Eukaryotic initiation factor 4A3 inhibits Wnt/ß-catenin signaling and regulates axis formation in zebrafish embryos.

A key step in the activation of canonical Wnt signaling is the interaction between ß-catenin and Tcf/Lefs that forms the transcription activation complex and facilitates the expression of target genes. Eukaryotic initiation factor 4A3 (EIF4A3) is an ATP-dependent DEAD box-family RNA helicase and acts as a core subunit of the exon junction complex (EJC) to control a series of RNA post-transcriptional processes. In this study, we uncover that EIF4A3 functions as a Wnt inhibitor by interfering with the formation of ß-catenin/Tcf transcription activation complex. As Wnt stimulation increases, accumulated ß-catenin displaces EIF4A3 from a transcriptional complex with Tcf/Lef, allowing the active complex to facilitate the expression of target genes. In zebrafish embryos, eif4a3 depletion inhibited the development of the dorsal organizer and pattern formation of the anterior neuroectoderm by increasing Wnt/ß-catenin signaling. Conversely, overexpression of eif4a3 decreased Wnt/ß-catenin signaling and inhibited the formation of the dorsal organizer before gastrulation. Our results reveal previously unreported roles of EIF4A3 in the inhibition of Wnt signaling and the regulation of embryonic development in zebrafish.

Characterization of Morreton virus as an oncolytic virotherapy platform for liver cancers.

BACKGROUND: Morreton virus (MORV) is an oncolytic Vesiculovirus , genetically distinct from vesicular stomatitis virus (VSV). AIM: To report that MORV induced potent cytopathic effects (CPEs) in cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) in vitro models. APPROACH AND RESULTS: In preliminary safety analyses, high intranasal doses (up to 10 10 50% tissue culture infectious dose [TCID 50 ]) of MORV were not associated with significant adverse effects in immune competent, non-tumor-bearing mice. MORV was shown to be efficacious in a Hep3B hepatocellular cancer xenograft model but not in a CCA xenograft HuCCT1 model. In an immune competent, syngeneic murine CCA model, single intratumoral treatments with MORV (1 × 10 7 TCID 50 ) triggered a robust antitumor immune response leading to substantial tumor regression and disease control at a dose 10-fold lower than VSV (1 × 10 8 TCID 50 ). MORV led to increased CD8 + cytotoxic T cells without compensatory increases in tumor-associated macrophages and granulocytic or monocytic myeloid-derived suppressor cells. CONCLUSIONS: Our findings indicate that wild-type MORV is safe and can induce potent tumor regression via immune-mediated and immune-independent mechanisms in HCC and CCA animal models without dose limiting adverse events. These data warrant further development and clinical translation of MORV as an oncolytic virotherapy platform.

A nomogram-based prediction model for dysphagia in patients with chronic obstructive pulmonary disease: A cross-sectional study.

AIM AND OBJECTIVES: To investigate the prevalence of dysphagia in patients with COPD, identify the risk factors for dysphagia, develop a visual clinical prediction model and quantitatively predict the probability of developing dysphagia. BACKGROUND: Patients with COPD are at high risk of dysphagia, which is strongly linked to the acute exacerbation of their condition. The use of effective tools to predict its risk may contribute to the early identification and treatment of dysphagia in patients with COPD. DESIGN: A cross-sectional design. METHODS: From July 2021 to April 2023, we enrolled 405 patients with COPD for this study. The clinical prediction model was constructed according to the results of a univariate analysis and a logistic regression analysis, evaluated by discrimination, calibration and decision curve analysis and visualized by a nomogram. This study was reported using the TRIPOD checklist. RESULTS: In total, 405 patients with COPD experienced dysphagia with a prevalence of 59.01%. A visual prediction model was constructed based on age, whether combined with cerebrovascular disease, chronic pulmonary heart disease, acute exacerbation of COPD, home noninvasive positive pressure ventilation, dyspnoea level and xerostomia level. The model exhibited excellent discrimination at an AUC of .879. Calibration curve analysis indicated a good agreement between experimental and predicted values, and the decision curve analysis showed a high clinical utility. CONCLUSION: The model we devised may be used in clinical settings to predict the occurrence of dysphagia in patients with COPD at an early stage. RELEVANCE TO CLINICAL PRACTICE: The model can help nursing staff to calculate the risk probability of dysphagia in patients with COPD, formulate personalized preventive care measures for high-risk groups as soon as possible to achieve early prevention or delay of dysphagia and its related complications and improve the prognosis. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

