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INTRODUCTION: Preeclampsia (PE) is an immensely prevalent condition that poses a significant risk to both maternal and fetal health. It is recognized as a primary cause of perinatal morbidity and mortality. Despite extensive research efforts, the precise impact of JDP2 on trophoblast invasion and migration in the context of preeclampsia remains unclear. MATERIALS AND METHODS: The present study aimed to investigate the differential expression of JDP2 between normal control and preeclampsia placentas through the use of quantitative polymerase chain reaction (qPCR), western blotting, and immunostaining techniques. Furthermore, the effects of JDP2 overexpression and silencing on the migration, invasion, and wound healing capabilities of HTR-8/SVneo cells were evaluated. In addition, this study also examined the impact of JDP2 on epithelial-mesenchymal transition (EMT)-associated biomarkers and the Wnt/ß-catenin pathway. RESULTS: In the present investigation, it was ascertained that Jun dimerization protein 2 (JDP2) exhibited a substantial decrease in expression levels in placentae afflicted with preeclampsia in comparison to those of normal placentae. Impairment in migration and invasion was noted upon JDP2 down-regulation, whereas augmentation of migration and invasion was observed upon JDP2 overexpression in HTR-8/SVneo cells. Subsequently, western blot and immunofluorescence assays were conducted, revealing marked alterations in EMT-associated biomarkers, such as E-cadherin, N-cadherin, and ß-catenin, thereby indicating that JDP2 can facilitate cell invasion by modulating the EMT process in HTR-8/SVneo cells. Finally, activation of Wnt/ß-catenin signaling was observed as a result of JDP2. After that, IWR-1, a Wnt inhibitor, was used in the recovery study. IWR-1 could inhibit the role of JDP2 in promoting migration and invasion in HTR-8/SVneo cells. CONCLUSION: Our findings elucidated the impact of JDP2 on trophoblast invasion and migration in preeclampsia by suppressing the EMT through the Wnt/ß-catenin signaling pathway, thereby offering a potential prognostic and therapeutic biomarker for this condition.
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We aimed to investigate the species composition of a small mammal community and the prevalence of Echinococcus spp. in a typical endemic area of the Tibetan Plateau. One pika and five rodent species were identified based on the morphological characteristics of 1278 small mammal specimens collected during 2014-2019. Detection of Echinococcus DNA in tissue samples from small mammal specimens revealed that Ochotona curzoniae (pika, total prevalence: 6.02%, 26/432), Neodon fuscus (5.91%, 38/643), N. leucurus (2.50%, 3/120), and Alexandromys limnophilus (21.74%, 10/46) were infected by both E. multilocularis and E. shiquicus; Cricetulus longicaudatus (16.67%, 1/6) was infected by E. shiquicus; and no infection was detected in N. irene (0/15). Neodon fuscus and O. curzoniae were the two most abundant small mammal species. There was no significant difference in the prevalence of pika and the overall rodent species assemblage (6.26%, 53/846); however, the larger rodent populations suggested that more attention should be paid to their role in the transmission of echinococcosis in the wildlife reservoir, which has long been underestimated. Moreover, although DNA barcoding provides a more efficient method than traditional morphological methods for identifying large numbers of small mammal samples, commonly used barcodes failed to distinguish the three Neodon species in this study. The close genetic relationships between these species suggest the need to develop more powerful molecular taxonomic tools.
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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.
Subject(s)
Cesarean Section , Conservative Treatment , Hysterectomy , Placenta Accreta , Humans , Placenta Accreta/surgery , Placenta Accreta/therapy , Female , Pregnancy , Cesarean Section/adverse effects , Conservative Treatment/methods , Hysterectomy/methods , Blood Loss, Surgical , Treatment Outcome , Blood Transfusion/statistics & numerical dataABSTRACT
Fiber optic hydrophones (FOHs) offer the notable advantage of electromagnetic interference resistance. Nevertheless, overcoming the challenge of sustaining stable, high-performance operation in intricate underwater settings at a low cost remains a considerable obstacle for them. To circumvent the restrictions noted above, we employed a miniaturized FOH, utilizing an easily fabricated extrinsic Fabry-Perot interferometer (EFPI) which is made up of a composite chromium-aluminum (Cr-Al) membrane and fiber. The linear demodulation also suppresses the drift issue in the output spectrum. The average sound pressure sensitivity of the sensor, according to experimental findings, is around -139.15â dB re 1â V/µPa, while the equivalent noise sound pressure at 1 kHz is 51.52â dB re 1 µPa/Hz1/2. This sensor has a lot of potential because of features like sensitive low-frequency response and noise performance.
