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BACKGROUND & AIMS: Patients with intrahepatic cholangiocarcinoma (iCCA) respond poorly to immune checkpoint blockades (ICBs). In this study, we aimed to dissect the potential mechanisms underlying poor response to ICBs and explore a rational ICB-based combination therapy in iCCA. METHODS: scRNA-seq dataset GSE151530 was analyzed to investigate the differentially expressed genes in malignant cells following ICBs therapy. RNA-seq analysis and western blot assays were performed to examine the upstream and downstream signaling pathways of CD73. Subcutaneous tumor xenograft models were utilized to investigate the impact of CD73 on iCCA growth. Plasmid AKT/NICD-induced spontaneous murine iCCAs were used to explore the therapeutic efficacy of CD73 enzymatic inhibitor AB680 combined with PD-1 blockade. Time-of-flight mass cytometry (CyTOF) was conducted to identify the tumor-infiltrating immune cell populations and their functional changes in murine iCCAs treated with AB680 in combination with PD-1 antibody. RESULTS: scRNA-seq analysis identified elevated CD73 expression in malignant cells in response to ICBs therapy. Mechanistically, ICBs therapy upregulated CD73 expression in malignant cells via TNF-α/NF-κB signaling pathway. In vivo studies revealed that CD73 inhibition suppressed the growth of subcutaneous tumors, and achieved synergistic depression effects with gemcitabine and cisplatin (GC). Adenosine produced by CD73 activates AKT/GSK3ß/ß-catenin signaling axis in iCCA cells. CD73 inhibitor AB680 potentiates anti-tumor efficacy of PD-1 antibody in murine iCCAs. CyTOF analysis showed that AB680 combined with anti-PD-1 therapy promoted the infiltration of CD8+ T, CD4+ T cells, and NK cells in murine iCCAs, while simultaneously decreased the proportions of macrophages and neutrophils. Moreover, AB680 combined with anti-PD-1 significantly upregulated the expression of Granzyme B, Tbet and co-stimulatory molecule ICOS in infiltrating CD8+ T cells. CONCLUSIONS: CD73 inhibitor AB680 limits tumor progression and potentiates therapeutic efficacy of GC chemotherapy or anti-PD-1 treatment in iCCA. AB680 combined with anti-PD-1 therapy effectively elicits anti-tumor immune response.
Subject(s)
5'-Nucleotidase , Bile Duct Neoplasms , Cholangiocarcinoma , Immune Checkpoint Inhibitors , Programmed Cell Death 1 Receptor , Cholangiocarcinoma/drug therapy , Cholangiocarcinoma/pathology , Cholangiocarcinoma/immunology , Animals , 5'-Nucleotidase/antagonists & inhibitors , 5'-Nucleotidase/metabolism , Mice , Bile Duct Neoplasms/drug therapy , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/immunology , Bile Duct Neoplasms/metabolism , Humans , Immune Checkpoint Inhibitors/pharmacology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , GPI-Linked Proteins/antagonists & inhibitors , GPI-Linked Proteins/metabolism , Xenograft Model Antitumor Assays , Cell Line, Tumor , Disease ProgressionABSTRACT
PURPOSE: Hepatocellular carcinoma (HCC) is a critical global health concern, with existing treatments benefiting only a minority of patients. Recent findings implicate the chemokine ligand 17 (CCL17) and its receptor CCR4 as pivotal players in the tumor microenvironment (TME) of various cancers. This investigation aims to delineate the roles of CCL17 and CCR4 in modulating the tumor's immune landscape, assessing their potential as therapeutic interventions and prognostic markers in HCC. METHODS: 873 HCC patients post-radical surgery from 2008 to 2012 at Zhongshan Hospital, Fudan University were retrospectively examined. These individuals were stratified into a training cohort (n = 354) and a validation cohort (n = 519). Through immunohistochemical analysis on HCC tissue arrays, the expressions of CCL17, CCR4, CD73, CD47, HHLA2, and PD-L1 were quantified. Survival metrics were analyzed using the Cox model, and a prognostic nomogram was devised via R software. RESULTS: The investigation confirmed the presence of CCL17 and CCR4 within the cancerous and stromal compartments of HCC tissues, associating their heightened expression with adverse clinical markers and survival outcomes. Notably, the interplay between CD73 and CCR4 expression in tumor stroma highlighted a novel cellular entity, CCR4 + CD73 + stromal cells, impacting overall and relapse-free survival. A prognostic nomogram amalgamating these immunological markers and clinical variables was established, offering refined prognostic insights and aiding in the management of HCC. The findings suggest that reduced CCR4 and CCR4 + CD73 + cell prevalence may forecast improved outcomes post-TACE. CONCLUSION: This comprehensive evaluation of CCR4, CCL17, and associated markers introduces a nuanced understanding of the HCC immunological milieu, proposing CCR4 + CD73 + stromal cells as critical to HCC pathogenesis and patient stratification.
