Elevated PGT promotes proliferation and inhibits cell apoptosis in preeclampsia by Erk signaling pathway.

Prostaglandins participate in maternal recognition of pregnancy, implantation and maintenance of gestation. Prostaglandin transporter (PGT), as a candidate molecule of prostaglandin carriers, might be involved in the pathogenesis of preeclampsia. In preeclampsia (PE) patients' placental tissue, we identified PGT by RNA sequencing, measured its expression pattern by quantitative real-time PCR and Western blot. PGT was found to be upregulated in preeclamptic placental tissue. The expression pattern of PGT in PE was double confirmed by eight Gene Expression Omnibus (GEO) databases. In abortion tissues at 6-8 weeks, we then observed the cellular location of PGT by Immunofluorescence technique (IF) and found PGT located in trophoblast cell of the placenta of early pregnancy. In vitro studies revealed that forced expression of PGT in HTR8/Sveno cell inhibited its apoptosis, but promoted its proliferation by activating Erk signaling. In vivo study, we used reduced uterine perfusion pressure (RUPP) rat model and L-NAME-induced preeclampsia-like rats to study the possible role of PGT in preeclampsia. And PGT was found to be upregulated in both preeclampsia rat models by Immunohistochemical (IHC) staining. Newly identified PGT plays an important role in trophoblast proliferation via Erk signaling, providing new insights for understanding the pathogenesis of PE.

Age affects the association between socioeconomic status and infertility: a cross-sectional study.

BACKGROUND: Previous studies have shown the interaction between age and socioeconomic status (SES) on the risk of infertility in the UK, but the association is still unclear in the United States. Therefore, the present study investigated the effect of age on the relationship between SES and the risk of infertility in American women. METHODS: The study included adults who participated in the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2018. The poverty income ratio (PIR) was used to represent the SES of the population. With participants stratified according to age category (< 35 years; ≥ 35 years), we further assessed differences in the relationship between PIR and infertility risk among participants of different age groups using multivariate logistic regression and interaction tests. RESULTS: Approximately 3,273 participants were enrolled in the study. There were 399 cases of infertility and 2,874 cases without infertility. In women ≥ 35 years of age, PIR levels were significantly higher in infertile participants than in non-infertile participants, but no such difference was found in those < 35 years of age. The association of PIR with the risk of infertility appeared to differ between age < 35 years and age ≥ 35 years (OR: 0.99, 95%Cl: 0.86-1.13 vs. OR: 1.24, 95%Cl: 1.12-1.39) in a fully adjusted model. Furthermore, an interaction between age and PIR increased the risk of infertility (p-value for interaction < 0.001). CONCLUSION: Our study found that age may influence the association between PIR and infertility. It is imperative to perform further studies to provide more evidence.

Implications of serum uric acid for female infertility: results from the national health and nutrition examination survey, 2013-2020.

BACKGROUND: There is limited concrete evidence connecting serum uric acid levels to female infertility. Therefore, this study aimed to find out if serum uric acid levels are independently related to female infertility. METHODS: From the National Health and Nutrition Examination Survey (NHANES) 2013-2020, a total sample of 5872 chosen female participants between the ages of 18 and 49 were identified for this cross-sectional study. The serum uric acid levels (mg/dL) of each participant were tested, and the reproductive health questionnaire was used to evaluate each subject's reproductive status. Both in the analyses of the full sample and each subgroup, logistic regression models were used to evaluate the relationship between the two variables. A stratified multivariate logistic regression model was used to perform the subgroup analysis based on serum uric acid levels. RESULTS: Infertility was found in 649 (11.1%) of the 5,872 female adults in this study, with greater mean serum uric acid levels (4.7 mg/dL vs. 4.5 mg/dL). Serum uric acid levels were associated with infertility in both the initial and adjusted models. According to multivariate logistic regression, the odds of female infertility were found to be significantly higher with rising serum uric acid levels (Q4 [≥ 5.2 mg/dL] vs. Q1 [≤ 3.6 mg/dL]), adjusted odds ratio [aOR] = 1.59, p = 0.002]. The data suggests that there is a dose-response relationship between the two. CONCLUSIONS: The results from this nationally representative sample from the United States confirmed the idea that there is a link between increased serum uric acid levels and female infertility. Future research is necessary to evaluate the relationship between serum uric acid levels and female infertility and explicate the underlying mechanisms of this relationship.

