Search

For the purpose of a quantitative understand for IMS network's attack effect, this paper introduced an evaluation method for IMS's attack effect based on fuzzy comprehensive evaluation. It constructed the attack index tree on the basis of analyzing the possible attack flow, and introduced analytic hierarchy process to compute the indexes' power, and made comprehensive evaluation for IMS attack effects using the fuzzy comprehensive evaluation. To reduce the warp brought by the single fuzzy operator's properties, it selected several operators with different properties to evaluate and took the mean as the finally result. Finally, the examples validate the evaluation method is able to distinguish the attack effects resulted by different attack methods effectively, and can provide a reference to the security of IMS. [ABSTRACT FROM AUTHOR]

An 8-wk feeding trial was conducted to evaluate the potential of replacing fish meal with canola meal in experimental diets for genetically improved farmed tilapia (GIFT) strain of Nile tilapia, Oreochromis niloticus (mean initial weight: 20.0 ± 0.62 g, means ± SD), reared in fresh water. Six isonitrogenous (30% crude protein) and isolipidic (10%) diets were formulated with canola meal included at six levels of 0 (control), 11, 22, 33, 44, and 55%, replacing 0, 15, 30, 45, 60, and 75% fish meal, respectively. Growth performance and feed utilization showed no significant differences among the treatments. In general, dietary canola meal supplementation showed significant effect on hepatic composition of tilapia, but not muscle composition. Viscerosomatic index tended to increase with increasing dietary canola meal levels from 0 to 44%, and then declined when dietary canola meal levels further increased from 44 to 55%. Dietary fish meal replacement by canola meal significantly influenced several hepatic enzymatic activities, including succinate dehydrogenase, lactate dehydrogenase, malic dehydrogenase, lipoprotein lipase, and hepatic lipase, suggesting that dietary fish meal replacement by canola meal had significant effects on nutrient metabolism in the liver. Based on the information above, 75% of dietary fish meal could be replaced by canola meal with no effect on growth performance of GIFT strain of Nile tilapia. Use of canola meal in practical diets for GIFT stain of Nile tilapia may allow producers and feed mills to formulate more economical diets. [ABSTRACT FROM AUTHOR]

An 8-week feeding trial was conducted to determine the effect of dietary conjugated linoleic acid ( CLA) on growth performance, muscle fatty acid profile, hepatic intermediary metabolism and antioxidant responses in genetically improved farmed Tilapia ( GIFT) strain of O reochromis niloticus (initial body weight: 42.6 ± 0.4 g, mean ± standard deviation). Three replicated groups of GIFT strain of Nile tilapia were hand-fed to satiation, twice a day, with the diets in which CLA oil, containing mainly the bioactive cis-9, trans-11 and trans-10, cis-12 isomers, was included at 0 (control), 0.5%, 1%, 1.5%, 2% and 2.5%, respectively, at the expense of fish oil to maintain the constant lipid and energy levels. Growth performance and feed utilization showed no significant differences among the treatments ( P > 0.05). The dietary inclusion of CLA modified total percentages of the main groups of fatty acids. Increasing saturated fatty acid content and reduced mono-unsaturated fatty acid contents in muscle were observed with increasing dietary CLA inclusion ( P < 0.05). Total n-3 fatty acids and total polyunsaturated fatty acids tended to decline with increasing dietary CLA levels ( P < 0.05), but n-6 fatty acids showed no significant differences among the treatments ( P > 0.05). Dietary CLA supplementation resulted in the significant increase in the trans-10, cis-12 and cis-9, trans-11 CLA isomers in muscle ( P < 0.05) and also significantly influenced several hepatic enzymatic activities, such as succinate dehydrogenase, lactate dehydrogenase, malic dehydrogenase, lipoprotein lipase and hepatic lipase activities ( P < 0.05). Reduced superoxide dismutase and glutathione peroxidase activities, and the decline in malondialdehyde levels were observed in fish fed the CLA-supplemented diets ( P < 0.05), indicating that dietary CLA supplementation showed a powerful antioxidant effect for this fish species. Our study was the first report involved in the effect of dietary CLA inclusion on hepatic intermediary metabolism and antioxidant responses in fish, which could be used as indicators of nutritional and physiological status of the fish species. [ABSTRACT FROM AUTHOR]

To construct a rational and efficient communication structure and a high-efficient data storage path for CMP system, a kind of scalable and configurable CMP architecture utilizing multi-channel Cache ( AUMCC) is proposed in this article anti its prototype system is established based on FPGA and LOEN3 processor. Multi-channel Cache is adopted as 12 Cache in AUMCC. AUMCC can be configured to be private L2 Cache structure or shared L2 Cache structure based on the access mode of multi-channel Cache. Simulation and testing results show that AUMCC architecture can achieve about 37% performance improvement compared with shared L2 Cache BUS-centric (SCA) architecture, and the hierarchy characteristic of AUMCC assures the good scalability. [ABSTRACT FROM AUTHOR]

A flexible dicarboxylic acid, 4,4'-{[1,3-phenylenebis-(methylene)]bis(oxy) dibenzoic acid (H 2 L), in combination with 1,10-phenanthroline (phen) was used to reacted with Zn(II) ions under hydrothermal conditions, successfully affording a new metal-organic framework of [Zn(L)(phen)(H 2 O)] n (1). Luminescence sensing property investigations indicate that, compound 1 is sensitive detector of Fe3+ ions based on quenching of luminescence. Its treatment activity on the child allergic purpura was assessed and the specific mechanism of the compound was explored at the same time. First of all, the content of the inflammatory cytokine released into the skin tissue was measured with ELISA detection kit after the compound treatment. Apart from this, the activation ability of the AMPK inflammatory signaling pathway was measured with real time RT-PCR. [Display omitted] • A new Zn(II)-based compound has been prepared. • It can be used as a sensor for Fe3+ ​ion. • It has the potential choice for the allergic purpura therapy. [ABSTRACT FROM AUTHOR]

We report fabrication and characterization of organic heterojunction UV detectors based on N,N'-bis(naphthalenl-yl)-N,N'-bis (phenyl) benzidine (NPB)and fullerene C60. The effects of different thicknesses of NPB and C60 layers are studied and compared. Notably, the optimal thicknesses of electron acceptor C60 and electron donor NPB are 40 nm and 80 nm, respectively. The J–V characteristic curves of the device demonstrate a three-order-of-magnitude difference when illuminated under a 350 nm UV light and in the dark at −0.5 V. The device exhibits high sensitivity in the region of 320–380 nm with the peak located around 350 nm. Especially, it shows excellent photo-response characteristic with a responsivity as high as 315 mA/W under the illumination of 192 μW·cm−2 350 nm UV light at −5 V. These results indicate that the NPB/C60 heterojunction structure device might be used as low-cost low-voltage UV photodetectors. [ABSTRACT FROM AUTHOR]

