[Simultaneous determination of six benzodiazepine sedatives residue in aquatic products by high performance liquid chromatography-triple quadrupole mass spectrometry].

OBJECTIVE: To establish a method for the simultaneous determination of 6 benzodiazepine sedatives residue in aquatic products by high performance liquid chromatography-triple quadrupole mass spectrometry. METHODS: The samples were extracted with acetonitrile and purified by C_(18 )solid phase extraction column. The sample solution was separated by Waters ACQUITY UPLC BEH C_(18 )column(2.1 mm×50 mm, 1.7 µm) using 0.1% formic acid and methanol as mobile phase for gradient elution, determined in multiple reaction monitoring mode and quantified by internal standard method. RESULTS: Six benzodiazepine sedatives had a good linear relationship in the range of 1.0-50.0 µg/L with r>0.9990, the limits of detection and limits of quantification were 0.3 and 1.0 µg/kg. Average recoveries for the analytes at 3 spiked levels ranged from 74.2%-108.0% with relative standard deviations of 1.1%-6.7%(n=6). CONCLUSION: The method is simple, rapid, sensitive and accurate, which is suitable for simultaneous determination of 6 benzodiazepine sedatives residue in aquatic products.

Current research and evidence gaps on placental development in iron deficiency anemia.

Studying the effects of maternal iron deficiency anemia (IDA) is complex owing to its diverse causes, each independently impacting the placenta and fetus. Simple treatment with iron supplements does not always resolve the anemia. Therefore, delving into how IDA alters placental development at a molecular level is crucial to further optimize treatment. This review addresses the effects of IDA on placental structures and functions, including changes in oxygen levels, blood vessels, and the immune system. Profound understanding of physiological characteristics and regulatory mechanisms of placental development is key to explain the mechanisms of abnormal placental development in pregnancy-associated disorders. In turn, future strategies for the prevention and treatment of pregnancy complications involving the placenta can be devised. These studies are significant for improving human reproductive health, enhancing sociodemographic qualities, and even lifelong wellbeing, a focal point in future placental research.

Pregnancy outcomes of fetal reduction in patients with intrauterine haematoma following double embryo transfer.

RESEARCH QUESTION: Is there an association between intrauterine haematoma (IUH) and pregnancy outcomes in patients who undergo fetal reduction after double embryo transfer (DET), and if so, what is the relationship between IUH-related characteristics and pregnancy outcomes? DESIGN: Clinical information and pregnancy outcomes of women who underwent fetal reduction after DET were analysed. Patients with other systematic diseases, ectopic pregnancy or heterotopic pregnancy, monochorionic twin pregnancies and incomplete data were excluded. Stratification of IUH pregnancies was undertaken based on IUH-related characteristics. The main outcome was incidence of fetal demise (<24 weeks), with other adverse pregnancy outcomes considered as secondary outcomes. RESULTS: Thirty-four IUH patients and 136 non-IUH patients who underwent fetal reduction after DET were included based on a 1:4 match for age, cycle type and fertilization method. IUH patients had a higher incidence of early fetal demise (20.6% versus 7.4%, P = 0.048), threatened abortion (48.1% versus 10.3%, P<0.001) and postpartum haemorrhage (PPH; 14.8% versus 4.0%, P = 0.043) compared with non-IUH patients. IUH was an independent risk factor for early fetal demise [adjusted OR (aOR) 3.34, 95% CI 1.14-9.77] and threatened abortion (aOR 8.61, 95% CI 3.28-22.61) after adjusting for potential confounders. IUH pregnancies undergoing fetal reduction that resulted in miscarriage had larger IUH volumes and earlier diagnosis (both P < 0.03). However, IUH characteristics (i.e. volume, changing pattern, presence or absence of cardiac activity) were not associated with threatened abortion or PPH. CONCLUSIONS: Fetal reduction should be performed with caution in IUH pregnancies after DET as the risk of fetal demise is relatively high. Particular attention should be given to IUH patients with early signs of threatened abortion and inevitable fetal demise.

Tumor cell-released kynurenine biases MEP differentiation into megakaryocytes in individuals with cancer by activating AhR-RUNX1.

