Body mass index and death by cognitive impairment.

BACKGROUND: Epidemiological studies have reported that among participants with impaired cognitive, overweight and mild obesity are associated with substantially improved survival, this finding has been termed the "obesity paradox" and has led to uncertainty about secondary prevention. AIMS: To explore whether the association of BMI with mortality differed in different MMSE score, and whether the obesity paradox in patient with cognitive impairment (CI) is real. METHODS: The study used data from CLHLS, a representative prospective population-based cohort study in China, which included 8348 participants aged ≥ 60 years between 2011 and 2018. The independent association between BMI and mortality in differed MMSE score by calculating hazard ratios (HRs) in multivariate Cox regression analysis. RESULTS: During a median (IQR) follow-up of 41.18 months, a total of 4216 participants died. In the total population, underweight increased the risk of all-cause mortality (HRs, 1.33; 95% CI 1.23-1.44), compared with normal weight, and overweight was associated with a decreased risk of all-cause mortality (HR 0.83; 95% CI 0.74-0.93). However, compared to normal weight, only underweight was associated with increased mortality risk among participants with MMSE scores of 0-23, 24-26, 27-29, and 30, and the fully-adjusted HRs (95% CIs) for mortality were 1.30 (1.18, 1.43), 1.31 (1.07, 1.59), 1.55 (1.34, 1.80) and 1.66 (1.26, 2.20), respectively. The obesity paradox was not found in individuals with CI. Sensitivity analyses carried out had hardly any impact on this result. CONCLUSION: We found no evidence of an obesity paradox in patients with CI, compared with patients of normal weight. But underweight individuals may have increased mortality risk whether in the population with CI or not. And overweight/obese people with CI should continue to aim for normal weight.

Prediction and analysis of COVID-19 daily new cases and cumulative cases: times series forecasting and machine learning models.

BACKGROUND: COVID-19 poses a severe threat to global human health, especially the USA, Brazil, and India cases continue to increase dynamically, which has a far-reaching impact on people's health, social activities, and the local economic situation. METHODS: The study proposed the ARIMA, SARIMA and Prophet models to predict daily new cases and cumulative confirmed cases in the USA, Brazil and India over the next 30 days based on the COVID-19 new confirmed cases and cumulative confirmed cases data set(May 1, 2020, and November 30, 2021) published by the official WHO, Three models were implemented in the R 4.1.1 software with forecast and prophet package. The performance of different models was evaluated by using root mean square error (RMSE), mean absolute error (MAE) and mean absolute percentage error (MAPE). RESULTS: Through the fitting and prediction of daily new case data, we reveal that the Prophet model has more advantages in the prediction of the COVID-19 of the USA, which could compose data components and capture periodic characteristics when the data changes significantly, while SARIMA is more likely to appear over-fitting in the USA. And the SARIMA model captured a seven-day period hidden in daily COVID-19 new cases from 3 countries. While in the prediction of new cumulative cases, the ARIMA model has a better ability to fit and predict the data with a positive growth trend in different countries(Brazil and India). CONCLUSIONS: This study can shed light on understanding the outbreak trends and give an insight into the epidemiological control of these regions. Further, the prediction of the Prophet model showed sufficient accuracy in the daily COVID-19 new cases of the USA. The ARIMA model is suitable for predicting Brazil and India, which can help take precautions and policy formulation for this epidemic in other countries.

Increased Toll-Like Receptor-Myeloid Differentiation Factor 88 Expression at the Maternal-Fetal Interface Is Associated with Spontaneous Abortion.

