Single-cell RNA sequencing of cervical exfoliated cells reveals potential biomarkers and cellular pathogenesis in cervical carcinogenesis.

Cervical cancer (CC) is a common gynecological malignancy. Despite the current screening methods have been proved effectively and significantly decreased CC morbidity and mortality, deficiencies still exist. Single-cell RNA sequencing (scRNA-seq) approach can identify the complex and rare cell populations at single-cell resolution. By scRNA-seq, the heterogeneity of tumor microenvironment across cervical carcinogenesis has been mapped and described. Whether these alterations could be detected and applied to CC screening is unclear. Herein, we performed scRNA-seq of 56,173 cervical exfoliated cells from 15 samples, including normal cervix, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and malignancy. The present study delineated the alteration of immune and epithelial cells derived during the cervical lesion progression. A subset of lipid-associated macrophage was identified as a tumor-promoting element and could serve as a biomarker for predicting the progression of LSIL into HSIL, which was then verified by immunofluorescence. Furthermore, cell-cell communication analysis indicated the SPP1-CD44 axis might exhibit a protumor interaction between epithelial cell and macrophage. In this study, we investigated the cervical multicellular ecosystem in cervical carcinogenesis and identified potential biomarkers for early detection.

Emerging role of mesenchymal stromal cells in gynecologic cancer therapy.

Mesenchymal stromal cells (MSCs) show considerable promise in regenerative medicine with superior anti-fibrotic, immunomodulatory, and angiogenic functions. More recently, discovered with the tumor tropism, MSCs have been exploited as the basis of targeted cancer therapy. In this scenario, MSCs can directly home to tumor tissues and play anti-tumor properties. In addition, MSCs, MSC-derived exosomes and MSC-derived membranes are often developed as carriers for precisely delivering cytotoxic agents to cancer sites, including chemotherapeutic drugs, therapeutic genes, or oncolytic viruses. However, it has revealed the tumorigenic risk of MSCs as an important component within the tumor microenvironment, hampering the translation of MSC-based cancer therapies into clinical settings. Therefore, in this review, we introduce the specific tumor-tropic ability of MSCs and underlying mechanisms. We also summarize the current application of MSC-based therapeutic approaches in treating gynecologic cancers, mainly including cervical, ovarian, and endometrial cancers. Moreover, we discuss the main challenges that the current MSC-based cancer therapies are facing.

The Role of ZNF275/AKT Pathway in Carcinogenesis and Cisplatin Chemosensitivity of Cervical Cancer Using Patient-Derived Xenograft Models.

Zinc finger protein 275 (ZNF275) is a C2H2-type transcription factor that is localized on chromosome Xq28. Whether ZNF275 participates in modulating the biological behaviors of cervical cancer has not been determined to our knowledge. The present study employed CCK-8, BrdU, flow cytometry, and a transwell assay to investigate the cell viability, proliferation, apoptosis, migration, and invasion of cervical cancer cells. The application of Western blotting and immunohistochemistry (IHC) aims to assess ZNF275 protein expression and identify the signaling pathway relevant to ZNF275-mediated effects on cervical cancer. The therapeutic impact of the combined therapy of the AKT inhibitor triciribine and cisplatin was evaluated on cervical cancer patient-derived xenograft (PDX) models expressing high ZNF275. The current research illustrated that cervical cancer tissue exhibited a higher expression of ZNF275 in contrast to the surrounding normal cervical tissue. The downregulation of ZNF275 suppressed cell viability, migration, and invasion, and facilitated the apoptosis of SiHa and HeLa cells via weakening AKT/Bcl-2 signaling pathway. Moreover, triciribine synergized with cisplatin to reduce cell proliferation, migration, and invasion, and enhanced the apoptosis of SiHa cells expressing high ZNF275. In addition, the combination treatment of triciribine and cisplatin was more effective in inducing tumor regression than single agents in cervical cancer PDX models expressing high ZNF275. Collectively, the current findings demonstrated that ZNF275 serves as a sufficiently predictive indicator of the therapeutic effectiveness of the combined treatment of triciribine and cisplatin on cervical cancer. Combining triciribine with cisplatin greatly broadens the therapeutic options for cervical cancer expressing high ZNF275, but further research is needed to confirm these results.

Riding apoptotic bodies for cell-cell transmission by African swine fever virus.

