Maternal outcomes of conservative management and cesarean hysterectomy for placenta accreta spectrum disorders: a systematic review and meta-analysis.

BACKGROUND: Cesarean hysterectomy as a traditional therapeutic maneuver for placenta accreta spectrum (PAS) has been associated with serious morbidity, conservative management has been used in many institutions to treat women with PAS. This systematic review aims to compare maternal outcomes according to conservative management or cesarean hysterectomy in women with placenta accreta spectrum disorders. METHODS: A systematic literature search was performed in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, and four Chinese databases (Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Chinese Wanfang database and VIP database) to May 2024. Included studies were to be retrospective or prospective in design and compare and report relevant maternal outcomes according to conservative management (the placenta left partially or totally in situ) or cesarean hysterectomy in women with PAS. A risk ratio (RR) with 95% confidence interval (95% CI) was calculated for categorical outcomes and weighted mean difference (WMD) with 95% CI for continuous outcomes. The Newcastle-Ottawa Quality Assessment Scale was used to assess the observational studies. All analyses were performed using STATA version 18.0. RESULTS: Eight studies were included in the meta-analysis. Compared with cesarean hysterectomy, PAS women undergoing conservative management showed lower estimated blood loss [WMD - 1623.83; 95% CI: -2337.87, -909.79], required fewer units of packed red blood cells [WMD - 2.37; 95% CI: -3.70, -1.04] and units of fresh frozen plasma transfused [WMD - 0.40; 95% CI: -0.62, -0.19], needed a shorter mean operating time [WMD - 73.69; 95% CI: -90.52, -56.86], and presented decreased risks of bladder injury [RR 0.24; 95% CI: 0.11, 0.50], ICU admission [RR 0.24; 95% CI: 0.11, 0.52] and coagulopathy [RR 0.20; 95% CI: 0.06, 0.74], but increased risk for endometritis [RR 10.91; 95% CI: 1.36, 87.59] and readmission [RR 8.99; 95% CI: 4.00, 12.21]. The incidence of primary or delayed hysterectomy rate was 25% (95% CI: 19-32, I2 = 40.88%) and the use of uterine arterial embolization rate was 78% (95% CI: 65-87, I2 = 48.79%) in conservative management. CONCLUSION: Conservative management could be an effective alternative to cesarean hysterectomy when women with PAS desire to preserve the uterus and are informed about the limitations of conservative management. PROSPERO ID: CRD42023484578.

The predictive value of conventional magnetic resonance imaging combined with intravoxel incoherent motion parameters for evaluating maternal and neonatal clinical outcomes in patients with placenta accreta spectrum disorders.

INTRODUCTION: We aimed to identify factors predictive of adverse maternal and neonatal outcomes in patients with placenta accreta spectrum (PAS) disorders using magnetic resonance imaging (MRI) and intravoxel incoherent motion (IVIM) parameters. METHOD: Fifty-six normal singleton pregnancies at 33-39 weeks of gestation underwent MRI examination at 1.5 T. The IVIM parameters were obtained from the placenta. The correlation between the f value and postpartum hemorrhage (PPH) and between the f value and transfused units of red blood cells (RBCs) was estimated by linear regression. The correlation between various influencing factors (clinical risk factors, MRI features, and IVIM parameters) and poor outcomes was investigated using univariate and multivariate analyses. RESULT: The interobserver agreement ranged from fair to excellent (k = 0.30-0.88). Multivariate analyses showed that previous cesarean sections, low signal intensity bands on T2WI and the D value were independent risk factors for adverse outcomes. The combination of three risk factors demonstrated the highest AUC of 0.903, with a sensitivity and specificity of 73.10 % and 96.90 %, respectively. Last, f was positively correlated with PPH and units of RBCs transfused. DISCUSSION: Preoperative MRI features and IVIM parameters may be used to predict poor outcomes in patients with invasive placental disorders like PAS.

