A new diagnostic technique for identifying Angiostrongylus spp. larvae in intermediate snail species by examining the buccal cavity.

BACKGROUND: Angiostrongyliasis is a zoonotic parasitic disease caused by the rat lungworm Angiostrongylus cantonensis. The intermediate hosts of A. cantonensis are gastropods, and snail species such as Pomacea canaliculata play a key role in the transmission of human angiostrongyliasis. Detecting A. cantonensis infection in snails is an important component of epidemiological surveillance and the control of angiostrongyliasis. METHODS: In this study, a new method for diagnosing A. cantonensis infection in gastropods was developed by recovering larvae from the buccal cavity of three snail species. The entire buccal cavity of a snail was extracted, and the tissue was pressed between two microscope slides to observe whether A. cantonensis larvae were present. Our new method was compared with traditional pathogenic detection methods of lung microscopy, tissue homogenization, and artificial digestion. We artificially infected 160 P. canaliculata, 160 Cipangopaludina chinensis, and 160 Bellamya aeruginosa snails with A. cantonensis. Then, the four different detection methods were used to diagnose infection in each snail species at 7, 14, 21, and 28 days post exposure. RESULTS: We found no significant difference in the percentages of infected P. canaliculata snails using the four methods to detect A. cantonensis larvae. The radula pressing method had a mean detection rate of 80%, while the lung microscopy (81.3%), tissue homogenization (83.8%), and artificial digestion (85%) methods had slightly greater detection rates. Similarly, the percentages of infected C. chinensis snails that were detected using the radula pressing (80%), tissue homogenization (82.1%), and artificial digestion (83.8%) methods were not significantly different. Finally, the percentages of infected B. aeruginosa snails that were detected using the radula pressing (81.3%), tissue homogenization (81.9%), and artificial digestion (81.4%) methods were not significantly different. These results showed that the radula pressing method had a similar detection rate to traditional lung microscopy, tissue homogenization, or artificial digestion methods. CONCLUSIONS: This study demonstrates a new method for the qualitative screening of gastropods that act as intermediate hosts of A. cantonensis (and other Angiostrongylus species), provides technical support for the control of human angiostrongyliasis, and furthers research on A. cantonensis.

α-HBDH is a superior to LDH in predicting major adverse cardiovascular events in patients with acute aortic dissection.

Objective: Acute aortic dissection (AAD) with a high mortality and postoperative complications remains presently no effective indicators to conjunctly predict the short-term mortality and the prognosis. This study aimed to investigate the predictive role of α-HBDH on in-hospital mortality and postoperative Major adverse cardiovascular events (MACE) in patients with AAD. Methods: In this retrospective study, a total of 369 enrolled patients from 2015 to 2021 were divided into three groups (T1: low, T2: medium and T3: high) based on the tertiles of α-HBDH levels on admission. In terms of the preoperative, intraoperative and postoperative indicators among 3 groups, the relationship between α-HBDH and studying endpoints was determined by logistic regression models, along with the consolidation using Kaplan-Meier and restricted cubic spline (RCS) analysis for predicting the in-hospital death and MACE complications. Last, subgroup analysis further verified the predictive value of α-HBDH. Results: Logistic regression analysis showed that α-HBDH was independently associated with in-hospital mortality of patients with AAD [OR(95CI): 4.771(1.043-21.832), P = 0.044] and MACE [OR(95CI): 9.869(2.148-45.349), P = 0.003]. Moreover, Kaplan-Meier analysis also showed an increased α-HBDH levels associated with poor survival within 30 days (log rank test, P < 0.01), especially in acute Stanford A dissection. RCS presented that 204 U/L was the optimal cut-off value of α-HBDH for in-hospital mortality and postoperative MACE, which facilitated clinical stratification of patients with AAD. Subgroup analysis confirmed a stable correlation between α-HBDH level and hospital mortality and MACE (P > 0.05). Conclusions: α-HBDH is a predictor of the in-hospital mortality and postoperative MACE, guiding admission stratification of patients with AAD.

Association of inactivated COVID-19 vaccination with maternal coagulation function in early pregnancy.