AIMS: Toll-like receptors (TLRs) form a group of pattern recognition receptors that play a major role in maintaining innate host immunity. Myeloid differentiation factor 88 (MyD88) is an adaptor molecule that is essential for signaling via the TLR family. To analyze the mechanism of the imbalance in the innate immune system mediated by TLRs-MyD88 in spontaneous abortion, we detected the expression of TLR-2, TLR-4, TLR-7, and MyD88 in placentae and deciduas. METHODS: The expression of TLR-2, TLR-4, TLR-7, and MyD88 in the placentae and deciduas of abortion-prone mice (n = 10) and normal pregnant mice (n = 10) were analyzed by immunochemistry, western blot, and real-time polymerase chain reaction. RESULTS: There were higher protein expression levels of TLR-2, TLR-4, TLR-7, and MyD88 in the placentae and deciduas in the abortion-prone group than in the normal pregnant group. However, TLR-2, TLR-4, and TLR-7 showed lower gene expression, while MyD88 manifested higher gene expression in placentae and deciduas of abortion-prone mice matings. CONCLUSIONS: TLR-2, TLR-4, TLR-7, and MyD88 were expressed in the placenta and decidua of both the abortion-prone pregnant and normal pregnant mice. The overexpression of TLRs may excessively activate the innate immune system mediated by MyD88, which is considered to be related to the pathogenesis of spontaneous abortion.

The Spatiotemporal Pattern and Its Determinants of Hemorrhagic Fever With Renal Syndrome in Northeastern China: Spatiotemporal Analysis.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is a significant zoonotic disease mainly transmitted by rodents. However, the determinants of its spatiotemporal patterns in Northeast China remain unclear. OBJECTIVE: This study aimed to investigate the spatiotemporal dynamics and epidemiological characteristics of HFRS and detect the meteorological effect of the HFRS epidemic in Northeastern China. METHODS: The HFRS cases of Northeastern China were collected from the Chinese Center for Disease Control and Prevention, and meteorological data were collected from the National Basic Geographic Information Center. Times series analyses, wavelet analysis, Geodetector model, and SARIMA model were performed to identify the epidemiological characteristics, periodical fluctuation, and meteorological effect of HFRS in Northeastern China. RESULTS: A total of 52,655 HFRS cases were reported in Northeastern China from 2006 to 2020, and most patients with HFRS (n=36,558, 69.43%) were aged between 30-59 years. HFRS occurred most frequently in June and November and had a significant 4- to 6-month periodicity. The explanatory power of the meteorological factors to HFRS varies from 0.15 ≤ q ≤ 0.01. In Heilongjiang province, mean temperature with a 4-month lag, mean ground temperature with a 4-month lag, and mean pressure with a 5-month lag had the most explanatory power on HFRS. In Liaoning province, mean temperature with a 1-month lag, mean ground temperature with a 1-month lag, and mean wind speed with a 4-month lag were found to have an effect on HFRS, but in Jilin province, the most important meteorological factors for HFRS were precipitation with a 6-month lag and maximum evaporation with a 5-month lag. The interaction analysis of meteorological factors mostly showed nonlinear enhancement. The SARIMA model predicted that 8,343 cases of HFRS are expected to occur in Northeastern China. CONCLUSIONS: HFRS showed significant inequality in epidemic and meteorological effects in Northeastern China, and eastern prefecture-level cities presented a high risk of epidemic. This study quantifies the hysteresis effects of different meteorological factors and prompts us to focus on the influence of ground temperature and precipitation on HFRS transmission in future studies, which could assist local health authorities in developing HFRS-climate surveillance, prevention, and control strategies targeting high-risk populations in China.

Effects of KCa channels on biological behavior of trophoblasts.