Perinatal Transmission of 2019 Coronavirus Disease-Associated Severe Acute Respiratory Syndrome Coronavirus 2: Should We Worry?

We present 2 cases of coronavirus disease 2019 (COVID-19)-associated severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the third trimester of pregnancy. Both mothers and newborns had excellent outcomes. We failed to identify SARS-CoV-2 in all of the products of conception and the newborns. This report provided evidence of low risk of intrauterine infection by vertical transmission of SARS-CoV-2.

Predictive value of serum Golgi protein 73 for prominent hepatic necroinflammation in chronic HBV infection.

As a noninvasive marker, serum alanine aminotransferase (ALT) has limitations, because a large proportion of patients chronically infected with hepatitis B virus (HBV) suffer from severe hepatic necroinflammation, but have normal or mildly elevated ALT. In the present study, we aimed to investigate the potential value of serum Golgi protein 73 (GP73) in predicting significant hepatic necroinflamation among chronic HBV infected patients. A cohort of 497 chronic HBV infected patients was retrospectively recruited. Liver biopsy was performed in all patients and serum GP73 levels were measured by enzyme-linked immunosorbent assay. Serum GP73 increased in parallel with the increase in hepatic necroinflammatory activity grade (r = 0.682) and the stage of liver fibrosis (r = 0.539). The positive correlation of serum GP73 with the degree of hepatic necroinflammatory activity was statistically significant, while serum GP73 with the stage of liver fibrosis was weaker than that with hepatic necroinflammation. Furthermore, serum GP73 levels were significantly greater in patients with normal or mildly elevated ALT and significant hepatic necroinflammation (≥G2) than in patients with minimal to mild hepatic necroinflammation. The sensitivity and specificity of GP73 for the diagnosis of G2 hepatic necroinflammation was 42.35% and 95.0%, respectively, at a cut-off value of 88.38 ng/mL. When the cut-off value was set at 124.76 ng/mL, the sensitivity and specificity of GP73 for the diagnosis of G3 hepatic necroinflammation was 55.56% and 97.29%, respectively. These findings indicate that GP73 holds promise as an important candidate for diagnosing significant hepatic necroinflammation.

Human mesenchymal stem cells derived exosomes improve ovarian function in chemotherapy-induced premature ovarian insufficiency mice by inhibiting ferroptosis through Nrf2/GPX4 pathway.

BACKGROUND: Chemotherapy exposure has become a main cause of premature ovarian insufficiency (POI). This study aimed to evaluate the role and molecular mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hUMSC-Exos) in ovarian function protection after chemotherapy. METHODS: hUMSC-Exos were applied to cyclophosphamide-induced premature ovarian insufficiency mice and human ovarian granulosa tumor cells (KGN) to determine their effects on follicular development and granulosa cell apoptosis. Evaluation was done for iron ion and reactive oxygen species (ROS) production, lipid peroxidation levels, and changes in iron death-related molecules (nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Glutathione Peroxidase enzyme 4 (GPX4), and Solute carrier family 7 member 11 cystine glutamate transporter (SLC7A11; xCT)). Furthermore, rescue experiments using an Nrf2 inhibitor were performed to assess the therapeutic effects of hUMSC-Exos on granulosa cells. RESULTS: hUMSC-Exos promoted ovarian hormone levels and primary follicle development in POI mice and reduced granulosa cell apoptosis. After hUMSC-Exos treatment, the ROS production, free iron ions and lipid peroxidation levels of granulosa cells decreased, and the iron death marker proteins Nrf2, xCT and GPX4 also decreased. Furthermore, the Nrf2 inhibitor ML385 significantly attenuated the effects of hUMSC-Exos on granulosa cells. CONCLUSION: hUMSC-Exos inhibit ferroptosis and protect against CTX-induced ovarian damage and granulosa cell apoptosis through the Nrf2/GPX4 signaling pathway, revealing a novel mechanism of hUMSC-Exos in POI therapy.