Subject(s)
5'-Nucleotidase , Biomarkers, Tumor , Carcinoma, Hepatocellular , Chemokine CCL17 , GPI-Linked Proteins , Liver Neoplasms , Receptors, CCR4 , Tumor Microenvironment , Humans , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/immunology , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Liver Neoplasms/immunology , Chemokine CCL17/metabolism , Female , Male , Prognosis , Receptors, CCR4/metabolism , Middle Aged , Biomarkers, Tumor/metabolism , 5'-Nucleotidase/metabolism , Retrospective Studies , Tumor Microenvironment/immunology , GPI-Linked Proteins/metabolism , Aged , AdultABSTRACT
Lymph node metastasis (LNM) facilitates distant tumor colonization and leads to the high mortality in patients with intrahepatic cholangiocarcinoma (ICC). However, it remains elusive how ICC cells subvert immune surveillance within the primary tumor immune microenvironment (TIME) and subsequently metastasize to lymph nodes (LNs). In this study, scRNA-seq and bulk RNA-seq analyses identified decreased infiltration of dendritic cells (DCs) into primary tumor sites of ICC with LNM, which was further validated via dual-color immunofluorescence staining of 219 surgically resected ICC samples. Tumor-infiltrating DCs correlated with increased CD8+ T cell infiltration and better prognoses in ICC patients. Mechanistically, ß-catenin-mediated CXCL12 suppression accounted for the impaired DC recruitment in ICC with LNM. Two mouse ICC cell lines MuCCA1 and mIC-23 cells were established from AKT/NICD or AKT/YAP-induced murine ICCs respectively and were utilized to construct the footpad tumor LNM model. We found that expansion and activation of conventional DCs (cDCs) by combined Flt3L and poly(I:C) (FL-pIC) therapy markedly suppressed the metastasis of mIC-23 cells to popliteal LNs. Moreover, ß-catenin inhibition restored the defective DC infiltration into primary tumor sites and reduced the incidence of LNM in ICC. Collectively, our findings identify tumor cell intrinsic ß-catenin activation as a key mechanism for subverting DC-mediated anti-tumor immunity in ICC with LNM. FL-pIC therapy or ß-catenin inhibitor could merit exploration as a potential regimen for mitigating ICC cell metastasis to LNs and achieving effective tumor immune control.
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Introduction: Post-transcriptional RNA modifications are crucial regulators of tumor development and progression. In many biological processes, N1-methyladenosine (m1A) plays a key role. However, little is known about the links between chemical modifications of messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) and their function in bladder cancer (BLCA). Methods: Methylated RNA immunoprecipitation sequencing and RNA sequencing were performed to profile mRNA and lncRNA m1A methylation and expression in BLCA cells, with or without stable knockdown of the m1A methyltransferase tRNA methyltransferase 61A (TRMT61A). Results: The analysis of differentially methylated gene sites identified 16,941 peaks, 6,698 mRNAs, and 10,243 lncRNAs in the two groups. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the differentially methylated and expressed transcripts showed that m1A-regulated transcripts were mainly related to protein binding and signaling pathways in cancer. In addition, the differentially genes were identified that were also differentially m1A-modified and identified 14 mRNAs and 19 lncRNAs. Next, these mRNAs and lncRNAs were used to construct a lncRNA-microRNA-mRNA competing endogenous RNA network, which included 118 miRNAs, 15 lncRNAs, and 8 mRNAs. Finally, the m1A-modified transcripts, SCN2B and ENST00000536140, which are highly expressed in BLCA tissues, were associated with decreased overall patient survival. Discussion: This study revealed substantially different amounts and distributions of m1A in BLCA after TRMT61A knockdown and predicted cellular functions in which m1A may be involved, providing evidence that implicates m1A mRNA and lncRNA epitranscriptomic regulation in BLCA tumorigenesis and progression.
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BACKGROUND Postpartum hemorrhage (PPH) may be primary or secondary and is defined as the loss of 500 ml or more of blood within the first 24 h after birth. The Bakri balloon tamponade (BBT) is an intrauterine device used as an adjunctive treatment for refractory PPH. The aim of this study was to present the real-world experience from a single center on the effectiveness of the BBT for the treatment of PPH. MATERIAL AND METHODS This cohort study of 279 women was conducted in a real-world setting. Patients' characteristics and clinical outcomes between the BBT Success group and BBT Failure group were analyzed by t test or chi-square test. The primary outcome was the success rate of BBT. The secondary outcomes were the perinatal outcomes. RESULTS The success rate of BBT was 88.89% (248/279). A blood transfusion rate of 65.95% (184/279) was observed. After using the BBT, significant differences were observed in intervention (P<0.001), blood loss (P<0.001), indwelling time of BBT (P<0.001), and blood transfusion (P<0.001) between the Success group and Failure group. The Success group showed greater range of descent in blood loss (991.56.15±13.65 mL in Success group vs 816.23±7.57 mL in Failure group). Of the 31 women with BBT failure, 87.10% (27/31) received uterine artery embolization (UAE), 96.77% (30/31) received blood transfusion, and none required a hysterectomy. CONCLUSIONS The findings from this study from a single center in China supported those from previous studies showing that the BBT was an effective treatment to control PPH.