Reports of rare but severe thrombotic events after receiving some COVID-19 vaccines brought concerns for the possibility of vaccine-induced coagulation abnormality. However, no study has reported the impacts of COVID-19 vaccination on coagulation function in pregnant women. We aimed to explore whether vaccination with inactivated COVID-19 vaccines before pregnancy was associated with coagulation changes in pregnant women. We conducted a retrospective cohort study in a tertiary-care hospital in Shanghai, China. A total of 5166 pregnant women were included, of whom 2721 (52.7%) completed vaccination before conception. Compared with unvaccinated women, the mean serum levels of prothrombin time (PT) and fibrinogen (FIB) were lower in vaccinated women by 0.09 (ß = -0.09, 95% confidence interval [CI], -0.13, -0.05) mg/L and 0.11 (ß = -0.11, 95% CI, -0.15, -0.07) mg/L, and the mean D-Dimer (D-D) levels were higher by 0.12 (ß = 0.12, 95% CI, 0.09, 0.15) mg/L. However, no significant association was observed between COVID-19 vaccination and serum levels of activated partial thromboplastin time (APTT), fibrinogen degradation product (FDP) or thrombin time (TT). Our findings suggested that inactivated COVID-19 vaccination before conception resulted in a small change in maternal coagulation function, but this might not have clinical significance.

Sox10 escalates vascular inflammation by mediating vascular smooth muscle cell transdifferentiation and pyroptosis in neointimal hyperplasia.

Vascular smooth muscle cells (VSMCs) can transdifferentiate into macrophage-like cells in the context of sustained inflammatory injury, which drives vascular hyperplasia and atherosclerotic complications. Using single-cell RNA sequencing, we identify that macrophage-like VSMCs are the key cell population in mouse neointimal hyperplasia. Sex-determining region Y (SRY)-related HMG-box gene 10 (Sox10) upregulation is associated with macrophage-like VSMC accumulation and pyroptosis in vitro and in the neointimal hyperplasia of mice. Tumor necrosis factor α (TNF-α)-induced Sox10 lactylation in a phosphorylation-dependent manner by PI3K/AKT signaling drives transcriptional programs of VSMC transdifferentiation, contributing to pyroptosis. The regulator of G protein signaling 5 (RGS5) interacts with AKT and blocks PI3K/AKT signaling and Sox10 phosphorylation at S24. Sox10 silencing mitigates vascular inflammation and forestalls neointimal hyperplasia in RGS5 knockout mice. Collectively, this study shows that Sox10 is a regulator of vascular inflammation and a potential control point in inflammation-related vascular disease.

No association of vaccination with inactivated COVID-19 vaccines before conception with pregnancy complications and adverse birth outcomes: A cohort study of 5457 Chinese pregnant women.

Data on the safety of inactivated COVID-19 vaccines in pregnant women is limited and monitoring pregnancy outcomes is required. We aimed to examine whether vaccination with inactivated COVID-19 vaccines before conception was associated with pregnancy complications or adverse birth outcomes. We conducted a birth cohort study in Shanghai, China. A total of 7000 healthy pregnant women were enrolled, of whom 5848 were followed up through delivery. Vaccine administration information was obtained from electronic vaccination records. Relative risks (RRs) of gestational diabetes mellitus (GDM), hypertensive disorders in pregnancy (HDP), intrahepatic cholestasis of pregnancy (ICP), preterm birth (PTB), low birth weight (LBW), and macrosomia associated with COVID-19 vaccination were estimated by multivariable-adjusted log-binomial analysis. After exclusion, 5457 participants were included in the final analysis, of whom 2668 (48.9%) received at least two doses of an inactivated vaccine before conception. Compared with unvaccinated women, there was no significant increase in the risks of GDM (RR = 0.80, 95% confidence interval [CI], 0.69, 0.93), HDP (RR = 0.88, 95% CI, 0.70, 1.11), or ICP (RR = 1.61, 95% CI, 0.95, 2.72) in vaccinated women. Similarly, vaccination was not significantly associated with any increased risks of PTB (RR = 0.84, 95% CI, 0.67, 1.04), LBW (RR = 0.85, 95% CI, 0.66, 1.11), or macrosomia (RR = 1.10, 95% CI, 0.86, 1.42). The observed associations remained in all sensitivity analyses. Our findings suggested that vaccination with inactivated COVID-19 vaccines was not significantly associated with an increased risk of pregnancy complications or adverse birth outcomes.

Wounding characteristics and treatment principles of ground anti-armored vehicle ammunition against armored crew.

