Conformation-dependent blockage of activated VWF improves outcomes of traumatic brain injury in mice.

Traumatic brain injury-induced coagulopathy (TBI-IC) causes life-threatening secondary intracranial bleeding. Its pathogenesis differs mechanistically from that of coagulopathy arising from extracranial injuries and hemorrhagic shock, but it remains poorly understood. We report results of a study designed to test the hypothesis that von Willebrand factor (VWF) released during acute TBI is intrinsically hyperadhesive because its platelet-binding A1-domain is exposed and contributes to TBI-induced vascular leakage and consumptive coagulopathy. This hyperadhesive VWF can be selectively blocked by a VWF A2-domain protein to prevent TBI-IC and to improve neurological function with a minimal risk of bleeding. We demonstrated that A2 given through intraperitoneal injection or IV infusion reduced TBI-induced death by >50% and significantly improved the neurological function of C57BL/6J male mice subjected to severe lateral fluid percussion injury. A2 protected the endothelium from extracellular vesicle-induced injury, reducing TBI-induced platelet activation and microvesiculation, and preventing a TBI-induced hypercoagulable state. A2 achieved this therapeutic efficacy by specifically blocking the A1 domain exposed on the hyperadhesive VWF released during acute TBI. These results suggest that VWF plays a causal role in the development of TBI-IC and is a therapeutic target for this life-threatening complication of TBI.

The pathogenesis of prevalent aerobic bacteria in aerobic vaginitis and adverse pregnancy outcomes: a narrative review.

BACKGROUND: Aerobic vaginitis is a common cause of vaginal discharge in reproductive-age women, increasing the risk of negative pregnancy outcomes such as premature delivery, abortion, premature rupture of membranes and stillbirth. However, the aetiology and pathogenesis of aerobic vaginitis causing negative pregnancy outcomes are still unclear, and there is no unified and standardized treatment method for aerobic vaginitis in the pregnancy period. METHODS: We conducted a literature search of published studies in the English language focusing on aerobic vaginitis and its association with adverse pregnancy outcomes utilizing PubMed and Web of Science from January 1973 through June 2021. The common pathogenic bacteria of aerobic vaginitis during pregnancy, such as group B Streptococcus, Escherichia coli, Staphylococcus aureus, Enterococcus faecalis and Klebsiella pneumoniae, as well as the related adverse pregnancy outcomes and existing treatments were reviewed. RESULTS: A total of 4534 articles were identified, and 97 studies that had inclusion criteria were subjected to careful review. The pathogenic bacteria of aerobic vaginitis can produce different toxins or affect the local immunity of patients and then lead to the occurrence of infection. Fresh wet mount microscopy is the preferred diagnostic method for aerobic vaginitis. Clindamycin is a common antibiotic used for aerobic vaginitis in pregnant women. The use of products combining probiotics has achieved excellent treatment success. CONCLUSIONS: Future research in this field can provide insights regarding the mechanism of aerobic vaginitis-induced adverse pregnancy outcomes in humans and ways to prevent their occurrence.

Aerobic vaginitis is an infection of the vagina that increases the risk of negative pregnancy outcomes. The aetiology and pathogenesis of aerobic vaginitis causing negative pregnancy outcomes are still unclear. This paper reviews the common pathogenic bacteria of aerobic vaginitis during pregnancy, and the related adverse pregnancy outcomes. We also review the existing treatment. Currently, it is believed that the microflora in aerobic vaginitis is composed of commensal aerobic microorganisms of intestinal origin, and the most frequently encountered bacteria are group B Streptococcus, Escherichia coli, Staphylococcus aureus, Enterococcus faecalis and Klebsiella pneumoniae. The pathogenic bacteria of aerobic vaginitis can produce different toxins or affect the local immunity of patients and then lead to the occurrence of infection. Fresh wet mount microscopy is the preferred diagnostic method for aerobic vaginitis. Clindamycin is a common antibiotic used for aerobic vaginitis in pregnant women. The use of products combining probiotics has achieved excellent treatment success. This study provides a reference for future research and early diagnosis and treatment during pregnancy. Future research in this field can provide insights regarding the mechanisms of aerobic vaginitis-induced adverse pregnancy outcomes in humans and ways to prevent their occurrence.