Subject(s)
Balloon Occlusion , Postpartum Hemorrhage , Pregnancy , Humans , Female , Postpartum Hemorrhage/therapy , Cohort Studies , Aircraft , ChinaABSTRACT
OBJECTIVE: To investigate the role of hippocampal neurodevelopment in the antidepressant effect of baicalin. METHODS: Forty male Institute of Cancer Research mice were divided into control, corticosterone (CORT, 40 mg/kg), CORT+baicalin-L (25 mg/kg), CORT+baicalin-H (50 mg/kg), and CORT+fluoxetine (10 mg/kg) groups according to a random number table. An animal model of depression was established by chronic CORT exposure. Behavioral tests were used to assess the reliability of depression model and the antidepressant effect of baicalin. In addition, Nissl staining and immunofluorescence were used to evaluate the effect of baicalin on hippocampal neurodevelopment in mice. The protein and mRNA expression levels of neurodevelopment-related factors were detected by Western blot analysis and real-time polymerase chain reaction, respectively. RESULTS: Baicalin significantly ameliorated the depressive-like behavior of mice resulting from CORT exposure and promoted the development of dentate gyrus in hippocampus, thereby reversing the depressive-like pathological changes in hippocampal neurons caused by CORT neurotoxicity. Moreover, baicalin significantly decreased the protein and mRNA expression levels of glycogen synthase kinase 3ß (GSK3ß), and upregulated the expression levels of cell cycle protein D1, p-mammalian target of rapamycin (mTOR), doublecortin, and brain-derived neurotrophic factor (all P<0.01). There were no significant differences between baicalin and fluoxetine groups (P>0.05). CONCLUSION: Baicalin can promote the development of hippocampal neurons via mTOR/GSK3ß signaling pathway, thus protect mice against CORT-induced neurotoxicity and play an antidepressant role.
Subject(s)
Corticosterone , Fluoxetine , Male , Animals , Mice , Fluoxetine/pharmacology , Fluoxetine/therapeutic use , Fluoxetine/metabolism , Depression/drug therapy , Depression/chemically induced , Glycogen Synthase Kinase 3 beta/metabolism , Reproducibility of Results , Antidepressive Agents/pharmacology , Hippocampus , TOR Serine-Threonine Kinases/metabolism , RNA, Messenger/genetics , Behavior, Animal , Disease Models, Animal , Mammals/genetics , Mammals/metabolismABSTRACT
BACKGROUND: The COVID-19 pandemic and relevant prevention and control measures may affect the mental health and induce depressive symptoms in fathers with concurrent partner delivery exposure. This study aims to investigate the prevalence of depression in fathers with simultaneous exposure to COVID-19 pandemic and the effects of family functions on paternal perinatal depression (PPD) risk. METHODS: A cross-sectional study was conducted among the perinatal fathers recruited in a large tertiary hospital in Wuhan across the whole pandemic period from 31 December 2019 to 11 April 2020. Edinburgh Postnatal Depression Scale (EPDS) and APGAR family function scale were used to evaluate PPD and family function, respectively. Chi-square test and multivariable-adjusted logistic regression model were applied for data analysis. RESULTS: Among the 1187 participants, the prevalence of PPD was 13.82% throughout the COVID-19 pandemic. Compared with that in the time period before the announcement of human-to-human transmission on 19 January 2020, the depression risk was significantly lower during the traffic restriction (OR = 0.54, 95% CI: 0.34, 0.86) and public transportation reopening periods (OR = 0.29, 95% CI: 0.14, 0.59). Poor/fair family functions was associated with elevated depression risk (OR = 2.93, 95% CI: 1.90, 4.52). Individuals reporting a low family income and smoking had high depression risks. CONCLUSIONS: A declined risk of PPD was observed over the traffic restriction period of the COVID-19 pandemic. An improved family function may help alleviate the risk of PPD during the pandemic. Health authorities are recommended to formulate targeted prevention and control strategies to handle PPD.
