To editor: Wernicke encephalopathy (WE) is an acute neurological disorder caused by a deficiency of vitamin B1 (thiamine), with a prevalence of 1.3% in autopsy studies.1 Eighty-four percent of patients with WE will develop Korsakoff syndrome, which is characterized by amnesia and confusion.2 Although WE is more common in alcoholics, it can also be caused by vomiting, malnourishment, and other situations. Hyperemesis gravidarum, a severe form of vomiting in pregnancy affecting 0.3% to 3% of pregnancies, can also cause thiamine deficiency.3 Although there are no specific diagnostic criteria for hyperemesis gravidarum, it is generally defined as persistent vomiting in pregnancy that has no other identifiable cause. Risk factors of hyperemesis gravidarum include a family history of hyperemesis, multiple gestation, and history of hyperemesis gravidarum. Hyperemesis gravidarum can be associated with other complications such as nutritional deficiencies, esophageal injury, psychosocial effects, and poor fetal outcomes.3 We report a case of WE associated with hyperemesis gravidarum. This case suggests that providers should have a high degree of suspicion for WE and initiate early treatment in pregnant women with severe vomiting and neurologic symptoms.4 The patient provided informed consent for publication of this case. Case presentation A 16-year-old (gravida 1, para 0) patient was transferred to our institution from a local emergency department for inpatient care at 15+4 weeks of gestation secondary to hyperemesis, altered mental status, slurred speech, difficulty ambulating, visual changes, and difficulty hearing. Her mother reported nausea and vomiting for the past 2 months with emesis occurring 4 times a day. The family also reported other symptoms such as progressive weakness, amnesia, and excessive somnolence. She had a history of generalized anxiety disorder, major depressive disorder, and one prior episode of intentional overdose of acetaminophen before pregnancy. It is possible that her symptoms were not recognized earlier due to this history as the mother stated that the patient liked to be alone. She denied tobacco, alcohol, or drug use and did not have any other known risk factors for hyperemesis gravidarum. Initial examination at the outside emergency department showed that the patient had notable ataxia and was not oriented to time or location. However, she was able to follow simple commands and answer straightforward questions. At this time, differential diagnoses for her included metabolic encephalopathy, drug abuse, alcohol intoxication, intracranial hemorrhage, cerebrovascular accident, cavernous sinus thrombosis, hyperemesis gravidarum, viral syndrome, and seizures. Laboratory results, including complete blood count, alcohol level, urine drug screen and urinalysis, were all negative. A complete metabolic panel showed hypokalemia to 2.7 mEq/L. A computed tomography of the head with contrast was initially obtained to rule out acute intra
{"title":"Wernicke-Korsakoff Syndrome from Hyperemesis Gravidarum","authors":"Vaishnavi Jagat Patel, Jennifer Vu, Gisela Mercado, Sreenivas Avula, Shad Deering","doi":"10.1097/fm9.0000000000000198","DOIUrl":"https://doi.org/10.1097/fm9.0000000000000198","url":null,"abstract":"To editor: Wernicke encephalopathy (WE) is an acute neurological disorder caused by a deficiency of vitamin B1 (thiamine), with a prevalence of 1.3% in autopsy studies.1 Eighty-four percent of patients with WE will develop Korsakoff syndrome, which is characterized by amnesia and confusion.2 Although WE is more common in alcoholics, it can also be caused by vomiting, malnourishment, and other situations. Hyperemesis gravidarum, a severe form of vomiting in pregnancy affecting 0.3% to 3% of pregnancies, can also cause thiamine deficiency.3 Although there are no specific diagnostic criteria for hyperemesis gravidarum, it is generally defined as persistent vomiting in pregnancy that has no other identifiable cause. Risk factors of hyperemesis gravidarum include a family history of hyperemesis, multiple gestation, and history of hyperemesis gravidarum. Hyperemesis gravidarum can be associated with other complications such as nutritional deficiencies, esophageal injury, psychosocial effects, and poor fetal outcomes.3 We report a case of WE associated with hyperemesis gravidarum. This case suggests that providers should have a high degree of suspicion for WE and initiate early treatment in pregnant women with severe vomiting and neurologic symptoms.4 The patient provided informed consent for publication of this case. Case presentation A 16-year-old (gravida 1, para 0) patient was transferred to our institution from a local emergency department for inpatient care at 15+4 weeks of gestation secondary to hyperemesis, altered mental status, slurred speech, difficulty ambulating, visual changes, and difficulty hearing. Her mother reported nausea and vomiting for the past 2 months with emesis occurring 4 times a day. The family also reported other symptoms such as progressive weakness, amnesia, and excessive somnolence. She had a history of generalized anxiety disorder, major depressive disorder, and one prior episode of intentional overdose of acetaminophen before pregnancy. It is possible that her symptoms were not recognized earlier due to this history as the mother stated that the patient liked to be alone. She denied tobacco, alcohol, or drug use and did not have any other known risk factors for hyperemesis gravidarum. Initial examination at the outside emergency department showed that the patient had notable ataxia and was not oriented to time or location. However, she was able to follow simple commands and answer straightforward questions. At this time, differential diagnoses for her included metabolic encephalopathy, drug abuse, alcohol intoxication, intracranial hemorrhage, cerebrovascular accident, cavernous sinus thrombosis, hyperemesis gravidarum, viral syndrome, and seizures. Laboratory results, including complete blood count, alcohol level, urine drug screen and urinalysis, were all negative. A complete metabolic panel showed hypokalemia to 2.7 mEq/L. A computed tomography of the head with contrast was initially obtained to rule out acute intra","PeriodicalId":53202,"journal":{"name":"Maternal-Fetal Medicine","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135147449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01DOI: 10.1097/fm9.0000000000000206
Laura Torrejón-Rodríguez, Álvaro Solaz-García, Inmaculada Lara-Cantón, Alejandro Pinilla-González, Marta Aguar, Máximo Vento
Abstract Extreme preterm infants (<28 weeks' gestation) often require positive pressure ventilation with oxygen during postnatal stabilization in the delivery room. To date, optimal inspired fraction of oxygen (FiO 2 ) still represents a conundrum in newborn care oscillating between higher (>60%) and lower (<30%) initial FiO 2 . Recent evidence and meta-analyses have underscored the predictive value for survival and/or relevant clinical outcomes of the Apgar score and the achievement of arterial oxygen saturation measured by pulse oximetry ≥85% at 5 minutes after birth. New clinical trials comparing higher versus lower initial FiO 2 have been launched aiming to optimize postnatal stabilization of extreme preterm while avoiding adverse effects of hypoxemia or hyperoxemia.
