Home A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
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A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women

  • Xinzhuan Jia , Lan Wei , Na Zhang , Bolin Zheng , Mengya Li , Hongxia Wang , Erhuan Liu , Jie Xu , Guangyu Sun and Zhengmao Zhang EMAIL logo
Published/Copyright: December 6, 2023

Abstract

In areas with high incidence of tuberculosis (TB), there are more infertile women who underwent in vitro fertilization (IVF) and have latent TB infection (LTBI), and thus, their potential risks should be paid enough attention. The purpose of our study aimed to analyze the relationship between LTBI and clinical pregnancy outcomes of IVF and fresh embryo transfer (IVF–FET). This was a retrospective study of 628 infertile women who had undergone IVF–FET in the Fourth Affiliated Hospital of Hebei Medical University from January 2019 to December 2021. The women experienced no clinical symptoms, negative imaging, and T-SPOT.TB-positive diagnosis of LTBI. We divided the study population into the LTBI group and the non-LTBI group. The clinical pregnancy rate in the LTBI group was significantly lower than that in the non-LTBI group (40.54% vs 49.51%, P = 0.031), and there was no significant difference in live birth rate and miscarriage rate between the two groups. Logistic regression analysis showed that LTBI was an independent risk factor for decreased clinical pregnancy rate in infertile women undergoing IVF–FET. In conclusion, LTBI affects clinical pregnancy rate of IVF–FET in infertile women, and therefore, clinicians (especially in countries with a high TB burden) need to pay attention to LTBI before IVF and embryo transfer.

1 Introduction

Tuberculosis (TB) is a public health and social problem of global concern. In 2020, an estimated 10 million new TB cases were reported globally, with adult women accounting for 32%. Two-thirds of the new cases were in eight developing countries, with China accounting for 8.4% of the total reported cases [1]. Among new cases, about 80% of TB patients were converted from latent TB infection (LTBI) [2].

TB is one of the main causes of infertility [3]. It is estimated that about 5–13% of reproductive women aged between 20 and 40 years have LTBI [4]. With the popularization of assisted reproductive technology, more and more infertile patients are undergoing in vitro fertilization and embryo transfer (IVF–ET) to become pregnant. In areas with high incidence of TB, such as China and India, the number of women undergoing IVF should be higher and the potential risks should be taken seriously. For high-risk groups, timely detection of LTBI and preventive anti-TB treatment (ATT) are important measures for TB prevention and control. There are currently no published studies analyzing whether LTBI affects clinical pregnancy outcomes of IVF–ET. To assess the relationship between LTBI and clinical pregnancy outcomes of IVF and fresh embryo transfer (IVF–FET), we conducted the retrospective study based on a case-registry database.

2 Materials and methods

2.1 Research design

This is a retrospective study, whose subjects were infertile women who underwent IVF–FET at the Department of Reproductive Medicine of the Fourth Affiliated Hospital of Hebei Medical University from January 1, 2019, to December 31, 2021. The inclusion criteria were: (1) age of infertile women ≥18 years; (2) detecting T-SPOT.TB before IVF–ET treatment; (3) there was no abnormality in chest CT before IVF–FET treatment; (4) fresh embryo transfer; and (5) complete medical records. The exclusion criteria were: (1) previous history of TB and ATT; (2) active pulmonary TB; (3) diabetes mellitus, malignant tumors, AIDS, and autoimmune diseases; (4) receiving glucocorticoid or/and immunosuppressant therapy within the last 3 months; (5) chromosomal abnormalities; and (6) IVF–ET caused by male factors. The data needed for this study came from the case registration database of the Fourth Affiliated Hospital of Hebei Medical University.

A total of 1,131 cases were screened according to the inclusion criteria. According to exclusion criteria, 503 cases were excluded. Of the remaining 628 patients, there were 222 LTBI cases and 406 non-LTBI cases. A total of 481 patients (76.59%) [including 176 patients (79.28%) in the LTBI group and 305 patients (75.12%) in the non-LTBI group] had undergone laparoscopy/hysteroscopy before IVF–FET and were histologically negative (TB-DNA, NTM-DNA). The other patients did not undergo laparoscopy/hysteroscopy because the salpingography and pelvic B-ultrasound results were normal.

This retrospective analysis was conducted in accordance with the World Medical Association Code of Ethics (Declaration of Helsinki) and was approved by the Ethics Committee of the Fourth Affiliated Hospital of Hebei Medical University (approval number: 2021KS010). All the patients gave up the need for informed consent.

