure on the proliferation and cell cycle of human chorionic trophoblast cells
  96. Investigation of genotype diversity of 7,804 norovirus sequences in humans and animals of China
  97. Characteristics and karyotype analysis of a patient with turner syndrome complicated with multiple-site tumors: A case report
  98. Aggravated renal fibrosis is positively associated with the activation of HMGB1-TLR2/4 signaling in STZ-induced diabetic mice
  99. Distribution characteristics of SARS-CoV-2 IgM/IgG in false-positive results detected by chemiluminescent immunoassay
  100. SRPX2 attenuated oxygen–glucose deprivation and reperfusion-induced injury in cardiomyocytes via alleviating endoplasmic reticulum stress-induced apoptosis through targeting PI3K/Akt/mTOR axis
  101. Aquaporin-8 overexpression is involved in vascular structure and function changes in placentas of gestational diabetes mellitus patients
  102. Relationship between CRP gene polymorphisms and ischemic stroke risk: A systematic review and meta-analysis
  103. Effects of growth hormone on lipid metabolism and sexual development in pubertal obese male rats
  104. Cloning and identification of the CTLA-4IgV gene and functional application of vaccine in Xinjiang sheep
  105. Antitumor activity of RUNX3: Upregulation of E-cadherin and downregulation of the epithelial–mesenchymal transition in clear-cell renal cell carcinoma
  106. PHF8 promotes osteogenic differentiation of BMSCs in old rat with osteoporosis by regulating Wnt/β-catenin pathway
  107. A review of the current state of the computer-aided diagnosis (CAD) systems for breast cancer diagnosis
  108. Bilateral dacryoadenitis in adult-onset Still’s disease: A case report
  109. A novel association between Bmi-1 protein expression and the SUVmax obtained by 18F-FDG PET/CT in patients with gastric adenocarcinoma
  110. The role of erythrocytes and erythroid progenitor cells in tumors
  111. Relationship between platelet activation markers and spontaneous abortion: A meta-analysis
  112. Abnormal methylation caused by folic acid deficiency in neural tube defects
  113. Silencing TLR4 using an ultrasound-targeted microbubble destruction-based shRNA system reduces ischemia-induced seizures in hyperglycemic rats
  114. Plant Sciences
  115. Seasonal succession of bacterial communities in cultured Caulerpa lentillifera detected by high-throughput sequencing
  116. Cloning and prokaryotic expression of WRKY48 from Caragana intermedia
  117. Novel Brassica hybrids with different resistance to Leptosphaeria maculans reveal unbalanced rDNA signal patterns
  118. Application of exogenous auxin and gibberellin regulates the bolting of lettuce (Lactuca sativa L.)
  119. Phytoremediation of pollutants from wastewater: A concise review
  120. Genome-wide identification and characterization of NBS-encoding genes in the sweet potato wild ancestor Ipomoea trifida (H.B.K.)
  121. Alleviative effects of magnetic Fe3O4 nanoparticles on the physiological toxicity of 3-nitrophenol to rice (Oryza sativa L.) seedlings
  122. Selection and functional identification of Dof genes expressed in response to nitrogen in Populus simonii × Populus nigra
  123. Study on pecan seed germination influenced by seed endocarp
  124. Identification of active compounds in Ophiopogonis Radix from different geographical origins by UPLC-Q/TOF-MS combined with GC-MS approaches
  125. The entire chloroplast genome sequence of Asparagus cochinchinensis and genetic comparison to Asparagus species
  126. Genome-wide identification of MAPK family genes and their response to abiotic stresses in tea plant (Camellia sinensis)
  127. Selection and validation of reference genes for RT-qPCR analysis of different organs at various development stages in Caragana intermedia
  128. Cloning and expression analysis of SERK1 gene in Diospyros lotus
  129. Integrated metabolomic and transcriptomic profiling revealed coping mechanisms of the edible and medicinal homologous plant Plantago asiatica L. cadmium resistance
  130. A missense variant in NCF1 is associated with susceptibility to unexplained recurrent spontaneous abortion
  131. Assessment of drought tolerance indices in faba bean genotypes under different irrigation regimes
  132. The entire chloroplast genome sequence of Asparagus setaceus (Kunth) Jessop: Genome structure, gene composition, and phylogenetic analysis in Asparagaceae