African swine fever virus (ASFV), a devastating pathogen to the worldwide swine industry, mainly targets macrophage/monocyte lineage, but how the virus enters host cells has remained unclear. Here, we report that ASFV utilizes apoptotic bodies (ApoBDs) for infection and cell-cell transmission. We show that ASFV induces cell apoptosis of primary porcine alveolar macrophages (PAMs) at the late stage of infection to productively shed ApoBDs that are subsequently swallowed by neighboring PAMs to initiate a secondary infection as evidenced by electron microscopy and live-cell imaging. Interestingly, the virions loaded within ApoBDs are exclusively single-enveloped particles that are devoid of the outer layer of membrane and represent a predominant form produced during late infection. The in vitro purified ApoBD vesicles are capable of mediating virus infection of naive PAMs, but the transmission can be significantly inhibited by blocking the "eat-me" signal phosphatidyserine on the surface of ApoBDs via Annexin V or the efferocytosis receptor TIM4 on the recipient PAMs via anti-TIM4 antibody, whereas overexpression of TIM4 enhances virus infection. The same treatment however did not affect the infection by intracellular viruses. Importantly, the swine sera to ASFV exert no effect on the ApoBD-mediated transmission but can partially act on the virions lacking the outer layer of membrane. Thus, ASFV has evolved to hijack a normal cellular pathway for cell-cell spread to evade host responses.

Grape Seed Proanthocyanidins Improve the Quality of Fresh and Cryopreserved Semen in Bulls.

Oxidative stress leads to a decrease in semen quality during semen cryopreservation and fresh semen production. Grape seed proanthocyanidins (GSPs) are endowed with well-recognized antioxidant, anti-inflammatory, anti-cancer, and anti-aging activities. Therefore, the objective of this experiment was to explore the effects of GSPs on the quality of fresh and cryopreserved semen to provide a basis for GSPs as a new dietary additive and semen diluent additive for males' reproduction. Fresh semen from three healthy bulls aged 3 to 5 years old were gathered and mixed with semen diluents dissolved with 0 µg/mL, 30 µg/mL, 40 µg/mL, 50 µg/mL, and 60 µg/mL GSPs respectively. The motility, physiological structures (acrosome integrity, membrane integrity, mitochondrial activity), and antioxidant capacity of frozen-thawed sperm were measured after storage in liquid nitrogen for 7 days (d). Bulls were fed with 20 mg/kg body weight (BW) GSPs in their diet for 60 days; the weight of the bull is about 600 kg. Then, the reproductive performance and antioxidant indexes of bulls were measured before and after feeding. The results demonstrated that GSPs supplementation significantly increased sperm motility, physiological structures, GSH-Px, and CAT enzyme activities and significantly decreased MDA content in sperm during semen cryopreservation. The optimal concentration of GSPs was 40 µg/mL (p < 0.05). After 20 mg/kg (body weight) GSP supplementation, sperm motility was significantly heightened (p < 0.05), the sperm deformity rate was significantly reduced (p < 0.05), and antioxidant enzyme activities (such as SOD, CAT, and GSH-Px) were significantly enhanced (p < 0.05), and the production of MDA was significantly suppressed (p < 0.05) in serum compared with that before feeding. In conclusion, these results reveal that a certain concentration of GSPs has a good protective effect on sperm damage caused by semen cryopreservation and the reproductive performance reduction caused by stress in bulls, which may be attributed to the antioxidant function of GSPs. In summary, GSPs are a useful cryoprotective adjuvant and dietary additive for bull sperm quality.

Methylation of BRD4 by PRMT1 regulates BRD4 phosphorylation and promotes ovarian cancer invasion.

Bromodomain-containing protein 4 (BRD4), the major component of bromodomain and extra-terminal domain (BET) protein family, has important functions in early embryonic development and cancer development. However, the posttranslational modification of BRD4 is not well understood. Multiple approaches were used to explore the mechanism of PRMT1-mediated BRD4 methylation and to determine the biological functions of BRD4 and PRMT1 in ovarian cancer. Here we report that BRD4 is asymmetrically methylated at R179/181/183 by PRMT1, which is antagonized by the Jumonji-family demethylase, JMJD6. PRMT1 is overexpressed in ovarian cancer tissue and is a potential marker for poor prognosis in ovarian cancer patients. Silencing of PRMT1 inhibited ovarian cancer proliferation, migration, and invasion in vivo and in vitro. PRMT1-mediated BRD4 methylation was found to promote BRD4 phosphorylation. Compared to BRD4 wild-type (WT) cells, BRD4 R179/181/183K mutant-expressing cells showed reduced ovarian cancer metastasis. BRD4 arginine methylation is also associated with TGF-ß signaling. Our results indicate that arginine methylation of BRD4 by PRMT1 is involved in ovarian cancer tumorigenesis. Targeting PRMT1-mediated arginine methylation may provide a novel diagnostic target and an effective therapeutic strategy for ovarian cancer treatment.

