Prenatal diagnosis of interrupted aortic arch using high-definition flow render mode and spatiotemporal image correlation.

OBJECTIVES: To evaluate the clinical utility of two dimensional (2D) ultrasound combined with spatiotemporal image correlation (STIC) in diagnosing interrupted aortic arch (IAA) in fetal life. METHODS: A total of 53 cases of fetal IAA were diagnosed using 2D ultrasound combined with STIC, and 53 normal fetuses of the same gestational week were selected. These cases were retrospectively analyzed to assess the utility of employing 2D ultrasound combined with STIC in the diagnosis of IAA. RESULTS: 2D ultrasound combined with STIC detected 22 cases of type A IAA, 24 cases of type B IAA, and seven cases of type C IAA. Furthermore, combining 2D ultrasound with STIC enabled dynamic visualization of the IAA, aiding in prenatal diagnosis. The diagnostic coincidence rate of IAA was found to be higher in the HD-flow combined with STIC than that in the 2D combined with HD-flow. CONCLUSION: HD-flow combined with STIC can assist in diagnosing fetal IAA, and this technique has important clinical value.

Prenatal Ultrasound Diagnosis of Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome with Persistent Hyperplastic Primary Vitreous: A Case Report.

INTRODUCTION: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome is a rare autosomal dominant disorder characterized by megalencephaly (i.e., overgrowth of the brain), polymicrogyria, focal hypoplasia of the cerebral cortex, and polydactyly. Persistent hyperplastic primary vitreous (PHPV) involves a spectrum of congenital ocular abnormalities that are characterized by the presence of a vascular membrane behind the lens. CASE PRESENTATION: Here, we present a case of foetal MPPH with PHPV that was diagnosed using prenatal ultrasound. Ultrasound revealed the presence of megalencephaly, multiple cerebellar gyri, and hydrocephalus. Whole-exome sequencing confirmed the mutation of the AKT3 gene, which led to the consideration of MPPH syndrome. Moreover, an echogenic band with an irregular surface was observed between the lens and the posterior wall of the left eye; therefore, MPPH with PHPV was suspected. CONCLUSION: MPPH syndrome with PHPV can be diagnosed prenatally.

Prenatal diagnosis of fetal conotruncal defects by using 2D ultrasound and HD live flow combined with spatiotemporal image correlation.

INTRODUCTION: To explore the diagnostic value of spatiotemporal image correlation (STIC) for different types of fetal conotruncal defects (CTDs). METHODS: The clinical data and STIC images of 174 fetuses with CTDs diagnosed via prenatal ultrasound were analyzed retrospectively. RESULTS: Among the 174 cases of CTDs, 58 were tetralogy of Fallot (TOF); 30, transposition of great arteries (TGA) (D-TGA, 23 cases; cc-TGA, 7 cases); 26, double outlet of the right ventricle (DORV); 32, persistent arterial trunk (PTA) (type A1, 15 cases; type A2, 11 cases; type A3, 5 cases; type A4, 1 case); and 28, pulmonary atresia (PA) (ventricular septal defect, 24 cases; ventricular septal integrity, 4 cases). Among the cases, 156 were complicated with complex congenital intracardiac and extracardiac malformations. The abnormal display rate of the four-chamber view of two-dimensional echocardiography was low. The display rate of the permanent arterial trunk was the highest (90.6%) in STIC imaging. CONCLUSIONS: STIC imaging can be used in the diagnosis of different types of CTDs, especially in persistent arterial trunks, and thus has great value for the clinical treatment and prognosis of these defects.

Clinical value of prenatal ultrasound in diagnosis and classification of common arterial trunk.