The mutation rate of rpoB gene showed an upward trend with the increase of MIRU10, MIRU39 and QUB4156 repetitive number.

BACKGROUND: Mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) is a frequently used typing method for identifying the Beijing genotype of Mycobacterium tuberculosis (Mtb), which is easily transformed into rifampicin (RIF) resistance. The RIF resistance of Mtb is considered to be highly related with the mutation of rpoB gene. Therefore, this study aimed to analyze the relationship between the repetitive number of MIRU loci and the mutation of rpoB gene. METHODS: An open-source whole-genome sequencing data of Mtb was used to detect the mutation of rpoB gene and the repetitive number of MIRU loci by bioinformatics methods. Cochran-Armitage analysis was performed to analyze the trend of the rpoB gene mutation rate and the repetitive number of MIRU loci. RESULTS: Among 357 rifampicin-resistant tuberculosis (RR-TB), 304 strains with mutated rpoB genes were detected, and 6 of 67 rifampicin susceptible strains were detected mutations. The rpoB gene mutational rate showed an upward trend with the increase of MIRU10, MIRU39, QUB4156 and MIRU16 repetitive number, but only the repetitive number of MIRU10, MRIU39 and QUB4156 were risk factors for rpoB gene mutation. The Hunter-Gaston discriminatory index (HGDI) of MIRU10 (0.65) and QUB4156 (0.62) was high in the overall sample, while MIRU39 (0.39) and MIRU16 (0.43) showed a moderate discriminatory Power. CONCLUSION: The mutation rate of rpoB gene increases with the addition of repetitive numbers of MIRU10, QUB4156 and MIRU39 loci.

Synergistic combination of cytotoxic chemotherapy and cyclin-dependent kinase 4/6 inhibitors in biliary tract cancers.

BACKGROUND AND AIMS: Biliary tract cancers (BTCs) are uncommon, but highly lethal, gastrointestinal malignancies. Gemcitabine/cisplatin is a standard-of-care systemic therapy, but has a modest impact on survival and harbors toxicities, including myelosuppression, nephropathy, neuropathy, and ototoxicity. Whereas BTCs are characterized by aberrations activating the cyclinD1/cyclin-dependent kinase (CDK)4/6/CDK inhibitor 2a/retinoblastoma pathway, clinical use of CDK4/6 inhibitors as monotherapy is limited by lack of validated biomarkers, diffident preclinical efficacy, and development of acquired drug resistance. Emerging studies have explored therapeutic strategies to enhance the antitumor efficacy of CDK4/6 inhibitors by the combination with chemotherapy regimens, but their mechanism of action remains elusive. APPROACH AND RESULTS: Here, we report in vitro and in vivo synergy in BTC models, showing enhanced efficacy, reduced toxicity, and better survival with a combination comprising gemcitabine/cisplatin and CDK4/6 inhibitors. Furthermore, we demonstrated that abemaciclib monotherapy had only modest efficacy attributable to autophagy-induced resistance. Notably, triplet therapy was able to potentiate efficacy through elimination of the autophagic flux. Correspondingly, abemaciclib potentiated ribonucleotide reductase catalytic subunit M1 reduction, resulting in sensitization to gemcitabine. CONCLUSIONS: As such, these data provide robust preclinical mechanistic evidence of synergy between gemcitabine/cisplatin and CDK4/6 inhibitors and delineate a path forward for translation of these findings to preliminary clinical studies in advanced BTC patients.