Dynamic volume variation of uterine leiomyomas during pregnancy.

OBJECTIVE: To investigate the volume variation of uterine leiomyomas and explore factors predicting their growth trends during pregnancy. METHOD: A retrospective observational study was performed on pregnant women with uterine leiomyomas between January 2016 and April 2020. The uterine leiomyoma volume was acquired from obstetrical ultrasound at the first, second, and third trimesters of gestation. A binary logistic regression analysis was conducted to explore the factors influencing the volume variation of uterine leiomyomas during pregnancy. RESULTS: A total of 278 pregnant women diagnosed with uterine leiomyomas were enrolled. The volumetric increase in uterine leiomyomas during pregnancy exhibited a higher growth rate from the first to second trimester (34.09%) than that from the second to third trimester (30.08%). Smaller uterine leiomyomas were more likely to increase in size from the first to second trimester and from the first to third trimester. Retroplacental uterine leiomyomas were more likely to increase in volume than that for uterine leiomyomas located away from the placenta in pregnant women from the second to third trimester. CONCLUSION: The uterine leiomyoma volume was potentially enlarged in a nonlinear growth pattern during pregnancy, which was associated with the former volume of uterine leiomyomas and the spatial relationship between leiomyoma-placental site.

Establishment and genetically characterization of patient-derived xenograft models of cervical cancer.

PURPOSE: Patient-derived xenograft (PDX) models were established to reproduce the clinical situation of original cancers and have increasingly been applied to preclinical cancer research. Our study was designed to establish and genetically characterize cervical cancer PDX models. METHODS: A total of 91 fresh fragments obtained from 22 surgically resected cervical cancer tissues were subcutaneously engrafted into female NOD-SCID mice. Hematoxylin and eosin (H&E) staining was performed to assess whether the established PDX models conserved the histological features of original patient cervical cancer tissues. Moreover, a Venn diagram was applied to display the overlap of all mutations detected in whole-genome sequencing (WGS) data from patient original cervical cancer (F0) and F2-, F3-PDX models. The whole exome sequencing (WES) and the "maftools" package were applied to determine the somatic mutations among primary cervical cancers and the established PDX models. RESULTS: Our study successfully developed a panel of cervical cancer PDX models and the latency time of cervical cancer PDX model establishment was variable with a progressive decrease as the passage number increased, with a mean time to initial growth of 94.71 days in F1 engraftment to 40.65 days in F3 engraftment. Moreover, the cervical cancer PDX models preserved the histological features of their original cervical cancer. WGS revealed that the genome of original cervical cancer was preserved with high fidelity in cervical cancer PDX models throughout the xenografting and passaging process. Furthermore, WES demonstrated that the cervical cancer PDX models maintained the majority somatic mutations of original cervical cancer, of which the KMT2D, LRP1B, NAV3, TP53, FAT1, MKI67 and PKHD1L1 genes were identified as the most frequently mutated genes. CONCLUSIONS: The cervical cancer PDX models preserved the histologic and genetic characteristics of their original cervical cancer, which helped to gain a deeper insight into the genetic alterations and lay a foundation for further investigation of the molecular targeted therapy of cervical cancer.

Quantification and influencing factors of perioperative hidden blood loss in patients undergoing laparoscopic ovarian cystectomy for benign ovarian tumours.