{"title":"Clinical Parameters in the First 5 Minutes after Birth Have a Predictive Value for Survival of Extremely Preterm Infants","authors":"Laura Torrejón-Rodríguez, Álvaro Solaz-García, Inmaculada Lara-Cantón, Alejandro Pinilla-González, Marta Aguar, Máximo Vento","doi":"10.1097/fm9.0000000000000206","DOIUrl":"https://doi.org/10.1097/fm9.0000000000000206","url":null,"abstract":"Abstract Extreme preterm infants (<28 weeks' gestation) often require positive pressure ventilation with oxygen during postnatal stabilization in the delivery room. To date, optimal inspired fraction of oxygen (FiO 2 ) still represents a conundrum in newborn care oscillating between higher (>60%) and lower (<30%) initial FiO 2 . Recent evidence and meta-analyses have underscored the predictive value for survival and/or relevant clinical outcomes of the Apgar score and the achievement of arterial oxygen saturation measured by pulse oximetry ≥85% at 5 minutes after birth. New clinical trials comparing higher versus lower initial FiO 2 have been launched aiming to optimize postnatal stabilization of extreme preterm while avoiding adverse effects of hypoxemia or hyperoxemia.","PeriodicalId":53202,"journal":{"name":"Maternal-Fetal Medicine","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135963377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01DOI: 10.1097/fm9.0000000000000205
Tayla Lanxner Battat, Offer Erez
Abstract Preterm delivery is a major global health problem associated with increased neonatal morbidity and mortality. To develop effective strategies to reduce preterm birth, it is important to address the causes of and risk factors for this condition. Maternal metabolism plays a crucial role in pregnancy outcomes, as it affects the availability of nutrients, energy, and other essential factors required for fetal development and growth. Several aspects of maternal metabolism can potentially contribute to the risk of preterm delivery. Severe energy deficiency as observed in women suffering from eating disorders can affect the hypothalamic-pituitary-gonadal axis resulting in amenorrhea and infertility, suggesting that maintaining a minimum maternal weight is essential to uphold a functional reproductive system, thus ensuring a successful pregnancy. Maternal undernutrition as observed in past famine and observations and animal studies may affect fetal growth and trigger an early activation of the parturition pathway leading to preterm delivery. A correlation exists between maternal size and gestation duration. Obesity is associated with a higher likelihood of medically indicated preterm birth. Low maternal body mass index and low gestational weight gain during pregnancy have been associated with preterm birth, potentially due to fetal-maternal metabolic imbalance; however, the exact mechanism remains to be determined, thus emphasizing the importance of appropriate weight management before and during pregnancy. Addressing metabolic-related risk factors for preterm delivery requires a comprehensive approach to reduce the burden of preterm delivery and improve neonatal outcomes. This review aims to explore various aspects of fetal-maternal metabolic imbalance that could potentially contribute to preterm birth. By doing so, we suggest a novel and comprehensive approach that sheds light on the intricate connection between fetal-maternal imbalance and the susceptibility to preterm birth.
{"title":"Spontaneous Preterm Birth: a Fetal-Maternal Metabolic Imbalance","authors":"Tayla Lanxner Battat, Offer Erez","doi":"10.1097/fm9.0000000000000205","DOIUrl":"https://doi.org/10.1097/fm9.0000000000000205","url":null,"abstract":"Abstract Preterm delivery is a major global health problem associated with increased neonatal morbidity and mortality. To develop effective strategies to reduce preterm birth, it is important to address the causes of and risk factors for this condition. Maternal metabolism plays a crucial role in pregnancy outcomes, as it affects the availability of nutrients, energy, and other essential factors required for fetal development and growth. Several aspects of maternal metabolism can potentially contribute to the risk of preterm delivery. Severe energy deficiency as observed in women suffering from eating disorders can affect the hypothalamic-pituitary-gonadal axis resulting in amenorrhea and infertility, suggesting that maintaining a minimum maternal weight is essential to uphold a functional reproductive system, thus ensuring a successful pregnancy. Maternal undernutrition as observed in past famine and observations and animal studies may affect fetal growth and trigger an early activation of the parturition pathway leading to preterm delivery. A correlation exists between maternal size and gestation duration. Obesity is associated with a higher likelihood of medically indicated preterm birth. Low maternal body mass index and low gestational weight gain during pregnancy have been associated with preterm birth, potentially due to fetal-maternal metabolic imbalance; however, the exact mechanism remains to be determined, thus emphasizing the importance of appropriate weight management before and during pregnancy. Addressing metabolic-related risk factors for preterm delivery requires a comprehensive approach to reduce the burden of preterm delivery and improve neonatal outcomes. This review aims to explore various aspects of fetal-maternal metabolic imbalance that could potentially contribute to preterm birth. By doing so, we suggest a novel and comprehensive approach that sheds light on the intricate connection between fetal-maternal imbalance and the susceptibility to preterm birth.","PeriodicalId":53202,"journal":{"name":"Maternal-Fetal Medicine","volume":"abs/1509.05208 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136010020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract In 2019, preterm births (PTB) accounted for approximately 0.66 million deaths globally. PTB is also associated with a significantly higher risk of mortality and long-term complications for newborns. Long-term studies associated several factors, including disruption of immune tolerance and inflammation, with PTB. However, the pathogenesis of PTB remains unclear. Gonadal steroid hormones are critical for pregnancy maintenance and regulation of immune and inflammatory responses. However, it is not clear how unbalanced gonadal steroid hormones, such as imbalanced estrogen/androgen or estrogen/progesterone contribute to PTB. In this review, we discuss how gonadal steroid hormones mediate dysfunction in immune tolerance and inflammatory responses, which are known to promote the occurrence of PTB, and provide insight into PTB prediction.