Tumor-derived factors are thought to regulate thrombocytosis and erythrocytopenia in individuals with cancer; however, such factors have not yet been identified. Here we show that tumor cell-released kynurenine (Kyn) biases megakaryocytic-erythroid progenitor cell (MEP) differentiation into megakaryocytes in individuals with cancer by activating the aryl hydrocarbon receptor-Runt-related transcription factor 1 (AhR-RUNX1) axis. During tumor growth, large amounts of Kyn from tumor cells are released into the periphery, where they are taken up by MEPs via the transporter SLC7A8. In the cytosol, Kyn binds to and activates AhR, leading to its translocation into the nucleus where AhR transactivates RUNX1, thus regulating MEP differentiation into megakaryocytes. In addition, activated AhR upregulates SLC7A8 in MEPs to induce positive feedback. Importantly, Kyn-AhR-RUNX1-regulated MEP differentiation was demonstrated in both humanized mice and individuals with cancer, providing potential strategies for the prevention of thrombocytosis and erythrocytopenia.

Mechanism of trophoblast cell-derived microparticles mediated immunocontraceptive response.

PROBLEM: Immunomodulation profoundly affects the process of human implantation. Trophoblast cell-derived microparticles (Tr-MPs) may activate specific T cells to attack trophoblast cells, thus potentially acting as an immunocontraceptive vaccine. The safety and persistence of Tr-MP vaccine are needed to address. METHOD OF STUDY: Flow cytometry and confocal fluorescent microscopy were conducted to detect cellular absorptivity and localization of Tr-MPs in bone marrow-derived dendritic cells (BMDCs). The phenotype and cytokine secretion of BMDC and T cells were performed by flow cytometry and enzyme-linked immuno sorbent assay (ELISA). The constructed vaccine female moused model were used to observe the infertile effect and safety of Tr-MPs. RESULTS: As compared with non-irradiation exposure groups, the number of MPs released by trophoblast cells in ultraviolet immunized groups significantly increased. The phagocytosis of Tr-MPs led to the maturation of dendritic cells (DCs), which, in turn, activate T cells. Then cytotoxic T cells attacking trophoblast cells. In mouse model, female mice were infertile after receiving Tr-MPs, and the effect of contraception is transient and safety. CONCLUSION: Using Tr-MPs to initiate an adaptive immune response against alloantigens in trophoblast cells. Tr-MPs may be a new candidate for the development of contraceptive vaccines due to its effectiveness, safety, and reversibility.

Effect modification by aging on the associations of nicotine exposure with cognitive impairment among Chinese elderly.

Active and passive exposure to tobacco smoke may increase risk of cognitive decline. However, effects of enhanced the aging process on the association of urinary nicotine metabolites with cognitive impairment remain unclear. In this study, 6657 Chinese older adults completed the physical examinations and cognitive tests. We measured urinary nicotine metabolite levels, mitochondrial DNA copy number (mtDNA-CN), and relative telomere length (RTL) and analyzed effects of urinary nicotine metabolites and their interaction with mtDNA-CN or RTL on cognitive impairment by generalized linear models and qg-computation, respectively. Each 1-unit increase in urinary 3-OHCot, 3-OHCotGluc, CotGluc, or NicGluc levels corresponded to a 1.05-, 1.09-, 1.04-, and 0.90-fold increased risk of cognitive impairment. Each 1-quantile increment in the mixture level of 8 nicotine metabolites corresponded to an increment of 1.40- and 1.34-fold risk of cognitive impairment in individuals with longer RTL or low mtDNA-CN. Urinary 3-OHCotGluc and RTL or mtDNA-CN exhibited an additive effect on cognitive impairment in addition to the mixture of 8 nicotine metabolites and mtDNA-CN. The findings suggested that aging process may increase the risk of tobacco-related cognitive impairment.

Effects of vaginal microbiota and cervical cerclage on obstetric outcomes of twin pregnancies with cervical incompetence: a retrospective study.

PURPOSE: To determine the role of vaginal microbiota in the efficacy of cervical cerclage in obstetric outcomes of twin pregnancies. METHODS: This retrospective study enrolled 68 twin pregnant women diagnosed with cervical incompetence (CIC) and 68 twin pregnancies without CIC. The CIC group was further divided into two subgroups: cerclage group (n = 51) and non-cerclage group (n = 17), according to whether cervical cerclage was performed in the second trimester. Data of vaginal microbiota and obstetric outcomes were collected and compared. RESULTS: Cervical incompetence had harmful effect on both pregnancy outcomes and vaginal microecology, characterized by earlier gestational week at delivery (30.3 ± 5.6 vs 35.6 ± 1.1, P < 0.001), a lower birth weight of newborns (OR 0.40; 95% CI 0.22-0.74), a higher vaginal pH value (OR 0.11; 95% CI 0.04-0.30) and a lower abundance of Lactobacillus (OR 0.34; 95% CI 0.17-0.70). In addition, compared with the vaginal microbiota after cerclage, less normal diversity of bacterial flora (OR 0.35; 95% CI 0.12-1.01), less Lactobacillus (OR 0.40; 95% CI 0.18-0.91) and more Gardnerella vaginalis (OR 18.92; 95% CI 2.38-150.35) appeared before cerclage. Besides, the unhealthy vaginal environment also had an unfavorable influence on the neonatal outcomes, increased neonatal mortality rate was observed in the group of vaginal pH > 4.5 (P < 0.05). Fortunately, compared with the non-cerclage group, the cerclage group had a longer interval from diagnosis to delivery (≥ 8 weeks) and more of the newborns' birth weight were not less than 1500 g (P < 0.05). CONCLUSION: A healthy vaginal environment is essential to improve the obstetric outcome for twin pregnancies with cervical cerclage.