This retrospective, monocentric study quantified hidden blood loss (HBL) and investigated its influencing factors in benign ovarian tumour patients undergoing laparoscopic ovarian cystectomy. Data from 153 patients who underwent laparoscopic ovarian cystectomy were retrospectively reviewed. HBL was calculated using the formula derived from 'Nadler' and 'Cross'. Pearson correlation was carried out to measure the association between HBL and potential risk factors. The average HBL was 280.22 ± 168.42 mL, accounting for 84.13 ± 19.20% of total blood loss (TBL) (347.48 ± 179.05 mL), which was a change of almost fourteen-fold relative to median visible blood loss [20.00 mL (10.00 mL, 57.5 mL)]. Surgical time, number of excisional tumours and preoperative albumin values were risk factors for HBL. HBL represents a large proportion more than 80% of TBL in patients undergoing laparoscopic ovarian cystectomy. Collectively, HBL is helpful for estimating intraoperative blood loss and better guidance of haemostatic agents, which reduces postoperative complications and expedites postoperative recovery. Additionally, the estimation of HBL also contributes to the summary, reflection and improvement of surgical technique.IMPACT STATEMENTWhat is already known on this subject? There has been a growing number of surgical patients with perioperative anaemia, which appears to be inconsistent with measured levels of visible intraoperative blood loss and postoperative drainage. This substantial but easily underestimated blood loss is known as hidden blood loss. To date, no published articles have evaluated HBL and its related risk factors in benign ovarian tumour patients undergoing laparoscopic ovarian cystectomy.What the results of this study add? HBL accounts for a large amount of TBL in laparoscopy for benign ovarian tumours. Surgical time, number of excisional tumours and preoperative albumin values are risk factors for HBL.What the implications are of these findings for clinical practice and/or further research? The management of HBL is important for the administration of perioperative blooding loss. In this context, HBL can be applied to estimate intraoperative blood loss and be better guidance of haemostatic agents to reduce postoperative complications and hasten postoperative rehabilitation. Additionally, the estimation of HBL also contributes to the summary, reflection and improvement of surgical technique.

Differences in chemotaxis of human mesenchymal stem cells and cervical cancer cells.

In the last decade, there has been a rapid expansion in tumor targeted therapy using mesenchymal stem cells (MSCs) based on their unique tropism towards cancer cells. Despite similarities in morphology, immunophenotype, and differential potent in vitro, MSCs originated from different tissues do not necessarily have equivalent biological behaviors. It is important to screen the most chemotactic MSCs to cancer cells. In this study, different MSCs were isolated from various human tissues including adipose, umbilical cord, amniotic membrane, and chorion. The chemotaxis of human MSCs to cervical cancer cells was measured by CCK-8, ELISA and Transwell invasion assays. Western blotting was performed to explore the underlying mechanisms. MSCs derived from distinct sources can be differently recruited to cervical cancer cells, among which chorion-derived MSC (CD-MSC) possessed the strongest tropic capacity. CXCL12 was found to be highly secreted by cervical cancer cells, in parallel with the expression of CXCR4 in all MSCs. CD-MSC displayed the highest level of CXCR4. These results indicated that CXCL12/CXCR4 pathway contributed to the different chemotaxis to cervical cancer cells of each MSCs. This study proposed that CD-MSC with the highest CXCR4 expression is a promising therapeutic vehicle for targeted therapy in cervical cancer.

Erratum: Nucleic acids and proteins carried by exosomes of different origins as potential biomarkers for gynecologic cancers.

[This corrects the article DOI: 10.1016/j.omto.2021.12.005.].

Nucleic acids and proteins carried by exosomes of different origins as potential biomarkers for gynecologic cancers.

Exosomes are extracellular vesicles with a diameter of 30-150 nm that function in mediating intercellular communication and intercellular material exchange. The liposomal membrane of exosomes protects the cargo carried by exosomes from degradation and assists in transporting cargo to recipient cells to regulate a variety of physiological and pathological processes. The incidence of gynecologic cancers is increasing annually, which is extremely harmful to the lives and health of women because such cancers are challenging to detect at the early stage. Recently, exosomes have emerged as novel biomarkers for diagnosing and predicting the development of gynecologic cancers. In particular, non-coding RNAs (microRNAs [miRNAs], long non-coding RNAs [lncRNAs], and circular RNAs [circRNAs]) carried by exosomes have been extensively investigated in gynecologic cancers. Therefore, the purpose of this review is to focus on the potential roles of exosomes of different origins in ovarian cancer, cervical cancer, and endometrial cancer, which will help to determine the molecular mechanism of carcinogenesis.

Applications of Multi-omics Approaches for Exploring the Molecular Mechanism of Ovarian Carcinogenesis.

Ovarian cancer ranks as the fifth most common cause of cancer-related death in females. The molecular mechanisms of ovarian carcinogenesis need to be explored in order to identify effective clinical therapies for ovarian cancer. Recently, multi-omics approaches have been applied to determine the mechanisms of ovarian oncogenesis at genomics (DNA), transcriptomics (RNA), proteomics (proteins), and metabolomics (metabolites) levels. Multi-omics approaches can identify some diagnostic and prognostic biomarkers and therapeutic targets for ovarian cancer, and these molecular signatures are beneficial for clarifying the development and progression of ovarian cancer. Moreover, the discovery of molecular signatures and targeted therapy strategies could noticeably improve the prognosis of ovarian cancer patients.