Age and sex trend differences in hemoglobin levels in China: a cross-sectional study.

BACKGROUND: Both age and gender are the influence factors of hemoglobin concentration. However, the changing trend of hemoglobin levels between males and females with age remains unclear. This study aimed to explore their changing characteristics in different genders. METHODS: A cross-sectional study was conducted in Physical Examination Center of the First Affiliated Hospital of Wannan Medical College in Wuhu, China from 2014 to 2016. The generalized linear model was applied to explore the relationship between age, gender and hemoglobin levels. RESULTS: Among the 303,084 participants, the mean age for females and males was 46.9 ± 13.4(15-98) and 48.1 ± 13.7(14-98) years old, respectively. Generalized smoothing splines showed that hemoglobin levels increased up to age 25 and then decreased in men; in women the levels increased up until age 20, and then decreased, with slight increase again (ß = 0.244, P < 0.01). After dividing all participants into hyperglycemia and normal groups, only the normal female group showed a significant upward trend (ß = 0.257, P < 0.01) between ages 50-59. CONCLUSIONS: Hemoglobin concentration changes with age and the curve is different in males and females. The slightly upward trend of female hemoglobin in the age range of 50-59 years old should be considered in developing the reference range of hemoglobin making.

Carbohydrates and secondary compounds of alpine tundra shrubs in relation to experimental warming.

BACKGROUND: It is critical to understand the sensitivity, response direction and magnitude of carbohydrates and secondary compounds to warming for predicting the structure and function of the tundra ecosystem towards future climate change. RESULTS: Open-top chambers (OTCs) were used to passively increase air and soil temperatures on Changbai Mountain alpine tundra. After seven years' continuous warming (+ 1.5 °C), the vegetation coverage, nonstructural carbohydrates (soluble sugars and starch) and secondary compounds (total phenols, flavonoids and triterpenes) of leaves and roots in three dominant dwarf shrubs, Dryas octopetala var. asiatica, Rhododendron confertissimum and Vaccinium uliginosum, were investigated during the growing season. Warming did not significantly affect the concentrations of carbohydrates but decreased total phenols for the three species. Carbohydrates and secondary compounds showed significantly seasonal pattern and species-specific variation. No significant trade-off or negative relationship between carbohydrates and secondary compounds was observed. Compared to Dr. octopetala var. asiatica, V. uliginosum allocated more carbon on secondary compounds. Warming significantly increased the coverage of Dr. octopetala var. asiatica, did not change it for V. uliginosum and decreased it for Rh. confertissimum. Rh. confertissimum had significantly lower carbohydrates and invested more carbon on secondary compounds than the other two species. CONCLUSIONS: Enhanced dominance and competitiveness of Dr. octopetala var. asiatica was companied by increased trend in carbohydrate concentrations and decreased ratio of secondary compounds to total carbon in the warming OTCs. We, therefore, predict that Dr. octopetala var. asiatica will continue to maintain dominant status, but the competition ability of V. uliginosum could gradually decrease with warming, leading to changes in species composition and community structure of the Changbai tundra ecosystem under future climate warming.

RNA-binding protein hnRNP UL1 binds κB sites to attenuate NF-κB-mediated inflammation.