2.2 T-SPOT.TB detection

T-SPOT.TB of the peripheral blood was tested within 3 months prior to IVF treatment. The T-SPOT.TB test kit is manufactured by Oxford Immunote, UK. Five milliliters of peripheral venous blood of every subject was mixed into a heparin-anticoagulated test tube immediately after the collection, and the peripheral blood mononuclear cells were isolated within 4 h to prepare the cell suspension. The collected suspension was transferred to an antigen-coated four-well plate. In these wells, positive (phytohemagglutinin, PHA) and negative controls, Panel A (early secretory antigen targe-6, ESAT-6) and Panel B (culture filtrate proteins, CFP-10), were analyzed. Then, the cell suspension of 100 μl containing 2.5 × 105 cells was added into every single well. The prepared plate was incubated for 16–20 h in a 5% CO2 oven at 37°C. The enzyme-linked immunospot assay (ELISPOT) reader (CTL-ImmunoSpotS5 Versa Analyser) was used to read spot-forming cells (SFCs). According to the reaction of antigen A or antigen B hole, when the SFC in the negative control hole equals 0–5, (antigen A or antigen B hole SFC) − (negative control hole SFC) ≥ 6, the result is positive; when the SFC in the negative control hole equals 6 to10, (antigen A or antigen B hole SFC) ≥ 2 × (negative control hole SFC), the result is also positive. Otherwise, it is negative.

2.3 Research objects grouping

According to the results of peripheral blood interferon-γ release assay (IGRA) before IVF treatment, the subjects were divided into two groups: no TB-related symptoms and no evidence of active TB in bacteriology and imaging examinations. T-SPOT.TB positive was defined as the LTBI group while T-SPOT.TB negative was defined as the non-LTBI group (Figure 1).

Figure 1 
                  Study flow chart.
Figure 1

Study flow chart.

2.4 IVF–ET scheme

All the subjects had undergone the cycle of ovarian stimulation, egg retrieval, and IVF–FET. Ovarian stimulation regiments include gonadotropin-releasing hormone agonist (GnRH-a) long regimen, GnRH-a ultra-long regimen, and GnRH antagonist regimen. The choice was based on the doctor’s discretion. Ultrasound monitoring was conducted and serum estradiol (E2) levels were measured during ovulation induction. Human chorionic gonadotropin (hCG) triggered ovulation when the dominant follicle diameter was ≥18 mm and E2 levels reached 150–300 ng/L. About 36 h after hCG administration, cumulus–oocyte complexes were recovered under ultrasound guidance, and IVF was performed. On the third day, the embryos in the cleavage stage were scored and graded (based on blastomere number, cell symmetry, and division). I–III cleavage stage embryos were identified as transferable embryos. Phase I–II embryos were defined as good-quality embryos which met the following criteria: (1) containing 6–8 cells 3 days after fertilization; (2) containing homogeneous blastomere; and (3) the degree of breakage was less than 10%. On the same day, these fresh embryos were transferred to the patients.

2.5 Evaluation indicators

(1) Clinical pregnancy rate = Number of clinical pregnancies/Number of transplanted embryos × 100%

(2) Live birth rate = Number of live births/Number of embryos transferred × 100%,

(3) Miscarriage rate = Number of miscarriages/Number of clinical pregnancies × 100% .

2.6 Pregnancy outcome

The primary outcome is the clinical pregnancy rate. Clinical pregnancy is defined by embryo sac detection through ultrasound 30 days after embryo transfer. Secondary outcomes are live birth rate and miscarriage rate. Live birth is defined as the delivery of a viable infant. Miscarriage is defined as fetus loss before the 24th week of pregnancy [5].

2.7 Statistical analysis

Statistical analysis was performed using SPSS 20.0. Continuous variables were expressed as mean ± standard deviation (SD) or as median [interquartile range (IQR)] and were analyzed using independent-sample t-tests or the Mann–Whitney U test, as appropriate. Categorical variables were summarized with numbers (N) and proportions (%), and were analyzed using the chi-square test. Chi-square test was used to compare the pregnancy outcomes between the LTBI group and the non-LTBI group. Multivariate logistic regression was used to assess the effects of exposure factors on the pregnancy outcomes. Two-sided P-value <0.05 was considered statistically significant.

3 Result

3.1 Baseline data of infertile patients in the LTBI and non-LTBI groups

The LTBI and non-LTBI groups were compared for age, body mass index (BMI), duration of infertility, causes of infertility (unknown reasons, fallopian tube factors, other female factors), COH regimen (GnRH-a long regimen, GnRH-a ultra-long regimen, GnRH antagonist regimen), basal hormone levels (follicle-stimulating hormone, luteinization hormone, E2, testosterone), anti-Müllerian hormone (AMH), number of total sinus follicles, endometrium thickness on hCG day, and number of good-quality embryos on the third day, and there was no significant difference (P > 0.05, Table 1).