Prothrombotic state associated with preeclampsia.

PURPOSE OF REVIEW: Preeclampsia is a common complication of pregnancy and contributes significantly to maternal and fetal morbidity and mortality. A protective hypercoagulable state is often developed during late pregnancy and can evolve into a prothrombotic state in patients with preeclampsia. The underlying mechanism of this prothrombotic transition remains poorly understood. We discuss recent progress in understanding the pathophysiology of preeclampsia and associated prothrombotic state. RECENT FINDINGS: The hypercoagulable state developed during pregnancy is initiated by placental factors and progresses into the prothrombotic state in preeclampsia when the placenta is subjected ischemic and oxidative injuries. The cause of the preeclampsia-induced prothrombotic state is multifactorial, involving not only placental factors but also maternal conditions, which include genetic predisposition, preexisting medical conditions, and conditions acquired during pregnancy. Endotheliopathy is the primary pathology of preeclampsia and contributes to the prothrombotic state by inducing the dysregulation of coagulation, platelets, and adhesive ligands. SUMMARY: Patients with preeclampsia often develop a severe prothrombotic state that predisposes them to life-threatening thrombosis and thromboembolism during and after pregnancy. Early recognition and treatment of this prothrombotic state can improve maternal and infant outcomes of preeclampsia patients.

Placenta-derived extracellular vesicles induce preeclampsia in mouse models.

Preeclampsia is a pregnancy-induced condition that impairs the mother's health and results in pregnancy termination or premature delivery. Elevated levels of placenta-derived extracellular vesicles (pcEV) in the circulation have been consistently associated with preeclampsia, but whether these vesicles induce preeclampsia or are the product of preeclampsia is not known. Guided by a small cohort study of preeclamptic patients, we examined the impact of pcEV on the pathogenesis of preeclampsia in mouse models. We detected pcEV in pregnant C56BL/6J mice with a peak level of 3.8±0.9×107/mL at 17-18 days post-coitum. However, these pregnant mice developed hypertension and proteinuria only after being infused with vesicles purified from injured placenta. These extracellular vesicles released from injured placenta disrupted endothelial integrity and induced vasoconstriction. Enhancing the clearance of extracellular vesicles prevented the development of the extracellular vesicle-induced preeclampsia in mice. Our results demonstrate a causal role of pcEV in preeclampsia and identify microvesicle clearance as a new therapeutic strategy for the treatment of this pregnancy-associated complication.

Extracellular mitochondria released from traumatized brains induced platelet procoagulant activity.

Coagulopathy often develops soon after acute traumatic brain injury and its cause remains poorly understood. We have shown that injured brains release cellular microvesicles that disrupt the endothelial barrier and induce consumptive coagulopathy. Morphologically intact extracellular mitochondria accounted for 55.2% of these microvesicles, leading to the hypothesis that these extracellular mitochondria are metabolically active and serve as a source of oxidative stress that activates platelets and renders them procoagulant. In testing this hypothesis experimentally, we found that the extracellular mitochondria purified from brain trauma mice and those released from brains subjected to freeze-thaw injury remained metabolically active and produced reactive oxygen species. These extracellular mitochondria bound platelets through the phospholipid-CD36 interaction and induced α-granule secretion, microvesiculation, and procoagulant activity in an oxidant-dependent manner, but failed to induce aggregation. These results define an extracellular mitochondria-induced and redox-dependent intermediate phenotype of platelets that contribute to the pathogenesis of traumatic brain injury-induced coagulopathy and inflammation.

Aerobic vaginitis in late pregnancy and outcomes of pregnancy.