N6-methyladenosine (m6A) Modification in Preeclampsia.

Recently, epitranscriptional modification of N6-methyladenosine (m6A) has received growing attention in the research on the pathogenesis of preeclampsia. Advances in m6A sequencing have revealed the molecular mechanism and importance of m6A modification. In addition, epitranscriptional modification of m6A is closely related to the metabolic processes of placental tissues and cells in preeclampsia. This article reviews the composition, mode of action, and bioinformatics analysis of m6A modification-related proteins, and their biological function in the progression of preeclampsia. The relationship between m6A modification and preeclampsia risk factors, such as diabetes, cardiovascular disease, obesity, and psychological stress, is summarized to provide new ideas for studying PE-targeting molecules.

Whether induction of labor ahead in low-risk women improves pregnancy outcomes?: A retrospective cohort, observational study.

The appropriate timing of delivery for pregnancies has always been a concern for medical staff, and the timing of elective labor induction at 41 weeks in low-risk pregnant women has always been controversial. We compared maternal and fetal outcomes between gestational age at 40 0/7 to 40 6/7 and 41 0/7 to 41 6/7 weeks. This retrospective cohort study was conducted at the obstetrics department of Jiangsu Province Hospital from January 1st to December 31st in 2020. Maternal medical records and neonatal delivery data were collected. One-way analysis of variance, Mann-Whitney U test, χ2 test, Fisher exact test and logistig regression analysis were performed. The study included 1569 pregnancies, with 1107 (70.6%) delivered at 40 0/7 to 40 6/7 weeks and 462 (29.4%) delivered at 41 0/7 to 41 6/7 weeks. Intrapartum cesarean section (8% vs 16%, P < .001), meconium-stained amniotic fluid (13% vs 19%, P = .004), episiotomy (41% vs 49%, P = .011), and macrosomia (13% vs 18%, P = .026) were significantly lower at 40 0/7 to 40 6/7 weeks. The premature rupture of membranes rate (22% vs 12%, P < .001), vaginal delivery rate of artificial rupture of membrane induction (83% vs 71%, P = .006) and balloon catheter combined with oxytocin induction (88% vs 79%, P = .049) were significantly higher at 40 0/7 to 40 6/7 weeks. Low-risk women who delivered at 40 0/7 to 40 6/7 weeks showed better outcomes in terms of the mother's and baby's health, such as decreased rates of intrapartum cesarean section, meconium-stained amniotic fluid, episiotomy, and macrosomia, compared with those who delivered at 41 0/7 to 41 6/7 weeks.

Once We Find Grade III Meconium Stained Amniotic Fluid, Must We Act as Early as Possible?

Background: Grade III meconium stained amniotic fluid (MSAF) is a common obstetric disease, and has the greatest impact on poor maternal and neonatal outcomes. Question or Hypothesis or Aim: There is no consensus on treatment, especially on the timing of delivery. Methods: We collected the medical records of 345 women who gave birth with grade III MSAF and analyzed the difference in baseline characteristics and maternal and neonatal outcomes relative to different labor stage, observation times in the first stage of labor, and the presence or absence of abnormal fetal heart rate (FHR) or thick amniotic fluid. Findings: Higher rate of cesarean section was observed when grade III MSAF was found in active labor. Intervention occurred at an observation time of 90-120 min, but there were no significant differences in maternal or neonatal outcomes shown when the observation time was greater than 3 or 4 hours. However, a higher rate of admission to the neonatal intensive care unit was demonstrated in cases with grade III MSAF with abnormal FHR either in the first or second stage of labor or in cases with thick MSAF in the second stage of labor. Discussion: Higher rate of composite adverse neonatal outcomes was found when secondary MSAF (a transition from clear AF to MSAF) was diagnosed >3 h before delivery. Conclusion: In the first stage of labor, an observation time of greater than 4 hours might be possible after grade III MSAF is found if the labor has progressed and is without abnormal FHR.