Subject(s)
COVID-19 , Depression, Postpartum , China/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Depression, Postpartum/epidemiology , Fathers , Female , Humans , Male , Pandemics , Pregnancy , Prevalence , Risk Assessment , Risk Factors , SARS-CoV-2ABSTRACT
Labor induction is commonly used for achieving successful vaginal delivery. This study aimed to compare the effectiveness of dinoprostone and Cook's balloon as labor-inducing agents in primipara women at term. A retrospective cohort study among primipara women was conducted in Hubei Maternity and Child Health Hospital. Basic clinical characteristics were collected. The main outcomes were vaginal delivery rate, cesarean section rate and forceps delivery rate. Obstetric and perinatal outcomes were also compared. Univariate and multivariate analyses were further performed to evaluate the predictors for vaginal delivery within 24 h. A total of 845 eligible primipara women undergoing labor induction were recruited. Of them, 141 women were induced with dinoprostone (dinoprostone group, DG), and 704 with Cook's balloon (Cook's balloon group, CG). Groups were homogeneous except more women with premature rupture of membranes in DG, with gestational hypertension in CG (P<0.05). The vaginal delivery rate within 12 h was 1.98% and 16.52% in CG and DG respectively (P=0.0001). Besides, the vaginal delivery rate within 24 h was 37.62% and 52.26% in CG and DG respectively (P=0.0079). DG showed the lower rate of oxytocin augmentation, artificial rupture of membrane and postpartum hemorrhage and the shorter interval from insertion to active labor than CG (P<0.05). Multivariate regression analysis revealed that abortion history, oxytocin augmentation, artificial rupture of membrane, and obstetric analgesia were independent predictors for vaginal delivery within 24 h. In conclusion, dinoprostone was more effective than Cook's balloon to induce labor and achieve vaginal birth in the sample of primipara women at term.
Subject(s)
Delivery, Obstetric/methods , Dinoprostone/administration & dosage , Labor, Induced/methods , Parity/drug effects , Adult , Cesarean Section/methods , Female , Gestational Age , Humans , Parity/physiology , Pregnancy , Retrospective StudiesABSTRACT
BACKGROUND: Nelumbo nucifera Gaertn stem (Hegeng [HG]) is a traditional Chinese medicine that is used to treat mental symptoms in East Asia. However, scientific evidence is generally lacking to support this traditional claim. Aim of the Study. This study's aim is to investigate the antidepression effect of HG and to further explore the possible molecular mechanisms that are involved in its actions. Materials and Methods. HG aqueous extract was administered intragastrically for 21 days after the chronic unpredictable mild stress (CUMS) procedure, and its effect on memory, learning, and emotion was assessed using animal behavioral tests. HG aqueous extract was characterized using HPLC. Immunofluorescence was used to measure the neural cell-adhesion molecule (NCAM) and growth-associated protein-43 (GAP-43) expression. RESULTS: Depression-like behaviors increased in the CUMS group compared with the control (CON) group, while they were reduced in the high-dose HG (H-HG) and fluoxetine (FLU) groups (p < 0.05). Additionally, NCAM and GAP-43 expression was reduced in the CUMS group compared with the CON group, but it increased in the H-HG and FLU groups (p < 0.05). CONCLUSIONS: These findings show the potential antidepressant effects of HG through mechanisms involving regulation of NCAM and GAP-43. This provides a new theoretical basis for its potential application as an antidepressant-like agent.
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China's universal two-child policy was released in October of 2015. How would this new policy influence the rate of overall cesarean delivery (CD) in China? The objective of this paper is to investigate the trend of overall CD rate with the increase of number of multiparous women based on a big childbirth center of China (a tertiary hospital) in 2016. In this study, 22 530 cases from the medical record department of a big childbirth center of China from January 1 to December 31 in 2016 were enrolled as research objects. Electronic health records of these selected objects were retrieved. According to the history of childbirth, the selected cases were divided into primiparous group containing 16 340 cases and multiparous group containing 6190 cases. Chi-square test was carried out to compare the rate of CD, neuraxial labor analgesia, maternity insurance between the two groups; t-test was performed to compare the in-hospital days and gestational age at birth between the two groups. Pearson correlation coefficient was used to evaluate the relationship among observed monthly rate of multiparas, overall CD rate, and Elective Repeat Cesarean Delivery (ERCD) rate. The results showed that the CD rate in multiparous group was 55.46%, which was higher than that in primiparous group (34.66%, P<0.05). The rate of neuraxial labor analgesia in multiparas group was 9.29%, which was lower than that in primiparas group (35.94%, P<0.05). However, the rate of maternity insurance was higher in multiparas group (57.00%) than that in primiparas group (41.08%, P<0.05). The hospital cost and in-hospital days in multiparas group were higher, and the gestational age at birth in multiparas group was lower than in primiparas group (P<0.05). The overall CD rate slightly dropped in the first 4 months of the year (P<0.05), then increased from 36.27% (April) to 43.21% (December) (P<0.05). The rate of multiparas women and ERCD had the same trend (P<0.05). There were linear correlations among the rate of overall CD, the rate of multiparas women and the rate of ERCD rate (P<0.05). With the opening of China's two-child policy, the increasing rate of overall CD is directly related with the high rate of ERCD. Trials of Labor After Cesarean Section (TOLAC) in safe mode to reduce overall CD rate are warranted in the future.