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Preeclampsia (PE) manifests as a pregnancy-specific complication arising from compromised placentation characterized by inadequate trophoblast invasion. A growing body of evidence underscores the pivotal involvement of pseudogenes, a subset of long noncoding RNAs, in the pathological processes of PE. This study presents a novel finding, demonstrating a significant downregulation of the pseudogene PDIA3P1 in PE placental tissues compared to normal tissues. In vitro functional assays revealed that suppressing PDIA3P1 hindered trophoblast proliferation, invasion, and migration, concurrently upregulating the expression of secreted frizzled-related protein 1 (SFRP1). Further exploration of the regulatory role of PDIA3P1 in PE, utilizing human trophoblasts, established that PDIA3P1 exerts its function by binding to HuR, thereby enhancing the stability of Snail expression in trophoblasts. Overall, our findings suggest a crucial role for PDIA3P1 in regulating trophoblast properties and contributing to the pathogenesis of PE, offering potential targets for prognosis and therapeutic intervention.
Subject(s)
Down-Regulation , Pre-Eclampsia , RNA, Long Noncoding , Snail Family Transcription Factors , Trophoblasts , Adult , Female , Humans , Pregnancy , Cell Movement/genetics , Cell Proliferation/genetics , Down-Regulation/genetics , Phenotype , Pre-Eclampsia/genetics , Pre-Eclampsia/metabolism , Pre-Eclampsia/pathology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Snail Family Transcription Factors/metabolism , Snail Family Transcription Factors/genetics , Trophoblasts/metabolism , Trophoblasts/pathologyABSTRACT
Ferroptosis, a nonapoptotic form of cell death, is an emerging potential therapeutic target for various diseases, including cancer. However, the role of ferroptosis in pancreatic cancer remains poorly understood. Pancreatic ductal adenocarcinoma (PDAC) is characterized by a poor prognosis and chemotherapy resistance, attributed to its high Kirsten rats arcomaviral oncogene homolog mutation rate and severe nutritional deficits resulting from a dense stroma. Several studies have linked rat sarcoma (RAS) mutations to ferroptosis, suggesting that inducing ferroptosis may be an effective strategy against oncogenic RAS-bearing tumors. We investigated the role of Family With Sequence Similarity 60 Member A (FAM60A) in this study, a protein closely associated with a poor prognosis and highly expressed in PDAC and tumor tissue from KrasG12D/+;Trp53R172H/+; Pdx1-Cre mice, in regulating ferroptosis, tumor growth, and gemcitabine sensitivity in vitro and in vivo. Our results demonstrate that FAM60A regulates 3 essential metabolic enzymes, ACSL1/4 and GPX4, to protect PDAC cells from ferroptosis. Furthermore, we found that YY1 transcriptionally regulates FAM60A expression by promoting its transcription, and the Hippo-YY1 pathway is restricted in the low-amino-acid milieu in the context of nutrient deprivation, leading to downstream suppression of peroxisome proliferator-activated receptor and ACSL1/4 and activation of GPX4 pathways. Importantly, FAM60A knockdown sensitized PDAC cells to gemcitabine treatment. A new understanding of FAM60A transcriptional regulation pattern in PDAC and its dual function in ferroptosis reliever and chemotherapy resistance is provided by our study. Targeting FAM60A may therefore offer a promising therapeutic approach for PDAC by simultaneously addressing 2 major features of the disease (high RAS mutation rate and tumor microenvironment nutrient deficiency) and preventing tumor cell metabolic adaptation.