Identification of underlying mechanisms and hub gene-miRNA networks of the genomic subgroups in preeclampsia development.

Preeclampsia is a hypertensive disorder of pregnancy that can lead to multiorgan complications in the mother and fetus. Our study aims to uncover the underlying mechanisms and hub genes between genomic subgroups of preeclampsia. A total of 180 preeclampsia cases from 4 gene profiles were classified into 3 subgroups. Weighted gene coexpression analysis was performed to uncover the genomic characteristics associated with different clinical features. Functional annotation was executed within the significant modules and hub genes were predicted using Cytoscape software. Subsequently, miRNet analysis was performed to identify potential miRNA-mRNA networks. Three key subgroup-specific modules were identified. Patients in subgroup II were found to develop more severe preeclampsia symptoms. Subgroup II, characterized by classical markers, was considered representative of typical preeclampsia patients. Subgroup I was considered as an early stage of preeclampsia with normal-like gene expression patterns. Moreover, subgroup III was a proinflammatory subgroup, which presented immune-related genomic characteristics. Subsequently, miR-34a-5p and miR-106a-5p were found to be correlated with all 3 significant gene modules. This study revealed the transcriptome classification of preeclampsia cases with unique gene expression patterns. Potential hub genes and miRNAs may facilitate the identification of therapeutic targets for preeclampsia in future.

Maternal and neonatal outcomes of repeated antepartum bleeding in 493 placenta previa cases: a retrospective study.

OBJECTIVE: To explore the effect of antepartum bleeding caused by PP on pregnancy outcomes. STUDY DESIGN: We retrospectively analyzed 493 pregnant women complicated with PP. Patients were divided into antepartum repeated bleeding and non-bleeding groups. Maternal characteristics and pregnancy outcomes were compared. RESULTS: The risk of antepartum hemorrhage was 2.038 times higher when gravidity was 5 (95% CI 1.104-3.760, p = .023). Pregnant women with a history of more than three intrauterine procedures had a 1.968 times higher risk of antepartum hemorrhage (95% CI 1.135-3,412, p = .016) compared to pregnant women without any intrauterine procedures. The risk of antepartum bleeding was found to be decreasing with the pregnancy advancing; When the placenta edge was noted to be over cervical os, the risk of antepartum bleeding was 4.385-fold than the low-lying plcaenta cases (95%CI2.454-8.372, p = .000). In the respect of maternal outcomes, the repeated bleeding group, the risk of emergency surgery was 7.213 times higher than elective surgery (95% CI 4.402-11.817, p = .000). As for the neonatal outcomes, the risk of asphyxia was 2.970 times and the risk of neonatal intensive care unit (NICU) admission was 2.542-fold higher in repeated bleeding group compared to non-bleeding group, respectively. CONCLUSIONS: Obstetricians should be aware of the increased risk of antepartum bleeding especially for ≤34 weeks and placenta edge over cervical os PP patients, they have a higher risk of antepartum bleeding. These women have higher possibility of emergency C-section and need preterm newborn resuscitation.

A Benzenesulfonamide-Based Mitochondrial Uncoupler Induces Endoplasmic Reticulum Stress and Immunogenic Cell Death in Epithelial Ovarian Cancer.