The wound mechanism, injury characteristics and treatment principles of anti-armored vehicle ammunition against armored crew in the past 20 years are summarized in this paper. Shock vibration, metal jet, depleted uranium aerosol and post armor breaking effect are the main factors for wounding armored crew. Their prominent characteristics are severe injury, high incidence of bone fracture, high rate of depleted uranium injury, and high incidence of multiple/combined injuries. During the treatment, attention must be paid on that the space of armored vehicle is limited, and the casualties should be moved outside of the cabin for comprehensive treatment. Especially, the management of depleted uranium injury and burn/inhalation injury are more important than other injuries for the armored wounds.

Predictive value of admission CO2 combining power combined with serum sodium for the prognosis in acute Stanford type A aortic dissection patients.

Acute Stanford type A aortic dissection (ATAAD) with sudden onset and high mortality requiries a standard Bentall operation and a accurate prognosis in common, together with alteration of CO2 combining power (CO2CP) and serum sodium rase concern, hence, we evaluated the prognostic value of CO2CP combined with serum sodium in ATAAD patients. This retrospective study included 183 patients who underwent Bentall operation for ATAAD from 2015 to 2021 in the Fourth Hospital of Hebei Medical University, subsequently followed grouping by the levels of CO2CP and serum sodium. The study endpoint was 30-day all-cause mortality, and the prognostic value of CO2CP combined with serum sodium levels in ATAAD patients were evaluated with multivariate logistic regression method. The postoperative incidence of in-hospital death and adverse events in patients with ATAAD were 18% and 25.7%, respectively. Combination of CO2CP and serum sodium for predicting ATAAD death and adverse events presented a higher predictive value than each single indicator with ROC curve analysis (the AUC of CO2CP combined with serum sodium was 0.786, 95% CI 0.706-0.869, P < 0.001), along with CO2CP < 22.5 mmol/L + serum sodium > 138.5 mmol/L group had the worst prognostic. Multivariate regression analyse showed that CO2CP < 22.5 mmol/L combined with serum sodium > 138.5 mmol/L preferably predicted the prognosis of ATAAD (OR =6.073, 95% CI 2.557-14.425, P < 0.001). Consistently, the cumulative 30-day survival after surgery in ATAAD patients with the low CO2CP and high serum sodium simultaneously was the worst (log-rank P < 0.05). The combination of CO2CP and serum sodium increases the predictive value of prognosis, which is conducive to risk stratification of patients with ATAAD.

Association of COVID-19 vaccination before conception with maternal thyroid function during early pregnancy: A single-center study in China.

Despite the high vaccination coverage, potential COVID-19 vaccine-induced adverse effects, especially in pregnant women, have not been fully characterized. We examined the association between COVID-19 vaccination before conception and maternal thyroid function during early pregnancy. We conducted a retrospective cohort study in Shanghai, China. A total of 6979 pregnant women were included. Vaccine administration was obtained from electronic vaccination records. Serum levels of thyroid hormone were measured by fluorescence and chemiluminescence immunoassays. Among the 6979 included pregnant women, 3470 (49.7%) received at least two doses of an inactivated vaccine. COVID-19 vaccination had a statistically significant association with both maternal serum levels of free thyroxine (FT4) and thyroid stimulating hormone (TSH). Compared with unvaccinated pregnant women, the mean FT4 levels were lower in pregnant women who had been vaccinated within 3 months before the date of conception by 0.27 pmol/L (ß = -0.27, 95% confidence interval [CI], -0.42, -0.12), and the mean TSH levels were higher by 0.08 mIU/L (ß = 0.08, 95% CI, 0.00, 0.15). However, when the interval from vaccination to conception was prolonged to more than 3 months, COVID-19 vaccination was not associated with serum FT4 or TSH levels. Moreover, we found that COVID-19 vaccination did not significantly associate with maternal hypothyroidism. Our study suggested that vaccination with inactivated COVID-19 vaccines before conception might result in a small change in maternal thyroid function, but this did not reach clinically significant levels.

Analysis on Early and Late Operation Results and Risk Factors of Elderly Acute Type-A Aortic Dissection.