Subject(s)
Cesarean Section/statistics & numerical data , Elective Surgical Procedures/statistics & numerical data , Adolescent , Adult , Cesarean Section/trends , China , Electronic Health Records , Family Planning Policy , Female , Humans , Maternal Age , Parity , Pregnancy , Retrospective Studies , Tertiary Care Centers , Young AdultABSTRACT
AIM: Gestational hypertension is a common disorder of pregnancy. This study aims to evaluate the effect of labor induction with dinoprostone vaginal suppositories (Propess) on pregnancy outcomes in pregnant women with gestational hypertension. METHODS: The retrospective study included 375 patients with gestational hypertension. All patients were included into three groups according to the characteristics at admission. Women who had initiated labor spontaneously at admission were enrolled in Spontaneous labor group. According to Bishop score, other patients underwent labor induction with Propess or oxytocin were enrolled in Propess group or Oxytocin group. Demographic information and perinatal outcome data were collected. RESULTS: The vaginal delivery rate of the women with gestational hypertension was respectively 93.5% (Spontaneous labor group), 77.0% (Propess group), and 52.5% (Oxytocin group) in three groups with significant difference (P < 0.001). The duration of labor was 8.29 ± 3.70 h (Spontaneous labor group), 8.45 ± 5.21 h (Propess group) and 12.37 ± 11.47 h (Oxytocin group) in three groups, respectively. No differences were found in the intrapartum fever (P = 0.588), intrapartum hemorrhage (P = 0.953), intrapartum maximum blood pressure (P = 0.301 and P = 0.535) and post-partum hemorrhage (P = 0.075) among three groups. Neonatal outcomes were similar among three groups (Neonatal hospitalization rate, P = 0.437; 1-min Apgar score, P = 0.304; 5-min Apgar score, P = 0.340; Birth weight, P = 0.089). No poor maternal and neonatal outcomes occurred. CONCLUSION: Pregnant women with gestational hypertension could have favorable pregnancy outcomes. Using Propess as a mode of labor induction in gestational hypertension is safe and effective, without increasing intrapartum blood pressure and inducing poor pregnancy outcomes.
Subject(s)
Delivery, Obstetric/statistics & numerical data , Dinoprostone/administration & dosage , Hypertension, Pregnancy-Induced/therapy , Labor, Induced/methods , Oxytocics/administration & dosage , Administration, Intravaginal , Adult , Female , Humans , Labor, Obstetric/drug effects , Pregnancy , Pregnancy Outcome , Retrospective Studies , SuppositoriesABSTRACT
OBJECTIVE: To investigate the effects of gestational diabetes mellitus (GDM) on time to delivery and perinatal outcomes in full-term pregnancies underwent dinoprostone-induced labor. METHODS: GDM patients that underwent labor induction with dinoprostone vaginal inserts were retrospectively recruited. Full-term pregnancies with normal glucose tolerance (NGT) that underwent labor induction at the same period were recruited as control. Time to delivery and perinatal outcomes were compared between the two groups. RESULTS: A total of 1555 pregnancies with 226 GDM and 1329 NGT were recruited. GDM pregnancies had older ages, lower gestational age, higher body mass index (BMI) and abortion history, and more multigravida than NGT pregnancies (P< 0.05). Univariate analysis showed no significant difference in time to delivery and delivery rates between the two groups. However, after adjusted in a multivariate analysis model, the delivery rates of GDM women delivered within 12, 24, 36 or 48 h and those vaginally delivered within 12 or 36 h were significantly lower than those in the NGT group (P< 0.05). Perinatal outcomes were clinically similar between the two groups. CONCLUSION: GDM did not affect the time to delivery, cesarean delivery and other perinatal outcomes in Chinese women underwent dinoprostone-induced labor. However, it may be associated with the lower rates of delivery within different time intervals.
Subject(s)
Diabetes, Gestational/physiopathology , Pregnancy Outcome , Adult , Body Mass Index , Cesarean Section , Dinoprostone/therapeutic use , Female , Gestational Age , Humans , Labor, Induced , Oxytocics/therapeutic use , Pregnancy , Retrospective Studies , Term Birth , Time FactorsABSTRACT
OBJECTIVE: This study aimed to qualify relevant factors for vaginal delivery among women who underwent labor induction with vaginal dinoprostone (PGE2) insert in a Chinese tertiary maternity hospital. MATERIAL AND METHODS: A retrospective study was conducted in Hubei Maternal and Child Health Hospital. A total of 1656 pregnancies that underwent labor induction with vaginal dinoprostone insert between January and August 2016 were finally included in this study. Data were analyzed using univariate and multivariable regression modeling. RESULTS: Of 1656 women with PGE2-induced labor at term, 396 (23.91%) gave birth by cesarean section, 1260 (76.09%) had a vaginal delivery among which 921 (55.61%) delivered vaginally within 24 h. Multivariable regression analysis showed that maternal age (p < .001, OR = 0.89, 95%CI 0.85-0.93), parity (multiparous versus nulliparous, p < .001, OR = 8.74, 95%CI 4.36-17.50), baseline fetal heart rate (p = .009, OR = 0.98, 95%CI 0.96-0.99), and birth weight (p < .001, OR = 0.37, 95%CI 0.28-0.51) were significantly correlated with vaginal delivery. Moreover, body mass index (p < .001, OR = 1.11, 95%CI 1.05-1.19), parity (multiparous versus nulliparous, p < .001, OR = 6.57, 95%CI 2.37-18.23), baseline fetal heart rate (p = .004, OR = 0.96, 95%CI 0.94-0.99), and birth weight (p < .001, OR = 0.34, 95%CI 0.21-0.54) were independent predictors of vaginal delivery within 24-h. CONCLUSIONS: Our findings suggested a vaginal delivery rate of 76.09% when dinoprostone vaginal insert was used for labor induction, which was markedly higher than the overall annual vaginal delivery rate of 65.1% in China during 2014. Maternal age, parity, baseline fetal heart rate, and birth weight were significant factors for vaginal delivery. This study enables us to better understand the efficiency of dinoprostone and the potential predictors of vaginal delivery in dinoprostone-induced labor, which may be helpful to guide the clinical use of dinoprostone and therefore provide better service clinically.