Heterogeneous nuclear ribonucleoproteins (hnRNPs), a family of RNA-binding proteins, play important roles in various biological processes. However, the roles of hnRNPs members in immunity and inflammation remain to be fully understood. By a functional screening for hnRNPs members in LPS-stimulated macrophage inflammatory response, we identified hnRNP UL1 as a negative regulator of NF-κB-mediated inflammation. hnRNP UL1 constrains NF-κB-triggered transcriptional expression of pro-inflammatory cytokines in response to innate stimuli. Perturbation of hnRNP UL1 enhanced pro-inflammatory cytokine production in macrophages. In vivo deficiency of hnRNP UL1 increased the pro-inflammatory cytokine production once challenged with LPS. Accordingly, the expression of hnRNP UL1 decreased in peripheral blood mononuclear cells of rheumatoid arthritis patients. Mechanistically, hnRNP UL1 competes with NF-κB to bind κB sites to constrain the magnitude and duration of inflammatory response. Meanwhile, the broadly and dynamically binding of hnRNP UL1 on the target genes' promoter during inflammatory response is unraveled. Our study adds new insight into the functions of hnRNPs in NF-κB-mediated inflammation, proposing a potential therapeutic strategy for controlling inflammatory autoimmune diseases.

Prediction of carotid plaque by blood biochemical indices and related factors based on Fisher discriminant analysis.

OBJECTIVE: This study aims to establish the predictive model of carotid plaque formation and carotid plaque location by retrospectively analyzing the clinical data of subjects with carotid plaque formation and normal people, and to provide technical support for screening patients with carotid plaque. METHODS: There were 4300 subjects in the ultrasound department of Maanshan People's Hospital collected from December 2013 to December 2018. We used demographic and biochemical data from 3700 subjects to establish predictive models for carotid plaque and its location. The leave-one-out cross-validated classification, 600 external data validation, and area under the receiver operating characteristic curve (AUC) were used to verify the accuracy, sensitivity, specificity, and application value of the model. RESULTS: There were significant difference of age (F = - 34.049, p < 0.01), hypertension (χ2 = 191.067, p < 0.01), smoking (χ2 = 4.762, p < 0.05) and alcohol (χ2 = 8.306, p < 0.01), Body mass index (F = 15.322, p < 0.01), High-density lipoprotein (HDL) (F = 13.840, p < 0.01), Lipoprotein a (Lp a) (F = 52.074, p < 0.01), Blood Urea Nitrogen (F = 2.679, p < 0.01) among five groups. Prediction models were built: carotid plaque prediction model (Model CP); Prediction model of left carotid plaque only (Model CP Left); Prediction model of right carotid plaque only (Model CP Right). Prediction model of bilateral carotid plaque (Model CP Both). Model CP (Wilks' lambda = 0.597, p < 0.001, accuracy = 78.50%, sensitivity = 78.07%, specificity = 79.07%, AUC = 0.917). Model CP Left (Wilks' lambda = 0.605, p < 0.001, accuracy = 79.00%, sensitivity = 86.17%, specificity = 72.70%, AUC = 0.880). Model CP Right (Wilks' lambda = 0.555, p < 0.001, accuracy = 83.00%, sensitivity = 81.82%, specificity = 84.44%, AUC = 0.880). Model CP Both (Wilks' lambda = 0.651, p < 0.001, accuracy = 82.30%, sensitivity = 89.50%, specificity = 72.70%, AUC = 0.880). CONCLUSION: Demographic characteristics and blood biochemical indexes were used to establish the carotid plaque and its location discriminant models based on Fisher discriminant analysis (FDA), which has high application value in community screening.

FGFR2-IIIb Expression by Immunohistochemistry Has High Specificity in Cholangiocarcinoma with FGFR2 Genomic Alterations.