The Ca2+-activated potassium (KCa) channels are involved in many cellular functions, but their roles in trophoblasts are unclear. This study aimed to clarify the effects of KCa channels on the biological behavior of trophoblasts. The localization and expression of the three types of KCa channels, including large-conductance KCa channels (BKCa), intermediate-conductance KCa channels (IKCa), and small-conductance KCa channels (SKCa), were detected in human chorionic villi taken from pregnant women between 5 and 8 weeks of gestation (n = 15) and HTR-8/SVneo cells. The effects of KCa channels on proliferation, apoptosis, and migration of HTR-8/SVneo cells were examined by using the activators or inhibitors of KCa channels. Results showed that KCa channels were mainly localized on the membrane and in the cytoplasm of trophoblasts in human chorionic villi and HTR-8/SVneo cells. The proliferation and migration of HTR-8/SVneo cells were inhibited by activating KCa channels. Apoptosis of trophoblasts was promoted through activating BKCa channels but was not affected by neither activating nor inhibiting IKCa and SKCa channels. This study substantiated the abovementioned biological roles of KCa channels in trophoblast cells, which is fundamental to further research on whether dysfunction of KCa channels is involved in the pathogenesis of pregnancy-related complications.

Climate and socio-economic factors drive the spatio-temporal dynamics of HFRS in Northeastern China.

Background: Hemorrhagic fever with renal syndrome (HFRS) occurs widely in Northeastern China, but the mechanism and interactions of meteorological and socio-economic factors on the transmission of HFRS are still largely unknown. Objective: We explored the effects of socioeconomic-environmental factors on the spatio-temporal variation of HFRS incidence from 2001 to 2019 in Northeastern China. Specifically, the relative importance and contribution rates (CR) of determinants of HFRS were identified by boosted regression tree and variance partitioning analysis, respectively. Structural equation models (SEMs) were used to explain the roles of climatic and socio-economic factors in the transmission of HFRS. And a negative binomial regression was used to identify the risk effect between monthly meteorological variables and HFRS with 0-6 months lags in Northeastern China. Results: Over the past decades, the high-risk areas of HFRS were mainly concentrated in the northern and eastern areas of Northeastern China. Additionally, HFRS mainly presented a decreasing trend from 2001 to 2019 in most areas of Northeastern China, but slightly increased in the cities of Daqing, Songyuan, Baicheng, and Tonghua. The temporal dynamics of the incidence of HFRS were primarily explained by the variations in population density (CR = 27.30%), climate (CR = 13.30%), and economic condition(CR = 1.90%). The spatial variations of HFRS were medicated by the climate (CR = 16.95%) and population density (CR = 9.45%) and medical health care (CR = 2.25%). The SEM models indicated that humid and warm climates were conducive to the incidence and increase of HFRS, but the improvement in education and an increase in population density reduced the transmission of HFRS. Conclusion: Climate and population density appeared to mediate the spatio-temporal variation of HFRS in Northeastern China. These findings may provide valuable empirical evidence for the management of HFRS in endemic areas.

Clinical and genomic analysis of hypermucoviscous Klebsiella pneumoniae isolates: Identification of new hypermucoviscosity associated genes.

Introduction: Hypermucoviscous Klebsiella pneumoniae (HmKp) poses an emerging and highly pathogenic global health threat. This study aimed to investigate the clinical and genomic characteristics of HmKp isolates to better understand the virulence mechanisms of the hypermucoviscous (HMV) phenotype. Methods: From May 2018 to August 2021, 203 non-repeat K. pneumoniae isolates causing invasive infections were collected from a hospital in Beijing, China. Isolates were divided into HmKp (n=90, 44.3%) and non-HmKp (n=113, 55.7%) groups according to string test results. Results: Multivariate regression showed that diabetes mellitus (odds ratio [OR]=2.20, 95% confidence interval (CI): 1.20-4.05, p=0.010) and liver abscess (OR=2.93, CI 95%:1.29-7.03, p=0.012) were associated with HmKp infections. K. pneumoniae was highly diverse, comprising 87 sequence types (STs) and 54 serotypes. Among HmKp isolates, ST23 was the most frequent ST (25/90, 27.8%), and the most prevalent serotypes were KL2 (31/90, 34.4%) and KL1 (27/90, 30.0%). Thirteen virulence genes were located on the capsular polysaccharide synthesis region of KL1 strains. HmKp isolates were sensitive to multiple antibiotics but carried more SHV-type extended spectrum ß-lactamase (ESBL) resistance genes (p<0.05), suggesting that the emergence of ESBL-mediated multidrug resistance in HmKp should be monitored carefully during treatment. Phylogenetic analysis disclosed that HmKp isolates were highly diverse. Comparative genomic analysis confirmed that the HMV phenotype is a plasmid-encoded virulence factor. Seventeen HmKp genes were highly associated with HmKp, and included rmpAC, 7 iron-acquisition-related genes, and pagO, which may promote liver abscess formation. Discussion: This investigation provides insight into the mechanisms producing the HMV phenotype.