Short rib-polydactyly syndrome type III (SRPS3) is a lethal perinatal skeletal disorder consisting of polydactyly and multi-system organ abnormalities. To further assess the pathogenicity of two pairs of compound heterozygotes and to search for novel molecular etiology, X-rays and hematoxylin and eosin staining were conducted in three cases: Two retrospective samples and a newly identified patient with SRPS3. In addition, next-generation sequencing was used to evaluate a fetus with SRPS3. Typical radiological features of the three cases included a long, narrow thorax with short ribs, shortened long bones, spurs at the metaphysis of the long bones and congenital bowing of the femurs. The present study also observed atypical histopathological changes, together with the absence of proliferation and abundance of retaining cartilage in the primary spongiosum. In addition, two novel compound heterozygous variants were identified in the dynein cytoplasmic 2 heavy chain 1 (DYNC2H1) gene of the fetus: NM_001080463.1, c.6591_6593delTGG (chr11:103055738-103055740); NM_001080463.1, c.7883T>C (chr11:103070000). The findings of the present study provided further confirmation of the pathogenicity of two compound heterozygous variants in two retrospective samples and identified novel compound heterozygous variants. These findings may improve our knowledge of the histopathological and radiological changes in patients with SRPS3 and the relative effects of DYNC2H1 variants. The findings of the present study may facilitate the clinical and molecular diagnosis of SRPS3. [ABSTRACT FROM AUTHOR]

• Significant estrogenic activities of flavonoid monomers purified from LCC were found. • Molecular docking study confirmed ERs as molecular targets of the flavonoid monomers. • The molecular mechanism was depend on the ERE-independent gene regulation. The main purpose of this study was to evaluate the estrogenic properties of total flavonoids (TFs) and five flavonoid monomers (cardamonin (Car), pinostrobin chalcone (PC), wogonin (Wo), chrysin (Chr) and Pinocembrin (PI)) from leaves of Carya cathayensis Sarg (LCC). TFs from LCC were isolated and determined using HPLC. The 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were performed to assess the effects of flavonoids on cell proliferation and cell cycle, respectively. The molecular docking technique was applied to investigate binding conformations of the monomers from LCC to the estrogen receptor ERα and ERβ. Gene and protein expression patterns were assessed using quantitative real-time PCR (qRT-PCR) and western blot, respectively. The results showed that TFs, Car, PC, Wo and Chr promoted proliferation of MCF-7 cells and cell transition from the G1 to S phase, and inhabitation of MCF-7 cell proliferation was observed after the treatment of PI. Molecular docking studies confirmed ERs as molecular targets for the monomers. TFs, Car, PC, Wo and Chr from LCC promoted gene expression of ERα, ERβ, progesterone receptor (PR) and pS2. Our collective results demonstrated that TFs and monomers from LCC may exert ER agonist activity through competitively bind to ER, inducing ER upregulation and active ER to estrogen response element (ERE)- independent gene regulation. As an abundant natural product, LCC may provide a novel medicinal source for treatment of diseases caused by estrogen deficiency. [ABSTRACT FROM AUTHOR]

Background: In 2005, the FDA cautioned that exposure to paroxetine, a selective serotonin reuptake inhibitor (SSRI), during the first trimester of pregnancy may increase the risk of cardiac malformations. Since then, the association between maternal use of SSRIs during pregnancy and congenital malformations in infants has been the subject of much discussion and controversy. The aim of this study is to systematically review the associations between SSRIs use during early pregnancy and the risk of congenital malformations, with particular attention to the potential confounding by indication.Methods: The study protocol was registered with PROSPERO (CRD42018088358). Cohort studies on congenital malformations in infants born to mothers with first-trimester exposure to SSRIs were identified via PubMed, Embase, Web of Science, and the Cochrane Library databases through 17 January 2018. Random-effects models were used to calculate summary relative risks (RRs).Results: Twenty-nine cohort studies including 9,085,954 births were identified. Overall, use of SSRIs was associated with an increased risk of overall major congenital anomalies (MCAs, RR 1.11, 95% CI 1.03 to 1.19) and congenital heart defects (CHD, RR 1.24, 95% CI 1.11 to 1.37). No significantly increased risk was observed when restricted to women with a psychiatric diagnosis (MCAs, RR 1.04, 95% CI 0.95 to 1.13; CHD, RR 1.06, 95% CI 0.90 to 1.26). Similar significant associations were observed using maternal citalopram exposure (MCAs, RR 1.20, 95% CI 1.09 to 1.31; CHD, RR 1.24, 95% CI 1.02 to 1.51), fluoxetine (MCAs, RR 1.17, 95% CI 1.07 to 1.28; CHD, 1.30, 95% CI 1.12 to 1.53), and paroxetine (MCAs, RR 1.18, 95% CI 1.05 to 1.32; CHD, RR 1.17, 95% CI 0.97 to 1.41) and analyses restricted to using women with a psychiatric diagnosis were not statistically significant. Sertraline was associated with septal defects (RR 2.69, 95% CI 1.76 to 4.10), atrial septal defects (RR 2.07, 95% CI 1.26 to 3.39), and respiratory system defects (RR 2.65, 95% CI 1.32 to 5.32).Conclusions: The evidence suggests a generally small risk of congenital malformations and argues against a substantial teratogenic effect of SSRIs. Caution is advisable in making decisions about whether to continue or stop treatment with SSRIs during pregnancy. [ABSTRACT FROM AUTHOR]