OBJECTIVE: To explore the early and late operation results and risk factors of elderly acute type-A aortic dissection. METHODS: The regression analysis was conducted on the data of patients diagnosed with acute type-A aortic dissection in our hospital from January 2018 to January 2020, and a total of 98 patients aged over 70 years were included in the study. The patients were listed into the early operation group (a total of 51 patients operated within 3 days after admission) and the late operation group (a total of 47 patients operated within 10 days after admission) according to the time of operation. The operation results, postoperative complications and death were compared between the two groups, and the prognosis risk factors were analyzed through Logistic multi-factor regression. RESULTS: The operative time, aortic obstruction time and extracorporeal circulation time of the late operation group were all higher than those in the early operation group (p <0.05). The postoperative complications and mortality in the late operation group (12.77%) were higher than those in the early operation group (3.92%) (p < 0.05). The Logistic multi-factor regression showed that late operation (p=0.005, OR=4.213, 95% CI=1.567~11.201), postoperative acute renal insufficiency (p=0.028, OR=3.281, 95% CI=0.937~10.283), and postoperative pulmonary infection (p=0.033, OR=1.421, 95% CI=0.417~8.329) were risk factors affecting postoperative mortality (p <0.05). CONCLUSION: The early operation can effectively reduce the postoperative complications of elderly acute type-A aortic dissection, so early operation should be performed according to the conditions of patients and hospital.

The N6-Methyladenosine Regulator ALKBH5 Mediated Stromal Cell-Macrophage Interaction via VEGF Signaling to Promote Recurrent Spontaneous Abortion: A Bioinformatic and In Vitro Study.

Successful conception requires the synchrony of multiple systems and organs. Dysregulation of stromal cell-immune cell interactions has been proposed to be associated with recurrent spontaneous abortion. However, the mechanism of this regulation has not been well elucidated. N6-methyladenosine is one of the most common RNA modifications, and is involved in many pathological processes. Our group has demonstrated that abnormal patterns of m6A modification inhibit trophoblast invasion and contribute to adverse pregnancy outcomes. The association between m6A regulators and stromal cell-immune cell interactions is unclear. We obtained RNA-seq profiles from a GEO dataset and identified differentially expressed m6A regulators between healthy controls and patients with a recurrent spontaneous abortion history. ROC curves, functional enrichment and subclassification analysis were applied to elucidate the role of m6A regulators in pregnancy. We verified the expression of m6A regulators and constructed an overexpression cell line in a coculture system to reveal ALKBH5 function in stromal cell-macrophage interactions. We identified 11 differentially expressed m6A regulators between healthy controls and patients with a recurrent spontaneous abortion history. Then, we identified the correlation between "eraser" genes and "writer" genes. We tested the predictive abilities of the 11 m6A regulators based on another dataset and verified their expression in primary human endometrial stromal cells. We then subclassified three distinct patterns using the 11 genes and visualized genes related to immune infiltration and macrophage function in each cluster. ALKBH5 was proven to be correlated with recurrent spontaneous abortion. To verify the role of ALKBH5 in RSA, we constructed an ALKBH5-overexpression cell line. Finally, we cocultured the overexpression cell line with THP-1 cells. A decrease in M2 differentiation was observed, and this bias could be attributed to the hyposecretion of VEGF in stromal cells. N6-methyladenosine regulators play a pivotal role in stromal cell-immune cell interactions at the maternal-fetal interface. Overexpression of the m6A "eraser" gene ALKBH5 in stromal cells resulted in the hyposecretion of VEGF. Dysregulation of VEGF might impair macrophage recruitment and M2 differentiation, which could be the potential cause of recurrent spontaneous abortion.

Association of COVID-19 vaccination before conception with maternal liver function during early pregnancy: a cohort study of 7745 Chinese pregnant women.