OBJECTIVES: To investigate the clinical value of prenatal ultrasound in the diagnosis of the common arterial trunk (CAT) classification and associated malformations. MATERIALS AND METHODS: The 2D ultrasound images, spatiotemporal image correlations (STICs) and clinical data of 88 fetuses diagnosed with CAT malformations by prenatal ultrasound were retrospectively analyzed and classified. The correlation between different types, fetal malformation and pregnancy outcomes were analyzed. RESULTS: Among the 88 fetuses, there were 39 cases (44.32%) of type A1, 40 cases (45.45%) of type A2, 8 cases (9.09%) of type A3, and 1 case of type A4 (1.14%). There were 16 cases (18.18%) with isolated CAT, 48 cases (54.55%) with complex intra-cardiac structural abnormalities, and 24 cases (27.27%) with intra-cardiac and extra-cardiac structural abnormalities. In extra-cardiac structural malformations, 14 cases were associated with 1 other system abnormality, 4 cases with 2 other system abnormalities, 3 cases with 3 other system abnormalities, while 3 cases were combined with 4 other system abnormalities, among which the facial and physical abnormalities had the highest incidence (39.13%). The STIC images were completely displayed in all 88 cases. There was a statistical difference between isolated CAT and CAT combined with other abnormalities in fetal pregnancy outcomes. CONCLUSIONS: Prenatal ultrasound had a high clinical application value in CAT classification. Pregnancy outcomes were highly correlated with the classification and associated intra-cardiac and extra-cardiac structural malformations. The early evaluation of fetal prognosis before birth has important value for clinical intervention.

Quinone Derivatives as Promising Anti-Helicobacter pylori Agents from Aerial Parts of Mitracarpus hirtus.

Seven new naphthoquinone diglycosides (1-7), three new anthraquinones (8-10), and eight known analogues were obtained from the aerial parts of Mitracarpus hirtus collected from West Africa in a bioassay-guided phytochemical investigation. All isolated compounds were elucidated by comparison with the literature and interpretation of spectroscopic data, and the absolute configurations of the new naphthoquinone diglycosides (1-10) were confirmed by chemical methods and ECD calculations. Notably, compound 1 was found to be the first naphthoquinone diglycoside containing carboxylic acid and isopentenyl side chains isolated from a species in the genus Mitracarpus. Compounds 6-18 showed antibacterial activity against multiple Helicobacter pylori strains with MIC values ranging from 0.0625 to 64 µg/mL. Particularly, 1-hydroxybenzoisochromanquinone (17) and benzo[g]isoquinoline-5,10-dione (18), with MIC values of 0.0625 and 0.125 µg/mL, displayed 32-512-fold higher potencies than a positive control, metronidazole. Compound 18 also demonstrated high antibiofilm activity and killed biofilm-encased Helicobacter pylori cells more effectively than metronidazole.

Screening and identification of a specific peptide binding to breast cancer cells from a phage-displayed peptide library.

OBJECTIVES: Breast cancer is a popular fatal malignant tumor for women with high of rates incidence and mortality. Development of the new approaches for breast cancer targeted diagnosis and chemotherapy is emergently needed by the current clinical practice, the important first step is finding a breast cancer specifically binding molecule or fragment as early clinical indicators. RESULTS: By a phage-displayed peptide library, a 12-mer peptide, CSB1 was screened out using MCF-7 cells as the target. The consequently results under immunofluorescence and laser scanning confocal microscope (LSCM) indicated that CSB1 bound MCF-7 cells and breast cancer tissues specifically and sensitively with high affinity. Bioinformatics analysis suggested that the peptide CSB1 targets the 5-Lipoxygenase-Activating Protein (FLAP), which has been implicated in breast cancer progression and prognosis. CONCLUSIONS: The peptide, CSB1 is of the potential as a candidate to be used for developing the new approaches of molecular imaging detection and targeting chemotherapy of breast cancer in the future.

Development of a novel drug targeting delivery system for cervical cancer therapy.