Changes of Lipoxin A4 and the Anti-inflammatory Role During Parturition.

Parturition is the physiological process of newborn birth; more and more evidences show that parturition is closely related to the occurrence and resolution of inflammation. However, the inflammatory media and the mechanism are not very clear during parturition. Here, we investigate the inflammatory event during human parturition and in mouse model. We found that the pro-inflammatory cytokines (IL-6, IL-8, and IL-1ß) and cells (neutrophil and macrophage) are decreased in pregnant women in labor and in mouse labor model. Mechanistically, increased stress stimulates the high-level adrenaline production in labor. Then, adrenaline upregulates the expression of 12/15-LOX (lipoxygenase) to produce more lipoxin A4 (LXA4), which is an inflammation inhibitor. Thus, LXA4 promotes the elimination of inflammation during labor to protect the body from excessive inflammatory damages. In addition, using BOC-2, the inhibitor of LXA4 receptor could reboot the pro-inflammatory cytokines. Our study indicates that LXA4 is induced by adrenaline in labor and appropriate interference of this pathway may be a potential strategy to regulate the inflammatory process in parturition.

Vanishing twin syndrome is associated with first-trimester intrauterine hematoma in twin pregnancies after in vitro fertilization.

Research question: Is there an association between intrauterine hematoma (IUH), vanishing twin syndrome (VTS), and subsequent complications in twin pregnancies after in vitro fertilization (IVF)? What are the risk factors for these complications? Design: Women who presented with two live gestational sacs following double embryo transfer were included. Patients with systematic diseases, artificial fetal reduction, and incomplete data were excluded. Further stratification of IUH pregnancies was performed according to IUH-related characteristics (i.e., volume, changing pattern, and relationship with fetal cardiac activities). The primary outcome was the incidence of VTS, while adverse outcomes in the surviving singleton and the gestational age of VTS were secondary outcomes. Results: The incidence of IUH was 13.8%. A total of 1,078 twin pregnancies including 539 IUH pregnancies and 539 non-IUH pregnancies were included. IUH pregnancy was associated with higher risks of VTS (26.9% vs. 18.7%, p = 0.001) as well as a higher incidence of preterm birth (p = 0.001, crude OR = 1.98, 95% CI 1.28-3.09, adjusted OR = 1.19, 95% CI 1.09-1.24), threatened abortion (p < 0.001, crude OR = 9.12, 95% CI 2.90-28.69, adjusted OR = 6.63, 95% CI 1.69-14.67), and postpartum hemorrhage (p = 0.024, crude OR = 3.13, 95% CI 1.09-8.99, adjusted OR = 1.16, 95% CI 1.08-1.32) in the surviving singleton. There was no significant difference in risks of other complications. The absence of fetal cardiac activities at the diagnosis of IUH predicted VTS (p < 0.001, crude OR 4.67, 95% CI 3.67-5.78, adjusted OR 3.33, 95% CI 1.56-5.14) and fetal loss at smaller gestational age (7.81 ± 2.10 vs. 11.39 ± 5.60 weeks, p < 0.001), while an IUH with an increasing volume did not increase the risk of VTS but might induce threatened abortion in the surviving fetus (p < 0.001, crude OR 1.84, 95% CI 1.32-2.55, adjusted OR 1.72, 95% CI 1.13-2.13). Conclusions: IUH was a risk factor for VTS in twin pregnancies following double embryo transfer and elevated the risks of threatened abortion, preterm birth, and postpartum hemorrhage in the surviving singleton. The absence of fetal cardiac activities at the diagnosis of IUH elevated the risks of VTS, while an IUH with an increasing volume was associated with threatened abortion without elevating the risks of VTS. An IUH diagnosed before the presence of fetal cardiac activities also resulted in an earlier miscarriage. The study suggests that attention be paid to twin pregnancies with first-trimester IUH to prevent VTS and subsequent adverse perinatal outcomes. Highlights: First-trimester intrauterine hematoma (IUH) following double embryo transfer is associated with a higher incidence of vanishing twin syndrome (VTS) and elevated subsequent risk of threatened abortion, preterm birth, and postpartum hemorrhage in the surviving singleton. Other perinatal outcomes were not associated with the diagnosis of first-trimester IUH. The absence of fetal cardiac activities at the diagnosis of IUH was of predictive value toward VTS, while an IUH with an increasing size was associated with threatened abortion without elevating the risk of VTS. Incomplete fetal cardiac activities and earlier detection of an IUH might also predict miscarriage at smaller gestational age.