Synergistic impact of diabetes and cognitive impairment on all-cause and cause-specific mortality in Chinese older adults: A prospective population-based cohort study.

Background: Diabetes mellitus (DM) or cognitive impairment (CI) is known to be strongly associated with mortality. DM commonly coexists with CI and proportionally increases with age. However, little is known about the combined effect of cognitive function and diabetes on mortality. This study aimed to evaluate the combined effects of DM and CI on all-cause and cause-specific mortality in Chinese older adults. Methods: This prospective population-based cohort study was based on the Beijing Elderly Comprehensive Health Cohort Study. A total of 4,499 older adults were included. Cox's proportional hazard models were utilized to calculate the effect of DM and CI on all-cause, cardiovascular disease (CVD) mortality and cancer mortality, and a multiplicative term was introduced to study a potential interaction between DM and CI on outcomes. Results: During a median follow-up of 6.8 years (ranging from 6.6 to 11.7 years), 667 (14.8%) participants died from all causes, 292 from CVD, and 215 from cancer. In the fully adjusted model, participants with coexisting DM and CI had the highest risk of all-cause mortality [hazard ratios (HRs), 3.08; 95% confidence intervals (CIs), 2.30,4.11] and CVD mortality (HRs, 3.85; 95% CIs, 2.60,5.71) compared with individuals with normal cognition and non-DM. We also found a multiplicative interaction between DM and CI in respect to all-cause (HRs, 2.46; 95% CI, 1.87,3.22) and CVD mortality (HRs, 3.15 95% CI, 2.19,4.55). In the diabetic population, CI was associated with an increased risk of all-cause mortality (HRs, 2.09; 95% CIs, 1.51,2.89) and CVD mortality (HRs, 3.16; 95% CIs, 2.02,5.05) compared with the normal cognition group. Restricted cubic spline revealed a linear inverse association between Mini-Mental State Examination (MMSE) score and all-cause, CVD mortality in the total sample and participants without diabetes. However, a nearly reverse J association was observed between MMSE and mortality from all causes and CVD in the diabetes group. Conclusion: The findings highlighted that cognitive impairment concomitant with diabetes further increases the risk of mortality. In addition to strengthening routine screening of cognitive functioning in older adults with early-stage diabetes, more extensive assessment of prognostic risks has high clinical value for developing comprehensive treatment plans.

Cognitive impairment assessed by Mini-Mental State Examination predicts all-cause and CVD mortality in Chinese older adults: A 10-year follow-up study.