'Targeting peptides' have demonstrated their value in diagnostic imaging and therapy and novel peptide probes specific to cervical cancer were developed. In the M13KE phage dodecapeptide (12-mer) peptide library, the phage clone S7 showed the best binding to the cancer cells as confirmed by immunofluorescence and flow cytometry assays, and was selected for continued studies. Its binding peptide, CSP3, was synthesized from the sequence of S7's 12-mer at the N-terminus of the minor coat protein pIII of this M13KE phage vector. The peptide's binding was analyzed by the same assays used for S7. It was also assessed using competitive inhibition and binding to a tissue chip. The results demonstrated that the CSP3 peptide bound to cervical carcinoma cells with high sensitivity and specificity. The positive results indicated that the peptide CSP3, conjugated with nanomaterials and chemotherapeutics, may be developed as a targeting vehicle for therapeutic drug delivery against cervical cancer, especially cervical cancer with multiple drug resistance. For this aim, we prepared a CSP3 conjugated liposome drug delivery system containing doxorubicin (DOX) and microRNA101 (miR101) expression plasmids (CSP3-Lipo-DOX-miR101), and the primary result showed that the system demonstrated significantly enhanced cytotoxicity to SiHa cells and DOX resistant SiHa cells, SiHa/ADR. Our results showed that CSP3 is a cervical cancer targeting 12aa peptide with high specificity and sensitivity, and the CSP3 conjugated drug delivery system, CSP3-Lipo-DOX-miR101 has promising potential for development as an efficient drug system for the therapy of cervical cancer.

Annexin A2 Enhances the Progression of Colorectal Cancer and Hepatocarcinoma via Cytoskeleton Structural Rearrangements.

Annexin A2 (ANXA2) is reported to be associated with cancer development. To investigate the roles ANXA2 plays during the development of cancer, the RNAi method was used to inhibit the ANXA2 expression in caco2 (human colorectal cancer cell line) and SMMC7721 (human hepatocarcinoma cell line) cells. The results showed that when the expression of ANXA2 was efficiently inhibited, the growth and motility of both cell lines were significantly decreased, and the development of the motility relevant microstructures, such as pseudopodia, filopodia, and the polymerization of microfilaments and microtubules were obviously inhibited. The cancer cell apoptosis was enhanced without obvious significance. The possible regulating pathway in the process was also predicted and discussed. Our results suggested that ANXA2 plays important roles in maintaining the malignancy of colorectal and hepatic cancer by enhancing the cell proliferation, motility, and development of the motility associated microstructures of cancer cells based on a possible complicated signal pathway.

GenCLiP 2.0: a web server for functional clustering of genes and construction of molecular networks based on free terms.

UNLABELLED: Identifying biological functions and molecular networks in a gene list and how the genes may relate to various topics is of considerable value to biomedical researchers. Here, we present a web-based text-mining server, GenCLiP 2.0, which can analyze human genes with enriched keywords and molecular interactions. Compared with other similar tools, GenCLiP 2.0 offers two unique features: (i) analysis of gene functions with free terms (i.e. any terms in the literature) generated by literature mining or provided by the user and (ii) accurate identification and integration of comprehensive molecular interactions from Medline abstracts, to construct molecular networks and subnetworks related to the free terms. AVAILABILITY AND IMPLEMENTATION: http://ci.smu.edu.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

DVL/GSK3/ISL1 pathway signaling: unraveling the mechanism of SIRT3 in neurogenesis and AD therapy.