BACKGROUND: FGFR2 genomic alterations are observed in 10-20% of cholangiocarcinoma (CCA). Although FGFR2 fusions are an important actionable target, FGFR2 protein expression has not been thoroughly characterized. AIMS: To evaluate FGFR2 protein expression in cholangiocarcinoma harboring FGFR2 genomic alterations. METHODS: FGFR2 protein expression was evaluated in 99 CCA cases with two different antibodies. FGFR2 genomic alterations were confirmed via next-generating sequencing (NGS) or FISH. Primary objective was to determine the specificity and sensitivity of FGFR2 immunohistochemistry staining for detecting FGFR2 genomic alterations. Secondary objectives included overall FGFR2 immunohistochemistry staining in CCA patients, and evaluation of whether FGFR2 expression correlates with clinical outcomes including overall survival (OS), progression-free survival (PFS), and time-to-tumor recurrence (TTR). RESULTS: Immunohistochemistry staining with two antibodies against FGFR2, FPR2-D, and clone 98706 showed high accuracy (78.7% and 91.9%) and specificity (82.9% and 97.7%), and moderate sensitivity (53.9% and 57.1%), respectively, when compared with the standard methods for detecting FGFR2 genomic alterations. In a median follow-up of 72 months, there were no statistically significant differences in OS, PFS, and TTR, for patients with positive or negative FGFR2 staining. CONCLUSION: FGFR2 protein expression by immunohistochemistry has high specificity and therefore could be used to imply the presence of FGFR2 genomic alterations in the context of a positive test. In the case of a negative test, NGS or FISH would be necessary to ascertain cases with FGFR2 genomic alterations.

Implications of gender-based variabilities in bone mineral density and hemoglobin levels.

BACKGROUND: Studies reported that there is a relationship between volumetric bone mineral density (vBMD) and hemoglobin (HGB) in sickle cell anemia, chronic obstructive pulmonary disease, inflammatory bowel disease, and chronic kidney disease, it is not clear whether this association exists in normal populations or different genders. In order to further clarify the relationship between vBMD and HGB, and provide the basis for the diagnosis of related diseases, this study was conducted in the physical examination population. METHODS: A cross-sectional study was conducted on a health check-up population from Wannan area of China from January to December 2018. The study involved 1238 individuals aged 23 to 85 years. Linear regression analysis and smooth curve were applied to determine the relationship of HGB and vBMD. RESULTS: The average level of vBMD in the population was 130.11 ± 79.51 mg/cm3, after adjusting for age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglycerides (TG), glucose (GLU), high-density lipoprotein (HDL) and low-density lipoprotein (LDL). A U-shape relationship was established between vBMD and HGB, the cut off value of HGB was 130 g/L. After gender stratification, the results showed a U-shaped curve relationship between vBMD and HGB in male group, and a linear relationship between vBMD and HGB in female group. The vBMD decreased with HGB when HGB < 120 g/L, and increased when HGB ≥ 120 g/L in male group. CONCLUSION: The relationship between vBMD and HGB in the male physical examination population presents a U-shaped curve.

A 0.8 V, 5.3-5.9 GHz Sub-Sampling PLL with 196.5 fsrms Integrated Jitter and -251.6 dB FoM.

This paper proposes a hybrid dual path sub-sampling phase-locked loop (SSPLL), including a proportional path (P-path) and an integral path (I-path), with 0.8 V supply voltage. A differential master-slave sampling filter (MSSF), replacing the sub-sampling charge pump (SSCP), composed the P-path to avoid the degraded feature caused by the decreasing of the supply voltage. The I-path is built by a rail-to-rail SSCP to suppress the phase noise of the voltage-controlled oscillator (VCO) and avoid the trouble of locking at the non-zero phase offset (as in type-I PLL). The proposed design is implemented in a 40-nm CMOS process. The measured output frequency range is from 5.3 to 5.9 GHz with 196.5 fs root mean square (RMS) integrated jitter and -251.6 dB FoM.

Impact of family history of diabetes on blood glucose, lipid levels and perinatal outcomes in pregnant women with gestational diabetes mellitus.