The purpose of this study was to investigate the risk factors and pregnancy outcomes for aerobic vaginitis (AV) in late pregnancy. A total of 624 pregnant women who were treated in the perinatal unit at Tianjin Medical University General Hospital and 365 nonpregnant women who were evaluated at a health management center from January 2015 to June 2016 were recruited for this case-control study. A questionnaire covering personal hygiene habits and sociodemographic factors was administered to pregnant women to analyze risk factors for AV. Bacterial vaginosis, AV, vulvovaginal candidiasis, and Trichomonas vaginitis were scored according to standardized definitions. Pregnancy outcomes were followed up and recorded. The chi-square test and univariate and multivariate logistic regression analyses were used for statistical evaluation. The prevalence of vaginal infection in pregnant and nonpregnant women were 27.9% and 15.3%, respectively (P < 0.05). AV was identified more frequently in pregnant women than in nonpregnant women (4.2% vs. 1.4%; P < 0.05). A history of vaginal infection within 1 year (odds ratio [OR] = 3.219, 95% confidence interval [CI] 1.103-9.346) and external hemorrhoids (OR = 11.233, 95% CI 4.647-27.155) were independent risk factors for AV during pregnancy. A higher incidence of premature rupture of membranes (PROM) was significantly associated with AV (P < 0.05). AV is common in late pregnancy. Clinicians should pay more attention to vaginal microbiota evaluations during pregnancy.

Incarceration of the gravid uterus: a case report and literature review.

BACKGROUND: Incarceration of the gravid uterus is a rare obstetric disorder that contributes to pregnancy-related complications. To understand its clinical characteristics and managements, we have reviewed the etiology, risk factors, clinical characteristics and current treatments of an incarcerated gravid uterus based on 162 cases reported in the English language literature, including our patient. CASE PRESENTATION: A 25-year-old primigravida, with a history of lymphatic tuberculosis, infertility due to blocked fallopian tubes and received in vitro fertilization. The patient presented with urine retention and lower abdominal pain in the early second trimester. Uterine incarceration was diagnosed based on pelvic examination and abdominal ultrasound. A Foley catheter was placed and manual reposition was successful. No episode of retention was experienced after the further enlargement of the uterus and its ascent. A healthy infant was delivered vaginally on 38th week of pregnancy. CONCLUSIONS: Uterine incarceration due to pelvic adhesions is rare and, because of it non-specific clinical presentations, is often misdiagnosed. Abdominal ultrasound is instrumental for the diagnosis because it can directly image the disturbed uterine and pelvic anatomy. There are limited treatment options for uterine incarceration, but definitive diagnosis allows procedures to treat and to reduce severe complications of uterine incarceration.

Ferulic acid ameliorated placental inflammation and apoptosis in rat with preeclampsia.

Preeclampsia (PE) occurs specifically during pregnancy characterized by new-onset hypertension. The pathogenesis of PE was complicated, and inflammation may be central to the pathogenesis of PE. Ferulic acid (FA) is recognized to prevent cell damage and apoptosis induced by oxidative stress and inflammation. In our study, we used NG-nitro-l-arginine methyl ester (L-NAME)-induced rat model of PE to investigate whether FA improved PE and its possible mechanism. We found that FA significantly reduced blood pressure, urine volume, and urinary protein level in rats with PE. Meanwhile, FA decreased L-NAME induced higher expression of circulating TNF-α、IL-6、IL-1ß and PlGF, it reduced placental TNF-α and NF-κB p65. Furthermore, FA rescued L-NAME induced decreasing expression of IL-4 and IL-10 expression in the circulation and placenta of rats. FA also ameliorated placental apoptosis in L-NAME induced rats by increasing Bcl-2 whereas decreasing Bax expression in placenta. It suggested FA as a potential candidate for the treatment of various disorders including L-NAME induced preeclampsia in rats through decreasing placental inflammation and apoptosis.

Factors affecting residual/recurrent cervical intraepithelial neoplasia after cervical conization with negative margins.