BACKGROUND: The established association between Alzheimer's disease (AD) and compromised neural regeneration is well-documented. In addition to the mitigation of apoptosis in neural stem cells (NSCs), the induction of neurogenesis has been proposed as a promising therapeutic strategy for AD. Our previous research has demonstrated the effective inhibition of NSC injury induced by microglial activation through the repression of oxidative stress and mitochondrial dysfunction by Sirtuin 3 (SIRT3). Nonetheless, the precise role of SIRT3 in neurogenesis remains incompletely understood. METHODS: In vivo, SIRT3 overexpression adenovirus was firstly injected by brain stereotaxic localization to affect the hippocampal SIRT3 expression in APP/PS1 mice, and then behavioral experiments were performed to investigate the cognitive improvement of SIRT3 in APP/PS1 mice, as well as neurogenic changes in hippocampal region by immunohistochemistry and immunofluorescence. In vitro, under the transwell co-culture condition of microglia and neural stem cells, the mechanism of SIRT3 improving neurogenesis of neural stem cells through DVL/GSK3/ISL1 axis was investigated by immunoblotting, immunofluorescence and other experimental methods. RESULTS: Our findings indicate that the overexpression of SIRT3 in APP/PS1 mice led to enhanced cognitive function and increased neurogenesis. Additionally, SIRT3 was observed to promote the differentiation of NSCs into neurons during retinoic acid (RA)-induced NSC differentiation in vitro, suggesting a potential role in neurogenesis. Furthermore, we observed the activation of the Wnt/ß-catenin signaling pathway during this process, with Glycogen Synthase Kinase-3a (GSK3a) primarily governing NSC proliferation and GSK3ß predominantly regulating NSC differentiation. Moreover, the outcomes of our study demonstrate that SIRT3 exerts a protective effect against microglia-induced apoptosis in neural stem cells through its interaction with DVLs. CONCLUSIONS: Our results show that SIRT3 overexpressing APP/PS1 mice have improved cognition and neurogenesis, as well as improved neurogenesis of NSC in microglia and NSC transwell co-culture conditions through the DVL/GSK3/ISL1 axis.

Efficacy and tolerability of the Subcutaneous Semaglutide for type 2 Diabetes patients: an updated systematic review and meta-analysis.

OBJECTIVES: To update and assess the efficacy and tolerability of once weekly subcutaneous semaglutide in patients with type 2 diabetes (T2D). MATERIALS AND METHODS: PubMed, Science Direct, Cochrane Library, Clinical trial, Springer, OVID, China National Knowledge Infrastructure (CNKI), WanFang Data and China Science and Technology Journal Database (VIP) were searched from inception to January 18, 2023. Randomized controlled trials (RCTs) comparing subcutaneous semaglutide with placebo or any other antidiabetic agent in adults with T2D were eligible. The risk ratio (RR) and mean difference (MD) with 95% confidence intervals (CIs) were determined to synthesize the results. RESULTS: A total of 17 trials enrolling 14,940 T2D patients were included. For efficacy, compared with placebo, semaglutide exhibited beneficial effects on glycosylated hemoglobin A1c (HbA1c) control [MD -0.97%, 95% CI (-1.33, -0.62), I2 = 91%; MD -1.36%, 95% CI (-1.59, -1.13), I2 = 84%, semaglutide 0.5 and 1.0 mg, respectively], body weight reduction, blood pressure control. At the same time, subcutaneous semaglutide 0.5 and 1 mg reduced HbA1c by 0.56% (95% CI 0.32 to 0.80) and 0.63% (95% CI 0.35 to 0.91) compared to other glucose-lowering agents. For tolerability, semaglutide did not increase the incidence of adverse events (AEs) and serious adverse events (SAEs), severe or blood glucose (BG) confirmed hypoglycaemia, acute pancreatitis and diabetic retinopathy compared to placebo or active comparators, but did increase the risk of nausea, diarrhea and vomiting. CONCLUSIONS: Semaglutide has a better effect on glycaemic control and weight loss than other therapies. Nevertheless, semaglutide was associated with increased incidence of gastrointestinal-related disorders. Further large, multicenter randomized controlled clinical trials are still needed to obtain more robust evidence to better guide clinical treatment decisions.

Efficacy and safety of oral semaglutide in type 2 diabetes mellitus: A systematic review and meta-analysis.