Clinical immunity and medical cost of COVID-19 patients under grey relational mathematical model.

This study was to explore the performance of immune function and compositions of hospitalization cost for patients with COVID-19 as well as the application of a grey relational mathematical model (GRMM). A total of 100 COVID-19 patients diagnosed by nucleic acid test and chest CT examination in our hospital were collected in this study. They were divided into 2 groups: non-severe group (mild and moderate patients, n = 57 cases), and severe group (severe and critical patients, n = 43 cases) based on the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7) published by the World Health Organization (WHO). The general clinical data, blood routine indexes, cellular immune and humoral immune function test indexes, and the composition of hospitalization costs of the two groups of patients were collected and analyzed. The results showed that the average age, proportion of males, smoking history, and the number and proportion of patients in the non-severe group were smaller than those in the severe group (P < 0.05); the severe group had significantly more shortness of breath patients than the non-severe group (P < 0.05). Compared with the non-severe group, the number of white blood cells (WBC), the number and proportion of neutrophils, and the count of neutrophils/lymphocytes in the severe group increased obviously (P < 0.05), and the number of lymphocytes and the proportion of monocytes decreased dramatically (P < 0.05); the number and proportion of CD3+, CD4+, CD8+, and CD19+ in the severe group were much lower in contrast to those in the non-severe group (P < 0.05), while the ratio of CD4+/CD8+ was greatly higher in contrast to that of non-severe patients (P < 0.05). Compared with the non-severe group, the bed fee, laboratory test fee, diagnosis fee, and medicine fee of the severe group were increased observably (P < 0.05). The changes in hospitalization cost of patients in the severe group was related to bed fees, laboratory fees, and expenses of proprietary Chinese medicines, while the hospitalization cost of patients in the severe group was related to bed fees, laboratory fees, and examination fees. The results revealed that elderly COVID-19 patients with basic diseases were prone to develop severe disease, immune cell depletion may be one of the reasons for the development of severe patients, and the medical insurance policy greatly reduced the hospitalization costs of COVID-19 patients.

Recovery of uterine and ovarian function in patients with complete placenta previa after caesarean delivery: A retrospective study.

ABSTRACT: This retrospective study was designed to explore the recovery of uterine and ovarian function in patients with complete placenta previa (PP) after caesarean delivery (CD). 136 complete placenta previa patients (group completed placenta previa) and 140 patients without complete PP (group non-PP, control group) were included in this study from Jan 2016 to Dec 2018. Subgroup analysis of patients with complete PP was made to determine the impact of different hemostatic methods used during CD on the recovery of uterine function. There were no statistically significant differences between the 2 groups in postpartum menstrual cycle changes, ovarian hormone, and uterine vascular supply as measured by pulsatility index and systolic/diastolic ratio (P > .05). However, the group with complete PP had a reduced endometrial thickness (0.47 ±â€Š0.11 vs 0.50 ±â€Š0.12, P < .001), a lower uterine resistance index at 42nd days (0.84 ±â€Š0.03 vs 0.90 ±â€Š0.03, P < .001), and a delayed resumption menstruation (7.07 ±â€Š2.61 vs 5.31 ±â€Š2.16, P < .001) when compared with control group. Subgroup analysis showed that RI index of all subgroups in completed PP group was lower, endometrial thickness was thinner and the time to menstrual recovery was longer than that of non-PP group. In conclusion, the endometrial thickness and blood supply at 42nd days, not ovarian function, maybe affected after CD in patients with complete PP.

The prenatal diagnosis and genetic counseling of chromosomal micro-duplication on 10q24.3 in a fetus: A case report and a brief review of the literature.