To identify factors for predicting residual or recurrent cervical intraepithelial neoplasia (CIN) after cervical conization with negative margins. A total of 172 patients with histologically verified high-grade squamous intraepithelial lesions who underwent conization with negative margins were recruited at the General Hospital of Tianjin Medical University from December 2006 to January 2016. Follow-up comprised clinical examination, a liquid-based cytology test, a human papillomavirus (HPV) DNA genotyping test, colposcopy assessment, and if indicated, colposcopy-directed punch biopsy. The Kaplan-Meier method was used to analyze the median recurrent time, whereas log-rank tests and Cox regression models were used to determine the predictors of residual/recurrent CIN. Fourteen residual/recurrent cases (8.1%) were identified in 172 patients. In univariate analysis, cytologic abnormalities on follow-up (P = .000), conization method (P = .017), HPV positivity at any visit (P = .000), persistent HPV infection postconization (P = .000), persistent infection with the same HPV genotype (P = .000), and HPV positivity at 18 months after conization (P = .000) were predictive factors of residual/recurrent CIN. The results of multivariate analysis further revealed that persistent HPV infection postconization (P = .035), HPV positivity at 18 months after conization (P = .017), and cytologic abnormalities on follow-up (P = .000) had an increased risk of residual/recurrent CIN. During follow-up, patients with persistent HPV infection or cytologic abnormalities were at high risk of residual/recurrent CIN and should be identified for close surveillance and monitoring. Meanwhile, patients with HPV who became negative within 18 months after treatment had a low risk of recurrence.

Analysis of clinical factors correlated with the accuracy of colposcopically directed biopsy.

PURPOSE: Many factors affect the accuracy of colposcopically directed biopsy (CDB). This study aimed to compare the histological results of CDB with those of cone specimens and to determine clinical factors associated with the accuracy of CDB in defining the extent and severity of cervical intraepithelial neoplasia. METHODS: We studied 513 patients diagnosed with cervical intraepithelial neoplasia by CDB who underwent conization between September 2012 and December 2016. We retrospectively evaluated the agreement between histological results on biopsies and cone specimens and analyzed factors influencing the accuracy of the results. RESULTS: The overall agreement between the histological results on biopsy and the corresponding cone specimens was 74.1%; underestimation occurred in 6.4% of cases. The agreement between histological results on biopsy and cone specimen was 54.5% for low-grade lesions, 78.2% for high-grade lesions, and 28.9% for microinvasive cervical cancer. The overall agreement between high-grade cytology and the final histological diagnosis was 86.7%. By univariate analysis, patient age (p = 0.026), menopausal status (p = 0.018), type of transformation zone (p = 0.003), number of biopsies (p = 0.002), and cone width (p = 0.015) were found to be associated with the accuracy of CDB. However, multivariate logistic regression revealed that cone width (p = 0.044) was the only independent factor correlated with CDB accuracy. CONCLUSIONS: Our data suggest that old age (≥50), postmenopausal status, and transformation zone type 3 might be positively associated with the under-diagnosis of CDB. Three or more biopsies and cone width ≥21 mm might improve CDB accuracy. However, cone width was the only independent factor correlated with CDB accuracy.

Acute Fatty Liver of Pregnancy: Analysis on the Diagnosis and Treatment of 15 Cases.

OBJECTIVE: To describe our experience with the diagnosis and management of acute fatty liver of pregnancy (AFLP). STUDY DESIGN: The medical records of pregnant women with AFLP were reviewed for symptoms, laboratory findings, treatment, and maternal and fetal outcomes during a 10-year period between January 2003 and December 2013. RESULTS: During the study period 15 women had AFLP as their discharge diagnosis. The mean gestational age at onset was 36 ± 1 weeks. Eleven cases were primigravidas, and 2 had multiple gestations. All patients presented with nausea, vomiting, and epigastric distress followed by jaundice in the third trimester of pregnancy. Raised transaminases and serum bilirubin as well as coagulopathy were found in all patients (100%), while hypoglycemia was found in 8 patients (53%). Ultrasound examination showed enhanced echo or fatty liver in 11 patients. Maternal morbidity included hepatic encephalopathy (n = 1), renal failure (n = 3), ascites (n = 6), hypoglycemia (n = 8), postpartum hemorrhage (n = 6), upper gastrointestinal hemorrhage (n = 1), and preeclampsia (n = 1). Emergency cesarean section was performed in 12 cases and supracervical hysterectomy was performed in 1 patient due to postpartum hemorrhage and disseminated intravascular coagulation (DIC); all patients survived. All neonates survived except for 2 fetal death cases before admission. CONCLUSION: Early diagnosis and prompt progressive management, including early termination of pregnancy and comprehensive supportive care, are crucial for improving the prognoses of both mother and newborn.