To investigate the impact of family history of diabetes (FHD) on blood glucose, lipid levels and perinatal outcomes in pregnant women with gestational diabetes mellitus (GDM). A total of 1265 GDM women who gave childbirth in Women's Hospital, Zhejiang University School of Medicine during January to December 2019 were enrolled in the study, including 253 women with FHD and 1012 women without FHD. The -test or test were used to compare the blood lipid, blood glucose levels and perinatal outcomes including large for gestational age infant, small for gestational age infant, macrosomia, cesarean delivery, preeclampsia, preterm labor, postpartum hemorrhage, fetal distress. The correlation between FHD and perinatal outcomes were estimated by Logistic regression analysis. The high density lipoprotein level at third-trimester was significantly lower in GDM women with FHD (<0.05); and the women with FHD also had higher fasting blood glucose oral glucose tolerance test (OGTT)1 h, OGTT 2 h and glycosylated hemoglobin level (all <0.01). In GDM women, FHD was an independent risk factor for preeclampsia (=3.27, 95%: 1.39-7.68). GDM women with FHD have lower high density lipoprotein and higher glucose levels. FHD is an independent risk factor for preeclampsia in GDM women.

Glutathione peroxidase 4 inhibits Wnt/ß-catenin signaling and regulates dorsal organizer formation in zebrafish embryos.

The Wnt/ß-catenin signaling pathway plays pivotal roles in axis formation during embryogenesis and in adult tissue homeostasis. Glutathione peroxidase 4 (GPX4) is a selenoenzyme and participates in the reduction of peroxides. Its synthesis depends on the availability of the element selenium. However, the roles of GPX4 in vertebrate embryonic development and underlying mechanisms are largely unknown. Here, we show that maternal loss of zebrafish gpx4b promotes embryonic dorsal organizer formation, whereas overexpression of gpx4b inhibits the development of the dorsal organizer. Depletion of human GPX4 and zebrafish gpx4b (GPX4/gpx4b) increases, while GPX4/gpx4b overexpression decreases, Wnt/ß-catenin signaling in vivo and in vitro Functional and epistatic studies showed that GPX4 functions at the Tcf/Lef level, independently of selenocysteine activation. Mechanistically, GPX4 interacts with Tcf/Lefs and inhibits Wnt activity by preventing the binding of Tcf/Lefs to the promoters of Wnt target genes, resulting in inhibitory action in the presence of Wnt/ß-catenin signaling. Our findings unravel GPX4 as a suppressor of Wnt/ß-catenin signals, suggesting a possible relationship between the Wnt/ß-catenin pathway and selenium via the association of Tcf/Lef family proteins with GPX4.

Quercetin prevents bone loss in hindlimb suspension mice via stanniocalcin 1-mediated inhibition of osteoclastogenesis.

Recent studies demonstrate that diet quercetin (Quer) has obvious bone protective effects on ovariectomized rodents but thus far there is no direct evidence to support the inhibitory effect of Quer on bone loss caused by long-term unloading. In the present study, we investigated whether Quer could prevent bone loss induced by unloading in mice. Mice were subjected to hindlimb suspension (HLS) and received Quer (25, 50, 100 mg· kg-1 ·day-1, ig) for 4 weeks. Before euthanasia blood sample was collected; the femurs were harvested and subjected to MicroCT analysis. We showed that Quer administration markedly improved bone microstructure evidenced by dose-dependently reversing the reduction in bone volume per tissue volume, trabecular number, and bone mineral density, and the increase of trabecular spacing in mice with HLS. Analysis of serum markers and bone histometric parameters confirmed that Quer at both middle and high doses significantly decreased bone resorption-related markers collagen type I and tartrate-resistant acid phosphatase 5b, and increased bone formation-related marker procollagen 1 N-terminal propeptide as compared with HLS group. Treatment with Quer (1, 2, 5 µM) dose-dependently inhibited RANKL-induced osteoclastogenesis through promoting the expression of antioxidant hormone stanniocalcin 1 (STC1) and decreasing ROS generation; knockdown of STC1 blocked the inhibitory effect of Quer on ROS generation. Knockdown of STC1 also significantly promoted osteoclastogenesis in primary osteoclasts. In conclusion, Quer protects bones and prevents unloading-caused bone loss in mice through STC1-mediated inhibition of osteoclastogenesis. The findings suggest that Quer has the potential to prevent and treat off-load bone loss as an alternative supplement.