Subject(s)
Delivery, Obstetric/statistics & numerical data , Dinoprostone/administration & dosage , Labor, Induced/methods , Oxytocics , Administration, Intravaginal , Adult , Cervical Ripening/drug effects , China , Dinoprostone/pharmacology , Female , Gestational Age , Heart Rate, Fetal , Humans , Maternal Age , Parity , Pregnancy , Retrospective StudiesABSTRACT
BACKGROUND: Water immersion delivery is a non-pharmacological approach to ease labor pain. This paper aims to investigate the effect of water immersion delivery on increasing strength of pelvic floor muscle (PFM) and relieving pelvic floor disorders (PFDs) during postpartum period. METHODS: A total of 2749 vaginal-delivery primiparas in postpartum 6-8 weeks were selected as research objects. Based on the modes of delivery, 600 patients were assigned into water immersion delivery group, 2149 were assigned into conventional delivery group. The scales of PFM strength and pelvic organ prolapsed (POP) were determined by specially trained personnel using digital palpation, and the symptoms of stress urinary incontinence (SUI) were investigated by questionnaire survey. The weak PFM strength was improved by doing Kegel exercise at home for 6-8 weeks. RESULTS: We found that â The rate of episiotomy in water immersion delivery group was 77.50% (465/600), which was lower than that in conventional delivery group (84.69%, 1820/2149) (Pâ<â.01); The primiparas without having an episiotomy have higher PFM strength than those having an episiotomy for both groups (Pâ<â.01). â¡There was a negative correlation between the scale of PFM strength and SUI or POP, wherein the r-values were -0.135 and -0.435, respectively (Pâ<â.01). â¢The rate of SUI was 6.50% (39/600) in water immersion delivery group and 6.89% (148/2149) in the conventional delivery group, wherein the intergroup difference was not significant (Pâ>â.05); â£The rates of vaginal wall prolapsed and uterus prolapsed were 29.83% (179/600) and 2.83% (17/600) in water immersion delivery group and 30.95% (665/2149) and 4.37% (94/2149) in the conventional delivery group, wherein the intergroup difference was not significant (Pâ>â.05). â¤After Kegel exercise, the strength of PFM was promoted (Pâ<â.01). CONCLUSION: Water immersion delivery has been proved to a beneficial alternative method for conventional delivery method. This delivery mode is associated with fewer episiotomy rate, and avoiding episiotomy is beneficial for maintaining PFM strength of women in postpartum 6-8 weeks. The strength of PFM during postpartum period can be improved by doing Kegel exercise at home.
Subject(s)
Delivery, Obstetric , Immersion , Labor Pain , Pelvic Floor Disorders/prevention & control , Pelvic Floor/physiopathology , Urinary Incontinence, Stress , Adult , Case-Control Studies , China , Delivery, Obstetric/adverse effects , Delivery, Obstetric/methods , Female , Humans , Labor Pain/diagnosis , Labor Pain/therapy , Labor Stage, First , Monitoring, Physiologic/methods , Muscle Strength/physiology , Pain Measurement/methods , Pelvic Floor Disorders/etiology , Pregnancy , Treatment Outcome , Urinary Incontinence, Stress/diagnosis , Urinary Incontinence, Stress/etiologyABSTRACT
This study aims to observe and evaluate the use of remifentanil in conscious sedation and analgesia for the safety and comfort of patients undergoing short-term endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (EST).Sixty-eight patients who underwent ERCP and EST were randomly divided into two groups: research group and control group. Patients in the research group were intravenously injected with remifentanil (80-2/3* age) for 1 to 2 minutes, combined with the intravenous injection of propofol (20-30âmg) during the course of treatment. ERCP surgery was performed when Ramsay sedation scale (RSS) score reached 2-3. During the surgery, patients were closely monitored for cough symptoms, aspiration, and respiratory and circulatory system performance, and timely treatment was performed. Sedative drugs were not given in patients in the control group.In research group, the circulatory and respiratory depression of patients was mild, only one patient needed to be treated, and there was no arrhythmia requiring treatment. Five patients had respiratory depression (blood oxygen saturation decreased to <90%), which was immediately corrected. There were no interruptions during surgery due to body movement, cough, or aspiration.The use of remifentanil for conscious sedation and analgesia can be broadly applied in short-term ERCP, which greatly improves patient comfort during the surgery. This approach may bear promise for a widespread use in future clinical practice.