Human Umbilical Cord Mesenchymal Stem Cells Promote Anti-Inflammation and Angiogenesis by Targeting Macrophages in a Rat Uterine Scar Model.

BACKGROUND: Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have demonstrated efficacy in repairing uterine scars, although the underlying mechanisms remain unclear. METHODS: Uterine injury was surgically induced in a rat model, followed by immediate transplantation of 5 × 10 ^ 5 hUC-MSCs to each side of the uterus. Uterine morphology was evaluated at days 14 and 30 using HE and Masson staining. Immunohistochemistry assessed macrophage polarization, angiogenesis and endometrial receptivity in the endometrium. Additionally, the regulatory effects of hUC-MSCs on macrophage polarization were explored through coculture. qRT-PCR quantified the expression of anti-inflammatory (IL10 and Arg1) and pro-inflammatory (iNOS and TNF-α) factors. Western blotting evaluated CD163 expression. RESULTS: Transplantation of hUC-MSCs promoted the healing of uterine injuries and tissue regeneration while inhibiting tissue fibrosis. Immunohistochemistry at days 14 and 30 post-transplantation demonstrated the polarization of macrophages toward the M2 phenotype in the uterine injury area in the presence of hUC-MSCs. Furthermore, hUC-MSC transplantation improved angiogenesis and endometrial receptivity in the uterine injury rat model, associated with increased IL10 expression. hUC-MSC-induced angiogenesis can be resisted by depleted macrophages. In vitro coculture experiments further demonstrated that hUC-MSCs promoted IL10 expression in macrophages while suppressing TNF-α and iNOS expression. Western blotting showed enhanced CD163 expression in macrophages following hUC-MSC treatment. CONCLUSIONS: hUC-MSCs contribute to the healing of uterine injuries by targeting macrophages to promote angiogenesis and the expression of anti-inflammatory factors.

Temporal and Spatial Variation of Toxic Metal Concentrations in Cultivated Soil in Jiaxing, Zhejiang Province, China: Characteristics and Mechanisms.

The toxic metal (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) pollution in 250 agricultural soil samples representing the urban area of Jiaxing was studied to investigate the temporal and spatial variations. Compared to the early 1990s, the pollution level has increased. Industry and urbanization were the main factors causing toxic metal pollution on temporal variation, especially the use of feed containing toxic metals. The soil types and crop cultivation methods are the main factors causing toxic metal pollution on spatial variation. Although the single-factor pollution indices of all the toxic metals were within the safe limits, as per the National Soil Environmental Quality Standard (risk screening value), if the background values of soil elements in Jiaxing City are used as the standard, the pollution index of all the elements surveyed exceeds 1.0, reaching a level of mild pollution. The soil samples investigated were heavily contaminated with toxic metal compounds, and their levels increased over time. This situation poses potential ecological and health risks.

Prognostic marker C3AR1 is associated with ovarian cancer cell proliferation and immunosuppression in the tumor microenvironment.