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies and requires new therapeutic strategies to improve clinical outcomes. EOC metastasizes in the abdominal cavity through dissemination in the peritoneal fluid and ascites, efficiently adapt to the nutrient-deprived microenvironment, and resist current chemotherapeutic agents. Accumulating evidence suggests that mitochondrial oxidative phosphorylation is critical for the adaptation of EOC cells to this otherwise hostile microenvironment. Although chemical mitochondrial uncouplers can impair mitochondrial functions and thereby target multiple, essential pathways for cancer cell proliferation, traditional mitochondria uncouplers often cause toxicity that precludes their clinical application. In this study, we demonstrated that a mitochondrial uncoupler, specifically 2,5-dichloro-N-(4-nitronaphthalen-1-yl)benzenesulfonamide, hereinafter named Y3, was an antineoplastic agent in ovarian cancer models. Y3 treatment activated AMP-activated protein kinase and resulted in the activation of endoplasmic reticulum stress sensors as well as growth inhibition and apoptosis in ovarian cancer cells in vitro Y3 was well tolerated in vivo and effectively suppressed tumor progression in three mouse models of EOC, and Y3 also induced immunogenic cell death of cancer cells that involved the release of damage-associated molecular patterns and the activation of antitumor adaptive immune responses. These findings suggest that mitochondrial uncouplers hold promise in developing new anticancer therapies that delay tumor progression and protect patients with ovarian cancer against relapse.

Aspirin reduces sFlt-1-mediated apoptosis of trophoblast cells in preeclampsia.

Preeclampsia (PE) is a hypertensive disorder that occurs during pregnancy. Low-dose aspirin is used to reduce the occurrence of early-onset PE; however, the mechanisms are not clear. The aim of this study was to reveal the underlying mechanism of aspirin in reducing sFlt-1-mediated apoptosis of trophoblast cells in PE. Serum sFlt-1 and sEng profiles and placental oxidative stress levels were significantly decreased in PE patients treated with aspirin compared with untreated patients without it, whereas serum PLGF and placental SOD profiles were increased in PE patients with aspirin. Aspirin attenuated the role of sFlt-1 in oxidative stress and endothelial dysfunction and reduced apoptosis of trophoblasts by inactivating the NF-κB signalling pathway in HTR-8/SVneo trophoblast cells. Blood pressure, urine protein, swelling of the villous vessels and mitochondrial parameters were noted to be much better after aspirin administrated to sFlt-1 treated pregnant mice. In conclusion, aspirin reverses the endothelial dysfunction and oxidative stress caused by sFlt-1 and thus reduces apoptosis of preeclamptic trophoblasts by inactivating NF-κB signalling pathway.

Evaluation of VEGF mediated pro-angiogenic and hemostatic effects and chemical marker investigation for Typhae Pollen and its processed product.

ETHNOPHARMACOLOGICAL RELEVANCE: Typhae Pollen (TP) is a well-known Traditional Chinese Medicine (TCM) to remove blood stasis. Carbonized Typhae Pollen (CTP), a processed product of TP after being stir-fried, has been widely applied to clinical practice with its capability of hemostasis. However, the underlying mechanism of TP and CTP are still not fully elucidated and discrimination against TP and CTP remains a challenge. AIM OF STUDY: The aim of this study is to investigate whether TP could remove blood stasis by promoting angiogenesis and the process of carbonizing it could enhance hemostatic effect. Meanwhile, some chemical markers for quality control of CTP had better to be found. MATERIAL AND METHODS: The changes of constituents between TP and CTP were analyzed by UPLC-QTOF-MS/MS. We investigated pro-angiogenic and hemostatic effects of TP and CTP in two zebrafish models: VRI-induced ISV insufficiency model and Ator-induced cerebral hemorrhage model. Subsequently, quantitative real-time PCR (qRT-PCR) was applied to investigate the mechanism of pharmacological effects. Finally, chemometric method was applied to find chemical markers. RESULTS: A total of 19 compounds were identified in qualitative analysis. The loss rate of each compound was calculated and compared. Two compounds (huaicarbon A/B) could only be detected in CTP and the content of flavonoid glycosides in CTP was significantly decreased compared with TP. The average content of the three identified flavonoid aglycones (quercetin, isorhamnetin and kaempferol) was increased about 30 percent in CTP. TP promoted pro-angiogenesis by up-regulating the expression of VEGFA, flt1 and kdr. After heating process, the pro-angiogenic activity was reduced and hemostatic activity was enhanced in CTP. Then qRT-PCR analysis found that CTP could significantly up-regulate the expression of VEGFA and vWF. In the discovery of markers, 6 chemical markers for discrimination of TP and CTP were obtained by chemometric method. CONCLUSION: Our research indicated that the pro-angiogenic activity of TP was involved in VEGF signaling pathway. After processing, hemostatic activity of CTP has been enhanced by up-regulating the expression of VEGFA and vWF. A chemical marker database was established to provide a scientific evidence for quality control, mechanism and the clinical application of TP and CTP.