RATIONALE: Split-hand/split-foot malformation (SHFM), also known as ectrodactyly, is a congenital limb malformation affecting the central rays of the autopod extending to syndactyly, median clefts of the hands and feet, aplasia/hypoplasia of phalanges, metacarpals and metatarsals. Duplication of this 10q24 region is associated with SHFM3. While the clinical and genetic heterogeneity of SHFM makes the prenatal diagnosis and genetic counseling more challenging and difficult. PATIENT CONCERNS: A physically normal pregnant woman had a systemic ultrasound at the second trimester, only identified the deformity of both hands and feet on the fetus. DIAGNOSES: The fetus was diagnosed as sporadic SHFM3. INTERVENTIONS: After seeking advice from genetic counseling, she decided to terminate the pregnancy. The induction of infant was done after appearance of bipedal clefts, lobster-claw appearance and partial loss of phalanges and metacarpals, leaving behind 2nd finger in the left hand and the 5th in the right hand. Furthermore, collection of umbilical cord is recommended to this fetus for genome-wide detection. OUTCOMES: An outcome of the gene detection from abortion shows that there is variation in copy number in genome of chromosome 1 and chromosome 10. LESSONS: This case study confirms an association between SHFM3 and chromosomal micro-duplication on 10q24.3, and the extension of clinical spectrum of SHFM3. It also proposes some prenatal diagnosis and genetic counseling to help in planning and management in affected pregnancy. This will reduce the congenital and development abnormalities in birth rate, as well as relive the economic, psychological, and physical burden to the affected families.

Placental Origins of Preeclampsia: Potential Therapeutic Targets.

Preeclampsia (PE) remains a leading cause of maternal and perinatal morbidity and mortality in obstetrics worldwide. No effective treatments to reduce its incidence and severity in clinical practice are currently available. A variety of hypotheses have been generated aiming to explain the origins of PE, notably being the genetic predispositions and placental dysfunction. As regard to placental dysfunction, much progress has been made in basic research and several potential therapeutic targets have been identified. This review will discuss in detail the potential therapeutic targets in PE models including uteroplacental blood flow, oxidative stress, vasoactive factors and inflammation/immune response, and introduce the evolving technologies for placental research nowadays.

Tetrodotoxin poisoning caused by Goby fish consumption in southeast China: a retrospective case series analysis.

OBJECTIVES: To investigate an unusual outbreak of tetrodotoxin poisoning in Leizhou, southeast China, a case series analysis was conducted to identify the source of illness. METHODS: A total of 22 individuals experienced symptoms of poisoning, including tongue numbness, dizziness, nausea and limb numbness and weakness. Two toxic species, Amoya caninus and Yongeichthys nebulosus, were morphologically identified from the batches of gobies consumed by the patients. Tetrodotoxin levels in the blood and Goby fish samples were detected using liquid chromatography-tandem mass spectrometry. RESULTS: The tetrodotoxin levels in the remaining cooked Goby fish were determined to be 2090.12 µg/kg. For Amoya caninus, the toxicity levels were 1858.29 µg/kg in the muscle and 1997.19 µg/kg in the viscera and for Yongeichthys nebulosus, they were 2783.00 µg/kg in the muscle and 2966.21 µg/kg in the viscera. CONCLUSION: This outbreak demonstrates an underestimation of the risk of Goby fish poisoning. Furthermore, the relationships among the toxic species, climates and marine algae present should be clarified in the future.

Tetrodotoxin poisoning caused by Goby fish consumption in southeast China: a retrospective case series analysis

OBJECTIVES: To investigate an unusual outbreak of tetrodotoxin poisoning in Leizhou, southeast China, a case series analysis was conducted to identify the source of illness. METHODS: A total of 22 individuals experienced symptoms of poisoning, including tongue numbness, dizziness, nausea and limb numbness and weakness. Two toxic species, Amoya caninus and Yongeichthys nebulosus, were morphologically identified from the batches of gobies consumed by the patients. Tetrodotoxin levels in the blood and Goby fish samples were detected using liquid chromatography-tandem mass spectrometry. RESULTS: The tetrodotoxin levels in the remaining cooked Goby fish were determined to be 2090.12 µg/kg. For Amoya caninus, the toxicity levels were 1858.29 µg/kg in the muscle and 1997.19 µg/kg in the viscera and for Yongeichthys nebulosus, they were 2783.00 µg/kg in the muscle and 2966.21 µg/kg in the viscera. CONCLUSION: This outbreak demonstrates an underestimation of the risk of Goby fish poisoning. Furthermore, the relationships among the toxic species, climates and marine algae present should be clarified in the future. .