{"title":"Mechanisms of Immune Tolerance and Inflammation via Gonadal Steroid Hormones in Preterm Birth","authors":"Yongmei Shen, Yaqi Li, Jiasong Cao, Wen Li, Qimei Lin, Jianxi Wang, Zhuo Wei, Ying Chang","doi":"10.1097/fm9.0000000000000199","DOIUrl":"https://doi.org/10.1097/fm9.0000000000000199","url":null,"abstract":"Abstract In 2019, preterm births (PTB) accounted for approximately 0.66 million deaths globally. PTB is also associated with a significantly higher risk of mortality and long-term complications for newborns. Long-term studies associated several factors, including disruption of immune tolerance and inflammation, with PTB. However, the pathogenesis of PTB remains unclear. Gonadal steroid hormones are critical for pregnancy maintenance and regulation of immune and inflammatory responses. However, it is not clear how unbalanced gonadal steroid hormones, such as imbalanced estrogen/androgen or estrogen/progesterone contribute to PTB. In this review, we discuss how gonadal steroid hormones mediate dysfunction in immune tolerance and inflammatory responses, which are known to promote the occurrence of PTB, and provide insight into PTB prediction.","PeriodicalId":53202,"journal":{"name":"Maternal-Fetal Medicine","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136009872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01DOI: 10.1097/fm9.0000000000000201
Taishun Li, Zhe Liu, Huixia Yang, Yali Hu
Abstract Objective This study aimed to reach a consensus among obstetric experts on the prevention and treatment of preterm single births in China. Methods Based on the scoping literature review and the 2014 edition of preterm birth of Clinical Diagnosis and Treatment guidelines, we generated the Delphi survey statements with five evaluation dimensions, including the definition of preterm birth, exclusion of risk factors for preterm birth, prevention, and prediction of preterm birth, treatment of preterm birth, and evaluation of intervention outcomes of preterm birth. Obstetric experts from the Obstetrics and Gynecology Branch of the Chinese Medical Association formed the expert group for this survey. All the obstetric experts participated two-round modified Delphi survey via an anonymous online survey and an online panel. Mean scores, rank sum, full score ratio, and the lowest score ratio were calculated to reflect the concentration of expert opinions. The coefficient of variation and Kendall W coefficient were used to reflect the expert opinion coordination degree of the survey statement. Results The expert response rate for both rounds of surveys was 100% (41/41). Experts reached an agreement on 36 statements in five dimensions of preterm birth prevention and treatment in the first round of the survey and reached a consensus on the remaining 13 statements in the second round. A total of 49 statements (mean scores ≥3, full score ratio ≥20%, coefficient of variation ≤0.3) were explicitly included in this guideline to form recommendations, while the remaining three clinical issues that did not reach a consensus require further determination based on evidence quality. The Kendall W coefficient in the two rounds of the Delphi survey were 0.20 ( P < 0.001) and 0.29 ( P < 0.001). Conclusion The five dimensions and 49 statements, agreed upon through a two-round Delphi study, determined the recommended statements to be included in the updated guidelines for the prevention and treatment of preterm birth in China. The defined lower limit is set at ≥28 gestational weeks; however, an update has been made to the definition of premature birth, specifying that “with the consent of the mother and her family, treatment is not abandoned for viable infants ≥26 gestational weeks.”