MiR-616-3p modulates cell proliferation and migration through targeting tissue factor pathway inhibitor 2 in preeclampsia.

OBJECTIVES: Despite improvements in diagnosis and treatment, preeclampsia (PE) continues to pose a significant risk of maternal and foetal morbidity and mortality if not addressed promptly. An increasing number of studies have suggested that tissue factor pathway inhibitor 2 (TFPI2) acts as a suppressor gene, possibly inhibiting multiple serine proteases affecting cell proliferation and migration. It plays an essential role in the occurrence and development of PE, but the pathogenesis remains unclear. MATERIALS AND METHODS: In our research, we performed western blotting, immunohistochemistry and qPCR assays to investigate TFPI2 and miR-616-3p expression in preeclamptic placental tissues. Cell assays were performed in HTR-8/SVneo and JEG3 cell lines. Cell proliferation and migration events were investigated by MTT, EdU and transwell assays. In conjunction with bioinformatics analysis, luciferase reporter assays were performed to elucidate the mechanism by which miR-616-3p binds to TFPI2 mRNA. RESULTS: We established that TFPI2 protein levels were significantly upregulated in PE placental tissues. In addition, we found that miR-616-3p binds specifically to the 3'-UTR region of TFPI2 mRNA. Furthermore, miR-616-3p knockdown or TFPI2 overexpression substantially impaired cell growth and migration, whereas miR-616-3p upregulation or TFPI2 knockdown stimulated cell proliferation and migration. This miR-616-3p/TFPI2 axis was also found to affect the epithelial-mesenchymal transition process in PE. CONCLUSIONS: Our results demonstrated that TFPI2 plays a vital role in the progression of PE and might provide a prospective therapeutic strategy to mitigate the severity of the disorder.

Genetic variation of rs3811463 is associated with gestational diabetes mellitus susceptibility.

Gestational diabetes mellitus (GDM) is a growing health concern, and it increases the risk of adverse pregnancy outcomes with substantial long-term adverse health impacts on mothers and their offspring. Several studies have revealed specific associations between genetic variants and the risk of GDM. Single nucleotide polymorphisms (SNPs) are the major type of genetic variation in humans. Let-7 microRNA targets are enriched for genes containing SNPs associated with glucose metabolism, including Lin28. In the present study, the effect of T/C variants of rs3811463 (a SNP located near to the let-7 binding site in Lin28) on GDM risk was investigated. A GDM rat model was successfully constructed using a high fat diet and streptozotocin injection, and the primary skeletal muscle cells were isolated. The cell transfection results demonstrated that rs3811463-T/C significantly affected the glucose uptake and insulin sensitivity. Reverse transcription-quantitative polymerase chain reaction analysis indicated that the C allele at rs3811463 regulated the expression of glucose metabolism-associated genes insulin-like growth factor two binding protein 2 and glucokinase. Western blot analysis data revealed that replacement of the T allele by the C allele at rs3811463 modulated the protein level of Sirtuin 1. Taken together, it was concluded that the let-7/Lin28 axis regulated glucose uptake and insulin sensitivity by modulating the expression of glucose metabolism-associated proteins. These findings provide novel evidence on the association between genetic variations of rs3811463 and GDM susceptibility.

The lncRNA TUG1 modulates proliferation in trophoblast cells via epigenetic suppression of RND3.