ABSTRACTMulticenter case series has reported patients with hepatic injury following COVID-19 vaccination, which raised concern for the possibility of vaccine-induced liver dysfunction. We aimed to assess the impact of COVID-19 vaccination on liver function of pregnant women, who may be uniquely susceptible to vaccine-induced liver dysfunction. We conducted a retrospective cohort study at a tertiary hospital in Shanghai, China. Vaccine administration was obtained from the electronic vaccination record. Serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total bile acid (TBA) and total bilirubin (TBIL) in early pregnancy were determined by enzymatic methods. Among the 7745 included pregnant women, 3832 (49.5%) received at least two doses of an inactivated vaccine. COVID-19 vaccination was significantly associated with higher levels of maternal serum TBA. Compared with unvaccinated pregnant women, the mean TBA levels increased by 0.17 µmol/L (ß = 0.17, 95% CI, 0.04, 0.31) for women who had been vaccinated within 3 months before the date of conception. Moreover, COVID-19 vaccination was significantly associated with an increased risk of maternal hyperbileacidemia. The risk of hyperbileacidemia increased by 113% (RR = 2.13; 95% CI, 1.17-3.87) for pregnant women who had been vaccinated within 3 months before conception compared with unvaccinated pregnant women. However, when the interval from complete vaccination to conception was prolonged to more than 3 months, COVID-19 vaccination was not associated with serum TBA levels or maternal hyperbileacidemia. Our findings suggest that vaccination with inactivated COVID-19 vaccines more than 3 months before conception have no detrimental effects on maternal liver function in early pregnancy.

A study of mechanical ventilation in the ICU after cardiac surgery: a bibliometric analysis.

Background: After cardiac surgery, patients are often admitted to the intensive care unit (ICU) due to various preoperative factors and continue to receive mechanical ventilation. This study sought to conduct a bibliometric analysis to summarize studies on mechanical ventilation among postoperative ICU patients who had undergone cardiac surgery. Methods: We searched the Science Citation Index Expanded (SCI-E) database using the following terms: "cardiac surgery (Topic)", "intensive care (Topic)" and "ventilation (Topic)". The search results were analyzed using R software. The analysis examined the number of publications of relevant articles and the annual change trend, the number of times an article was cited and the annual change trend, the distribution of countries conducting the research, the cooperation between countries and the citation frequency, the distribution of institutions conducting research, the cooperation between institutions, and the citation frequency, the number of published articles, the cooperation among researchers, and the citations frequency of researchers, the journals in which the articles were published, and the use of keywords. Results: A total of 1,969 relevant research papers were included in this study. The main countries that conducted the relevant research included the United States (US), China, Germany, and Canada. The research institutions were mainly located in the US and Canada, and the main researchers were from research institutions in these countries. The most cited authors were Zappitelli, Hichey, and Wypij. According to Bradford's law, 9 core journals in this field were identified. The results of the keyword analysis showed that in the past 10 years, research has focused on the mortality of patients, but only a few related random controlled trials have been conducted. Conclusions: More randomized controlled trials need to be conducted in this field to provide higher evidence-based medical evidence.

Association of History of Spontaneous or Induced Abortion With Subsequent Risk of Gestational Diabetes.

IMPORTANCE: Gestational diabetes (GD) is one of the most common and important complications of pregnancy. Identifying pregnant women who are at high risk of GD is crucial for implementing early prevention and intervention. OBJECTIVE: To examine whether a history of spontaneous abortion (SAB) or induced abortion is associated with increased risk of GD in subsequent pregnancies. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted at a tertiary hospital in Shanghai, China. Pregnant women who received routine antenatal care between January 2014 and December 2019 were included. Data analysis was performed from December 2020 to June 2021. EXPOSURES: Maternal history of abortion, including SAB and induced abortion, were extracted from medical records. MAIN OUTCOMES AND MEASURES: GD was diagnosed with a 75-g diagnostic oral glucose tolerance test. A multivariable-adjusted log-binomial analysis was used to estimate relative risks (RRs) and 95% CIs of GD associated with history of abortion. RESULTS: Among the 102 259 included pregnant women (mean [SD] age, 29.8 [3.8] years), 14 579 (14.3%) experienced only SAB, 17 935 (17.5%) experienced only induced abortion, and 4017 (3.9%) experienced both SAB and induced abortion. A total of 12 153 GD cases were identified, and the prevalence of GD was 11.9% (12 153 of 102 259 women) in this cohort. Pregnant women who experienced only SAB (RR, 1.25; 95% CI, 1.18-1.31) or both SAB and induced abortion (RR, 1.15; 95% CI, 1.05-1.27) were at higher risk of developing GD. The association of SAB history with GD occurred in a number-dependent manner. Compared with pregnant women with no history of abortion, the RR for GD increased by 18% (RR, 1.18; 95% CI, 1.11-1.26) for pregnant women with 1 SAB, by 41% (RR, 1.41; 95% CI, 1.27-1.57) for those with 2 SABs, and by 43% (RR, 1.43; 95% CI, 1.22-1.67) for those more than 2 SABs. However, no association between history of induced abortion and GD was observed. CONCLUSIONS AND RELEVANCE: This study found that a history of SAB was associated with increased risk of GD in subsequent pregnancies. Further research is needed to clarify this association and explore the potential biological mechanisms underlying the association.