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OBJECTIVE: To investigate the expressions of phosphatidylinositol proteoglycan 5 (GPC5) and tetrahydroxynonene (4-HNE) in the PCa tissue and their impact on tumor progression. METHODS: Using immunohistochemistry, we determined the expression rates of GPC5 and 4-HNE in 50 PCa and 50 BPH tissue samples, followed by comparative analysis of the correlation between their expressions and Gleason grading. RESULTS: The positive expression rate of GPC5 was 94.0% in the BPH tissue, remarkably higher than 86.7%, 66.7%, 75.0%, 55.6% and 33.3% in the PCa tissues of Gleason grades 1, 2, 3, 4 and 5 (P = 0.001), with a negative correlation between the positive expression rate of GPC5 and the Gleason grade of tumors (P = 0.021). In contrast, the positive expression rate of 4-HNE was 4.0% in the BPH tissue, dramatically lower than 55.6%, 66.7%, 75.0%, 77.8% and 88.9% in the PCa tissues of Gleason grades 1, 2, 3, 4 and 5 (P = 0.001), with a positive correlation between the expression rate of GPC5 and the Gleason grade of tumors (P = 0.001). After a follow-up of 10ï¼30 months, the expression rates of GPC5 and 4-HNE in the tissues converted to castration-resistant PCa (CRPC) showed a statistically significant difference from those remaining unconverted (P = 0.001, P = 0.048). There was a negative correlation between the positive expression rate of 4-HNE and that of GPC5 in the PCa tissue (R = ï¼0.983, P = 0.003). CONCLUSION: The low expression of GPC5 and high expression of 4-HNE are closely related to the pathological grade of PCa and its conversion to CRP, which may serve as new biological markers in assessing the malignancy and prognosis of tumors.
Subject(s)
Prostatic Hyperplasia , Prostatic Neoplasms , Male , Humans , Prostatic Hyperplasia/pathology , Prostatic Neoplasms/pathology , Prognosis , Neoplasm Grading , Immunohistochemistry , GlypicansABSTRACT
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.
Subject(s)
Cardiovascular Diseases , Pre-Eclampsia , Female , Pregnancy , Humans , Placenta , AdenosineABSTRACT
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.
Subject(s)
Infant, Newborn, Diseases , Pregnancy Complications , Infant, Newborn , Pregnancy , Female , Humans , Pregnancy Outcome/epidemiology , Retrospective Studies , Cesarean Section , Fetal Macrosomia , Labor, Induced , Gestational AgeABSTRACT
As an endemic freshwater crab group in China, the phylogenetic relationships within Sinopotamon are still controversial because of the limited taxon samples. In this study, the complete mitogenomes of Sinopotamon chishuiense with 17,311 bp and the nearly complete mitogenomes of S. wushanense with 16,785 bp were firstly sequenced and analyzed. Compared with other reported mitogenomes of Potamidae, some novel patterns of gene rearrangement were detected in these two Sinopotamon mitogenomes, which could be illuminated by the mechanisms of tandem duplication-random loss, recombination, and translocation. Phylogenetic analyses showed the nonmonophyly of the Sinopotamon and a sister group relationship with Tenuilapotamon. These crabs from the eastern and southern of the Yangtze River basin were more closely related while other crabs form the plateau areas formed a separate clade. Divergence time indicated that the Sinopotamon and its sister group Tenuilapotamon diverged from other potamiscine freshwater crabs approximately 42.65 Mya, which belongs to the recent main uplifts period of the Tibetan Plateau in the Late Miocene. Combined with the similar evolutionary rates and relatively stable habitat altitude of these Sinopotamon species, these results implied that the ecological environment may be relatively stable during the speciation. Overall, our study yielded worthy perceptions for the evolutionary and taxonomic relationship of Sinopotamon and will help to better clarify the gene rearrangement events of the invertebrate mitogenome and lay the foundation for further phylogenetic study of Sinopotamon. Overall, our study yielded valuable insights into the evolutionary history and taxonomic relationship of Sinopotamon and these results will help to better explain the gene rearrangement events of the invertebrate mitogenome and lay the foundation for further phylogenetic study of Sinopotamon.
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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.