Due to limited treatment options, pre-eclampsia (PE) is associated with fetal perinatal and maternal morbidity and mortality. During the causes of PE, failure of uterine spiral artery remodeling which might be related to functioning abnormally of trophoblast cells, result in the occurrence and progression of PE. Recently, abnormal expression of long non-coding RNAs (lncRNAs), as imperative regulators involved in human diseases progression (included PE), which has been indicated by increasing evidence. In this research, we found that TUG1, a lncRNA, was markedly reduced in placental samples from patients with PE. Loss-function assays indicated that knockdown TUG1 significantly affected cell proliferation, apoptosis, migration and network formation in vitro. RNA-seq revealed that TUG1 could affect abundant genes, and then explore the function and regulatory mechanism of TUG1 in trophoblast cells. Furthermore, RNA immunoprecipitation and chromatin immunoprecipitation assays validated that TUG1 can epigenetically inhibit the level of RND3 through binding to EZH2, thus promoting PE development. Therefore, via illuminating the TUG1 mechanisms underlying PE development and progression, our findings might furnish a prospective therapeutic strategy for PE intervention.

A Role of sFlt-1 in Oxidative Stress and Apoptosis in Human and Mouse Pre-Eclamptic Trophoblasts.

Pre-eclampsia (PE) is a hypertensive disorder that occurs during pregnancy, and is a multifactorial disease. The antiangiogenic factor, soluble fms-like tyrosine kinase 1 (sFlt-1), has been reported to be important in the pathogenesis of PE, but the mechanism of its involvement remains unknown. To test the effects of sFlt-1 on pregnancy, we injected pregnant mice with exogenous mouse sFlt-1. After 18 days of gestation, higher blood pressure, proteinuria, and histological differences were observed compared with controls. Mitochondrial swelling inside the trophoblast cells in the placenta of sFlt-1-treated pregnant mice was observed by electron microscopy, which suggested a role of sFlt-1 in oxidative stress in trophoblasts in PE. Furthermore, apoptosis markers were upregulated in sFlt-1-treated mice. In conclusion, sFlt-1 appears to play a role in oxidative stress, which promotes apoptosis of trophoblasts. This may be an important mechanism in the development of PE.

Effects of benazepril on functional activity of endothelial progenitor cells from hypertension patients.

The effect of angiotensin-converting enzyme inhibitors on hypertension patients regarding endothelial progenitor cell (EPC) functions is poorly understood. The aim of this study was to investigate the effects of benazepril on the proliferation, adhesion and migration capacity of EPCs and its possible mechanism. The functions of EPCs from hypertension patients were obviously reduced compared with control group, and this could be improved by benazepril in a dose-dependent manner, whereas this improvement were obviously blocked when AMD3100 were used together. Therefore, benazepril could obviously improve functions of EPCs from hypertension patients, and the potential mechanism may be related to SDF-1/CXCR4 axis.

Upregulation of long noncoding RNA SPRY4-IT1 modulates proliferation, migration, apoptosis, and network formation in trophoblast cells HTR-8SV/neo.

SPRY4-IT1 has been reported to have extremely high expression in normal placenta tissues. It is a Long noncoding RNA (lncRNA), which is associated with cell growth, migration, invasion, and apoptosis in melanoma. A 2.8-fold increase of SPRY4-IT1 expression was validated by Real-time reverse transcription-polymerase chain reaction (qRT-PCR) in severe preeclamptic placenta as compared with that of the normal ones (n=25) in this study. Furthermore, the role of SPRY4-IT1 in proliferation, migration, apoptosis, and network formation ability of trophoblast cells HTR-8/SVneo was assessed. Suppression of SPRY4-IT1 using siRNA treatment and its overexpression using plasmid targeting SPRY4-IT1 were performed in order to explore the biological function of SPRY4-IT1 in the development and progression of trophoblast cells HTR-8/SVneo, in vitro. The results showed that SPRY4-IT1 knockdown enhanced the cell migration and proliferation, and reduced the response of cells to apoptosis. However, exogenous SPRY4-IT1 overexpression significantly decreased the cell migration and proliferation, while increased cell apoptosis. Our study showed for the first time that aberrant expression of lncRNA SPRY4-IT1 might contribute to the abnormal condition of trophoblast cells HTR-8/SVneo. Therefore, we proposed SPRY4-IT1 as a novel lncRNA molecule, which might be associated with the pathogenesis of preeclampsia and might provide a new target for its early diagnosis and treatment.