Objective: Cognitive impairment (CI) has been demonstrated as a useful proxy measure of mortality in Western populations. However, the predictive value of CI in Chinese populations is unknown. We aimed to explore whether CI is independently associated with increased long-term all-cause and cardiovascular disease (CVD) mortality in Chinese older adults and the association of performance in specific MMSE sub-domains to subsequent mortality. Methods and results: A total of 4,499 older adults [mean (SD) age, 70.3(6.7) years] who received a sample investigation from 2011 to 2014 were followed up till 2021 for mortality. The Mini-Mental State Examination was used to assess cognitive function, and Cox's proportional hazard models were used to evaluate the effects of cognitive function on the risk of all-cause and CVD mortality. Demographic characteristics, lifestyle, and health status were included as covariates. During a 10-year follow-up, a total of 667 (14.8%) died. In the fully adjusted model, compared with cognitively normal participants with CI had a 1.33-fold [HR, 1.33; (95% CI, 1.10-1.61)] greater risk of all-cause mortality and a 1.45-fold [HR, 1.45; (95% CIs, 1.11-1.92)] greater risk of CVD mortality. After a similar multivariable adjustment, a per-SD increase in MMSE scores was associated with a reduced risk of all-cause mortality [HR, 0.85; (95% CI, 0.78-0.93)] and CVD mortality [HR, 0.74; (95% CI, 0.65-0.84)]. In the unadjusted model, MMSE sub-domains (apart from immediate recall) were associated with mortality. But only orientation and calculation and attention were still independently associated with all-cause and CVD mortality in a multivariable model. Conclusion: These findings confirmed that CI is a marker of all-cause and CVD mortality risk in Chinese older adults, independently of other commonly assessed risk factors, and some sub-domains of the MMSE may have stronger associations with mortality. Further research is needed to identify the mechanisms underlying the observed associations.

TREM-1 amplifies trophoblastic inflammation via activating NF-κB pathway during preeclampsia.

INTRODUCTION: Excessive activation of maternal systemic inflammation is one of the underlying causes of pathology during the disease course of preeclampsia (PE). The triggering receptor expressed on myeloid cells-1 (TREM-1) participates in the development and persistence of inflammation. We hypothesized that dysregulated TREM-1 may be involved in the pathogenesis of PE by promoting the secretion of trophoblastic pro-inflammatory cytokines that augment inflammation. METHODS: The localization of TREM-1 in placenta and the extravillous trophoblast cell line (TEV-1) was determined by immunohistochemical staining. The expression level of TREM-1 and pro-inflammatory cytokines in placentas were compared between normal pregnancies and PE. We used lipopolysaccharide (LPS) to simulate trophoblastic inflammation. TEV-1 cells were transfected with TREM-1 plasmid and si-TREM-1 respectively, and then were incubated with LPS. The expression levels of pro-inflammatory cytokines and key molecules featured in nuclear transcription factor-kappaB (NF-κB) pathway were detected. Transwell assays were used to detect the effects of TREM-1 on cell migration and invasion. RESULTS: TREM-1 was localized on both villous trophoblasts (VTs) and extravillous trophoblasts (EVTs). TREM-1 and pro-inflammatory cytokines were up-regulated in preeclamptic placenta. Overexpression of TREM-1 promoted the activation of NF-κB pathway and the release of pro-inflammatory factors induced by LPS, and enhanced migration and invasion of TEV-1 cells. Inhibition of TREM-1 significantly attenuated LPS-induced effects and suppressed migration and invasion. DISCUSSION: This study suggested that TREM-1 was up-regulated in PE, and may promote the production of downstream inflammatory factors by activating NF-κB pathway in trophoblastic cells, thus exerting pro-inflammatory effects in the pathogenesis of PE.

Correction to: HSP20 Exerts a Protective Effect on Preeclampsia by Regulating Function of Trophoblast Cells Via Akt Pathways.

Li F, Xie Y, Wu Y, et al. HSP20 exerts a protective effect on preeclampsia by regulating function of trophoblast cells via Akt pathways. Reproduct Sci. 2019;26:961-971. doi:10.1177/1933719118802057.

HSP20 Exerts a Protective Effect on Preeclampsia by Regulating Function of Trophoblast Cells Via Akt Pathways.