Gestational exposure to BDE-209 induces placental injury via the endoplasmic reticulum stress-mediated PERK/ATF4/CHOP signaling pathway.

Several epidemiological studies have reported significant associations between prenatal polybrominated diphenyl ethers (PBDEs) exposure and adverse birth outcomes. Placental injury is thought to mediate these associations. However, few study has investigated the adverse effects of PBDEs exposure on placental growth and development. We examined the impacts of gestational exposure to BDE-209, the most abundant PBDE conger detected in human samples, on placental structure and function, and its model of action in vivo and in vitro. Pregnant mice were exposed to 0, 2, 20, 200 mg/kg/day of BDE-209 by gavages from gestational day (GD) 0 to GD18. Results showed that gestational BDE-209 exposure significantly reduced placental weight, impaired placental vascular development and induced placental cell apoptosis. In addition, gestational BDE-209 exposure impaired placental transport and endocrine function as demonstrated by markedly downregulated expression of Glut1, Znt1, Pgf and Igf2 in BDE-209-treated placentas. Mechanistically, gestational exposure to BDE-209 upregulated the expression of GRP78, and 3 downstream proteins (p-eIF2α, ATF4 and CHOP) of the PERK signaling, suggesting the activation of endoplasmic reticulum (ER) stress and PERK signaling pathway in mouse placentas. Further in vitro study showed that PERK siRNA pretreatment markedly reversed BDE-209-induced cell apoptosis in human JEG-3 cells. Collectively, our results suggest that the activation of the ER stress-mediated PERK/ATF4/CHOP signaling pathway played a role in BDE-209-induced placental injury. Our findings provide new insight into the mechanisms of BDE-209 induced reproductive and developmental toxicity.

Serum uric acid in early pregnancy and risk of gestational diabetes mellitus: A cohort study of 85,609 pregnant women.

AIMS: Higher serum uric acid (UA) has been associated with increased risk of Type 2 diabetes mellitus. This cohort study examined whether there are any associations between serum UA in early pregnancy and the subsequent risk of gestational diabetes mellitus (GDM). METHODS: This cohort study was conducted in Shanghai, China, and included 85,609 pregnant women. Generalised additive models were used to estimate the associations of serum UA with risk of GDM. RESULTS: The prevalence of GDM was 14.0% (11,960/85,609). Non-linear associations between serum UA and GDM risk were observed and these associations varied by gestational ages. Only elevated serum UA levels at 13-18 weeks gestation was associated with substantially increased risk of GDM. Analysis by UA quintiles at 13-18 weeks gestation showed the odds ratios for GDM were 1.11 (95%CI, 1.03-1.20) for the second, 1.27 (95%CI, 1.17-1.37) for the third, 1.37 (95%CI, 1.27-1.48) for the fourth and 1.70 (95%CI, 1.58-1.84) for the fifth quintile of serum UA in comparison with the first quintile. Stratified analysis showed the associations of serum UA with GDM were stronger among pregnant women aged 35 years or older. CONCLUSION: We found higher serum UA at 13-18 gestational weeks was a risk factor for GDM. Our findings provide new evidence for the role of serum UA in the prevention and early intervention of GDM, and highlighted the need for monitoring serum UA at 13-18 gestational weeks.

Serum sodium on admission affects postoperative in-hospital mortality in acute aortic dissection patients.

BACKGROUND: Acute aortic dissection (AAD) is very fatal without surgical treatment. Higher serum sodium can increase in-hospital mortality of many diseases; however, the effect of serum sodium on postoperative in-hospital mortality in AAD patients remains unknown. METHODS: We collected a total of 415 AAD patients from January 2015 to December 2019. Patients were classified into four categories (Q1-Q4) according to the admission serum sodium quartile. The cox proportional hazards model evaluated the association between serum sodium and in-hospital mortality. All-cause in-hospital mortality was set as the endpoint. RESULTS: By adjusting many covariates, cox proportional hazards model revealed the in-hospital mortality risk of both Q3 and Q4 groups was 3.086 (1.242-7.671, P = 0.015) and 3.370 (1.384-8.204, P = 0.007) respectively, whereas the risk of Q2 group was not significantly increased. Univariate and multiple Cox analysis revealed that Stanford type A, serum glucose, α-hydroxybutyrate dehydrogenase and serum sodium were risk factors correlated with in-hospital death in AAD patients. CONCLUSION: The study indicates that the admission serum sodium of AAD patients has a vital impact on postoperative hospital mortality.