Decreased expression of SOX7 is correlated with poor prognosis in lung adenocarcinoma patients.

Lung adenocarcinoma is the most frequently histologic subtype and the most histologically heterogeneous form of lung cancer. De-regulation of Wnt/ß-catenin signaling pathway is implicated in lung carcinogenesis. SOX7, as a member of high mobility group (HMG) transcription factor family, plays a role in the modulation of the Wnt/ß-catenin signaling pathway. However, the expression pattern and clinicopathological significance of SOX7 in patients with lung adenocarcinoma is still unclear. To address this problem, the SOX7 mRNA expression was detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Immunohistochemical studies were performed on 288 pairs of adjacent normal lung and lung adenocarcinoma tissues with complete follow-up records. Association of SOX7 protein expression with clinical outcomes was evaluated using the Kaplan-Meier method and a multivariate Cox proportional hazards regression model. SOX7 mRNA expression was significantly down-regulated in lung adenocarcinoma compared with matched adjacent normal tissues (P < 0.001). SOX7 protein was expressed in the cytoplasm of lung adenocarcinoma cells in 106/288 (36.8 %) of cases, whereas its immunoreactivities were predominantly located in the cytoplasm of the adjacent normal tissues. The reduced SOX7 expression was correlated with poor differentiation (P = 0.002), lymph node metastasis (P = 0.011) and advanced TNM stage (P = 0.006). Regarding patient survival, the overall survival and the disease-free survival rates were both significantly lower in patients with SOX7-negative tumors than in those with SOX7-positive tumors (P = 0.018 and 0.013, respectively). Multivariate analysis using a Cox proportional-hazards model demonstrated that SOX7 expression status was an independent prognostic factor predicting the overall survival and the disease-free survival of patients with lung adenocarcinoma (P = 0.021 and 0.016, respectively).Our data suggest that the decreased expression of SOX7 is an important feature of lung adenocarcinoma. The expression level of SOX protein may be a useful prognostic marker for patients with lung adenocarcinoma.

Transfer of bone-marrow-derived mesenchymal stem cells influences vascular remodeling and calcification after balloon injury in hyperlipidemic rats.

Bone-marrow-derived mesenchymal stem cells (BM-MSCs) were found to markedly increase atherosclerotic lesion size. The aim of this paper was to investigate whether BM-MSCs contribute to vascular remodeling and calcification after balloon injury in hyperlipidemic rats. Labeled BM-MSCs were found in the lesion of hyperlipidemic rats after balloon injury. Comparing injury group, transferred BM-MSCs significantly triggered vascular negative remodeling, characterized by the changes of remodeling index (0.628 ± 0.0293 versus 0.544 ± 0.0217), neointimal area (0.078 ± 0.015 mm(2) versus 0.098 ± 0.019 mm(2)), PCNA index (23.91 ± 6.59% versus 43.11 ± 5.31%), and percentage of stenosis (18.20 ± 1.09% versus 30.58 ± 1.21%). Apparent vascular calcification was detected in medial layers at 6 weeks after balloon angioplasty, which may be associated with upregulation of bone morphogenetic protein-2 (BMP-2). Our data indicated that unselected BM-MSCs transfer may induce vascular remodeling and calcification after balloon injury in hyperlipidemic rats.

[Effect of endoplasmic reticulum stress-responsive protein glucose-regulated protein 78, 94 and endoplasmic reticulum apoptosis factor caspase-12 in trophocyte on the pathogenesis of preeclampsia].