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OBJECTIVE: To explore the mechanism of tetrahydroxynonene (4-HNE) in the androgen antagonistic effect of prostate cancer through the androgen receptor (AR) - mitogen activated protein kinase (MAPK) signaling pathway. METHOD: Prostate cancer LNCaP cells were divided into wild-type group (NC, control group) and transfection group. The transfection group was further divided into empty vector transfection group (NC-L7 group) and GSTA4 gene transfection group (A0718, GSTA4-OE group). The GSTA4-OE group received LNCaP cell culture and GSTA4 plasmid transfection to construct LNCaP stable 4-HNE cell lines, while the control group received LNCaP cell culture without GSTA4 plasmid transfection. Stimulating prostate cancer cells with different concentrations of 4-HNE (0, 40, 80, 120µmol/L) to activate the AR signaling pathway, Western blot was used to detect the expression of AR, MAKp, AKT, and PKCα proteins. Sixty cases of prostate cancer tissues and sixty cases of benign prostatic hyperplasia tissues were selected. Immunohistochemical staining was used to determine the positive expression rate of 4-HNE in the aforementioned tissues. The correlation between the positive expression of 4-HNE and tumor Gleason grade, as well as the progression of prostate cancer to CRPC, was analyzed. RESULT: The level of 4-HNE in the GSTA4-OE group cells was inhibited. Western blot analysis showed that compared with the control group, the GSTA4-OE group had PKC in cells α The protein expression level significantly decreased (P<0.05), while the expression levels of AR and AKT proteins significantly increased (P<0.05). After treating prostate cancer cells with 40, 80, and 120µmol/L 4-HNE, compared with the control group, the expression level of AKT in the treatment group was significantly reduced (P<0.01), while the expression levels of MAKP (P<0.01), PKC (P<0.01), and AR (P<0.01) were significantly increased. The immunohistochemical results showed that the positive rate of 4-HNE was 5.0% in 60 cases of benign prostatic hyperplasia tissue and 63.3% in 60 cases of prostate cancer tissue, with a statistically significant difference (P<0.01). The positive rates of 4-HNE in Gleason grades 1-5 were 41.2%, 50.0%, 63.6%, 81.8%, and 100.0%, respectively. The higher the Gleason grade, the higher the positive rate of 4-HNE, and the difference was statistically significant (P<0.05). During a follow-up period of 10-35 months, 33 patients advanced to CRCP, while 27 patients did not. The positive expression rate of 4-HNE in the two groups showed a statistically significant difference (P<0.01). CONCLUSION: Under the action of 4-HNE, the expression of AR-MAPK pathway related proteins increase. 4-HNE may promote the progression of prostate cancer through the AR-MAPK pathway, and 4-HNE is expected to become a new therapeutic target for CRPC.
Subject(s)
Prostatic Hyperplasia , Prostatic Neoplasms, Castration-Resistant , Male , Humans , Androgens , Androgen Antagonists , Proto-Oncogene Proteins c-akt , Mitogen-Activated Protein KinasesABSTRACT
BACKGROUND: MicroRNA-21 (miR-21) is related to hypertension and cardiac remodelling. Left atrium (LA) dilation is highly sensitive to small haemodynamic changes in the left ventricle (LV) that are induced by hypertension. This study aimed to elucidate the relationship between miR-21 expression and LA dilation in elderly patients with essential hypertension (EH). METHODS: In this cross-sectional study, one hundred elderly patients with EH were recruited for the study. According to their left atrium diameters (LADs), the patients were divided into the LA dilation group [42 patients (42%)] and the no-LA dilation group [58 patients (58%)]. The serum levels of miR-21 and chemical biomarkers used in the clinic, such as creatinine, blood urea nitrogen, uric acid, fasting blood glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol, Lp(a), apolipoprotein A1 (apoA1), and apolipoprotein B, were measured. All the patients underwent echocardiographic examination, and the LAD, interventricular septum (IVS), right atrium diameter (RAD), right ventricle diameter (RVD), left ventricular end-systolic diameter (LVESD), left ventricular end-systolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) were measured. RESULTS: The levels of miR-21 [8.02 (5.21, 14.39) vs. 6.05 (3.81, 8.95), P = 0.011] and LVEF (67.02 ± 3.82 vs. 64.14 ± 4.43, P = 0.001) were higher in the LA dilation group. The levels of creatinine [70.40 (64.45, 80.15) vs. 63.9(60.1, 73.43)], P = 0.020] were higher in the no-LA dilation group. The levels of HDLC (r = - 0.209, P = 0.037), apoA1 (r = -0.269, P = 0.007) and RAD (r = 0.203, P = 0.043) were significantly correlated with miR-21 expression. The LAD was significantly correlated with the RAD (r = 0.287, P = 0.004), RVD (r = 0.450, P < 0.001), LVEDD (r = 0.248, P = 0.013) and LVEF (r = 0.232, P = 0.020). Multivariate logistic regression revealed that miR-21 significantly influenced LA dilation in elderly patients with EH (P < 0.05). CONCLUSIONS: Circulating serum levels of miR-21 are increased in elderly patients with EH with LA dilation. miR-21 levels are significantly correlated with LA dilation in elderly patients with EH, and miR-21 may be a factor related to the clinical pathophysiological occurrence of and treatment for the progression of hypertension-related early heart damage in EH patients.