Decreased nitric oxide content mediated by asymmetrical dimethylarginine and protein l-arginine methyltransferase 3 in macrophages induces trophoblast apoptosis: a potential cause of recurrent miscarriage.

STUDY QUESTION: Is the protein l-arginine methyltransferase 3 (PRMT3)/asymmetrical dimethylarginine (ADMA)/nitric oxide (NO) pathway involved in the development of recurrent miscarriage (RM), and what is the potential mechanism? SUMMARY ANSWER: Elevated levels of PRMT3 and ADMA inhibit NO formation in the decidua, thereby impairing the functions of trophoblast cells at the maternal-foetal interface. WHAT IS KNOWN ALREADY: Decreased NO bioavailability is associated with RM. ADMA, an endogenous inhibitor of nitric oxide synthase (NOS), is derived from the methylation of protein arginine residues by PRMTs and serves as a predictor of mortality in critical illness. STUDY DESIGN, SIZE, DURATION: A total of 145 women with RM and 149 healthy women undergoing elective termination of an early normal pregnancy were enrolled. Ninety-six female CBA/J, 24 male DBA/2 and 24 male BALB/c mice were included. CBA/J × DBA/2 matings represent the abortion group, while CBA/J × BALB/c matings represent the normal control group. The CBA/J pregnant mice were then categorised into four groups: (i) normal + vehicle group (n = 28), (ii) abortion + vehicle group (n = 28), (iii) normal + SGC707 (a PRMT3 inhibitor) group (n = 20) and (iv) abortion + SGC707 group (n = 20). All injections were made intraperitoneally on Days 0.5, 3.5 and 6.5 of pregnancy. Decidual tissues were collected on Days 8.5, 9.5 and 10.5 of gestation. The embryo resorption rates were calculated on Day 9.5 and Day 10.5 of gestation. PARTICIPANTS/MATERIALS, SETTING, METHODS: NO concentration, ADMA content, NOS activity, expression levels of NOS and PRMTs in decidual tissues were determined using conventional assay kits or western blotting. PRMT3 expression was further analysed in decidual stromal cells, macrophages and natural killer cells. A co-culture system between decidual macrophages (DMs) and HTR-8/SVneo trophoblasts was constructed to study the roles of the PRMT3/ADMA/NO signalling pathway. Trophoblast apoptosis was analysed via Annexin V-fluorescein isothiocyanate/propidium iodide staining. CBA/J × DBA/2 mouse models were used to investigate the effects of SGC707 on embryo resorption rates. MAIN RESULTS AND THE ROLE OF CHANCE: Our results show that NO concentration and NOS activity were decreased, but ADMA content and PRMT3 expression were increased in the decidua of RM patients. Moreover, compared with the normal control subjects, PRMT3 expression was significantly up-regulated in the macrophages but not in the natural killer cells or stromal cells of the decidua from RM patients. The inhibition of PRMT3 results in a significant decrease in ADMA accumulation and an increase in NO concentration in macrophages. When co-cultured with DMs, which were treated with SGC707 and ADMA, trophoblast apoptosis was suppressed and induced, respectively. In vivo experiments revealed that the administration of SGC707 reduced the embryo resorption rate of CBA/J × DBA/2 mice. LIMITATIONS, REASONS FOR CAUTION: All sets of experiments were not performed with the same samples. The main reason is that each tissue needs to be reserved for clinical diagnosis and only a small piece of each tissue can be cut and collected for this study. WIDER IMPLICATIONS OF THE FINDINGS: Our results indicate that the PRMT3/ADMA/NO pathway is a potential marker and target for the clinical diagnosis and therapy of RM. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (2017YFC1001401), National Natural Science Foundation of China (81730039, 82071653, 81671460, 81971384 and 82171657) and Shanghai Municipal Medical and Health Discipline Construction Projects (2017ZZ02015). The authors have declared no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.