Verrucous Carcinoma of the Vulva: A 20 Year Retrospective Study and Literature Review.

OBJECTIVE: The aim of the study was to assess the clinicopathological characteristics of patients with verrucous carcinoma (VC) of the vulva. MATERIALS AND METHODS: We reviewed data on the age, disease course, clinical manifestation, pathologic diagnosis, treatment, and follow-up of patients with vulvar VC who were treated at Tianjin Medical University General Hospital and cases that were reported in the Chinese and English literature during the past 20 years. RESULTS: Six cases were identified in Tianjin Medical University General Hospital, the mean age of patients was 55 years, and their mean disease course was 26 months. Primary symptoms were exophytic neoplasm with pruritus and/or pain. Surgical treatment included wide local excision, simple vulvectomy, and radical vulvectomy with or without lymph node dissection in the groin. Vulvar VC occurred simultaneously with vulvar intraepithelial neoplasia in 2 cases and well-differentiated squamous cell carcinoma in 2 cases. The mean follow-up was 16.8 months with no recurrence in those 6 cases. During the 20-year period, 20 and 41 cases were reported in Chinese and English literature, respectively. Three cases were misdiagnosed with giant condyloma acuminatum in China. One case (1/20) was reported with coexistent squamous carcinoma in Chinese literature and 8 cases (8/41) in the English literature. The recurrence rate was 12.5% (2/19) and 17.5% (7/40) in Chinese and English literature, respectively. CONCLUSIONS: Vulvar VC is a distinct type of slow-growing, nonmetastatic tumor with unclear etiology. These tumors should be distinguished from giant condyloma acuminatum and well-differentiated squamous cell carcinoma. Surgery is the most effective treatment.

Analysis of the Risk Factors for Aerobic Vaginitis: A Case-Control Study.

AIMS: Aerobic vaginitis (AV) is a newly defined clinical entity which may interfere with women's reproductive health and have negative effects on pregnancy. This study was to identify the risk factors for AV. METHODS: Participants in this case-control study included healthy women and women with AV. All participants completed a standardized questionnaire covering sociodemographic factors, sexual behaviors, personal hygiene habits and health behaviors. Uni- and multivariate logistic regression analyses were used for statistical evaluation. RESULTS: A total of 290 women of reproductive age were enrolled. In the multivariate analysis, unmarried status (odds ratio [OR] 2.606, 95% confidence interval [CI] 1.257-5.402), use of an intrauterine device (OR 4.989, 95% CI 1.922-12.952), long-term use of antibiotics (OR 11.176, 95% CI 1.363-91.666) and frequent vaginal douching (OR 4.689, 95% CI 1.363-16.135) were independent risk factors for AV. On the contrary, consistent condom use (OR 0.546, 95% CI 0.301-0.991) and college-level education or above (OR 0.255, 95% CI 0.131-0.497) were independent protective factors. CONCLUSION: Measures that may be considered to prevent AV include enhancing education to improve women's knowledge related to reproductive health, especially unmarried women, encouraging them to consistently use condoms as a contraceptive method, to avoid long-term use of antibiotics and to stop frequent vaginal douching. © 2015 S. Karger AG, Basel.

Diagnostic and therapeutic advancements for aerobic vaginitis.