OBJECTIVES: To investigate the efficacy and safety of oral semaglutide 7 and 14 mg, the only orally delivered glucagon-like peptide-1 (GLP-1) receptor agonist tablet approved for type 2 diabetes mellitus (T2DM) patients. METHODS: Search several databases for randomized controlled trials (RCTs) of oral semaglutide in patients with T2DM from inception through May 31, 2021. The primary outcomes included change from baseline in hemoglobin A1c (HbA1c) and body weight. Risk ratios (RR), mean differences (MD), and 95% confidence intervals (CI) were calculated to evaluate the outcomes. RESULTS: This meta-analysis included 11 RCTs with a total of 9821 patients. Compared with placebo, semaglutide 7 and 14 mg reduced HbA1c by 1.06% (95% CI, 0.81-1.30) and 1.10% (95% CI, 0.88-1.31), respectively. While in comparison with other antidiabetic agents, semaglutide 7 and 14 mg reduced HbA1c by 0.26% (95% CI, 0.15-0.38) and 0.38% (95%CI, 0.31-0.45). Both doses of semaglutide could significantly reduce body weight. Semaglutide 14 mg did increase the incidence of medication discontinuation and gastrointestinal events (nausea, vomiting and diarrhea). CONCLUSION: Once-daily semaglutide 7 and 14 mg can significantly lowered HbA1c and body weight in patients with T2DM, and this effect increases with dose. Significantly, more gastrointestinal events occurred with semaglutide 14 mg.

Health systems efficiency in China and ASEAN, 2015-2020: a DEA-Tobit and SFA analysis application.

OBJECTIVE: To evaluate the health systems efficiency in China and Association of Southeast Asian Nations (ASEAN) countries from 2015 to 2020. DESIGN: Health efficiency analysis using data envelopment analysis (DEA) and stochastic frontier approach analysis. SETTING: Health systems in China and ASEAN countries. METHODS: DEA-Malmquist model and SFA model were used to analyse the health system efficiency among China and ASEAN countries, and the Tobit regression model was employed to analyse the factors affecting the efficiency of health system among these countries. RESULTS: In 2020, the average technical efficiency, pure technical efficiency and scale efficiency of China and 10 ASEAN countries' health systems were 0.700, 1 and 0.701, respectively. The average total factor productivity (TFP) index of the health systems in 11 countries from 2015 to 2020 was 0.962, with a decrease of 1.4%, among which the average technical efficiency index was 1.016, and the average technical progress efficiency index was 0.947. In the past 6 years, the TFP index of the health system in Malaysia was higher than 1, while the TFP index of other countries was lower than 1. The cost efficiency among China and ASEAN countries was relatively high and stable. The per capita gross domestic product (current US$) and the urban population have significant effects on the efficiency of health systems. CONCLUSIONS: Health systems inefficiency is existing in China and the majority ASEAN countries. However, the lower/middle-income countries outperformed high-income countries. Technical efficiency is the key to improve the TFP of health systems. It is suggested that China and ASEAN countries should enhance scale efficiency, accelerate technological progress and strengthen regional health cooperation according to their respective situations.

Exploring the Appropriate Price of Semaglutide for Type 2 Diabetes Patients Based on Cost-Utility Analysis in China.

Introduction: Semaglutide is the first and only oral version of a glucagon-like peptide-1 analogue approved by the FDA for the treatment of type 2 diabetes (T2D). This research was designed to explore the appropriate price of once-weekly (OW) semaglutide for T2D patients in China based on cost-utility analysis. Methods: The baseline patient cohorts of OW semaglutide and once-daily (OD) empagliflozin were sourced from a patient-level meta-analysis integrating the SUSTAIN 2, SUSTAIN 3, SUSTAIN 8 and PIONEER 2 trials. The long-term health and economic outcomes were simulated using the United Kingdom Prospective Diabetes Study Outcome Model 2 from the Chinese healthcare provider's perspective. The appropriate price of semaglutide was explored by binary search. One-way sensitivity analysis (one-way SA), probabilistic sensitivity analysis and scenario analysis were applied to solve the uncertainty. Results: Under the assumption that the annual cost of semaglutide is equal to that of OD empagliflozin, OW semaglutide was superior to OD empagliflozin due to its higher quality adjusted life years and lower total costs. After binary search, the incremental cost-utility ratio of OW semaglutide vs. OD empagliflozin was approximately equal to 3λ with an annual cost of semaglutide of $1,007.18 and approximately equal to λ with an annual cost of semaglutide of $708.11. Subsequently, the incremental cost-utility ratio of OW semaglutide vs. OD empagliflozin was approximately 3λ and λ, with annual costs of semaglutide of $877.43 and $667.04, respectively, adjusted by one-way SA. Ultimately, the cost-utility results with annual costs of semaglutide of $877.43 and $667.04 were robust to probabilistic sensitivity analysis and scenario analysis. Conclusion: In conclusion, the annual cost of semaglutide appears to be appropriate between $667.04 and $877.43 for T2D patients in China.