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Tumor-specific, hypoxia-activated prodrugs have been developed to alleviate the side effects of chemotherapy drugs. However, the release efficiency of hypoxia-activated prodrugs is restricted by the degree of tumor hypoxia, which further leads to poor cancer treatment effects. On the other hand, oxygen is consumed gradually in photodynamic therapy (PDT), which aggravates hypoxia at the tumor site. In this study, we combined hypoxia-activated prodrugs with PDT agents to promote the prodrugs release, thereby improving their bioavailability and therapeutic effects. As a proof of concept, a mitochondria-targeted molecular prodrug, CS-P, was designed and synthesized. It can be selectively activated by tumor hypoxia to release chemotherapeutic drugs and photosensitizers, and then further discharge drugs after light irradiation. The design strategy proposed in this paper provides a new idea for enhancing hypoxia-activated prodrug release and real-time monitoring prodrug release.
Subject(s)
Nanoparticles , Neoplasms , Photochemotherapy , Prodrugs , Cell Line, Tumor , Humans , Hypoxia , Neoplasms/drug therapy , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Prodrugs/pharmacology , Prodrugs/therapeutic useABSTRACT
46,XY disorders of sex development (DSD) present with diverse phenotypes and complicated genetic causes. Precise genetic diagnosis contributes to accurate management, and targeted next-generation sequencing (NGS) and whole-exome sequencing are powerful tools for investigating DSD. However, the prevalent variants resulting in 46,XY DSD remain unclear, especially those associated with mild forms, such as isolated hypospadias, inguinal cryptorchidism, and micropenis. From 2019 to 2021, 74 patients with 46,XY DSD (48 typical and 26 mild) from the First Affiliated Hospital of Sun Yat-sen University were enrolled in our cohort study for targeted NGS or whole-exome sequencing. Our targeted 46,XY DSD panel included 108 genes involved in disorders of gonadal development and differentiation, steroid hormone synthesis and activation, persistent Müllerian duct syndrome, idiopathic hypogonadotropic hypogonadism, syndromic disorder, and others. Variants were classified as pathogenic, likely pathogenic, variant of uncertain significance, likely benign, or benign following the American College of Medical Genetics guidelines. As a result, 28 of 74 (37.8%) patients with pathogenic and/or likely pathogenic variants acquired genetic diagnoses. The Mild DSD patients acquired a diagnosis rate of 30.7%. We detected 44 variants in 28 DSD genes from 31 patients, including 33 novel and 11 reported variants. Heterozygous (65%) and missense (70.5%) variants were the most common. Variants associated with steroid hormone synthesis and activation were the main genetic causes of 46,XY DSD. In conclusion, 46,XY DSD manifests as a series of complicated polygenetic diseases. NGS reveals prevalent variants and improves the genetic diagnoses of 46,XY DSD, regardless of severity.
Subject(s)
Disorder of Sex Development, 46,XY , Male , Humans , Cohort Studies , Disorder of Sex Development, 46,XY/genetics , High-Throughput Nucleotide Sequencing , Steroids , Hormones , MutationABSTRACT
Recently, hypoglycemic drugs belonging to sodium-glucose cotransporter 2 inhibitors (SGLT2i) have generated significant interest due to their clear cardiovascular benefits for heart failure with preserved ejection fraction (HFpEF) since there are no effective drugs that may improve clinical outcomes for these patients over a prolonged period. But, the underlying mechanisms remain unclear, particularly its effects on ferroptosis, a newly defined mechanism of iron-dependent non-apoptotic cell death during heart failure (HF). Here, with proteomics, we demonstrated that ferroptosis might be a key mechanism in a rat model of high-salt diet-induced HFpEF, characterized by iron overloading and lipid peroxidation, which was blocked following treatment with canagliflozin. Data are available via ProteomeXchange with identifier PXD029031. The ferroptosis was evaluated with the levels of acyl-CoA synthetase long-chain family member 4, glutathione peroxidase 4, ferritin heavy chain 1, transferrin receptor, Ferroportin 1, iron, glutathione, malondialdehyde, and 4-hydroxy-trans-2-nonenal. These findings highlight the fact that targeting ferroptosis may serve as a cardioprotective strategy for HFpEF prevention and suggest that canagliflozin may exert its cardiovascular benefits partly via its mitigation of ferroptosis.