Preeclampsia (PE) remains the leading cause of maternal and fetal morbidity and mortality. Excessive apoptosis of the placenta and poor remodeling of spiral arteries caused by insufficient invasion of trophoblast cells into uterus have been implicated in the pathogenesis of PE. Accumulating evidence showed that heat shock protein 20 (HSP20) is closely associated with the proliferation, apoptosis, and metastasis of tumor cells. However, little is known about whether HSP20 plays a role in the development of PE. In this study, we detected the apoptosis index and the expressions of HSP20 and apoptosis-associated proteins in the placentas from PE and normal pregnancies. We found that HSP20 was reversely related to the apoptosis rate and the levels of proapoptotic proteins. Moreover, we identified that HSP20 could suppress the proliferation and apoptosis of trophoblast cells, turning them into a more invasive phenotype. Additionally, H2O2-induced oxidative stress was significantly alleviated, and several key proteins on the Akt signaling pathway were upregulated in HSP20-overexpressing trophoblast cells. These findings strongly suggested that HSP20 might play a role in the remodeling of spiral arteries through affecting the invasiveness of extravillous trophoblast cells via Akt signaling pathway, and the dysregulation of it might contribute to the pathophysiology of PE.

Impairment of BKca channels in human placental chorionic plate arteries is potentially relevant to the development of preeclampsia.

Preeclampsia has known associations with insufficient placental perfusion. The large-conductance Ca2+-activated K+ (BKca) channels that have recently been found to play important roles in cellular growth and vasodilatation could potentially participate in the development of preeclampsia. However, the mechanisms by which downregulated BKca channels are involved in the development of preeclampsia remain unknown. In this study, we investigated the mechanism(s) underlying the impairment of vascular tone regulation by BKca channels in human placental chorionic plate arteries (CPAs) in preeclampsia. The levels of BKca channel α and ß1 subunits were compared using immunohistochemistry, western blotting, and RT-PCR in CPAs of normal and preeclamptic pregnant women. To explore the role of BKca channels in the regulation of proliferation and apoptosis in human placental CPA smooth muscle cells (SMCs), a specific BKca opener, NS1619, was used to investigate proliferative reduction and apoptotic induction in human placental chorionic plate arterie smooth muscle cells (CPASMCs) collected from normal pregnancies. The vasodilator effects of BKca channels and their response to SNP (an NO donor) in both groups were also evaluated by wire myography. We found that BKca channel ß1 subunits were less expressed in preeclamptic CPAs. After pretreatment with NS1619, cellular proliferation was significantly suppressed, and cellular apoptosis was dramatically promoted in cultured CPASMCs, demonstrating a relationship between increased Bax expression and decreased Bcl-2 expression in CPASMCs. Downregulated BKca is also associated with decreased vasodilatation and reduced susceptibility to NO donors. In conclusion, the decreased expression or activation of BKca channels may induce pathologic remodeling of human CPAs, weaken the vasodilation response, and decrease vascular sensitivity to vasoactive substances, thereby reducing fetal-placental blood flow and leading to the future development of preeclampsia.

Alteration of heat shock protein 20 expression in preeclamptic patients and its effect in vascular and coagulation function.

Preeclampsia (PE) is a pregnancy-specific, multi-system disorder and the leading cause of maternal and perinatal morbidity and mortality in obstetrics worldwide. Excessive vasoconstriction and dysregulated coagulation function are closely associated with PE. Heat shock protein 20 (HSP20) is ubiquitously expressed under normal physiological conditions and has important roles in vascular dilatation and suppression of platelet aggregation. However, the role of HSP20 in the pathogenesis of PE remains unclear. In this study, we collected chorionic plate resistance arteries (CPAs) and serum from 118 healthy pregnant women and 80 women with PE and detected the levels of HSP20 and its phosphorylated form. Both HSP20 and phosphorylated HSP20 were downregulated in CPAs from women with PE. Comparison of the vasodilative ability of CPAs from the two groups showed impaired relaxation responses to acetyl choline in preeclamptic vessels. In addition to the reduced HSP20 in serum from women with PE, the platelet distribution width and mean platelet volume were also decreased, and the activated partial thromboplastin time and thromboplastin time were elevated.With regard to the vital roles of HSP20 in mediating vasorelaxation and coagulation function, the decreased HSP20 might contribute to the pathogenesis of PE.