BACKGROUND: C3AR1 was reported in driving tumor immunity in multiple cancers. However, its roles in ovarian cancer remain unclear. This study aims to determine role of C3AR1 in prognosis and regulating tumor infiltrating immune cells of ovarian cancer (OC). MATERIALS AND METHODS: The expression, prognosis and clinical data related to C3AR1 were collected from public databases such as The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA) and Clinical Proteomics Tumor Analysis Alliance (CPTAC), and further analyze their relationship with immune infiltration. Immunohistochemistry verified the expression of C3AR1 in ovarian cancer and control tissues. C3AR1 was forced expressed in SKOV3 cells by plasmid transfection, and verified by qRT-PCR and Western blot. Cell proliferation were evaluated by EdU assay. RESULTS: Bioinformatics analysis (TCGA, CPTAC) and immunohistochemical staining of clinical samples confirmed higher C3AR1 expression in ovarian cancer than that in normal tissues. High C3AR1 expression predicted adverse clinical outcomes. KEGG and GO analysis showed that the biological processes of C3AR1 in ovarian cancer are mainly involved in T cell activation, cytokine and chemokine activation. C3AR1 expression was positively correlated with chemokines and their receptors in the tumor microenvironment, such as CCR1(R = 0.83), IL10RA (R = 0.92), and INFG (R = 0.74). In addition, increased C3AR1 expression predicted more infiltration of tumor-associated macrophages, dendritic cell and CD8 + T cell. Some important m6A regulators, such as IGF2BP2, ALKBH5, IGFBP3 and METL14, are significantly positively or negatively correlated with C3AR1. Finally, overexpression of C3AR1 significantly increased proliferation of SKOV3 cells. CONCLUSION: In summary, our study suggested that C3AR1 is associated with the prognosis and immune cell infiltration of ovarian cancer, and is a promising immunotherapeutic target.

Association of Serum Triglyceride and Stress Urinary Incontinence in Women From the National Health and Nutrition Examination Survey: A Cross-Sectional Study.

OBJECTIVE: To investigate the relationship between serum triglyceride levels and stress urinary incontinence (SUI) in women from the National Health and Nutrition Examination Survey. METHODS: Adults who participated in the National Health and Nutrition Examination Survey from 2005 to 2018 were included in the study. Univariate and multivariate logistic regressions were used to assess the relationship between serum triglyceride levels and the incidence and severity of SUI. RESULTS: Approximately 7973 participants (mean, 49.9 years of age) were enrolled in the study. Of those, 3367 had SUI, and 4606 did not have SUI. An adjusted multivariate logistic regression analysis demonstrated a positive correlation between serum triglyceride levels and the incidence of SUI (ORs, 1.05; 95% CI, 1-1.11, P = .045). Besides, subgroup analyses indicated that the results were robust among women with different characteristics. Additionally, serum triglyceride levels were positively associated with the severity of SUI. CONCLUSION: Serum triglyceride levels were closely related to the incidence and severity of SUI. Based on our findings, we suggest that serum triglycerides can be included as a risk indicator for screening high-risk groups of SUI.

Weakly-Supervised 3D Spatial Reasoning for Text-Based Visual Question Answering.

Text-based Visual Question Answering (TextVQA) aims to produce correct answers for given questions about the images with multiple scene texts. In most cases, the texts naturally attach to the surface of the objects. Therefore, spatial reasoning between texts and objects is crucial in TextVQA. However, existing approaches are constrained within 2D spatial information learned from the input images and rely on transformer-based architectures to reason implicitly during the fusion process. Under this setting, these 2D spatial reasoning approaches cannot distinguish the fine-grained spatial relations between visual objects and scene texts on the same image plane, thereby impairing the interpretability and performance of TextVQA models. In this paper, we introduce 3D geometric information into the spatial reasoning process to capture the contextual knowledge of key objects step-by-step. Specifically, (i) we propose a relation prediction module for accurately locating the region of interest of critical objects; (ii) we design a depth-aware attention calibration module for calibrating the OCR tokens' attention according to critical objects. Extensive experiments show that our method achieves state-of-the-art performance on TextVQA and ST-VQA datasets. More encouragingly, our model surpasses others by clear margins of 5.7% and 12.1% on questions that involve spatial reasoning in TextVQA and ST-VQA valid split. Besides, we also verify the generalizability of our model on the text-based image captioning task.

Macrophage polarisation in caesarean scar diverticulum.