Subject(s)
Ferroptosis , Heart Failure , Animals , Canagliflozin/pharmacology , Canagliflozin/therapeutic use , Heart Failure/drug therapy , Iron/metabolism , Rats , Stroke VolumeABSTRACT
The subphylum Myriapoda included four extant classes (Chilopoda, Symphyla, Diplopoda, and Pauropoda). Due to the limitation of taxon sampling, the phylogenetic relationships within Myriapoda remained contentious, especially for Diplopoda. Herein, we determined the complete mitochondrial genome of Polydesmus sp. GZCS-2019 (Myriapoda: Polydesmida) and the mitochondrial genomes are circular molecules of 15,036 bp, with all genes encoded on + strand. The A+T content is 66.1%, making the chain asymmetric, and exhibits negative AT-skew (-0.236). Several genes rearrangements were detected and we propose a new rearrangement model: "TD (N\R) L + C" based on the genome-scale duplication + (non-random/random) loss + recombination. Phylogenetic analyses demonstrated that Chilopoda and Symphyla both were monophyletic group, whereas Pauropoda was embedded in Diplopoda to form the Dignatha. Divergence time showed the first split of Myriapoda occurred between the Chilopoda and other classes (Wenlock period of Silurian). We combine phylogenetic analysis, divergence time, and gene arrangement to yield valuable insights into the evolutionary history and classification relationship of Myriapoda and these results support a monophyletic Progoneata and the relationship (Chilopoda + (Symphyla + (Diplopoda + Pauropoda))) within myriapod. Our results help to better explain the gene rearrangement events of the invertebrate mitogenome and lay the foundation for further phylogenetic study of Myriapoda.
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Repairing glans dehiscence after failed hypospadias repair is challenging for pediatric surgeons. Here, we introduced and evaluated a newly modified Mathieu technique, Mathieu combined tunnel (MCT), which involves multiple custom-designed flaps for the shortage of flap source material after repeated operations; we also constructed a tunnel to avoid the glans incision that may carry new risks of dehiscence. This retrospective study included 26 patients who were consecutively admitted to the First Affiliated Hospital of Sun Yat-Sen University (Guangzhou, China) for glans dehiscence repair after failed hypospadias repair from October 2014 to October 2020; sixteen patients underwent surgery using the MCT (MCT group) and ten patients underwent surgery using the tubularized incised plate (TIP) technique (TIP group). The operative time, blood loss, postoperative complications, normal urethral meatus rate, success rate, and Hypospadias Objective Penile Evaluation (HOPE) score were compared between the two groups. The MCT group achieved an overall satisfactory penile appearance and voiding function, with a higher rate of normal urethral meatus (15/16, 93.8%) and a lower rate of glans dehiscence (1/16, 6.2%), compared with the TIP group (70.0% and 30.0%, respectively). However, these differences were not statistically significant, possibly because of the limited number of patients (all P > 0.05). Mean postoperative HOPE scores were similar in the MCT group (mean ± standard deviation: 8.83 ± 0. 89) and TIP group (8.94 ± 0.57) (P > 0.05). No significant differences were found between the two groups in terms of blood loss and success rate, nor in the rates of various complications (e.g., fistula, urethral stricture, and glans dehiscence). In conclusion, the MCT technique appears to be feasible and reliable for repairing glans dehiscence after failed hypospadias repair.
Subject(s)
Hypospadias , Child , Female , Humans , Hypospadias/surgery , Infant , Male , Retrospective Studies , Treatment Outcome , Urethra/surgery , Urologic Surgical Procedures, Male/methodsABSTRACT
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.