An Ultralocalized Cas13a Assay Enables Universal and Nucleic Acid Amplification-Free Single-Molecule RNA Diagnostics.

Existing methods for RNA diagnostics, such as reverse transcription PCR (RT-PCR), mainly rely on nucleic acid amplification (NAA) and RT processes, which are known to introduce substantial issues, including amplification bias, cross-contamination, and sample loss. To address these problems, we introduce a confinement effect-inspired Cas13a assay for single-molecule RNA diagnostics, eliminating the need for NAA and RT. This assay involves confining the RNA-triggered Cas13a catalysis system in cell-like-sized reactors to enhance local concentrations of target and reporter simultaneously, via droplet microfluidics. It achieves >10 000-fold enhancement in sensitivity when compared to the bulk Cas13a assay and enables absolute digital single-molecule RNA quantitation. We experimentally demonstrate its broad applicability for precisely counting microRNAs, 16S rRNAs, and SARS-CoV-2 RNA from synthetic sequences to clinical samples with excellent accuracy. Notably, this direct RNA diagnostic technology enables detecting a wide range of RNA molecules at the single-molecule level. Moreover, its simplicity, universality, and excellent quantification capability might render it to be a dominant rival to RT-qPCR.

The prognostic value of the lysyl oxidase family in ovarian cancer.

BACKGROUND: Our study intended to evaluate the prognostic value of lysyl oxidase (LOX) and its four relevant members, the lysyl oxidase-like genes (LOXL1-4), in ovarian cancer (OC) patients. MATERIAL AND METHODS: The Kaplan-Meier plotter (KM plotter) database was used to investigate the prognostic power of the LOX family for OC patients. Overall survival (OS) and progression-free survival (PFS) were the clinical endpoints. The prognostic roles of the LOX family in OC patients were also analyzed according to various clinicopathological characteristics, including histological subtypes, clinical stages, pathological grades, and chemotherapeutic treatments. RESULTS: Overexpression of LOX, LOXL1, LOXL2, and LOXL3 mRNA indicated poor OS and PFS in OC patients, particularly in serous and grade II + III OC patients. Overexpression of LOXL4 mRNA resulted in worse PFS in OC patients. Overexpression of LOX and LOXL1 mRNA showed worse OS and PFS in stage III + IV OC patients, and overexpression of LOXL3 mRNA indicated worse OS and PFS in stage I + II OC patients. Overexpression of LOX, LOXL3, and LOXL4 mRNA indicated worse OS and PFS among OC patients who received platinum, taxol, and taxol + platinum chemotherapy. Overexpression of LOXL1 and LOXL2 mRNA was related to lower OS and PFS in OC patients who received platinum chemotherapy. CONCLUSION: LOX, LOXL1, LOXL2, and LOXL3 may become potential predictive markers for negative outcomes in OC patients. Moreover, the LOX family can serve as new molecular predictors for the efficiency of platinum-based chemotherapy in OC patients.

Evolving roles of lysyl oxidase family in tumorigenesis and cancer therapy.

The lysyl oxidase (LOX) family is comprised of LOX and four LOX-like proteins (LOXL1, LOXL2, LOXL3, and LOXL4), and mainly functions in the remodeling of extracellular matrix (ECM) and the cross-linking of collagen and elastic fibers. Recently, a growing body of research has demonstrated that LOX family is critically involved in the regulation of cancer cell proliferation, migration, invasion and metastasis. In this review, we discuss the roles of LOX family members in the development and progression of different types of human cancers. Furthermore, we also describe the potential inhibitors of LOX family proteins and highlight that LOX family might be an important therapeutic target for cancer therapy.

TRIM35 mediates protection against influenza infection by activating TRAF3 and degrading viral PB2.

Tripartite motif (TRIM) family proteins are important effectors of innate immunity against viral infections. Here we identified TRIM35 as a regulator of TRAF3 activation. Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon (IFN) in response to viral infection. Trim35-deficient mice were more susceptible to influenza A virus (IAV) infection than were wild-type mice. TRIM35 promoted the RIG-I-mediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1. IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3. TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2, thereby antagonizing its suppression of TRAF3 activation. Our in vitro and in vivo findings thus reveal novel roles of TRIM35, through catalyzing Lys63- or Lys48-linked polyubiquitination, in RIG-I antiviral immunity and mechanism of defense against IAV infection.