OBJECTIVE: To evaluate the relationship between pathogenesis of preeclampsia (PE) and the ultrastructure change of the endoplasmic reticulum in trophocyte, mRNA and protein expression levels of endoplasmic reticulum molecular chaperone glucose-regulated protein 78 (GRP78), glucose-regulated protein 94 (GRP94), endoplasmic reticulum apoptosis factor cysteine protease protein 12 (caspase-12). METHODS: Sixty-five pregnant women who were hospitalized in the First Affiliated Hospital of Nanjing Medical University from July 2008 to January 2010, were selected as the subject. Thirty pregnancy women diagnosed with PE were divided into PE group and 35 normal pregnant women were used as control group. Electron Microscopy was used to measure ultrastructure change of the endoplasmic reticulum in placenta trophocyte. Reverse transcription (RT) PCR and western blot were used to investigute the expression levels of GRP78, GRP94, caspase-12 mRNA and protein in placenta. RESULTS: (1) In control group the volume of endoplasmic reticulum does not increase; no swelling and no expansion of endoplasmic reticulum was found. In PE group the edema number of endoplasmic reticulum was reduced; the volume of endoplasmic reticulum increased; expansion and vacuolation of cavity and degranulation of the endoplasmic reticulum was observed significantly. (2) The mRNA and protein expression levels of GRP78 in placenta of PE group (2.59 ± 0.09 and 0.81 ± 0.31) were significantly higher than those in placenta of control group (1.16 ± 0.07 and 0.40 ± 0.10, P < 0.01). (3) The mRNA and protein expression levels of GRP94 in placenta of PE group (1.31 ± 0.91 and 0.55 ± 0.24) were significantly higher than those in placenta of control group (0.63 ± 0.57 and 0.22 ± 0.09, P < 0.01). (4) The mRNA and protein expression levels of caspase-12 in placenta of PE group (4.03 ± 0.65 and 1.56 ± 0.17) were significantly higher than those in placenta of control group (1.85 ± 0.85 and 0.91 ± 0.69, P < 0.01). CONCLUSION: The obvious expansion of endoplasmic reticulum in trophocyte and the increased expression levels of GRP78, GRP94 and caspase-12 indicate that endoplasmic reticulum stress-mediated apoptosis may be involved in the pathophysiological processes of PE.

[Bone marrow mesenchymal stem cell transplantation aggravates postangioplasty aortic restenosis in rats].

OBJECTIVE: To observe the effect of bone marrow mesenchymal stem cell transplantation on postangioplasty aortic restenosis in rats. METHODS: 48 SD rats were randomly divided into normal control group, balloon injury group, balloon injury and MSCs transplantation group. MSCs were pre-labeled by DAPI (25 microg/ml) and then infused into aorta through the balloon catheter (MSCs 2 x 10(6)/animal). Thoracic aorta were taken for histological examination (frozen and paraffin sections) at 1, 2, 6 weeks post angioplasty, respectively. DAPI labeled MSCs were detected under immunofluorescence microscopy. Expressions of c-kit, proliferating cell nuclear antigen (PCNA), smooth muscle alpha-actin (alpha-SMA) in aorta were determined by immunocytochemistry using related antibodies. RESULTS: The DAPI-labeled MSCs could be detected on impaired intimae and alpha-SMA expression was seen in these cells 1 weeks after MSCs transplantation. Similar weak c-kit expression in neointima was found in both injury and transplantation group at 2 weeks (P > 0.05). Expressions of PCNA and alpha-SMA in the neointima were significantly higher in transplantation group than in injury group at 2 weeks. Intima/tunica media area ratio and luminal stenosis ratio were significantly increased in transplantation group than injury group at 6 weeks (all P < 0.05). CONCLUSION: Bone marrow MSCs transplanted post aortic angioplasty could home to serious wounded aortic intima, differentiate into smooth muscle like cells, promote neointima cellular proliferation and aggravate postangioplasty aortic restenosis in rats.