{"title":"Using the Delphi Technique to Achieve Consensus on Prevention and Treatment of Preterm Single Birth in China","authors":"Taishun Li, Zhe Liu, Huixia Yang, Yali Hu","doi":"10.1097/fm9.0000000000000201","DOIUrl":"https://doi.org/10.1097/fm9.0000000000000201","url":null,"abstract":"Abstract Objective This study aimed to reach a consensus among obstetric experts on the prevention and treatment of preterm single births in China. Methods Based on the scoping literature review and the 2014 edition of preterm birth of Clinical Diagnosis and Treatment guidelines, we generated the Delphi survey statements with five evaluation dimensions, including the definition of preterm birth, exclusion of risk factors for preterm birth, prevention, and prediction of preterm birth, treatment of preterm birth, and evaluation of intervention outcomes of preterm birth. Obstetric experts from the Obstetrics and Gynecology Branch of the Chinese Medical Association formed the expert group for this survey. All the obstetric experts participated two-round modified Delphi survey via an anonymous online survey and an online panel. Mean scores, rank sum, full score ratio, and the lowest score ratio were calculated to reflect the concentration of expert opinions. The coefficient of variation and Kendall W coefficient were used to reflect the expert opinion coordination degree of the survey statement. Results The expert response rate for both rounds of surveys was 100% (41/41). Experts reached an agreement on 36 statements in five dimensions of preterm birth prevention and treatment in the first round of the survey and reached a consensus on the remaining 13 statements in the second round. A total of 49 statements (mean scores ≥3, full score ratio ≥20%, coefficient of variation ≤0.3) were explicitly included in this guideline to form recommendations, while the remaining three clinical issues that did not reach a consensus require further determination based on evidence quality. The Kendall W coefficient in the two rounds of the Delphi survey were 0.20 ( P < 0.001) and 0.29 ( P < 0.001). Conclusion The five dimensions and 49 statements, agreed upon through a two-round Delphi study, determined the recommended statements to be included in the updated guidelines for the prevention and treatment of preterm birth in China. The defined lower limit is set at ≥28 gestational weeks; however, an update has been made to the definition of premature birth, specifying that “with the consent of the mother and her family, treatment is not abandoned for viable infants ≥26 gestational weeks.”","PeriodicalId":53202,"journal":{"name":"Maternal-Fetal Medicine","volume":"48 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135963375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Objective This study focused on the prediction of preterm birth (PTB). It aimed to identify the transcriptomic signature essential for the occurrence of PTB and evaluate its predictive value in early, mid, and late pregnancy and in women with threatened preterm labor (TPTL). Methods Blood transcriptome data of pregnant women were obtained from the Gene Expression Omnibus database. The activity of biological signatures was assessed using gene set enrichment analysis and single-sample gene set enrichment analysis. The correlation among molecules in the interleukin 6 (IL6) signature and between IL6 signaling activity and the gestational week of delivery and latent period were evaluated by Pearson correlation analysis. The effects of molecules associated with the IL6 signature were fitted using logistic regression analysis; the predictive value of both the IL6 signature and IL6 alone were evaluated using receiver operating characteristic curves and pregnancy maintenance probability was assessed using Kaplan-Meier analysis. Differential analysis was performed using the DEseq2 and limma algorithms. Results Circulatory IL6 signaling activity increased significantly in cases with preterm labor than in those with term pregnancies (normalized enrichment score (NES) = 1.857, P = 0.001). The IL6 signature (on which IL6 signaling is based) was subsequently considered as the candidate biomarker for PTB. The area under the curve (AUC) values for PTB prediction (using the IL6 signature) in early, mid, and late pregnancy were 0.810, 0.695, and 0.779, respectively; these values were considerably higher than those for IL6 alone. In addition, the pregnancy curves of women with abnormal IL6 signature differed significantly from those with normal signature. In pregnant women who eventually had preterm deliveries, circulatory IL6 signaling activity was lower in early pregnancy (NES = −1.420, P = 0.031) and higher than normal in mid (NES = 1.671, P = 0.002) and late pregnancy (NES = 2.350, P < 0.001). In women with TPTL, the AUC values for PTB prediction (or PTB within 7 days and 48 hours) using the IL6 signature were 0.761, 0.829, and 0.836, respectively; the up-regulation of IL6 signaling activity and its correlation with the gestational week of delivery ( r = −0.260, P = 0.001) and latency period ( r = −0.203, P = 0.012) were more significant than in other women. Conclusion Our findings suggest that the IL6 signature may predict PTB, even in early pregnancy (although the predictive power is relatively weak in mid pregnancy) and is particularly effective in symptomatic women. These findings may contribute to the development of an effective predictive and monitoring system for PTB, thereby reducing maternal and fetal risk.