AIMS: To determine immunohistochemical features and correlations between M1/M2 polarisation status with disease severity of post-caesarean scar diverticulum (CSD). METHODS: Histological and immunohistological stainings were performed and inflammatory (CD16, CD163 and tumour necrosis factor-α (TNF-α)), fibrosis (α-smooth muscle actin (α-SMA)) and angiogenic (CD31) markers were examined in uterine tissues collected from patients with uterine scar diverticula (CSD) (n=37) and caesarean section (CS) (n=3). RESULTS: CSD tissues have higher expression of α-SMA, TNF-α, CD16 and CD31 and lower expression of CD163 than CS tissue (p<0.05). Compared with adjacent tissues, thick-walled blood vessels, glands and fibrotic sites have higher expression of α-SMA, TNF-α and CD16. Statistical correlation was observed between the expression of CD16 and TNF-α (R=0.693, p<0.001), α-SMA (R=0.404, p<0.05) and CD31 (R=0.253, p<0.05) in CSD tissues, especially with the ratio of CD16/CD163 (R=0.590, p<0.01). A more significant difference was observed between the expression of CD16/CD163 and α-SMA (R=0.556, p<0.001), TNF-α (R=0.633, p<0.0001) and CD31 (R=0.336, p<0.05). CONCLUSIONS: In this study, TNF-α, α-SMA, CD16 and CD31 proteins were overexpressed in all CSD cases, and CD16/CD163 was positively correlated with tissue inflammation, fibrosis and neovascularisation. Abnormal mononuclear macrophage infiltration may be involved in the origin and progression of CSD.

Artificial intelligence-aided method to detect uterine fibroids in ultrasound images: a retrospective study.

We explored a new artificial intelligence-assisted method to assist junior ultrasonographers in improving the diagnostic performance of uterine fibroids and further compared it with senior ultrasonographers to confirm the effectiveness and feasibility of the artificial intelligence method. In this retrospective study, we collected a total of 3870 ultrasound images from 667 patients with a mean age of 42.45 years ± 6.23 [SD] for those who received a pathologically confirmed diagnosis of uterine fibroids and 570 women with a mean age of 39.24 years ± 5.32 [SD] without uterine lesions from Shunde Hospital of Southern Medical University between 2015 and 2020. The DCNN model was trained and developed on the training dataset (2706 images) and internal validation dataset (676 images). To evaluate the performance of the model on the external validation dataset (488 images), we assessed the diagnostic performance of the DCNN with ultrasonographers possessing different levels of seniority. The DCNN model aided the junior ultrasonographers (Averaged) in diagnosing uterine fibroids with higher accuracy (94.72% vs. 86.63%, P < 0.001), sensitivity (92.82% vs. 83.21%, P = 0.001), specificity (97.05% vs. 90.80%, P = 0.009), positive predictive value (97.45% vs. 91.68%, P = 0.007), and negative predictive value (91.73% vs. 81.61%, P = 0.001) than they achieved alone. Their ability was comparable to that of senior ultrasonographers (Averaged) in terms of accuracy (94.72% vs. 95.24%, P = 0.66), sensitivity (92.82% vs. 93.66%, P = 0.73), specificity (97.05% vs. 97.16%, P = 0.79), positive predictive value (97.45% vs. 97.57%, P = 0.77), and negative predictive value (91.73% vs. 92.63%, P = 0.75). The DCNN-assisted strategy can considerably improve the uterine fibroid diagnosis performance of junior ultrasonographers to make them more comparable to senior ultrasonographers.

Prevalence, clinical characteristics, and outcomes of spontaneous portosystemic shunt in patients with hepatitis B-related cirrhosis: A multicenter study from China.

BACKGROUND: The impact of spontaneous portosystemic shunt (SPSS) on decompensated events and mortality for patients with hepatitis B-related cirrhosis remains poorly investigated. AIMS: To evaluate the prevalence, clinical characteristics, and outcomes of SPSS among patients with hepatitis B-related cirrhosis. METHODS: Patients who were diagnosed with hepatitis B-related cirrhosis were retrospectively recruited. All eligible patients were classified into SPSS and non-SPSS groups and their clinical characteristics and outcomes were compared and analyzed. RESULTS: Of the 1282 patients included in this study, SPSS was identified in 488 patients (38.1%). SPSS group had more severe liver function impairment, higher prevalence and severity of esophageal and gastric varices (EGV), and a higher prevalence of EGV bleeding (EGVB), portal vein thrombosis (PVT), hepatic encephalopathy (HE), ascites, and hepatocellular carcinoma (HCC, all P<0.05). During the follow-up period, SPSS group experienced a significantly higher incidence of EGVB, PVT, and HE (all P<0.05); however, there was no significant difference in the incidence of ascites, HCC, and mortality between the two groups (all P>0.05). CONCLUSION: With hepatitis B-related cirrhosis, SPSS was common and characterized by severe liver damage and a high prevalence of decompensated events. Moreover, patients with SPSS had higher risks of EGVB, PVT, and HE.