Upregulation of Tim-3 expression at feto-maternal interface may explain embryo survival in the CBAxDBA/2 model of abortion.

PROBLEM: To understand the mechanisms of action of Tim-3 at the maternal-fetal interface and explore how Tim-3 might be involved in the pathogenesis of abortion by constructing an in vitro trophoblast-lymphocyte system. METHODS OF STUDY: Female CBA/J × male DBA/2 matings were used as the abortion-prone model and CBA/J × male BALB/c matings as control. The expression of Tim-3 at the maternal-fetal interface and in the peripheral blood lymphocytes was measured by immunohistochemistry and Western blotting. The proliferation index of lymphocytes and levels of Th1/Th2-derived cytokines in peripheral blood and in the co-culture system were determined using CCK-8 assay and ELISA, respectively. RESULTS: The expression level of Tim-3 was higher in abortion-prone matings than that of control (P < .05). A preponderance of Th1 was observed in the co-culture system in the abortion-prone mating group. Recombinant Tim-3 Ig reversed the imbalance of Th1/Th2 immunity of abortion-prone matings by suppressing the secretion of IFN-γ and IL-2 but had no direct effect on the generation of IL-4. CONCLUSION: Tim-3 might contribute to successful pregnancy by restraining Th1 bias, and the maternal immune system might develop a strategy including upregulation of Tim-3 at the maternal-fetal interface and in peripheral blood so as to maintain moderate inflammatory responses against miscarriage.

Impaired Gal-9 Dysregulates the PBMC-Induced Th1/Th2 Imbalance in Abortion-Prone Matings.

Recurrent miscarriage is defined as the loss of 3 or more consecutive pregnancies; however, the underlying immunologic mechanisms that trigger pregnancy loss remain largely unelucidated. Galectin-9 (Gal-9) may modulate a variety of biologic functions and play an important role in Th1/Th2 immune deviation. To analyze the mechanism of Gal-9 in abortion, we used the classical abortion-prone mouse model (DBA/2-mated CBA/J mice) to detect the expression of Gal-9 at the maternal-fetal interface. We also mimicked the immune environment of pregnancy by culturing trophoblast cells with peripheral blood mononuclear cells (PBMCs) to explore how Gal-9 might be involved in the pathogenesis of abortion. We found that the expression levels of Gal-9 in abortion-prone matings were lower than that for controls. Using a coculture system, we detected a Th1 preponderance in the coculture from abortion-prone matings. Furthermore, Gal-9 blockade augmented the imbalance of Th1/Th2 immunity in abortion-prone matings by promoting the secretion of Th1-derived cytokines in coculture, while there was a Th2 preponderance when we administered recombinant Gal-9. In conclusion, our results suggest that the Gal-9 signal is important for the regulation of PBMC function toward a Th2 bias at the maternal-fetal interface, which is beneficial for the maintenance of a normal pregnancy.

Involvement of dysregulated IKCa and SKCa channels in preeclampsia.

INTRODUCTION: Excessive constriction of placental chorionic plate arteries (CPAs) may be associated with preeclampsia (PE). Nitric oxide (NO) as well as intermediate and small Ca2+-activated K+ channels (IKCa and SKCa) plays vital roles in vasodilation of CPAs. We hypothesized that dysregulated IKCa and SKCa channels may be involved in the pathogenesis of PE mediated by the impaired NO system on CPAs. METHODS: The location of IKCa and SKCa channels, activities of NO synthases (NOS), and expression levels of these molecules were studied on CPAs from 30 normal pregnancies and 30 PE. The vasodilating function of CPAs was measured under openers or blockers of IKCa/SKCa channels in the presence or absence of NO donor or inhibitor. RESULTS: IKCa and SKCa channels were located both on endothelium and on smooth muscles of CPAs and the expressions of them were downregulated in PE women comparing to those in normal pregnant women. The protein expressions of endothelial NOS (eNOS) and inducible NOS (iNOS) were downregulated on CPAs in PE accompanied by decreased activity of eNOS. Notably, the vasodilatory functions mediated by IKCa/SKCa channels and by NO were aberrant on preeclamptic CPAs. In addition, IKCa and SKCa channels were responsible for nitric oxide (NO)-attributable vasorelaxation and activity modulation of NO synthases. CONCLUSIONS: This study provides evidence that dysregulated IKCa and SKCa channels might contribute to fetal pathogenesis of PE through direct promotion of vascular constriction of CPAs and through affecting functions of NO and activities of NOS.