The relationship between selective serotonin-reuptake inhibitors (SSRIs) use during first trimester and cardiovascular-related malformations of infants is still uncertain. Therefore, we conducted this systematic review and meta-analysis to assess the aforementioned association. A systematic literature review identified studies for cohort studies about SSRIs use and cardiovascular-related malformations in PubMed and Web of Science. We summarized relative risk (RRs) and 95% confidence intervals (CIs) of cardiovascular-related malformations using random-effects model, and heterogeneity and publication-bias analyses were conducted. Eighteen studies met the inclusion criteria. Pregnant women who were exposed to SSRIs at any point during the first trimester had a statistically significant increased risk of infant cardiovascular-related malformations (RR = 1.26, 95%CI = 1.13-1.39), with moderate heterogeneity (I2 = 53.6). The corresponding RR of atrial septal defects (ASD), ventricular septal defects (VSD), ASD and/or VSD was 2.06 (95%CI = 1.40-3.03, I2 = 57.8), 1.15 (95%CI = 0.97-1.36; I2 = 30.3), and 1.27 (95%CI = 1.14-1.42; I2 = 40.0), respectively. No evidence of publication bias and significant heterogeneity between subgroups was detected by meta-regression analyses. In conclusion, SSRIs use of pregnant women during first trimester is associated with an increased risk of cardiovascular-related malformations of infants including septal defects. The safety of SSRIs use during first trimester should be discussed to pregnant women with depression. [ABSTRACT FROM AUTHOR]

Background: According to traditional Chinese medicine (TCM), drugs supplementing the vital energy, Qi, can eliminate tumors by restoring host immunity. The objective of this study is to investigate the underlying immune mechanisms of anti-tumor activity associated with Qi-supplementing herbs, specifically the paired use of Huangqi and Danggui., Methods: Analysis of compatibility regularity was conducted to screen the combination of Qi-supplementing TCMs. Using the MTT assay and a transplanted tumor mice model, the anti-tumor effects of combination TCMs were investigated in vitro and in vivo. High content analysis and flow cytometry were then used to evaluate cellular immunity, followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms. Finally, the anti-tumor activity and the mechanism of the active ingredients were verified by molecular experiments., Results: There is an optimal combination of Huangqi and Danggui that, administered as an aqueous extract, can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo. Based on network pharmacology analysis, PIK3R1 is the core target for the anti-tumor immunity activity of combined Huangqi and Danggui. Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract (quercetin, jaranol, isorhamnetin, kaempferol, calycosin, and suchilactone) that bind to PIK3R1. Jaranol is the most important component against breast cancer. The suchilactone/jaranol combination and, especially, the suchilactone/kaempferol combination are key for immunity enhancement and the anti-tumor effects of the extract., Conclusions: The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone., (© 2024 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

This study aims to investigate the molecular mechanism of tanshinone Ⅱ&#95;(A )(TaⅡ&#95;A) combined with endothelial progenitor cells-derived exosomes(EPCs-exos) in protecting the aortic vascular endothelial cells(AVECs) from oxidative damage via the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt) pathway. The AVECs induced by 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphocholine(POVPC) were randomly divided into model, TaⅡ&#95;A, EPCs-exos, and TaⅡ&#95;A+EPCs-exos groups, and the normal cells were taken as the control group. The cell counting kit-8(CCK-8) was used to examine the cell proliferation. The lactate dehydrogenase(LDH) cytotoxicity assay kit, Matrigel assay, DCFH-DA fluorescent probe, and laser confocal microscopy were employed to examine the LDH release, tube-forming ability, cellular reactive oxygen species(ROS) level, and endothelial cell skeleton morphology, respectively. The enzyme-linked immunosorbent assay was employed to measure the expression of interleukin(IL)-1β, IL-6, and tumor necrosis factor(TNF)-α. Real-time fluorescence quantitative PCR(qRT-PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of PI3K and Akt. Compared with the control group, the model group showed decreased cell proliferation and tube-forming ability, increased LDH release, elevated ROS level, obvious cytoskeletal disruption, increased expression of IL-1β, IL-6, and TNF-α, and down-regulated mRNA and protein levels of PI3K and Akt. Compared with the model group, TaⅡ&#95;A or EPCs-exos alone increased the cell proliferation and tube-forming ability, reduced LDH release, lowered the ROS level, repaired the damaged skeleton, decreased the expression of IL-1β, IL-6, and TNF-α, and up-regulated the mRNA and protein levels of PI3K and Akt. TaⅡ&#95;A+EPCs-exos outperformed TaⅡ&#95;A or EPCs-exos alone in regulating the above indexes. The results demonstrated that TaⅡ&#95;A and EPCs-exos exerted a protective effect on POVPC-induced AVECs by activating the PI3K/Akt pathway, and the combination of the two had stronger therapeutic effect.