Table 1

Characteristics of infertile patients undergoing fresh embryo transfer

Characteristics LTBI group (N = 222) Non-LTBI group (N = 406) t/U/χ 2 P value
Age, years (mean ± SD) 32.72 ± 5.05 32.46 ± 5.56 0.573 0.567
BMI, kg/m2 (mean ± SD) 22.05 ± 1.83 22.28 ± 2.07 1.392 0.165
Duration of infertility, years [median (IQR)] 3.00 (2.00, 5.00) 4.00 (2.00, 5.00) 450.86 0.992
Causes of infertility, N (%)
 Fallopian tube factors 139 (62.61%) 253 (62.31%) 0.328 0.849
 Unknown reasons 39 (17.57%) 66 (16.26%)
 Other female factors 44 (19.82%) 87 (21.43%)
Baseline hormone (mean ± SD)
 FSH, mIU/mL 6.60 ± 1.36 6.73 ± 1.36 1.206 0.228
 LH, mIU/mL 6.31 ± 1.73 6.15 ± 1.41 1.158 0.247
 E2, pg/mL 42.35 ± 6.22 42.15 ± 5.29 0.394 0.694
 T, ng/mL 0.24 ± 0.13 0.22 ± 0.12 1.620 0.106
 AMH, ng/mL (mean ± SD) 3.84 ± 1.72 3.98 ± 1.88 0.928 0.354
 COH regimen, N (%)
 GnRH-a long 122 (54.95%) 225 (55.42%) 0.526 0.769
 GnRH-a ultra-long 19 (8.56%) 41 (10.10%)
 GnRH antagonist 81 (36.49%) 140 (34.48%)
Endometrial thickness (hCG day), mm (mean ± SD) 10.31 ± 1.86 10.51 ± 1.71 1.295 0.196
No. of total sinus follicles (mean ± SD) 16.45 ± 6.79 17.12 ± 8.59 0.689 0.401
No. of good-quality embryos (Day 3) [median (IQR)] 2.00 (1.00, 3.00) 2.00 (1.00, 3.00) 448.43 0.917

BMI: body mass index; FSH: follicle-stimulating hormone; LH: luteinizing hormone; E2: estradiol; T: testosterone; AMH: anti-Müllerian hormone; COH: controlled ovarian hyperstimulation; GnRH: gonadotropin-releasing hormone; hCG: human chorionic gonadotropin.

3.2 Pregnancy outcomes in the LTBI and non-LTBI groups

The clinical pregnancy rate in the LTBI group was lower than that in the non-LTBI group (P < 0.05). Compared with the non-LTBI group, the LTBI group had a lower live birth rate and higher miscarriage rate, but there was no statistical significance (P > 0.05, Table 2).

Table 2

Pregnancy outcomes in the LTBI and non-LTBI groups

Pregnancy outcomes LTBI group (N = 222) Non-LTBI group (N = 406) χ 2 P value
Clinical pregnancy rate 40.54% (90/222) 49.51% (201/406) 4.641 0.031
Miscarriage rate 21.11% (19/90) 20.40% (41/201) 0.019 0.889
Live birth rate 25.23% (56/222) 30.54% (124/406) 1.984 0.159

3.3 Factors associated with pregnancy outcomes in infertile patients of IVF–ET

Multivariate logistic regression showed that LTBI (odds ratio [OR] = 0.695, 95% confidence interval [CI] 0.499–0.968, P = 0.032), age (OR = 0.953, 95% CI 0.935–0.982, P = 0.002), AMH (OR = 1.133,95% CI 1.038–1.236, P = 0.005), the number of good-quality embryos (OR = 1.139, 95% CI 1.004–1.243, P = 0.003), and COH regimen (P = 0.016) have significant effects on clinical pregnancy outcomes. After correcting these indicators, we found that LTBI was an independent risk factor for the decrease of clinical pregnancy rate in infertile women undergoing IVF–FET (OR 0.694, 95% CI 0.494–0.975, P = 0.035). LTBI (OR = 0.833, 95% CI 0.471–1.474, P = 0.531) had no significant effect on miscarriage. LTBI (OR = 0.767, 95% CI 0.530–1.110, P = 0.160) had no significant effect on live births.