摘要目的探讨早产(PTB)的预测方法。该研究旨在确定PTB发生的转录组特征，并评估其在妊娠早期、中期和晚期以及先兆早产(TPTL)妇女中的预测价值。方法从基因表达综合数据库中获取孕妇血液转录组数据。利用基因集富集分析和单样品基因集富集分析评估生物标记的活性。应用Pearson相关分析分析白细胞介素6 (il - 6)信号分子间的相关性以及il - 6信号活性与分娩周数和潜伏期的相关性。利用logistic回归分析拟合与IL6特征相关分子的影响;采用受试者工作特征曲线评估il - 6信号和单独il - 6的预测价值，采用Kaplan-Meier分析评估妊娠维持概率。采用DEseq2和limma算法进行差异分析。结果与足月妊娠组相比，早产组血液中il - 6信号活性明显升高(标准化富集评分(normalized enrichment score, NES) = 1.857, P = 0.001)。IL6信号(IL6信号的基础)随后被认为是PTB的候选生物标志物。妊娠早期、中期、晚期预测PTB的曲线下面积(AUC)分别为0.810、0.695、0.779;这些值明显高于单独使用IL6的值。此外，il - 6信号异常的妊娠曲线与正常的妊娠曲线有显著差异。在最终发生早产的孕妇中，循环il - 6信号活性在妊娠早期较低(NES = - 1.420, P = 0.031)，而在妊娠中期(NES = 1.671, P = 0.002)和妊娠晚期(NES = 2.350, P <0.001)。在TPTL女性中，使用il - 6信号预测PTB(或7天和48小时内PTB)的AUC值分别为0.761、0.829和0.836;il - 6信号活性上调及其与分娩周数(r = - 0.260, P = 0.001)和潜伏期(r = - 0.203, P = 0.012)的相关性显著高于其他孕妇。结论:我们的研究结果表明，即使在妊娠早期(尽管在妊娠中期的预测能力相对较弱)，il - 6特征也可以预测PTB，并且在有症状的女性中特别有效。这些发现可能有助于开发有效的PTB预测和监测系统，从而降低孕产妇和胎儿的风险。
{"title":"Predicting the Risk of Preterm Birth Throughout Pregnancy Based on a Novel Transcriptomic Signature","authors":"Yuxin Ran, Dongni Huang, Nanlin Yin, Yanqing Wen, Yan Jiang, Yamin Liu, Hongbo Qi","doi":"10.1097/fm9.0000000000000203","DOIUrl":"https://doi.org/10.1097/fm9.0000000000000203","url":null,"abstract":"Abstract Objective This study focused on the prediction of preterm birth (PTB). It aimed to identify the transcriptomic signature essential for the occurrence of PTB and evaluate its predictive value in early, mid, and late pregnancy and in women with threatened preterm labor (TPTL). Methods Blood transcriptome data of pregnant women were obtained from the Gene Expression Omnibus database. The activity of biological signatures was assessed using gene set enrichment analysis and single-sample gene set enrichment analysis. The correlation among molecules in the interleukin 6 (IL6) signature and between IL6 signaling activity and the gestational week of delivery and latent period were evaluated by Pearson correlation analysis. The effects of molecules associated with the IL6 signature were fitted using logistic regression analysis; the predictive value of both the IL6 signature and IL6 alone were evaluated using receiver operating characteristic curves and pregnancy maintenance probability was assessed using Kaplan-Meier analysis. Differential analysis was performed using the DEseq2 and limma algorithms. Results Circulatory IL6 signaling activity increased significantly in cases with preterm labor than in those with term pregnancies (normalized enrichment score (NES) = 1.857, P = 0.001). The IL6 signature (on which IL6 signaling is based) was subsequently considered as the candidate biomarker for PTB. The area under the curve (AUC) values for PTB prediction (using the IL6 signature) in early, mid, and late pregnancy were 0.810, 0.695, and 0.779, respectively; these values were considerably higher than those for IL6 alone. In addition, the pregnancy curves of women with abnormal IL6 signature differed significantly from those with normal signature. In pregnant women who eventually had preterm deliveries, circulatory IL6 signaling activity was lower in early pregnancy (NES = −1.420, P = 0.031) and higher than normal in mid (NES = 1.671, P = 0.002) and late pregnancy (NES = 2.350, P < 0.001). In women with TPTL, the AUC values for PTB prediction (or PTB within 7 days and 48 hours) using the IL6 signature were 0.761, 0.829, and 0.836, respectively; the up-regulation of IL6 signaling activity and its correlation with the gestational week of delivery ( r = −0.260, P = 0.001) and latency period ( r = −0.203, P = 0.012) were more significant than in other women. Conclusion Our findings suggest that the IL6 signature may predict PTB, even in early pregnancy (although the predictive power is relatively weak in mid pregnancy) and is particularly effective in symptomatic women. These findings may contribute to the development of an effective predictive and monitoring system for PTB, thereby reducing maternal and fetal risk.","PeriodicalId":53202,"journal":{"name":"Maternal-Fetal Medicine","volume":"186 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136010004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To editor: Cervical insufficiency, or cervical incompetence, is characterized by painless cervix dilatation during the second trimester without contractions.1 It is found in 0.1%–1% of all pregnancies and in up to 8.0% of women with recurrent second-trimester miscarriages.2–4 Cervical insufficiency is associated with premature birth, which is a leading cause of neonatal and perinatal mortality and morbidity. The standard approach is vaginal cervical cerclage, prolonging pregnancy duration and mitigating prematurity risks. In some cases, however, transvaginal cerclage failure or technical non-feasibility of placing a vaginal suture due to a short length or scarred cervix render abdominal cerclage a viable choice. This can be achieved via laparoscopic or open abdominal approaches.5–7 Laparoscopic abdominal cerclage (LAC) has emerged as a primary approach with comparable effectiveness to open abdominal cerclage, and fewer complications.7–10 LAC reportedly has a 70.0%–83.3% success rate for third-trimester delivery, and a live birth rate exceeding 90.0%,10 but failure still occurs.9 In cases of cervix dilatation after LAC failure laparoscopic cerclage removal may be suggested, but consensus on management is lacking. Emergency cervical cerclage (ECC) is recommended for women with cervical dilatation and exposed fetal membrane between 16+0 and 27+6 weeks of gestation, without bleeding, infection, or uterine activity.11,12 Accordingly, ECC may also be an effective way to prolong the duration of pregnancy, and reduce pregnancy loss in women with failed LAC. Whether ECC prolongs pregnancy in women with LAC failure has not been fully clarified, however, and neither have the potential complications of ECC in such women. The current study assessed the prolongation of pregnancy associated with ECC after LAC failure during the second trimester of pregnancy and evaluated the safety of ECC after LAC failure. Materials and methods The present retrospective