Hospital-acquired pneumonia caused by Acinetobacter baumannii is a major healthcare burden. Type VI Secretion System (T6SS) contributes to both virulence and drug resistance in this bacteria. This study aims to investigate the diagnostic value of hemolysin co-regulated protein (Hcp) gene in A. baumannii pneumonia and further explore the effect of hcp on clinical, pathogenicity and drug resistance. 53 clinical A. baumannii strains from patients' respiratory tract at a teaching hospital were included in this study. Real-time quantitative polymerase chain reaction (qRT-PCR) was carried out to examine the expression of hcp . Recombinant Hcp expression plasmids (pET-28a(+)- hcp ) were constructed and his-tagged Hcp were purified to stimulate Tohoku Hospital Pediatrics-1 (THP-1) macrophages. Nuclear Factor Kappa B p65 (NF-κBp65) and Interleukin 8 (IL-8) were detected by qRT-PCR. Antimicrobial susceptibility testing (AST) were examined by an automated instrument system. Hcp gene had 92.6% sensitivity and 75% specificity for distinguishing invasive or colonizing A. baumannii from the respiratory tract. His-tagged Hcp induced NF-κBp65 and IL-8 at gene level in THP-1 macrophages. Additional, high hcp expression isolates showed higher rate of antimicrobial agent exposure (< 30 days) of carbapenems, antibiotic combination therapy and multiple or extensive drug-resistant (MDR/XDR) and exhibited higher resistance rate to clinical commonly-used antimicrobial agents. Hcp gene could serve as a novel diagnostic biomarker to distinguish  A. baumannii respiratory tract infection from colonization and participate in eliciting inflammatory responses in vitro. T6SS/ hcp may play a role in the development of carbapenem-resistant A.   baumannii (CRAB), multiple or extensive drug-resistant  A. baumannii (MDRAB/XDRAB)., Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01083-8., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© Association of Microbiologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: To study the effect of borneol combined with astragaloside IV and Panax notoginseng saponins (BAP) on promoting neurogenesis by regulating microglia polarization after cerebral ischaemia-reperfusion(CI/R) in rats., Methods: A focal CI/R injury model was established. Evaluated the effects of BAP on ischaemic brain injury, on promoting neurogenesis, on inhibiting Inflammatory microenvironment and TLR4/MyD88/NFκB signalling pathway. A microglia oxygen-glucose deprivation reoxygenation (OGD/R) model was established that evaluated the effects of BAP on regulating the polarization of microglia and inflammatory microenvironment., Results: BAP can inhibit the expression of TLR4, MyD88 and NFκB proteins, reduce IL-1β and increase IL-10, reduce M1 type microglia and increase M2 microglia. The proliferation of neural stem cells increased, synaptic gap decreased, synaptic interface curvature increased, expression of SYN and PSD95 proteins increased, which improved the neurological dysfunction and reduced the volume of cerebellar infarction and nerve cell injury., Conclusion: BAP can reduce CI/R injury and promote neurogenesis, the effect is related to inhibition of the activation of TLR4/MyD88/NFκB, regulating the polarization of microglia from M1 type to M2 type and inhibition of inflammatory response., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Low caspofungin exposure is frequently encountered in patients with invasive candidiasis caused by Candida albicans. This study aimed to investigate the effects of caspofungin on C. albicans at sub-inhibitory concentrations., Methods and Results: First, a comparative transcriptomics analysis was performed on C. albicans receiving caspofungin at sub-minimum inhibitory concentrations (sub-MICs). The results showed that caspofungin significantly changed the mRNA expression profile in DAY185, with DE-mRNAs enriched in the functions of cell wall biosynthesis, metabolism, etc. Subsequently, cellular fitness, cell aggregation, energy metabolism activity and the proportion of persister cells of C. albicans were quantitatively and/or qualitatively assessed after sub-MIC caspofungin exposure. No significant changes in cell fitness and aggregation formation were observed during treatment of C. albicans with sub-MIC caspofungin. In C. albicans aggregation treated with sub-MIC caspofungin, we observed a decrease in respiratory metabolism and an increase in persister cells; this effect was more pronounced in als1ΔΔ than in DAY185., Conclusions: Pre-exposure to sub-MIC caspofungin suppresses C. albicans respiratory metabolism and promotes persister cell development., Significance and Impact of the Study: Caspofungin should be used with caution in patients with C. albicans infections, as anti-infection therapy may fail due to persister cells., (© 2022 Society for Applied Microbiology.)

Background: The widespread use of chemical insecticides has resulted in the development of resistance in German cockroaches worldwide, and biopesticides based on entomopathogenic fungi as active ingredients have become a promising alternative strategy. Resistance can change many of the physiological and biochemical characteristics of insect pests, such as cuticle thickness, detoxification enzyme activity, and even intestinal flora composition. Thus, potential interactions between pathogenic fungi and insecticide resistance may lead to unpredictable changes in pest susceptibility to fungi., Results: Beta-cypermethrin-resistant German cockroaches were more susceptible to infection with the fungus Metarhizium anisopliae regardless of age and sex. Histopathological results showed that the infection of resistant strains (R) by M. anisopliae was visibly faster than that of susceptible strains (S). The gut microbiota of the S strain indicated a stronger ability to inhibit fungi in vitro. The abundance of Parabacteroides, Lachnoclostridium, and Tyzzerella&#95;3 decreased significantly in the R strain, and most demonstrated the ability to regulate glucose and lipid metabolism, and antifungal infections. The expression levels of Akirin, BgTPS, and BgPo genes in the R strain were significantly lower than those in the S strain, while BgChi and CYP4G19 gene expression were significantly higher. The mortality of cockroaches infected with M. anisopliae decreased to varying degrees after RNA interference, reflecting the role of these genes in antifungal infection., Conclusions: Results confirmed that insecticide resistance may enhance cockroach susceptibility to fungi by altering intestinal flora and gene expression. Fungal biopesticides have high utilization value in pest control and insecticide resistance management strategies. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Preeclampsia (PE) is an important topic in obstetrics. In this study, we used weighted gene co-expression network analysis (WGCNA) to screen the key modules related to immune cell infiltration and to identify the hub genes for the molecular subtyping of PE. We first downloaded a set of PE transcriptional data (GSE75010; 157 samples: 80 PE and 77 non-PE) from the GEO database. We then analyzed the PE samples and non-PE samples for immune cell infiltration and screened cells with differences in such infiltration. Next, we downloaded the immune-related genes from an immune-related database to screen the expression profile of the immune-related genes. Then, we obtained a candidate gene set by screening the immune-related genes differentially expressed between the two groups. We used WGCNA to construct a weighted co-expression network for these candidate genes, mined co-expression modules, and then calculated the correlation between each module and immune cells with differential infiltration. We screened the modules related to infiltrating immune cells, identified the key modules' hub genes, and determined the key module genes that interacted with each other. Finally, we obtained the hub genes related to the infiltrating immune cells. We classified the preeclampsia patients by unsupervised cluster molecular typing, determined the difference of immune cell infiltration among the different PE subtypes, and calculated the expression of hub genes in these different subtypes. In conclusion, we found 41 hub genes that may be closely related to the molecular typing of PE.

Airway epithelial cells, the first barrier of the respiratory tract, play an indispensable role in innate immunity. Integrin β4 (ITGB4) is a structural adhesion molecule that is involved in the pathological progression of acute inflammatory diseases and is downregulated in asthmatic patients. Research has shown that endothelial ITGB4 has proinflammatory properties in acute lung injury (ALI). However, the role of epithelial ITGB4 in a murine ALI model is still unknown. This study investigated the role of ITGB4 in lipopolysaccharide (LPS)-induced ALI. We found that ITGB4 in the airway epithelium had remarkably increased after the introduction of LPS in vivo and in vitro. Then, we constructed airway epithelial cell-specific ITGB4 knockout (ITGB4 -/- ) mice to study its role in ALI. At a time point of 12 h after the tracheal injection of LPS, ITGB4 -/- mice showed increased macrophages (mainly M1-type macrophages) and neutrophil infiltration into the lungs; inflammation-related proteins including interleukin (IL)-6, tumor necrosis factor, and IL-17A were significantly elevated compared to their levels in ITGB4 +/+ mice. Furthermore, we investigated the role of ITGB4 in the anti-inflammatory response. Intriguingly, in the ITGB4 -/-  + LPS group, we found significantly reduced expression of anti-inflammatory factors, including IL-10 messenger RNA (mRNA) and ARG-1 mRNA. We also observed that monocyte chemotactic protein (MCP-1) increased significantly both in vivo and in vitro. Airway epithelium activates macrophages, most likely driven by MCP-1, which we confirmed in the coculture of epithelia and macrophages. These phenomena indicate that ITGB4 in airway epithelial cells plays an important role in the process of inflammation and activation of macrophages in ALI. Overall, these data demonstrated a novel link between airway epithelial ITGB4 and the inflammatory response in LPS-induced ALI., (© 2021 Wiley Periodicals LLC.)