BACKGROUND: Aerobic vaginitis (AV) is a newly defined clinical entity that is distinct from candidiasis, trichomoniasis and bacterial vaginosis (BV). Because of the poor recognition of AV, this condition can lead to treatment failures and is associated with severe complications, such as pelvic inflammatory disease, infertility, preterm birth and foetal infections. OBJECTIVE: This review describes the diagnosis and treatment of AV and the relationship between AV and pregnancy. RESULTS: The characteristics of AV include severely depressed levels of lactobacilli, increased levels of aerobic bacteria and an inflamed vagina. The diagnosis is made by microscopy on wet mounts of fresh vaginal fluid, and some distinct clinical features are recognized. Vaginal suppositories that contain kanamycin or clindamycin have shown curative effects in nonpregnant women. Additionally, the application of topical probiotics can restore the vaginal flora and reduce the recurrence of AV. Clindamycin vaginal suppositories and probiotics may be a better choice for gravida with AV than metronidazole. AV requires prompt attention, and the early diagnosis and treatment of AV during pregnancy significantly improves perinatal outcomes. CONCLUSION: Further research is needed to define the pathogenesis, diagnostic criteria and standard treatment guidelines for AV.

Endometrial carcinoma in a 15-year-old obese patient with persistent uterine bleeding.

Endometrial carcinoma is the most common malignancy of the upper female genital tract but is rare in teenagers. Here, we report the case of a 15-year-old, nulliparous, morbidly obese female with complaints of asthenia and menometrorrhagia lasting for six months. On examination, the patient had an enlarged uterus approximately 14 gestational weeks in size, and ultrasound revealed an intrauterine mass and polycystic ovaries. An endometrial biopsy performed during hysteroscopy revealed endometrioid adenocarcinoma, and magnetic resonance imaging showed myometrial invasion. The patient underwent a laparotomy involving total abdominal hysterectomy, right salpingo-oophorectomy, wedge-shape dissection of the left ovary, and pelvic and para-aortic lymphadenectomy. We analyze the pathogenesis of endometrial carcinoma in this case and discuss the risk factors for endometrial carcinoma, especially in young women. Gynecologists should be vigilant for persistent abnormal uterine bleeding and other signs of endometrial carcinoma in young women, especially those who have risk factors for the disease.

Clinical Features and Outcomes of Twin Pregnancies with Antiphospholipid Antibodies Positivity: A Retrospective Study.

Objective: This study aimed to evaluate the impact of twin pregnancies with antiphospholipid antibody (aPL) positivity, a rare and complex clinical condition that remains a huge challenge for management. Methods: This study enrolled twin-pregnant women at our hospital between January 2018 and August 2023. Women with and without aPL positivity were selected using propensity score matching (PSM). Clinical features and pregnancy outcomes were compared between the two groups in the PSM cohort. To analyze the effect of aPL positivity on pregnancy outcomes, multivariate logistic models were used to obtain adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results: Among the 773 women with twin pregnancies, aPL positivity was found in 26 women (3.36%). In the PSM cohort, there were 24 twin-pregnant women with positive aPL, and 48 women without aPL were selected as controls. Twin-pregnant women with aPL positivity had a higher proportion of abortion (8.33% vs 0, P = 0.043), preterm birth < 34 weeks (33.33% vs 8.33%, P = 0.007) and very low birthweight (<1500 g) (20.83% vs 4.17%, P = 0.016) than the control group. In addition, stillbirth of one fetus was observed in one twin-pregnant woman with positive aPL. Multivariate logistic regression analysis revealed that twin pregnancy with aPL positivity was associated with preterm birth < 34 weeks (aOR = 2.76, 95% CI: 0.83-4.70, P = 0.005), very low birthweight (<1500 g) (OR = 2.40, 95% CI: 0.18-4.67, P = 0.034) and small for gestational age (SGA) (aOR = 1.66, 95% CI: 0.22-3.10, P =0.024). Conclusion: Twin pregnancies with aPL positivity were correlated with obstetric complications, including abortion, preterm birth < 34 weeks and very low birthweight (<1500 g). The detection of aPL may be of clinical significance for women with twin pregnancies and should be considered in future studies.

Neuropilin-1high monocytes protect against neonatal inflammation.