Subject(s)
Anesthetics, Intravenous/therapeutic use , Cholangiopancreatography, Endoscopic Retrograde/methods , Conscious Sedation/methods , Piperidines/therapeutic use , Sphincterotomy, Endoscopic/methods , Anesthetics, Intravenous/administration & dosage , Female , Hemodynamics , Humans , Male , Oxygen/blood , Piperidines/administration & dosage , Propofol/administration & dosage , Remifentanil , Respiratory MechanicsABSTRACT
In the past decades, studies have shown that a balance between regulatory T cells (Tregs) and T helper 17 (Th17) cells plays a major role in autoimmune/inflammatory diseases as well as pregnancy complications. Decreased number and function of Tregs, and increased number of Th17 cells which often have an opposed effect of Tregs, are associated with these conditions. Recently, the plasticity of Tregs and Th17 cells has been reported to be involved in the pathogenesis of autoimmune/inflammatory diseases. Hence, we summarize the current knowledge of Tregs and Th17 cells plasticity with an emphasis on their reciprocal transdifferentiation in autoimmune/inflammatory diseases. Moreover, the regulators of the Tregs-to-Th17 cells transdifferentiation are discussed as well. Finally, by reviewing the immuno-inflammatory status of pregnancy complications, such as preeclampsia and unexplained recurrent pregnancy losses, a possibility of Tregs-to-Th17 cells transdifferentiation as an underlying immune-pathology of these conditions is discussed.
Subject(s)
Autoimmune Diseases/immunology , Inflammation/immunology , Pregnancy Complications/immunology , T-Lymphocytes, Regulatory/immunology , Th17 Cells/immunology , Animals , Cell Transdifferentiation , Female , Humans , Pregnancy , T-Lymphocytes, Regulatory/physiology , Th17 Cells/physiologyABSTRACT
OBJECTIVE: Resveratrol, a phytoalexin, is reported to activate AMP-activated protein kinase (AMPK) in vascular cells. Activation of AMPK induces vasorelaxation to lower blood pressure (BP). Whether resveratrol via activation of AMPK decreases, BP remains unknown. METHODS: Male wild-type (WT) mice and mice deficient in AMPKα2 (AMPKα2(-/-)) were fed with resveratrol (400 mg/kg). After 7 d, mice were implanted with deoxycorticosterone acetate (DOCA)-salt (150 mg/kg) for 35 d. BP was detected by the radiotelemetry method. Vessel contraction was determined by organ chamber. Active RhoA, Rho-associated kinase (ROCK) activity, phosphorylations of myosin light chain (MLC), and myosin phosphatase targeting subunit 1 (MYPT1) were assayed by western blot. RESULTS: Implantation of DOCA-salt dramatically increased systemic BPs (systolic BP and diastolic BP) in WT and AMPKα2(-/-) mice. However, treatment of resveratrol significantly decreased systemic BP in WT mice but not in AMPKα2(-/-) mice. In the organ chamber study, resveratrol inhibited agonist-induced vessel relaxation in WT mice aortas. Loss of AMPKα2 or AMPK inhibition by compound C reversed resveratrol-suppressed vasoconstriction in isolated mice aortas. In cultured vascular smooth muscle cells (VSMCs), activation of AMPK by resveratrol inhibited phenylephrine-enhanced MLC phosphorylation in a dose-dependent manner. CONCLUSIONS: Resveratrol via activation of AMPK lowers BP in DOCA-hypertensive mice through an AMPK/RhoA/ROCK2/MLCMLC pathway.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Blood Pressure/physiology , Hypertension/drug therapy , Muscle, Smooth, Vascular/drug effects , Stilbenes/pharmacology , AMP-Activated Protein Kinases/drug effects , Animals , Anticarcinogenic Agents/pharmacology , Blood Pressure/drug effects , Desoxycorticosterone Acetate/toxicity , Disease Models, Animal , Enzyme Activation , Hypertension/metabolism , Hypertension/physiopathology , Male , Mice , Mice, Inbred C57BL , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/physiopathology , Resveratrol , Vasoconstriction/drug effects , Vasoconstriction/physiology , Vasodilator AgentsABSTRACT
OBJECTIVE: To evaluate the significance of several Dermatophagoides pteronyssinus allergen extracts for skin prick test (SPT) in patients allergic to Dermatophagoides pteronyssinus. METHODS: Two hundred and nineteen patients enrolled in Peking Union Medical College Hospital underwent SPT and serum specific IgE assay to detect the Dermatophagoides pteronyssinus allergen. Three kinds of house dust mite allergen extracts were used for SPT, including the Dermatophagoides pteronyssinus extract prepared by our laboratory (group A), standardized Dermatophagoides pteronyssinus extract (group B), and mixed extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae (group C). Human serum specific IgE result was regarded as the reference standard for diagnosis of Dermatophagoides pteronyssinus allergy. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of SPT with the extracts of three groups. RESULTS: SPT results showed that the median wheal diameter of group A, group B, and group C was 0.43, 0.35, and 0.28 cm, respectively, with significant difference among three groups (P<0.05). The difference was significant between group A and B (P<0.01) as well as group A and C (P<0.01), but not between group B and C (P>0.05). There was no local urticaria or systemic allergic reactions following the procedure of SPT. Local reaction was observed in 5 patients and delayed reaction was in 2 patients of group A. As for group B and C, local reaction occurred in 3 cases and delayed reaction in 2 cases in each group. The area under ROC curve of SPT with extract in group A, group B, and group C was 0.765, 0.801, and 0.782, respectively. Based on the detection results of serum specific IgE, the sensitivity of SPT in diagnosis of Dermatophagoides pteronyssinus allergy with extract of group A, group B, and group C was 92.4%, 87.0%, and 81.5%, and the specificity was 60.6%, 73.2%, and 74.8%, respectively. CONCLUSION: The Dermatophagoides pteronyssinus extract for SPT prepared by our laboratory offers good sensitivity and specificity comparable to commercially available allergen extracts, and it may be an appropriate candidate for clinical screening and diagnosis of Dermatophagoides pteronyssinus allergy.
Subject(s)
Antigens, Dermatophagoides , Dermatophagoides pteronyssinus/immunology , Skin Tests/methods , Animals , Antigens, Dermatophagoides/immunology , Female , Humans , Male , ROC Curve , Sensitivity and SpecificityABSTRACT
OBJECTIVE: Oxygen desaturation is common among patients with sleep apnea. This study was designed to evaluate the methods used to express the severity of oxygen desaturation in patients with obstructive sleep apnea hypopnea syndrome. METHODS: The oxygen saturation data of 215 patients [suspected of having obstructive sleep apnea (OSA)] studied at the Sleep Centre of Peking Union Medical College Hospital were evaluated. Apnea-hypopnea index (AHI) and the following conventional indices of oxygen desaturation were compared: average oxygen saturation (AO(2)), lowest oxygen saturation (LO(2)), oxygen desaturation index (ODI), average desaturation and the percent of the total time with oxygen saturation level lower than 90% (T < 90%). RESULTS: There was a significant correlation between the oxygen saturation values measured by any method (AO(2), LO(2), ODI, average desaturation, T < 90%) and the severity of sleep AHI (r = -0.610, 0.983, -0.789, 0.782, 0.821, respectively, P = 0.001). CONCLUSIONS: The best method of expressing the severity of oxygen desaturation in patients with obstructive sleep apnea hypopnea syndrome needs the combination of several conventional indices of oxygen desaturation (lowest oxygen saturation, oxygen desaturation index, and the percent of the total time with oxygen saturation level lower than 90%).
Subject(s)
Hypoventilation/physiopathology , Oxygen/blood , Sleep Apnea, Obstructive/physiopathology , Adolescent , Adult , Aged , Aged, 80 and over , Circadian Rhythm , Female , Humans , Hypoventilation/blood , Hypoventilation/pathology , Male , Middle Aged , Oximetry/methods , Severity of Illness Index , Sleep Apnea, Obstructive/blood , Sleep Apnea, Obstructive/pathology , Sleep Stages , SyndromeABSTRACT
Growth hormone (GH) plays an important role in animal growth and development, and the growth hormone gene can be considered as a candidate gene for studying the weight in goats. The function of GH gene has been intensively studied in cattle and pigs, while in goats the study is still rare. In this paper 224 goats including LuBei White goat, Boer goat, hybrid generation 1 and backcross generation 1 of Boer goat and LuBei White goat were used. Two pairs of primers for 5' region of GH gene were designed according to the database of goat genomic sequence (Accession No. D00476) and polymorphisms were detected by PCR-SSCP. Homozygotes of the polymorphic fragment were cloned and sequenced. The result showed that there were five substitution mutations in the two fragments. Statistical analysis showed that in the fragment amplified by the first pair of primers, AA genotype had significant higher birth weight and weight of one year old than BB and AB genotypes in Boer goats (P<0.05). In hybrid generation 1 AA genotype also had higher birth weight and weight of one year old in significantly. While in LuBei White goats BB genotype had lower weight and the weaning weight was significant lower than the other two genotypes (P<0.05). In the fragment amplified by the second pair of primers there was no significant difference among different genotypes. From these results we can preliminarily draw the conclusion that GH gene may be a major gene or linked to the major gene to affect the weight traits and the polymorphic site could be used to select the goat weight in marker-assisted selection program.