Objective: To compare the clinical manifestations of pertussis in children of different ages and different immunization statuses in Wenzhou, and to explore the limitations of diagnostic criteria for pertussis., Methods: The clinical data of 288 children diagnosed with pertussis at Yuying Children's Hospital & the Second Affiliated Hospital of Wenzhou Medical University from October 2017 to December 2019 were retrospectively analyzed. The clinical characteristics of children of different ages and different immunization statuses were analyzed. Their clinical data were compared to relevant diagnostic criteria of pertussis in children of different ages according to the Recommendations for Diagnosis and Treatment of Chinese Children with Pertussis and the diagnosis conformity rate was analyzed., Results: Among the 288 children, 124 cases (43.06%) were 3 months old or younger, and 164 cases (288, 56.94%) were >3 months old. Among patients≤3 months of age, cyanosis, three-depression sign, face redness, dyspnea and peripheral blood lymphocyte ratio were significantly higher than those of patients >3 months of age. They also had higher incidence of pneumonia, higher proportion of developing severe pertussis, and longer stay at the hospital. All these findings showed statistically significant difference ( P <0.05). 83 children were fully immunized (receiving the full course of vaccination), and 205 were not fully immunized (not receiving the full course of vaccination or being unvaccinated). The proportion of children presenting cyanosis, shortness of breath, three depression sign and face redness in the incomplete immunization group was higher than that in the complete immunization group. In the incomplete immunization group, the proportion of lymphocytes was higher, the level of C-reactive protein (CRP) was lower, and the length of hospitalization was longer than those of the complete immunization group. All the differences were statistically significant ( P <0.05). Among patients aged ≤3 months, the conformity rate of diagnosis (112/114, 90.32%) upon admission was higher than that among patients aged >3 months (119/164, 72.56%). Among patients aged ≤3 months, 41.94% (52/124, while 54.03% (67/124) of the patients aged ≤3 months had WBC count <20×10 9 L -1 ., Conclusion: Pertussis in children ≤3 months of age in Wenzhou City were more serious, showing higher rate of diagnosis conforming to the recommended clinical diagnostic criteria than that in children >3 months old. The WBC threshold in routine blood test of ≤3 months old could be lowered appropriately and the current diagnostic criteria still needed improvement., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Objective: Currently, coronavirus disease 2019 (COVID-19) has spread worldwide and become a global health concern. Here, we report a familial cluster of six patients infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) in a northern Chinese region and share our local experience with regard the control of COVID-19., Methods: The demographic data, clinical features, laboratory examinations, and epidemiological characteristics of enrolled cases were collected and analyzed. Two family members (Cases 1 and 2) had Hubei exposure history and were admitted to the hospital with a confirmed diagnosis of COVID-19; eight familial members who had contact with them during the incubation period underwent quarantine in a hospital. We closely followed up all the family members and analyzed their clinical outcome., Results: Case 3 had negative SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) results but was suspected to have COVID-19 because of radiographic abnormalities. Cases 4 and 5 developed symptomatic COVID-19. Case 6 was considered an asymptomatic carrier as his SARS-CoV-2 RT-PCR result was positive. The other four family members with close contacts to COVID-19 patients had no evidence of SARS-CoV-2 infection., Conclusions: Our findings suggest that COVID-19 has infectivity during the incubation period and preventive quarantine is effective for controlling an outbreak of COVID-19 infection., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Lung cancer is one of the most common malignant neoplasms worldwide. CD24 is a marker of tumor stem cells that plays an important role in tumorigenesis. Hsp70 is an important molecular chaperone. However, the co-expression and interaction of CD24 and Hsp70, as well as the significance for the prognosis of lung cancer are still unclear. The expression levels of CD24 and Hsp70 were detected by immunohistochemistry and their correlation was analyzed. The expression levels of CD24 mRNA and protein were examined using qRT-PCR and western blotting in SPCA1, A549, H1975, and H1650 cell lines. A CD24-overexpressing cell model was established. The interaction between CD24 and Hsp70 was verified by co-immunoprecipitation and western blotting. CD24 and Hsp70 expression were significantly higher in lung cancer tissues than in adjacent tissues (CD24: p=0.008; Hsp70: p<0.001). CD24 protein expression showed a positive correlation with lymph node metastasis, TNM stage, and vascular cancer thrombus. Hsp70 protein expression showed a positive correlation with differentiation, lymph node metastasis, and TNM stage. CD24 and Hsp70 high expression were also correlated with poor survival. The positive co-expression rate of CD24 and Hsp70 in lung cancer tissues was 52.7% (49/93). CD24 and Hsp70 expression in lung cancer were positively correlated (r=0.368, p<0.001), and co-immunoprecipitation was verified that both endogenous and exogenous CD24 co-precipitated with Hsp70 directly or indirectly. When Hsp70 inhibitor VER15508 was added to A549 cells, Hsp70 and CD24 protein expression were significantly decreased. The present study demonstrated that CD24 and Hsp70 were highly expressed in lung cancer tissues, and associated with invasion, metastasis, and poor survival. Hsp70 may regulate CD24 expression. Co-expression of CD24 and Hsp70 may be a prognostic biomarker for lung cancer.