observational study included women who underwent ECC during the second trimester of pregnancy between October 2016 and May 2020. Women exhibiting cervical dilation, both with or without exposed unruptured fetal membranes following LAC were included. The study was conducted as part of a broader ongoing retrospective investigation involving pregnant women receiving antenatal care at the First Affiliated Hospital of Sun Yat-sen University and approved by ethical committees of the First Affiliated Hospital of Sun Yat-sen University (2022-458). Women who showed cervical dilation after LAC were initially identified in one of two ways: (1) those who were found to have a dilated cervix on ultrasound and (2) those who were identified by sterile speculum and digital cervical examination performed because of subjective complaints of pressure or discharge. Women who were confirmed cervical dilation with and without exposed unruptured fetal membranes after LAC in the absence of bleeding, uterine activity, or chorioamnioniti
{"title":"Emergency Cervical Cerclage Following Laparoscopic Abdominal Cerclage with Cervical Dilatation","authors":"Songqing Deng, Yanchun Liang, Yajing Wei, Jianhong Shang, Shuzhong Yao, Zilian Wang","doi":"10.1097/fm9.0000000000000202","DOIUrl":"https://doi.org/10.1097/fm9.0000000000000202","url":null,"abstract":"To editor: Cervical insufficiency, or cervical incompetence, is characterized by painless cervix dilatation during the second trimester without contractions.1 It is found in 0.1%–1% of all pregnancies and in up to 8.0% of women with recurrent second-trimester miscarriages.2–4 Cervical insufficiency is associated with premature birth, which is a leading cause of neonatal and perinatal mortality and morbidity. The standard approach is vaginal cervical cerclage, prolonging pregnancy duration and mitigating prematurity risks. In some cases, however, transvaginal cerclage failure or technical non-feasibility of placing a vaginal suture due to a short length or scarred cervix render abdominal cerclage a viable choice. This can be achieved via laparoscopic or open abdominal approaches.5–7 Laparoscopic abdominal cerclage (LAC) has emerged as a primary approach with comparable effectiveness to open abdominal cerclage, and fewer complications.7–10 LAC reportedly has a 70.0%–83.3% success rate for third-trimester delivery, and a live birth rate exceeding 90.0%,10 but failure still occurs.9 In cases of cervix dilatation after LAC failure laparoscopic cerclage removal may be suggested, but consensus on management is lacking. Emergency cervical cerclage (ECC) is recommended for women with cervical dilatation and exposed fetal membrane between 16+0 and 27+6 weeks of gestation, without bleeding, infection, or uterine activity.11,12 Accordingly, ECC may also be an effective way to prolong the duration of pregnancy, and reduce pregnancy loss in women with failed LAC. Whether ECC prolongs pregnancy in women with LAC failure has not been fully clarified, however, and neither have the potential complications of ECC in such women. The current study assessed the prolongation of pregnancy associated with ECC after LAC failure during the second trimester of pregnancy and evaluated the safety of ECC after LAC failure. Materials and methods The present retrospective observational study included women who underwent ECC during the second trimester of pregnancy between October 2016 and May 2020. Women exhibiting cervical dilation, both with or without exposed unruptured fetal membranes following LAC were included. The study was conducted as part of a broader ongoing retrospective investigation involving pregnant women receiving antenatal care at the First Affiliated Hospital of Sun Yat-sen University and approved by ethical committees of the First Affiliated Hospital of Sun Yat-sen University (2022-458). Women who showed cervical dilation after LAC were initially identified in one of two ways: (1) those who were found to have a dilated cervix on ultrasound and (2) those who were identified by sterile speculum and digital cervical examination performed because of subjective complaints of pressure or discharge. Women who were confirmed cervical dilation with and without exposed unruptured fetal membranes after LAC in the absence of bleeding, uterine activity, or chorioamnioniti","PeriodicalId":53202,"journal":{"name":"Maternal-Fetal Medicine","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136010000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-01DOI: 10.1097/fm9.0000000000000200
Longkun Ding, Lu Gao
Abstract Preterm birth is the leading cause of mortality and morbidity in newborns and children under 5 years-of-age. In order to improve the survival rate and quality of preterm infants, there is critical need to identify the specific mechanisms underlying the initiation of labor. Pregnancy represents a period of constant interactive dialog between mother and fetus. A disturbance in the pattern of maternal-fetal communication can induce physiological or pathological labor. Although a number of studies have investigated the contributions of maternal factors to the initiation of labor, the concept that fetal organ development and maternal adaptation are coordinated has emerged over recent years, thus emphasizing that factors of fetal origin may serve as hormonal signals for the initiation of labor. In this review, we summarize and discuss several specific mechanisms by which factors of fetal origin may influence parturition during term or preterm labor, including the specific regulation of fetal organs, including the lungs and accessory organs during pregnancy. Future research may focus on the specific pathways by which signals from the fetal lungs and other fetal organs interact with the maternal system to initiate eventual labor.