UCP1 modulates immune infiltration level and survival outcome in ovarian cancer patients.

BACKGROUND: The uncoupling proteins (UCPs) are critical genes associated with tumorigenesis and chemoresistance. However, little is known about the molecular mechanism of the UCPs in ovarian cancer (OV). MATERIAL AND METHODS: UCPs expression analysis was conducted using Gene Expression Profiling Interactive Analysis (GEPIA), and its potential in clinical prognosis was analyzed using Kaplan- Meier analyses. The influence of UCPs on immune infiltration was analyzed by TIMER. In addition, the correlation between UCPs expression and molecular mechanisms was investigated by TIMER and Cancer Single-cell State Atlas (CancerSEA). RESULTS: UCP1, UCP2, UCP3 and UCP5 expression levels correlated with a favorable prognosis and tumor progression. Moreover, UCP1 expression correlated to several immune cell markers and regulated tumorigenesis, such as tumor invasion, EMT, metastasis and DNA repair. In addition, UCP1 potentially involved in genes expression of SNAI2, MMP2, BRCA1 and PARP1. CONCLUSIONS: These results implied a critical role of UCP1 in the prognosis and immune infiltration of ovarian cancer. In addition, UCP1 expression participated in regulating multiple oncogenes and tumorigenesis.

An injectable thermosensitive Pluronic F127/hyaluronic acid hydrogel loaded with human umbilical cord mesenchymal stem cells and asiaticoside microspheres for uterine scar repair.

Uterine scar was one of the long-term complications cesarean section. In this study, an thermo-responsive injectable hydrogel loaded with human umbilical cord mesenchymal stem cells (UCMSCs) and asiaticoside microspheres (AMs) was used for uterine scar repair, which was prepared by optimizing the mixed ratio of aldehyde-functionalized Pluronic F127 (F127-CHO) and adipic dihydrazide-modified hyaluronic acid (AHA). The asiaticoside was loaded in Poly (DL-lactide-co-gycolide) (PLGA) by emulsion- diffusion-evaporation method. The hydrogel had appropriate pore size, good mechanical property, and slow release ability of asiaticoside. In vitro cell experiments demonstrated that F127-CHO/AHA/AMs could effectively promote stem cell adhesion and proliferation, promote angiogenesis, and provide a suitable microenvironment for cell survival. The F127-CHO/AHA/AMs/UCMSCs hydrogel was further used to repair uterine scar in female SD rats. The results showed that the prepared hydrogel could promote the proliferation of rat endometrial cells, promote the regeneration of glands, reduce the degree of endometrial fibrosis and restore the morphology of uterine cavity. The hydrogel could upregulate expression of Ki67 and IGF-1, downregulate TGF-ß1 expression and promote M1-M2 transition of macrophages. This study confirmed that the prepared hydrogel could be used as an effective transplantation strategy, which could be expected to achieve clinical transformation of uterine scar repair.