To explore the main active components and effects of cell cycle regulation mechanism of Astragali radix (AR) and Angelicae sinensis radix (ASR) on oxidative damage in vascular endothelial cells, a model of oxidative damage in human umbilical vein endothelial cells (HUVECs) induced by oxidized low-density lipoprotein (ox-LDL) treatment was developed. Based on the "knock-out/knock-in" model of the target component, cell viability, intracellular reactive oxygen species (ROS), and lactate dehydrogenase (LDH) leakage were assessed by Cell Counting Kit-8 assay, fluorescent probe 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA), and colorimetric assay, respectively, to evaluate the protective effect of the active components of AR and ASR (astragaloside IV (AS IV), astragaloside I (AS I), formononetin (FRM), calycosin (CAL), calycosin-7-O- β -D glucoside (CLG), and ferulic acid (FRA)) against oxidative damage. The cell cycle and expression of genes encoding cyclins and cyclin-dependent kinases (CDKs) were observed using flow cytometry and quantitative real-time polymerase chain reaction. The results showed that the combination of active components (ACC) significantly inhibited the decrease in cell viability as well as the increase in ROS and LDH release in HUVECs induced by ox-LDL treatment. AS IV and FRM promoted the proliferation of HUVECs but the proliferation index was decreased in the AS I and FRA groups; this inhibitory effect was counteracted by the ACC. The ACC reduced and increased the proportion of positive cells in G1 and S phases, respectively, followed by the upregulation of cyclin A ( CCNA ), cyclin E ( CCNE ), and CDK2 mRNA expression and downregulation of cyclin B ( CCNB ), cyclin D1 ( CCND1 ), CDK1 , CDK4 , and CDK6 mRNA expression, which significantly mitigated inhibition of HUVECs proliferation induced by ox-LDL treatment. Taken together, AS IV, AS I, FRM, CAL, CLG, and FRA were the primary pharmacodynamic substances of AR and ASR that alleviated oxidative injury in HUVECs. ACC mitigated the upregulation of intracellular ROS levels and LDH release induced by ox-LDL treatment, which promoted the cell cycle procession of HUVECs by regulating the expression of genes encoding cyclins and CDKs and thus preventing oxidative damage in HUVECs., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Cai-Xia Liu et al.)

Objective: Liver cancer is the second most common cause of death from cancer. Physical activity (PA) was found to be associated with lower risks of several types of cancer. However, the association between PA and the risk of liver cancer is still inconclusive. This systematic review and meta-analysis was aiming to summarize the association between PA and liver cancer risk., Methods: Literatures related were identified by searching PubMed, EMBASE, and Chinese Biomedical literature database from 1965 to 2017 without language limitation. Meta-analyses were performed using random effect model., Results: A total of 5 cohort studies involving 2 513 975 subjects were identified. The pooled relative risk of leisure-time PA with liver cancer risk was 0.92 [95% confidence interval (CI), 0.84-1.01]. There is no significant association between leisure-time PA and liver cancer risk. However, leisure-time PA significantly reduced liver cancer risk in never smokers. The pooled hazard ratio of daily total PA with liver cancer risk was 0.75 (95% CI, 0.66-0.86)., Conclusions: Daily total PA significantly reduces liver cancer risk, whereas leisure-time PA significantly reduces liver cancer risk only in never smokers.

Mild intrauterine hypoperfusion (MIUH) is a serious pathological event that affects the growth and development of fetuses and offspring. MIUH can lead to growth restriction, low birth weight, neurodevelopmental disorders, and other adverse clinical outcomes. To study the effects of MIUH on learning and memory function in offspring, a model of MIUH was established by placing a coil (length 2.5 mm, diameter 0.24 mm) on the uterine artery and ovarian uterine artery of Sprague-Dawley rats in the second trimester of pregnancy (day 17). Next, 120 mg/kg lithium chloride (the MIUH + Li group) or normal saline (the MIUH group) was injected intraperitoneally into these rats. In addition, 120 mg/kg lithium chloride (the Li group) or normal saline (the SHAM group) was injected intraperitoneally into pregnant rats without coil placement. The Morris water maze was used to detect changes in learning and memory ability in the offspring at 4 weeks after birth. In the MIUH group, the escape latency and journey length before reaching the platform were both increased, and the number of times that the platform was crossed and the activity time in the target quadrant within 90 seconds were both decreased compared with the SHAM group. Immunofluorescence double staining and western blot assays demonstrated that hippocampal nestin and Ki67 (both cell-proliferation-related proteins) expression was significantly downregulated in the MIUH group compared with the SHAM group. Furthermore, western blot assays were conducted to investigate changes in related signaling pathway proteins in the brains of offspring rats, and revealed that glycogen synthase kinase 3β (GSK3β) expression was upregulated and β-catenin expression was downregulated in the MIUH group compared with the SHAM group. In addition, compared with the MIUH group, the expression levels of p-GSK3β and β-catenin were upregulated in the MIUH + Li group. These results suggest that MIUH may affect learning and memory function in rat offspring by regulating the GSK3β signaling pathway. The experimental procedures were approved by Animal Ethics Committee of Shengjing Hospital of China Medical University (approval No. 2018PS07K) in June 2018., Competing Interests: None

Multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1) caused by phosphatidylinositol-glycan biosynthesis class N ( PIGN) mutations is an autosomal recessive disease involving many systems of the body, such as the urogenital, cardiovascular, gastrointestinal, and central nervous systems. Here, compound heterozygous variants NM&#95;012327.6:c.2427-2A > G and c.963G > A in PIGN were identified in a Chinese proband with MCAHS1. The features of the MCAHS1 family proband were evaluated to understand the mechanism of the PIGN mutation leading to the occurrence of MCAHS1. Ultrasound was conducted to examine the fetus, and his clinical manifestations were evaluated. Genetic testing was performed by whole-exome sequencing and the results were verified by Sanger sequencing of the proband and his parents. Reverse transcription-polymerase chain reaction was performed, and the products were subjected to Sanger sequencing. Quantitative PCR (Q-PCR) was conducted to compare gene expression between the patient and wild-type subjects. The compound heterozygous mutation NM&#95;012327.6:c.2427-2A > G and c.963G > A was identified by whole-exome sequencing and was confirmed by Sanger sequencing. The NM&#95;012327.6:c.2427-2A > G mutation led to skipping of exon 26, which resulted in a low expression level of the gene, as measured by Q-PCR. These findings provided a basis for genetic counseling and reproduction guidance in this family. Phenotype-genotype correlations may be defined by an expanded array of mutations., (Copyright © 2020 Xiao, Li, Meng, Li, Huang, Liu, Lyu and Na.)