{"title":"Factors of Fetal Origin in the Regulation of Labor Initiation and Preterm Birth","authors":"Longkun Ding, Lu Gao","doi":"10.1097/fm9.0000000000000200","DOIUrl":"https://doi.org/10.1097/fm9.0000000000000200","url":null,"abstract":"Abstract Preterm birth is the leading cause of mortality and morbidity in newborns and children under 5 years-of-age. In order to improve the survival rate and quality of preterm infants, there is critical need to identify the specific mechanisms underlying the initiation of labor. Pregnancy represents a period of constant interactive dialog between mother and fetus. A disturbance in the pattern of maternal-fetal communication can induce physiological or pathological labor. Although a number of studies have investigated the contributions of maternal factors to the initiation of labor, the concept that fetal organ development and maternal adaptation are coordinated has emerged over recent years, thus emphasizing that factors of fetal origin may serve as hormonal signals for the initiation of labor. In this review, we summarize and discuss several specific mechanisms by which factors of fetal origin may influence parturition during term or preterm labor, including the specific regulation of fetal organs, including the lungs and accessory organs during pregnancy. Future research may focus on the specific pathways by which signals from the fetal lungs and other fetal organs interact with the maternal system to initiate eventual labor.","PeriodicalId":53202,"journal":{"name":"Maternal-Fetal Medicine","volume":"2019 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136010001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-25DOI: 10.1097/fm9.0000000000000197
Krystal Koh, Shahul Hameed Mohamed Siraj
Introduction Laparoelytrotomy, or anterior vaginotomy, describes a transverse vaginal incision. It has been described since the 19th century1–3 as a method of delivering the fetus during a second stage cesarean section (CS).4,5 More recently, reports have been published on inadvertent laparoelytrotomy during emergency CS at full cervical dilatation, due to the anatomical changes that occur with prolonged duration of obstructed labor. There has been an increasing incidence CS performed at full dilatation, 6,7 likely due to increasing rates of failed operative delivery and reduced attempts at instrumental delivery. The difficulties of second-stage CS arise from the impaction of the fetal head in the maternal pelvis. With increased duration of the second stage of labor, fetal head impaction and stretching of the lower uterine section distort the normal anatomical landmarks that differentiate the vagina, cervix, and uterine body.8 De Lee9 described retraction of the cervical lip with cephalad advancement of the vagina, such that in obstructed labor, the cervix may retract to a point where most of the fetus lies within the vagina.1 Hence, a standard incision on what appears to be the lower uterine segment may risk incising into the bladder, vagina (i.e., inadvertent elytrotomy) or cervix. The possible levels of uterine incision during a CS in the second stage of labor are shown in Figure 1.Figure 1: Possible levels of uterine incision during second stage of labor. A Uterine incision at the original attachment of the uterovesical fold after retracting down the bladder. B At this level, inadvertent incision may involve the fully dilated and retracted cervix, vagina, or both. C Level of vaginal incision below the cervix after bladder has been retracted (laparoelytrotomy).Prolonged second stage of labor, emergency setting,10 and multiparity5 are described risk factors for elytrotomy. Complications encompass hemorrhage from uterine artery injury, bladder and ureteric injury and fistula, infection,11 laceration of adjacent ligaments, difficult approximation of the vaginal incision,12 uterine and cervical trauma, and fetal trauma.5 We present our repair technique during a case of inadvertent elytrotomy during an emergency second-stage CS. We also propose strategies for prevention, including our innovative classification of levels of the impacted fetal head and methods for disimpaction at each level. Our experience Our case was a middle-aged primigravida in her 40s who was admitted for term labor and progressed from a cervical dilatation of 2.5 cm to os full within 11.5 hours. However, she remained at full cervical dilatation for 3 hours before eventual delivery because of a combination of poor maternal efforts at pushing and a likely element of cephalopelvic disproportion. In view of nonreassuring fetal heart rate abnormalities, decision was made to expedite delivery. After an uneventful fetal delivery, it was noted that the intended uterine incision was in
{"title":"Inadvertent Laparoelytrotomy During the Second-Stage Cesarean Section: Relooking the Lost Art and Proposing Surgical Management and Prevention Strategies","authors":"Krystal Koh, Shahul Hameed Mohamed Siraj","doi":"10.1097/fm9.0000000000000197","DOIUrl":"https://doi.org/10.1097/fm9.0000000000000197","url":null,"abstract":"Introduction Laparoelytrotomy, or anterior vaginotomy, describes a transverse vaginal incision. It has been described since the 19th century1–3 as a method of delivering the fetus during a second stage cesarean section (CS).4,5 More recently, reports have been published on inadvertent laparoelytrotomy during emergency CS at full cervical dilatation, due to the anatomical changes that occur with prolonged duration of obstructed labor. There has been an increasing incidence CS performed at full dilatation, 6,7 likely due to increasing rates of failed operative delivery and reduced attempts at instrumental delivery. The difficulties of second-stage CS arise from the impaction of the fetal head in the maternal pelvis. With increased duration of the second stage of labor, fetal head impaction and stretching of the lower uterine section distort the normal anatomical landmarks that differentiate the vagina, cervix, and uterine body.8 De Lee9 described retraction of the cervical lip with cephalad advancement of the vagina, such that in obstructed labor, the cervix may retract to a point where most of the fetus lies within the vagina.1 Hence, a standard incision on what appears to be the lower uterine segment may risk incising into the bladder, vagina (i.e., inadvertent elytrotomy) or cervix. The possible levels of uterine incision during a CS in the second stage of labor are shown in Figure 1.Figure 1: Possible levels of uterine incision during second stage of labor. A Uterine incision at the original attachment of the uterovesical fold after retracting down the bladder. B At this level, inadvertent incision may involve the fully dilated and retracted cervix, vagina, or both. C Level of vaginal incision below the cervix after bladder has been retracted (laparoelytrotomy).Prolonged second stage of labor, emergency setting,10 and multiparity5 are described risk factors for elytrotomy. Complications encompass hemorrhage from uterine artery injury, bladder and ureteric injury and fistula, infection,11 laceration of adjacent ligaments, difficult approximation of the vaginal incision,12 uterine and cervical trauma, and fetal trauma.5 We present our repair technique during a case of inadvertent elytrotomy during an emergency second-stage CS. We also propose strategies for prevention, including our innovative classification of levels of the impacted fetal head and methods for disimpaction at each level. Our experience Our case was a middle-aged primigravida in her 40s who was admitted for term labor and progressed from a cervical dilatation of 2.5 cm to os full within 11.5 hours. However, she remained at full cervical dilatation for 3 hours before eventual delivery because of a combination of poor maternal efforts at pushing and a likely element of cephalopelvic disproportion. In view of nonreassuring fetal heart rate abnormalities, decision was made to expedite delivery. After an uneventful fetal delivery, it was noted that the intended uterine incision was in ","PeriodicalId":53202,"journal":{"name":"Maternal-Fetal Medicine","volume":"125 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135866560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-14DOI: 10.1097/fm9.0000000000000196