4 Discussion

Female genital TB (FGTB) is not an uncommon cause of infertility worldwide, especially in developing countries. IVF–ET has been shown to improve pregnancy outcomes in infertile women with FGTB. There is limited evidence on the clinical outcomes of IVF–ET in LTBI patients. In our study, a total of 628 patients were involved. The clinical pregnancy rate in the LTBI group was significantly lower than that in the non-LTBI group, and after correcting relevant indicators, LTBI was found to be an independent risk factor for the decrease in clinical pregnancy rate in the infertile women undergoing IVF–FET.

Currently, there is no gold standard for diagnosing LTBI. At present, the IGRA series products widely used in the world mainly include Quantiferon-TB gold In-tube (QFT-GIT) based on enzyme-linked immunosorbent assay and T-SPOT.TB based on ELISPOT. The sensitivity of QFT-GIT is largely affected by the immune status of the host, while the sensitivity of T-SPOT.TB is mainly affected by the antigen load. Our study was grouped according to the results of T-SPOT.TB. The T-SPOT.TB-positive subjects were included in the LTBI groups, of which 79.28% underwent laparoscopy/hysteroscopy without evidence of active genital TB infection and 20.72% did not undergo laparoscopy/hysteroscopy due to normal results of salpingography and pelvic B-ultrasonography. Subjects with active TB were not allowed to undergo IVF–ET.

Some scholars have reported that clinical pregnancy rate and live birth rate of IVF in TB patients, who have not previously received ATT, are lower than that of those who have previously received ATT, especially those with unexplained infertility [6]. The implantation rate and pregnancy rate of IVF in patients with tubal TB are similar to that in those without TB. However, compared to patients with tubal TB or without TB, those with endometrial TB experience significantly lower fertilization rate, good-quality embryo rate, and implantation rate, resulting in a decrease in the cumulative pregnancy rate [7]. Lin et al. reported that cured endometrial TB is associated with low live birth rates [8]. Different from our findings, this can be explained by the fact that the cohort and subgroup analyses vary across the studies.

Immunity plays an important role in both latent and active TB [9]. The three factors affecting successful implantation and pregnancy are uterine receptivity, endometrial regeneration, and cytokine regulation. LGTB-associated immune factors (such as vascular endothelial growth factor, various cytokines, leukemia inhibitors, and cell adhesion molecules such as E cadherin, mucin-1, MECA-79, and alphavbeta3 integrin) may play a role in the implantation of the zygote by changing endometrial receptivity [10,11,12,13,14,15,16]. Highly activated immune disorders of T-receptor cells and CD4+ lymphocytes have also been observed in LGTB, leading to implantation failure [17,18]. On the other hand, progesterone used during IVF may lead to increased immunosuppression of the Th1 response and decreased CD4+ T-cell proliferation [19], and TB may amplify this side effect into a clinical phenomenon. Undergoing IVF treatment may make women more susceptible to TB infection and be associated with worse perinatal outcomes [20].

However, there are still some limitations concerning this study. First, it was a single-center retrospective analysis with a small sample size. Second, the data did not include TB activity and new infections undergoing IVF treatment. In addition, multivariate logistic analysis was used in our study and the results are still indicative and need to be validated in a larger cohort.

5 Conclusion

LTBI is associated with lower clinical pregnancy rates in women undergoing IVF–FET. Clinicians (especially in high TB burden countries) need to pay attention to LTBI before IVF–ET.


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Acknowledgment

We thank all the authors of this article.

  1. Funding information: This study was supported by the Medical Science Research Program of Hebei Province (20230815). The funders were not involved in the design of the study, the collection and analysis of data, the publication, or the preparation of the article.

  2. Author contributions: JXZ conceived and designed the study; ZN, ZBL, and LMY performed the tests; WHX, LEH, XJ, and SGY analyzed the data; JXZ and WL wrote the manuscript; ZZM revised the manuscript. All authors read and approved the final version of the manuscript.

  3. Conflict of interest: The authors declare no conflict of interest.

  4. Data availability statement: Data may be obtained from the corresponding author upon reasonable request.

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Received: 2023-03-22
Revised: 2023-10-06
Accepted: 2023-11-12
Published Online: 2023-12-06

© 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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  66. F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway
  67. Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis
  68. Long noncoding RNA Mhrt alleviates angiotensin II-induced cardiac hypertrophy phenotypes by mediating the miR-765/Wnt family member 7B pathway
  69. Effect of miR-499-5p/SOX6 axis on atrial fibrosis in rats with atrial fibrillation
  70. Cholesterol induces inflammation and reduces glucose utilization
  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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