Objectives: Older antimicrobials such as fosfomycin are being considered as alternative agents in the treatment of drug-resistant organisms. However, there are limited data on the usefulness of fosfomycin against carbapenem-resistant Klebsiella pneumoniae (CRKP). This study aimed to investigate the prevalence of fosfomycin resistance and associated mechanisms in CRKP., Methods: A total of 99 clinical CRKP isolates were collected in the Second Affiliated Hospital of Wenzhou Medical University (Wenzhou, China) between January 2017 and June 2018. Fosfomycin susceptibility testing was performed by the agar dilution method. Carbapenemase and fosfomycin resistance genes were detected by PCR. Analysis of the murA, glpT, uhpT, uhpA, ptsI and cyaA genes was performed by PCR and sequencing of four fosfomycin-resistant fosA3-negative CRKP strains. Conjugation experiments were employed to determine the mobility of the fosA3 gene., Results: Of the 99 CRKP isolates, fosfomycin-non-susceptibility was detected in 48 (48.5%) isolates, among which the fosA3 gene was detected in 44. Among the four fosfomycin-resistant fosA3-negative CRKP isolates, one isolate possessed a single nucleotide insertion and deletion mutations as well as 219 nucleotide substitution mutations in murA, two isolates possessed deletion or mutation of large DNA fragments in glpT, and one isolate possessed a fragment insertion sequence in glpT. Transfection into Escherichia coli J53 via plasmid conjugation was successful for 19 (43.2%) of the 44 fosA3-positive CRKP isolates., Conclusion: The fosA3 gene is the primary mechanism of fosfomycin resistance in CRKP and can be transmitted widely by plasmid in hospitals. Mutations in murA and glpT were found in fosfomycin-resistant fosA3-negative CRKP., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Autosomal dominant non-syndromic hearing loss (ADNSHL) has a broad phenotypic spectrum which includes bilateral, symmetrical, and high-frequency sensorineural hearing loss, that eventually progresses into hearing loss at all frequencies. Several genetic variations have been identified as causal factors underlying deafness, autosomal dominant 5 ( DFNA5 ) gene-related hearing loss. Here, we report a novel mutation (c.991-1G > C) in DFNA5 , which co-segregated with late-onset ADNSHL in a Chinese family and was identified via exome sequencing and Sanger sequencing of DNA from peripheral blood of the family members. Further sequencing of cDNA derived from peripheral blood mRNA revealed that the c.991-1G >C mutation led to the skipping of exon 8, which is a known pathogenic mechanism for DFNA5-related hearing loss., (Copyright © 2020 Chen, Jia, Li, Lyu and Liu.)

Objective: To analyze the correlation between the Kellgren-Lawrence (K-L) score of knee osteoarthritis (KOA) patients with different degrees and their urine concentration of C-terminal telopeptide of collagen type II (CTX-II) and interleukin-1β (IL-1β), and to further evaluate the diagnostic value of CTX-II and IL-1β during the pathological process by producing an experimental osteoarthritis (OA) model in rabbits., Methods: From 1 January 2017 to 31 December 2018, a total of 34 subjects (7 mild, 9 moderate, 9 severe arthritis patients, and 9 healthy individuals) comprising 16 men and 18 women were included in this study. Patients were diagnosed according to the American College of Rheumatology (ACR) criteria. The urine of all subjects was collected to detect the concentration of CTX-II and IL-1β. The rabbits in the KOA group were subjected to protease (control group with saline) injection into the articular cavity of their right knees and immobilization with gypsum. We used radiological and histological examination to identify the KOA model. ELISA was applied to investigate the concentrations of CTX-II and IL-1β in urine and serum, and Spearman's rank correlation analysis was used to analyze the correlation., Results: There was no significant difference in the mean ages and body mass index (BMI) between groups. The mean ages of mild, moderate, and severe arthritis patients and healthy individuals were 54.29 ± 5.76, 58.44 ± 6.44, 59.89 ± 6.75, and 56.67 ± 4.18 years, respectively. The mean BMI of mild, moderate, and severe arthritis patients and healthy individuals were 23.59 ± 1.56, 23.57 ± 2.06, 24.46 ± 1.64, and 23.42 ± 1.35 kg/m 2 , respectively. The Kellgren-Lawrence (K-L) score was higher with the aggravation of KOA. The K-L scores of mild, moderate, and severe KOA patients were 1.14 ± 0.38, 2.56 ± 0.53, and 3.63 ± 0.52, respectively. The KOA symptoms of patients became more severe, with not only increased K-L scores but also elevated concentrations of CTX-II and IL-1β. Moreover, there was a positive correlation between CTX-II and IL-1β of all subjects (r = 0.974, P < 0.001), between K-L score and urine concentration of CTX-II (r = 0.900, P < 0.001), and between K-L score and IL-1β (r = 0.813, P < 0.001) of all subjects. Both were significantly increased in KOA group rabbits at all time points after surgery. The serum concentration of CTX-II and IL-1β was elevated as early as in the 2nd week (3.69 and 4.25 times) and reached a peak (5.41 and 7.23 times) in the 4th week after surgery. Then, until 12 weeks after surgery, the CTX-II and IL-1β concentrations in the KOA group were slightly reduced and remained around 4.5 and 6.3 times that in the control group. Moreover, there was a positive correlation between the serum concentration of IL-1β and CTX-II (r = 0.967, P < 0.001)., Conclusion: CTX-II and IL-1β, which were significantly increased during the process of KOA, can be used as biomolecular markers to provide guidelines for early diagnosis and treatment of KOA., (© 2019 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

A parental diagnosis was performed for an unborn foetus of a healthy couple, who was due for ultrasound detection of multiple malformations and abnormal amniotic fluid karyotypes. For an accurate diagnosis, routine G-banding analysis and next generation sequencing (NGS) were carried out. Finally, conventional cytogenetic analysis suggested that the foetus had a karyotype of47,XX,+mar[52]/46,XN, meanwhile NGS also revealed a partial tetrasomy of 27.84Mb from 4q26-q31.21 (117,385,735-145,225,759), and G-banding analysis excluded the couple to have carried the 4q26-q31.21 duplication. We have identified a de novo mosaic small supernumerary marker chromosomes (sSMC) derived from 4q26-q31.21 in a foetus with hemivertebra, polydactyly, abnormal ears, and heart and ventricular septal defect.