  133. Food Science
  134. Dietary food additive monosodium glutamate with or without high-lipid diet induces spleen anomaly: A mechanistic approach on rat model
  135. Binge eating disorder during COVID-19
  136. Potential of honey against the onset of autoimmune diabetes and its associated nephropathy, pancreatitis, and retinopathy in type 1 diabetic animal model
  137. FTO gene expression in diet-induced obesity is downregulated by Solanum fruit supplementation
  138. Physical activity enhances fecal lactobacilli in rats chronically drinking sweetened cola beverage
  139. Supercritical CO2 extraction, chemical composition, and antioxidant effects of Coreopsis tinctoria Nutt. oleoresin
  140. Functional constituents of plant-based foods boost immunity against acute and chronic disorders
  141. Effect of selenium and methods of protein extraction on the proteomic profile of Saccharomyces yeast
  142. Microbial diversity of milk ghee in southern Gansu and its effect on the formation of ghee flavor compounds
  143. Ecology and Environmental Sciences
  144. Effects of heavy metals on bacterial community surrounding Bijiashan mining area located in northwest China
  145. Microorganism community composition analysis coupling with 15N tracer experiments reveals the nitrification rate and N2O emissions in low pH soils in Southern China
  146. Genetic diversity and population structure of Cinnamomum balansae Lecomte inferred by microsatellites
  147. Preliminary screening of microplastic contamination in different marine fish species of Taif market, Saudi Arabia
  148. Plant volatile organic compounds attractive to Lygus pratensis
  149. Effects of organic materials on soil bacterial community structure in long-term continuous cropping of tomato in greenhouse
  150. Effects of soil treated fungicide fluopimomide on tomato (Solanum lycopersicum L.) disease control and plant growth
  151. Prevalence of Yersinia pestis among rodents captured in a semi-arid tropical ecosystem of south-western Zimbabwe
  152. Effects of irrigation and nitrogen fertilization on mitigating salt-induced Na+ toxicity and sustaining sea rice growth
  153. Bioengineering and Biotechnology
  154. Poly-l-lysine-caused cell adhesion induces pyroptosis in THP-1 monocytes
  155. Development of alkaline phosphatase-scFv and its use for one-step enzyme-linked immunosorbent assay for His-tagged protein detection
  156. Development and validation of a predictive model for immune-related genes in patients with tongue squamous cell carcinoma
  157. Agriculture
  158. Effects of chemical-based fertilizer replacement with biochar-based fertilizer on albic soil nutrient content and maize yield
  159. Genome-wide identification and expression analysis of CPP-like gene family in Triticum aestivum L. under different hormone and stress conditions
  160. Agronomic and economic performance of mung bean (Vigna radiata L.) varieties in response to rates of blended NPS fertilizer in Kindo Koysha district, Southern Ethiopia
  161. Influence of furrow irrigation regime on the yield and water consumption indicators of winter wheat based on a multi-level fuzzy comprehensive evaluation
  162. Discovery of exercise-related genes and pathway analysis based on comparative genomes of Mongolian originated Abaga and Wushen horse
  163. Lessons from integrated seasonal forecast-crop modelling in Africa: A systematic review
  164. Evolution trend of soil fertility in tobacco-planting area of Chenzhou, Hunan Province, China
  165. Animal Sciences
  166. Morphological and molecular characterization of Tatera indica Hardwicke 1807 (Rodentia: Muridae) from Pothwar, Pakistan
  167. Research on meat quality of Qianhua Mutton Merino sheep and Small-tail Han sheep
  168. SI: A Scientific Memoir
  169. Suggestions on leading an academic research laboratory group
  170. My scientific genealogy and the Toronto ACDC Laboratory, 1988–2022
  171. Erratum
  172. Erratum to “Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study”
  173. Erratum to “A two-microRNA signature predicts the progression of male thyroid cancer”
  174. Retraction
  175. Retraction of “Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis”
Downloaded on 13.3.2026 from https://www.degruyterbrill.com/document/doi/10.1515/biol-2022-0485/html
Scroll to top button