Anti-inflammatory property and functional substances of Lonicerae Japonicae Caulis.

ETHNOPHARMACOLOGICAL RELEVANCE: Lonicerae Japonicae Caulis, the dried stem and branch of Lonicera japonica Thunb., is a Chinese Materia Medica known as Ren Dong Teng in Chinese with long use history in the traditional Chinese medicine (TCM) prescriptions. Lonicerae Japonicae Caulis possesses heat-clearing and detoxifying functions according to the TCM theory. In recent years, a large amount of experimental and clinical studies proved good anti-inflammatory effects of some heat-clearing and detoxifying herbs. The present study aims to reveal the anti-inflammatory property and functional substances of Lonicerae Japonicae Caulis. MATERIALS AND METHODS: For anti-inflammatory activity test, LPS-induced RAW 264.7 macrophages, DSS-induced SPF male C57BL/6J mice model, and LPS-induced SPF male ICR mice model were used in vitro and in vivo, respectively. The behavioral changes, organ damage, and the expression of inflammatory factors such as TNT-α and IL-6 mRNA expression were measured for activity evaluation. Lonicerae Japonicae Caulis samples were prepared by solvent extraction and subsequent column chromatography. The main components were identified and determined using UPLC-UV analysis as well as NMR interpretation after purification. To testify the contribution of main components for the anti-inflammatory activity, different samples were also prepared by compound-knockout strategy. RESULTS: Ethanol extract of Lonicerae Japonicae Caulis could attenuate sickness symptoms in mice such as diarrhea, less activity, and depression. It could also alleviate multiple organ damage, and significantly inhibit the expression of pro-inflammatory factors such as TNF-α, IL-1ß, IL-6 and IFN-γ in mice. Furthermore, the isochlorogenic acid-rich and biflavonoid-rich fractions and isochlorogenic acids A and C, and ochnaflavone could significantly down-regulate the mRNA expression of TNF-α and IL-6 in LPS-induced RAW 264.7 macrophages. CONCLUSIONS: Lonicerae Japonicae Caulis possesses anti-inflammatory property. Its isochlorogenic acid-rich and biflavonoid-rich fractions do the major contribution. And their main components, isochlorogenic acids A and C, and ochnaflavone, take main responsibility for the anti-inflammatory property.

Urinary NMR metabolomic profiles discriminate inflammatory bowel disease from healthy.

BACKGROUND AND AIMS: Inflammatory bowel disease, a chronic inflammation of the intestinal tract, presents in two variations, Ulcerative Colitis (UC) and Crohn's disease (CD). Given that treatment of CD differs from UC, a single test that provided strong diagnostic ability would offer great clinical value. Two previous studies have indicated that CD can be distinguished from UC, and that both can be distinguished from non-IBD-type gastrointestinal disease, based on urinary and faecal metabolite profiling. METHODS: Analysis of healthy as well as CD and UC patients attending an IBD clinic was performed. IBD patients were classified into two groups (CD or UC) based on chart review of clinical, endoscopic, and histological assessment. Urine samples were obtained and analyzed using nuclear magnetic resonance (NMR) spectroscopy combined with targeted profiling techniques, followed by univariate and multivariate statistical analysis. RESULTS: Based on urinary metabolomics, individuals with IBD could be differentiated from healthy. Major differences between IBD and healthy included TCA cycle intermediates, amino acids, and gut microflora metabolites. Comparison of CD and UC patients revealed discrimination, but removal of patients with the surgical intervention confounder revealed that CD could not be discriminated from UC. CONCLUSIONS: This study highlights the potential for metabolomics to distinguish IBD from the healthy state but shows that careful consideration must be given to establishing disease-representative cohorts that are free of confounding factors.