[Association analysis of phenotypic traits of alkaloid content in Sophora alopecuroides with SSR molecular markers].

To further study and fully exploit the medicinal plant Sophora alopecuroides, the molecular markers related with the phenotypic traits of alkaloid content in S. alopecuroides should be detected. In this study, SSR molecular markers were used to analyze the genetic diversity and genetic structure of 23 S. alopecuroides populations, in combination with the association analysis between molecular markers and the alkaloid contents. The results showed that P, H, I, G_(st) and N_m values were 40.10%, 0.335 3, 0.504 5, 0.433 7 and 0.625 9 respectively, in 23 S. alopecuroides populations. This indicated that there was less gene exchange and higher genetic differentiation among different S. alopecuroides populations. The results of SSR unweighted pair-group method with arithmetic means(UPGMA) cluster showed that the S. alopecuroides populations relationship from Xinjiang was far from the populations of other regions, but the populations of S. alopecuroides from Gansu, Inner Mongolia and Qinghai were closely relevant to those from Ningxia. The 23 populations were further divided into 2 genetic subpopulations by the population structure analysis. Through association analysis, a total of 26 loci in 13 SSR markers were found to be significantly associated(P<0.005)with the content of MA, OMA, SC and OSC, and the rate of explanation on the phenotype variance of related markers ranged from 36.45% to 77.93%. Among the locus, 1 each were related with MA and OSC content at interpretation rate reached as high as 50% with high threshold(P<0.000 1). These results could provide support for the discovery of important genes in the alkaloid biosynthetic and metabolic pathway of S. alopecuroides.

Second-trimester maternal lipid profiles predict pregnancy complications in an age-dependent manner.

PURPOSE: Our objective was to investigate the combinatorial effect of maternal age and second-trimester maternal lipid profiles for pregnancy complications. METHODS: With 1:4 matching, this retrospective study selected 499 advanced maternal age women and 1996 younger controls. Logistic regression analysis was used to estimate the correlation between second-trimester lipid profiles [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)] and pregnancy complications [gestational diabetes mellitus (GDM), pregnancy-induced hypertension syndrome (PIH), preterm labor (PTL), and macrosomia]. Optimal cutoff points were determined by ROC curve analysis. RESULTS: In women aged 20-34 years, TG are a risk factor for PIH (OR 1.54, 95% CI 1.16-2.04) and PTL (OR 1.34, 95% CI 1.04-1.72). LDL-C was positively associated with macrosomia (OR 1.25, 95% CI 1.04-1.50), while HDL-C was negatively associated with PIH (OR 0.45, 95% CI 0.21-0.93). The optimal cutoff points for TG predicting PIH and PTL were separately ≥ 2.135 and 2.305 mmol/L. The optimal cutoff point for HDL-C identifying PIH was ≤ 1.995 mmol/L and for LDL-C identifying macrosomia was ≥ 3.425 mmol/L. As for advanced maternal age, only TG was an independent risk factor for PIH (OR 1.60, 95% CI 1.01-2.54), and its optimal cutoff point was ≥ 2.375 mmol/L. CONCLUSIONS: Second-trimester lipid profiles might predict pregnancy complications varied by maternal age. This suggested that individualized prenatal care strategies should be established for women with advanced and normal maternal age to prevent pregnancy complications.

Bispectral Index Monitoring During Anesthesia Promotes Early Postoperative Recovery of Cognitive Function and Reduces Acute Delirium in Elderly Patients with Colon Carcinoma: A Prospective Controlled Study using the Attention Network Test.