Short-term prognostic factors for hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is the abrupt exacerbation of declined hepatic function in patients with chronic liver disease. AIM: To explore the independent predictors of short-term prognosis in patients with hepatitis B virus (HBV)-related ACLF and to establish a predictive short-term prognosis model for HBV-related ACLF. METHODS: From January 2016 to December 2019, 207 patients with HBV-related ACLF attending the 910th Hospital of Chinese People's Liberation Army were continuously included in this retrospective study. Patients were stratified based on their survival status 3 mo after diagnosis. Information was collected regarding gender and age; coagulation function in terms of prothrombin time and international normalized ratio (INR); hematological profile in terms of neutrophil-to-lymphocyte ratio (NLR) and platelet count (PLT); blood biochemistry in terms of alanine aminotransferase, aspartate aminotransferase, total bilirubin (Tbil), albumin, cholinesterase, blood urea nitrogen (BUN), creatinine, blood glucose, and sodium (Na); tumor markers including alpha-fetoprotein (AFP) and Golgi protein 73 (GP73); virological indicators including HBV-DNA, HBsAg, HBeAg, Anti-HBe, and Anti-HBc; and complications including hepatic encephalopathy, hepatorenal syndrome, spontaneous peritonitis, gastrointestinal bleeding, and pulmonary infection. RESULTS: There were 157 and 50 patients in the survival and death categories, respectively. Univariate analysis revealed significant differences in age, PLT, Tbil, BUN, NLR, HBsAg, AFP, GP73, INR, stage of liver failure, classification of liver failure, and incidence of complications (pulmonary infection, hepatic encephalopathy, spontaneous bacterial peritonitis, and upper gastrointestinal bleeding) between the two groups (P < 0.05). GP73 [hazard ratio (HR): 1.009, 95% confidence interval (CI): 1.005-1.013, P = 0.000], middle stage of liver failure (HR: 5.056, 95%CI: 1.792-14.269, P = 0.002), late stage of liver failure (HR: 22.335, 95%CI: 8.544-58.388, P = 0.000), pulmonary infection (HR: 2.056, 95%CI: 1.145-3.690, P = 0.016), hepatorenal syndrome (HR: 6.847, 95%CI: 1.930-24.291, P = 0.003), and HBsAg (HR: 0.690, 95%CI: 0.524-0.908, P = 0.008) were independent risk factors for short-term prognosis in patients with HBV-related ACLF. Following binary logistics regression analysis, we arrived at the following formula for predicting short-term prognosis: Logit(P) = Ln(P/1-P) = 0.013 × (GP73 ng/mL) + 1.907 × (middle stage of liver failure) + 4.146 × (late stage of liver failure) + 0.734 × (pulmonary infection) + 22.320 × (hepatorenal syndrome) - 0.529 × (HBsAg) - 5.224. The predictive efficacy of the GP73-ACLF score was significantly better than that of the Model for End-Stage Liver Disease (MELD) and MELD-Na score models (P < 0.05). CONCLUSION: The stage of liver failure, presence of GP73, pulmonary infection, hepatorenal syndrome, and HBsAg are independent predictors of short-term prognosis in patients with HBV-related ACLF, and the GP73-ACLF model has good predictive value among these patients.

Effects of microwave ablation on serum Golgi protein 73 in patients with primary liver cancer.

BACKGROUND: Microwave ablation (MWA) is an effective treatment option for patients with primary liver cancer. However, it has been reported that the MWA procedure induces a hepatic inflammatory response and injury, which may negatively affect the efficacy of MWA. As such, the discovery of reliable markers to monitor the patient's response to MWA is needed. Golgi protein 73 (GP73) has been shown to be associated with chronic liver disease. To date, the potential value of serum GP73 in the dynamic monitoring during MWA of liver cancer remains unclear. AIM: To examine the effects of MWA on the serum levels of GP73 in patients with primary liver cancer. METHODS: A total of 150 primary liver cancer patients with a single small lesion (≤ 3 cm in diameter) were retrospectively enrolled spanning the period between January 2016 and October 2018. All of the patients received MWA for the treatment of primary liver cancer. Serum GP73, alpha-fetoprotein (AFP), and widely used liver biochemical indicators [serum albumin, total bilirubin (TBIL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)] were compared before MWA and at different time points, including 1, 2, and 4 wk following the ablation procedure. RESULTS: Complete tumor ablation was achieved in 95.33% of the patients at 1 mo after MWA. The 1-, 2-, and 3-year disease-free survival rates were 74.67%, 59.33%, and 54.00%, respectively. The serum AFP levels were significantly decreased at 1, 2, and 4 wk after MWA; they returned to the normal range at 12 wk after MWA; and they remained stable thereafter during follow-up in those cases without recurrence. In contrast, the serum GP73 levels were significantly increased at 1 and 2 wk after MWA. The serum GP73 levels reached the peak at 2 wk after MWA, started to decline after hepatoprotective treatment with glycyrrhizin and reduced glutathione, and returned to the pretreatment levels at 12 and 24 wk after MWA. Notably, the changes of serum GP73 in response to MWA were similar to those of TBIL, ALT, and AST. CONCLUSION: Serum GP73 is markedly increased in response to MWA of liver cancer. Thus, serum GP73 holds potential as a marker to monitor MWA-induced inflammatory liver injury in need of amelioration.