A prospective observational study evaluating the efficacy of prophylactic internal iliac artery balloon catheterization in the management of placenta previa-accreta: A STROBE compliant article.

We studied the efficacy of prophylactic internal iliac artery balloon catheterization for managing severe hemorrhage caused by pernicious placenta previa.This prospective observational study was conducted in Tongji Hospital, Wuhan, China. One hundred sixty-three women past 32-week's gestation with placenta previa-accreta were recruited and managed. Women in the balloon group accepted prophylactic internal iliac artery balloon catheterization before scheduled caesarean delivery and controls had a conventional caesarean delivery. Intraoperative hemorrhage, transfusion volume, radiation dose, exposure time, complications, and neonatal outcomes were discussed.Significant differences were detected in estimated blood loss (1236.0 mL vs 1694.0 mL, P = .01), calculated blood loss (CBL) (813.8 mL vs 1395.0 mL, P < .001), CBL of placenta located anteriorly (650.5 mL vs 1196.0 mL, P = .03), and anterioposteriorly (928.3 mL vs 1680.0 mL, P = .02). Prophylactic balloon catheterization could reduce intraoperative red blood cell transfusion (728.0 mL vs 1205.0 mL, P = .01) and lessen usage of perioperative hemostatic methods. The incidence of hysterectomy was lower in balloon group. Mean radiation dose was 29.2 mGy and mean exposure time was 92.2 seconds. Neonatal outcomes and follow-up data did not have significant difference.Prophylactic internal iliac artery balloon catheterization is an effective method for managing severe hemorrhage caused by placenta previa-accreta as it reduced intraoperative blood loss, lessened perioperative hemostatic measures and intraoperative red cell transfusions, and reduce hysterectomies.

Upregulation of the Tim-3/Gal-9 pathway and correlation with the development of preeclampsia.

OBJECTIVE: It is well documented that an imbalance in immune tolerance at the maternal-fetal interface is likely to play an essential role in the etiology of preeclampsia. However, the mechanisms underlying immune tolerance during preeclampsia are still poorly understood. Tim-3, a Th1-specific cell surface molecule, is a relatively newly described molecule with important immunological functions. It can regulate Th1 responses with its ligand galectin-9 (Gal-9), and has become an attractive candidate for exploring the pathogenesis of preeclampsia. STUDY DESIGN: Twenty normal pregnancies and 20 preeclamptic pregnancies were enrolled in the present study. We examined the expression and function of Tim-3/Gal-9 in decidual tissue at the RNA and protein levels. In order to analyze their correlation with the development of preeclampsia, we measured the expression of Tim-3 on peripheral blood leukocytes using flow cytometry. IFN-γ, IL-10, and IL-17 in the peripheral blood plasma were measured by ELISA. RESULTS: Tim-3/Gal-9 was upregulated in decidual tissue of preeclamptic vs. normotensive pregnancies. There was a significantly increased Th1 and Th17 response in PE as demonstrated by the upregulated levels of IFN-γ/IL-17, whereas IL-10 secreted by Th2 cells was sharply reduced. CONCLUSIONS: The present study showed that an abnormal Tim-3/Gal-9 pathway was able to facilitate the development of preeclampsia. Our data uncovered a novel mechanism by which the Tim-3/Gal-9 pathway regulates immune responses, and we now identify this pathway as a potential therapeutic target in preeclampsia.