BACKGROUND Bispectral index (BIS) monitoring can reduce the duration of anesthesia. This study aimed to evaluate the effects of BIS monitoring during surgery for resection of colon carcinoma in elderly patients using the Attention Network Test (ANT) to study alerting, orienting, and executive functions, and the Confusion Assessment Method (CAM). MATERIAL AND METHODS Eighty-one patients (65-75 years) underwent radical surgery for colon carcinoma with general intravenous anesthesia, propofol (6-8 mg/kg/h), vecuronium (0.03-0.05 mg/kg/min), and remifentanil (0.1-0.2 µg/kg/min). The BIS group (n=41) underwent adjustment of anesthesia to maintain a BIS value between 40-60; the non-BIS group (N=40) underwent standard intraoperative hemodynamic monitoring. Primary endpoints were alerting, orienting, and executive functions assessed pre-operatively and on postoperative days 1 and 5 using the ANT; the secondary endpoint was delirium during the first five postoperative days, assessed using the CAM. RESULTS Propofol and remifentanil doses were significantly lower in the BIS group compared with the non-BIS group (P<0.001). Alerting, orienting, and executive functions showed no differences between the two groups pre-operatively but were impaired in both groups on postoperative day 1 compared with pre-operative levels (P<0.001). On postoperative day 5, alerting (P=0.607) and orienting (P=0.851) functions recovered in the BIS group but remained impaired in the non-BIS group (P<0.001). Delirium was significantly lower in the BIS group compared with the non-BIS group (17.5% vs. 27.5%) (P<0.001). CONCLUSIONS BIS-guided anesthesia was associated with reduced anesthetic exposure, early postoperative recovery of alerting and orienting functions, and reduced postoperative delirium.

Can Mandibular Condylar Mobility Sonography Measurements Predict Difficult Laryngoscopy?

BACKGROUND: Limited mandibular condylar mobility plays an important role in difficult laryngoscopy. Indirect assessment methods, such as mouth opening, have been proven to be useful predictors of difficult laryngoscopy. Sonography is a new direct assessment method for the limited mandibular condylar mobility. However, whether this method could be used in predicting difficult laryngoscopy still remains unknown. This study aimed to observe its ability to predict difficult laryngoscopy. METHODS: Adult patients who were administered tracheal intubations for elective surgery under general anesthesia were enrolled in the study. Mandibular condylar mobility was assessed by sonography through condylar translation measurements. Beside mouth opening, other indirect variables that correlated with temporomandibular joint mobility, such as mandibular protrusion distance, upper lip bite test, and whether the condyle-tragus distance was <1 finger breadth, were also evaluated before anesthesia. The primary outcome was difficult laryngoscopy defined as the Cormack-Lehane level 3 or 4. RESULTS: A total of 484 patients were prospectively included, and difficult laryngoscopy was reported in 41 patients. The condylar translation prediction criterion for difficult laryngoscopy was ≤10 mm. The condylar translation was correlated with Cormack-Lehane level (Spearman correlation coefficient, -0.46; 99% confidence interval [CI], -0.55 to -0.36) and owned the highest area under the receiver operating characteristic curve (0.93; 99% CI, 0.90 to 0.96, compared with that of the other predictors, P < .001) with difficult laryngoscopy. The condylar translation ≤10 mm was with a considerable κ value (κ = 0.52; 99% CI, 0.37 to 0.67) to difficult laryngoscopy and proved to be an independent predictor by a multivariate logistic regression. CONCLUSIONS: Compared with indirect assessments, such as mouth opening and other parameters, mandibular condylar mobility, as assessed directly using sonography, was correlated with difficult laryngoscopy and demonstrated an independent and notably predictive property.

Synthesis and Evaluation of Novel Benzofuran Derivatives as Selective SIRT2 Inhibitors.

A series of benzofuran derivatives were designed and synthesized, and their inhibitory activites were measured against the SIRT1-3. The enzymatic assay showed that all the compounds showed certain anti-SIRT2 activity and selective over SIRT1 and SIRT3 with IC50 (half maximal inhibitory concentration) values at the micromolar level. The preliminary structure-activity relationships were analyzed and the binding features of compound 7e (IC50 3.81 µM) was predicted using the CDOCKER program. The results of this research could provide informative guidance for further optimizing benzofuran derivatives as potent SIRT2 inhibitors.