Shabih Manzar
An autopsy is performed with the primary objective of finding the definitive cause of death. Historically, it was done to know more about the anatomical details and pathological findings of the diseases. Extremely preterm (EP) infants are infants born at less than 28 weeks of gestation.1 According to the World Health Organization, more than 90% of EP babies born in low-income countries die within the first few days of life compared with less than 10% of EP babies in high-income settings.2 In addition to the high mortality, the EP infants had poor neurodevelopmental outcome.3 Among the causes of in-hospital mortality, necrotizing enterocolitis (NEC), respiratory distress syndrome, intraventricular hemorrhage (IVH), infections, and gastrointestinal causes are among the top.4 Autopsy (postmortem) of preterm infants can provide vital information about the cause of death and the accuracy of antemortem clinical diagnosis. In the preterm infant, because clinical manifestations are often nonspecific, diagnostic errors like unintentionally delayed, wrong, or missed diagnoses could occur. An autopsy could help in these scenarios. It has been reported that frequently classical autopsies have revised the initial diagnosis.5,6 However, conventional autopsy might have religious, social, and cultural reservations. Additionally, with technological advancement, an alternative could be offered to families. An autopsy could provide valuable information and contribute to determining the definitive cause of death (COD) in preterm infants. In a series of reports regarding the timing of death, 66% to 73% of preterm infants had died in less than 28 days of life.5,6 Hoffsten et al.5 looked at the incidence of autopsy in preterm infants between 2002 and 2018 and found that in 34.9% of the cases, CODs were revised by these autopsies. Interestingly, the revised CODs after autopsy included the expected problems of EP infants (NEC, IVH, etc.). Except for congenital anomalies and chromosomal abnormities (5.0%–9.9%),5 most of the diagnoses (pneumothorax, IVH, NEC) are known to occur in EP infants. Similarly, Elder and Zuccollo6 studied 74 extremely EP infants, of which 29 died in less than 28 days and had autopsies. The reported new diagnoses on autopsy included hemorrhages (pulmonary, IVH, cerebral), asphyxia, congenital malformations, heart defects, and iatrogenic cause—long line perforation of the right atrium and traumatic perforation of the stomach. The study was done in 2005; with the advent of technological advances, an echocardiogram is readily available to diagnose cardiac conditions earlier. A fetal echocardiogram is an integral part of antenatal ultrasound. Postnatal ultrasound screening for IVH is routine in neonatal intensive care unit. There has been a decrease in autopsy rate globally. Xiao et al.7 reported a decline in autopsy rates in Western countries, including United States. Swinton et al.8 and Brodlie et al. 9 reported rates of autopsies from Kansas, Missou
{"title":"The Persisting Value of Autopsies on Extremely Preterm Infants in the 21st Century","authors":"Shabih Manzar","doi":"10.1097/fm9.0000000000000196","DOIUrl":"https://doi.org/10.1097/fm9.0000000000000196","url":null,"abstract":"An autopsy is performed with the primary objective of finding the definitive cause of death. Historically, it was done to know more about the anatomical details and pathological findings of the diseases. Extremely preterm (EP) infants are infants born at less than 28 weeks of gestation.1 According to the World Health Organization, more than 90% of EP babies born in low-income countries die within the first few days of life compared with less than 10% of EP babies in high-income settings.2 In addition to the high mortality, the EP infants had poor neurodevelopmental outcome.3 Among the causes of in-hospital mortality, necrotizing enterocolitis (NEC), respiratory distress syndrome, intraventricular hemorrhage (IVH), infections, and gastrointestinal causes are among the top.4 Autopsy (postmortem) of preterm infants can provide vital information about the cause of death and the accuracy of antemortem clinical diagnosis. In the preterm infant, because clinical manifestations are often nonspecific, diagnostic errors like unintentionally delayed, wrong, or missed diagnoses could occur. An autopsy could help in these scenarios. It has been reported that frequently classical autopsies have revised the initial diagnosis.5,6 However, conventional autopsy might have religious, social, and cultural reservations. Additionally, with technological advancement, an alternative could be offered to families. An autopsy could provide valuable information and contribute to determining the definitive cause of death (COD) in preterm infants. In a series of reports regarding the timing of death, 66% to 73% of preterm infants had died in less than 28 days of life.5,6 Hoffsten et al.5 looked at the incidence of autopsy in preterm infants between 2002 and 2018 and found that in 34.9% of the cases, CODs were revised by these autopsies. Interestingly, the revised CODs after autopsy included the expected problems of EP infants (NEC, IVH, etc.). Except for congenital anomalies and chromosomal abnormities (5.0%–9.9%),5 most of the diagnoses (pneumothorax, IVH, NEC) are known to occur in EP infants. Similarly, Elder and Zuccollo6 studied 74 extremely EP infants, of which 29 died in less than 28 days and had autopsies. The reported new diagnoses on autopsy included hemorrhages (pulmonary, IVH, cerebral), asphyxia, congenital malformations, heart defects, and iatrogenic cause—long line perforation of the right atrium and traumatic perforation of the stomach. The study was done in 2005; with the advent of technological advances, an echocardiogram is readily available to diagnose cardiac conditions earlier. A fetal echocardiogram is an integral part of antenatal ultrasound. Postnatal ultrasound screening for IVH is routine in neonatal intensive care unit. There has been a decrease in autopsy rate globally. Xiao et al.7 reported a decline in autopsy rates in Western countries, including United States. Swinton et al.8 and Brodlie et al. 9 reported rates of autopsies from Kansas, Missou","PeriodicalId":53202,"journal":{"name":"Maternal-Fetal Medicine","volume":"145 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134972150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：