Prognostic Values of Transforming Growth Factor-Beta Subtypes in Ovarian Cancer.

PURPOSE: To explore the potential role of the transforming growth factor-beta (TGF-ß) subtypes in the prognosis of ovarian cancer patients. Materials and Methods. The prognostic roles of individual TGF-ß subtypes in women with ovarian cancer were retrieved from the Kaplan-Meier plotter (KM plotter) database. In addition, the Oncomine database and immunohistochemistry were used to observe the mRNA and protein expression of TGF-ß subtypes between human ovarian carcinoma and normal ovarian samples, respectively. RESULTS: TGF-ß1 and TGF-ß4 were totally uncorrelated with survival outcomes in women with ovarian cancer. Increased TGF-ß2 and TGF-ß3 mRNA expression was markedly related to unfavorable prognosis, especially in women with serous, poorly differentiated, and late-stage ovarian carcinoma. High expression levels of TGF-ß2 were related to worse progression-free survival (PFS) while TGF-ß3 was linked to unfavorable overall survival (OS) and PFS in women with TP53-mutated ovarian cancer. TGF-ß2 was associated with poor OS and PFS from treatment with chemotherapy with platins, Taxol, or a platin+Taxol. However, overexpression of TGF-ß3 was associated with poor OS from the use of platins and poor PFS of Taxol or a platin+Taxol in women with ovarian carcinoma. Furthermore, the expression of TGF-ß2 mRNA and protein was higher but only TGF-ß3 mRNA expression was higher in cancerous tissues than in normal ovarian samples. CONCLUSION: Higher expression of TGF-ß2 functioned as a significant predictor of poor prognosis in women with ovarian cancer, especially those with TP53 mutations or who were undergoing chemotherapy with platins, Taxol, or a platin+Taxol.

The diverse roles of SPOP in prostate cancer and kidney cancer.

Multiple studies have confirmed that speckle-type pox virus and zinc finger (POZ) protein (SPOP) functions as a substrate adaptor of cullin 3-based E3 ligase and has a crucial role in various cellular processes via specific targeting of proteins for ubiquitination and subsequent proteasomal degradation. Dysregulation of SPOP-mediated proteolysis might be involved in the development and progression of human prostate and kidney cancers. In prostate cancer, SPOP seems to function as a tumour suppressor by targeting several proteins, including androgen receptor (AR), steroid receptor coactivator 3 (SRC3) and BRD4, for degradation, whereas it might function as an oncoprotein in kidney cancer, for example, by targeting phosphatase and tensin homologue (PTEN) for proteasomal degradation. In addition, nuclear SPOP targets AR for degradation and has a role as a tumour suppressor in prostate cancer; however, in kidney cancer, SPOP largely accumulates in the cytoplasm and fails to promote degradation of AR located in the nucleus, resulting in activation of AR-driven pathways and cancer progression. Owing to the context-dependent function of SPOP in human malignancies, further assessment of the molecular mechanisms involving SPOP in prostate and kidney cancers is needed to improve our understanding of its role in the development of these cancer types. Treatments that target SPOP might become therapeutic strategies in these malignancies in the future.

Analysis of hidden blood loss and its influential factors in myomectomy.

OBJECTIVE: This study was performed to quantify hidden blood loss (HBL) and explore its influential factors in myomectomy. METHODS: Two hundred nine patients who underwent myomectomy by laparotomy or laparoscopy from 1 January 2017 to 31 December 2018 were analyzed. Each patient's estimated blood volume and total blood loss (TBL) were calculated by the Nadler formula and Gross formula, respectively. The HBL was calculated by subtracting the visible blood loss (VBL) from the TBL. A multivariate linear stepwise analysis was applied to identify the influential factors of HBL in myomectomy. RESULTS: The mean perioperative VBL and estimated TBL during myomectomy were 137.81 ±104.43 and 492.24 ± 225.00 mL, respectively. The mean HBL was 354.39 ± 177.69 mL, which accounted for 71.52% ± 15.75% of the TBL and was two to three times higher than the VBL. The duration of surgery, number of removed leiomyomas, and location of removed leiomyomas were independent risk factors for HBL in myomectomy. CONCLUSIONS: HBL accounted for a significant percentage of TBL in myomectomy. A full understanding of the HBL in perioperative blood management may improve patients' postoperative rehabilitation.