Knockdown of CYP1B1 suppresses the behavior of the extravillous trophoblast cell line HTR-8/SVneo under hyperglycemic condition.

Introduction: Trophoblast plays a vital role in the embryonic implantation and function of the placenta. Exposure to a hyperglycemic environment results in the abnormal function of trophoblasts during fetoplacental development, which leads to maternal complications and poor fetal outcomes. However, the precise mechanisms of placental pathology during hyperglycemia remain elusive. We investigated the role of CYP1B1 in the functional behavior of the extravillous trophoblast (EVT) cell line HTR-8/SVneo under hyperglycemic condition.Methods: We determined the expression of CYP1B1 via real-time polymerase chain reaction and Western blot. Specific CYP1B1 inhibitors and small interfering RNA were used to knockdown CYP1B1, whereas an agonist and an adenovirus were used to overexpress CYP1B1. The proliferation, migration, and invasion of the EVT cell line (i.e. HTR-8/SVneo) were assessed via colony formation, 5-ethynyl-2-deoxyuridine, wound healing, and transwell assay.Results: CYP1B1 is highly expressed in placentas from women with gestational diabetes mellitus. The blockage of CYP1B1 inhibits EVT activities induced by hyperglycemia in vitro, including proliferation, migration, and invasion, whereas the exogenous expression of CYP1B1 exhibits the opposite effects.Discussion: Our study may offer a new method for regulating EVT motility under hyperglycemic condition via CYP1B1.

Upregulated ARRDC3 limits trophoblast cell invasion and tube formation and is associated with preeclampsia.

OBJECTIVE: Bioinformatics analysis indicated that the arrestin ARRDC3 was upregulated in placental tissue from patients with preeclampsia (PE). The study aimed to confirm the finding by examining placenta samples from women with and without early-onset PE and to investigate ARRDC3 roles in trophoblast function. METHODS: ARRDC3 expression level and localization in placental tissue were determined by Western blot, real-time quantitative PCR and immunohistochemistry. An in vitro hypoxia and an in vitro ischemia (hypoxia/reoxygenation) cell models were used to determine the hypoxic and ischemic effects on ARRDC3 expression in extravillous trophoblast-derived HTR/8SVneo cells and trophoblast cell activity. The role of ARRDC3 in HTR8/SVneo cell proliferation, invasion and tube formation in vitro was investigated by testing the effects of ARRDC3 gene overexpression or siRNA-based gene silencing. RESULTS: ARRDC3 expression was significantly elevated in placental tissue from women with early-onset PE compared to preterm birth pregnancies. ARRDC3 protein was localized in human placental trophoblasts. Hypoxia and ischemia both enhanced ARRDC3 protein expression in HTR8/SVneo cells. Hypoxia altered trophoblast cell activities. Overexpression of ARRDC3 in HTR8/SVneo cells suppressed cell invasion and tube formation. ARRDC3 gene silencing, by contrast, promoted invasion and tube formation under hypoxic conditions. CONCLUSION: ARRDC3 was highly expressed in placental tissues of PE patients and directly affected biological activities of trophoblasts under hypoxic conditions. In regulation of ARRDC3- protein expression, ischemia (hypoxia/reoxygenation) are also important. These findings suggest that ARRDC3 may play a clinically significant role in the pathogenesis of PE.