Neonates are susceptible to inflammatory disorders such as necrotizing enterocolitis (NEC) due to their immature immune system. The timely appearance of regulatory immune cells in early life contributes to the control of inflammation in neonates, yet the underlying mechanisms of which remain poorly understood. In this study, we identified a subset of neonatal monocytes characterized by high levels of neuropilin-1 (Nrp1), termed Nrp1high monocytes. Compared with their Nrp1low counterparts, Nrp1high monocytes displayed potent immunosuppressive activity. Nrp1 deficiency in myeloid cells aggravated the severity of NEC, whereas adoptive transfer of Nrp1high monocytes led to remission of NEC. Mechanistic studies showed that Nrp1, by binding to its ligand Sema4a, induced intracellular p38-MAPK/mTOR signaling and activated the transcription factor KLF4. KLF4 transactivated Nos2 and enhanced the production of nitric oxide (NO), a key mediator of immunosuppression in monocytes. These findings reveal an important immunosuppressive axis in neonatal monocytes and provide a potential therapeutic strategy for treating inflammatory disorders in neonates.

Maternal Infection with Listeria monocytogenes in Twin Pregnancy.

Listeria monocytogenes is the conditional pathogenic bacteria, and pregnant women are at higher risk of infection due to depressed immunity. Infection with Listeria monocytogenes in twin pregnancy is rare but devastating, which puts forwards a great challenge for clinical management. Here, a 24-year-old woman was diagnosed with twin pregnancy, intrauterine death of one fetus and fever at 29+4 week of gestation. Two days later, she developed into pericardial effusion, pneumonedema and potential septic shock. The emergent cesarean delivery was performed after anti-shock treatment. One alive and another dead fetus were delivered. Then, she developed postpartum hemorrhage after the surgery. Urgent exploratory laparotomy was conducted at the sites of cesarean section and B-Lynch suture to stop bleeding. The culture of blood and maternal side of both placentas indicated Listeria monocytogenes. Following anti-infection therapy with ampicillin-sulbactam, she recovered well and discharged with negative result of blood bacterial culture and normal inflammatory indicators. The patient was hospitalized for a total of 18 days including 2 days in the intensive care unit (ICU), and the anti-infection treatment was conducted throughout the course. Symptoms of the Listeria monocytogenes infection in pregnancy are non-specific, which should be paid more attention in case of unexplained fever and fetal distress. The blood culture is effective for accurate diagnosis. Listeria monocytogenes infection is associated with poor pregnancy outcomes. Close monitoring of fetal condition, early intervention with antibiotics, timely termination of pregnancy and comprehensive management of complications are essential for better prognosis.

Pregnancy in women with autosomal recessive Alport syndrome caused by novel compound heterozygous mutations of COL4A3 gene: Two cases reports.

RATIONALE: Autosomal recessive Alport syndrome (ARAS) is an hereditary heterogeneous disease that poses a serious risk to pregnant women. PATIENT CONCERNS: We reported 2 cases of pregnancy with progressive proteinuria. The case 1 was a 21-year-old woman with 24-h proteinuria increased from 2.03 to 11.72 g at 13 to 35 weeks of gestation, and the case 2 was a 28-year-old woman with 24-h proteinuria increased from 2.10 to 9.32 g at 8 to 36 weeks of gestation. In advanced stage of pregnancy, the fetal development was smaller than the gestational age. DIAGNOSES: Sanger sequencing showed that novel compound heterozygous mutations [c.1315 G>T (p.G439C) and c.4847 G>A (p.C1616Y)] of the collagen type IV alpha 3 chain (COL4A3) gene were found in the 2 cases. Renal puncture pathology confirmed the diagnosis of ARAS. INTERVENTIONS: The 2 cases were treated with albumin, compounded amino acids, calcium, vitamin D, and low molecular weight heparin in addition to conventional treatment during pregnancy. Pregnancy was terminated by cesarean section at 36 to 37 weeks of gestation. After delivery, the patients were treated with Losartan for anti-proteinuric therapy for 1 year. OUTCOMES: The neonatal weights and Apgar scores were normal. The patients recovered well and 24-h proteinuria decreased to pre-pregnancy level. LESSONS: When pregnant women present with a persistent increasing proteinuria, ARAS needs to be considered. Sanger sequencing is useful to assist in the diagnosis of ARAS. Multidisciplinary treatments from nephrologists and gynecologists are needed to ensure the safety of pregnancy and the fetus.