Oxidative stress induced by hypoxia/ischemia resulted in the excessive reactive oxygen species (ROS) and the relative inadequate antioxidants. As the initial barrier to environmental pollutants and allergic stimuli, airway epithelial cell is vulnerable to oxidative stress. In recent years, the antioxidant effect of hydrogen sulfide (H 2 S) has attracted much attention. Therefore, in this study, we explored the impact of H 2 S on CoCl 2 -induced cell injury in 16HBE14o- cells. The effect of CoCl 2 on the cell viability was detected by Cell Counting Kit (CCK-8) and the level of ROS in 16HBE14o- cells in response to varying doses (100-1000 μ mol/L) of CoCl 2 (a common chemical mimic of hypoxia) was measured by using fluorescent probe DCFH-DA. It was shown that, in 16HBE14o- cells, CoCl 2 acutely increased the ROS content in a dose-dependent manner, and the increased ROS was inhibited by the NaHS (as a donor of H 2 S). Moreover, the calcium ion fluorescence probe Fura-2/AM and fluorescence dye Rh123 were used to investigate the intracellular calcium concentration ([Ca 2+ ] i ) and mitochondria membrane potential (MMP) in 16HBE14o- cells, respectively. In addition, we examined apoptosis of 16HBE14o- cells with Hoechst 33342. The results showed that the CoCl 2 effectively elevated the Ca 2+ influx, declined the MMP, and aggravated apoptosis, which were abrogated by NaHS. These results demonstrate that H 2 S could attenuate CoCl 2 -induced hypoxia injury via reducing ROS to perform an agonistic role for the Ca 2+ influx and MMP dissipation.

Purpose. The objective of the current study was to investigate whether hcp plays a role in the process of Acinetobacter baumannii infection and to examine clinically relevant factors that may affect hcp expression. Methodology. Seventy-seven A. baumannii isolates from patients with a respiratory infection at the Second Affiliated Hospital and Yuying Childrens Hospital of Wenzhou Medical University (Wenzhou, China) were included in this study. PCR was performed to screen for the presence of hcp. Quantitative real time polymerase chain reaction (qRT-PCR) was carried out to examine the expression of hcp . Results. A total of 77.9 % (60 of 77) of the A. baumannii clinical isolates possessed the hcp gene. Expression of hcp was found to be strain-specific and associated with the infection status. Higher gene expression of hcp was found for invasive A. baumannii isolates causing an infection relative to the colonization group, and for the same strain at a post-infection status compared with that prior to infection. Acid environment was also found to be a trigger of hcp gene expression. Conclusion. The type VI secretion system and hcp predominate in A. baumannii causing respiratory infections. Expression of hcp is regulated by the infection status and acid environment, and might play a role in the process of triggering infection by the colonizer.

Objective: To evaluate the treatment of pregnancies in different stages complicated by TRAP sequence at a single medical center in China., Study Design: A retrospective study evaluating 25 pregnancies with TRAP sequence was performed at Shengjing Hospital in Shenyang, Liaoning between 2012 and 2016. Patients were diagnosed by ultrasound and categorized into three groups (Ia, IIa and IIb) and were expectantly managed or performed RFA (radiofrequency ablation) according to their stage of TRAP sequence. Perinatal outcomes and survival rates were analyzed., Results: There were four cases in stage Ia, 19 cases in stage IIa, and two cases in stage IIb. Cases in stage Ia were expectantly managed. Among cases in stage IIa, we performed RFA (radiofrequency ablation) in 10 cases and expectant management in 6 cases, with the remainder of the patients refusing intrauterine treatment. We applied RFA to treat one case in stage IIb and the other was managed expectantly. For expectant management group and the RFA group, the survival rates were both 64%(7/11). All pump twins in stage Ia survived and the average gestational age at delivery was 37.9 weeks. In stage IIa, the overall survival rate of the pump twin was 70% (7/10) and the average gestational age at delivery was 35.8 weeks in cases treated by RFA. The survival rate was 50% (3/6) and the average gestational age at delivery was 32.8 weeks in expectantly managed cases in stage IIa. No pump twin survived in stage IIa without treatment (3 cases refused any therapy who were excluded) or in stage IIb., Conclusion: Expectant management is effective for treatment of TRAP sequence in stage Ia. In stage IIa, RFA improves the prognosis of pump twins., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: To analyze existing cohort studies and provide evidence for the use of prenatal selective serotonin reuptake inhibitor (SSRI) monotherapy and the associated risk of gestational hypertension and preeclampsia., Methods: A comprehensive search of English language articles published before 30th April 2017 was conducted on PubMed, EMBASE, and the Web of Science databases. Using data acquired, we summarized the relative risks (RRs) and 95% confidence intervals (CIs) of gestational hypertension and preeclampsia using the random-effects model. Heterogeneity between studies was also assessed with the I 2 statistic., Results: Seven cohort studies with 1,108,261 individuals were included for analysis. Compared with nonusers, those undertaking prenatal SSRI monotherapy were more likely to develop gestational hypertension or preeclampsia (summarized RR = 1.21, 95% CI: 1.05-1.40, I 2  = 71.3%), gestational hypertension (summarized RR = 1.14, 95% CI: 1.00-1.30, I 2  = 5.7%), and preeclampsia (summarized RR = 1.32, 95% CI: 0.99-1.78, I 2  = 83.3%). In addition, although subgroup analyses, which were stratified by study design, number of cases, geographic location, duration of SSRI monotherapy, registry databases, and adjustment for potential confounders and risk factors, were consistent with the main findings, not all of these showed statistical significance. No evidence of publication bias was detected., Conclusions: Women who receive SSRI monotherapy during pregnancy are at increased risk of gestational hypertension and preeclampsia.

Aims: To investigate the safety of fluoxetine use during pregnancy, and to better understand the relationship between maternal fluoxetine use during the first trimester and congenital malformations in infants., Methods: PubMed and Web of Science databases were systematically searched from inception to 21 March 2016. Additional studies were identified in a manual search of the reference lists. Two reviewers independently extracted data. A third reviewer checked the data. Estimates were pooled using a random-effects model to calculate the summarized relative ratios (RR) and 95% confidence intervals (CI)., Results: Among 1918 initially identified articles, 16 cohort studies were included. The offspring of pregnant women exposed to fluoxetine during the first trimester had a statistically increased risk of major malformations (RR = 1.18, 95% CI = 1.08-1.29), cardiovascular malformations (RR = 1.36, 95% CI = 1.17-1.59), septal defects (RR = 1.38, 95% CI = 1.19-1.61), and non-septal defects (RR = 1.39, 95% CI = 1.12-1.73) with low heterogeneity in infants. There were no significant observations of other system-specific malformations in the nervous system, eye, urogenital system, digestive system, respiratory system, or musculoskeletal system, respectively. There was no indication of publication bias., Conclusions: The results of this meta-analysis indicate maternal fluoxetine use is associated with a slightly increased risk of cardiovascular malformations in infants. Health care providers and pregnant women must weigh the risk-benefit potential of these drugs when making decisions about whether to treat with fluoxetine during pregnancy., (© 2017 The British Pharmacological Society.)