Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials.

BACKGROUND: Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs. METHODS: This systematic review and network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled trials of weight-lowering drugs in adults with overweight and obesity. We performed frequentist random-effect network meta-analyses to summarise the evidence and applied the Grading of Recommendations Assessment, Development, and Evaluation frameworks to rate the certainty of evidence, calculate the absolute effects, categorise interventions, and present the findings. The study was registered with PROSPERO, CRD 42021245678. FINDINGS: 14 605 citations were identified by our search, of which 132 eligible trials enrolled 48 209 participants. All drugs lowered bodyweight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification. High to moderate certainty evidence established phentermine-topiramate as the most effective in lowering weight (odds ratio [OR] of ≥5% weight reduction 8·02, 95% CI 5·24 to 12·27; mean difference [MD] of percentage bodyweight change -7·98, 95% CI -9·27 to -6·69) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·79, 95% CI -6·34 to -5·25). Naltrexone-bupropion (OR 2·69, 95% CI 2·10 to 3·44), phentermine-topiramate (2·40, 1·68 to 3·44), GLP-1 receptor agonists (2·22, 1·74 to 2·84), and orlistat (1·71, 1·42 to 2·05) were associated with increased adverse events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed substantially larger benefits than other drugs with a similar risk of adverse events as other drugs for both likelihood of weight loss of 5% or more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD -11·40, 95% CI -12·51 to -10·29). INTERPRETATION: In adults with overweight and obesity, phentermine-topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might be the most effective. FUNDING: 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University.

Time-dependent risk of fracture in adults with type 2 diabetes receiving anti-diabetic drug: A one-stage network meta-analysis.

AIMS: To assess the time-dependent risk of fracture in adults with type 2 diabetes receiving anti-diabetic drugs. MATERIALS AND METHODS: We searched MEDLINE, EMBASE, and Cochrane Library up to 18 November 2021, for randomized controlled trials (RCTs) and propensity-score-matched non-randomized studies (NRSs) comparing all anti-diabetic drugs with standard treatment or with each other on fracture in adults with type 2 diabetes. The study performed a one-stage network meta-analysis using discrete-time hazard regression with reconstructed individual time-to-event data. RESULTS: This network meta-analysis involved seven RCTs (65,051 adults with type 2 diabetes) with a median follow-up of 36 months and three propensity-score-based NRSs (17,954 participants) with a median follow-up of 27.3 months. Among anti-diabetic drugs, thiazolidinediones increased the overall hazard of fracture by 42% (95% credible interval [CrI], 3%-97%) and almost tripled the risk after 4 years (hazard ratio [HR], 2.74; 95% CrI, 1.53-4.80). Credible subgroup analysis suggested that thiazolidinediones increased the hazard of fracture only in females (HR, 2.19; 95% CrI, 1.26-3.74) but not among males (HR, 0.81; 95% CrI, 0.45-1.40). Moderate certainty evidence established that thiazolidinediones increase 92 fractures in five years per 1000 female patients. We did not find the risk of fractures with other anti-diabetic drugs including metformin, sulfonylureas, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors. CONCLUSIONS: Long-term use of thiazolidinediones elevates the risk of fracture among females with type 2 diabetes. There is no evidence eliciting fracture risk associated with other anti-diabetic drugs.

Sex-specific associations between skeletal muscle mass and incident diabetes: A population-based cohort study.

AIMS: To investigate the sex-specific associations between predicted skeletal muscle mass index (pSMI) and incident type 2 diabetes in a retrospective longitudinal cohort of Chinese men and women. MATERIALS AND METHODS: We enrolled Chinese adults without diabetes at baseline from WATCH (West chinA adulT health CoHort), a large health check-up-based database. We calculated pSMI to estimate skeletal muscular mass, and measured blood glucose variables and assessed self-reported history to identify new-onset diabetes. The nonlinear association between pSMI and incident type 2 diabetes was modelled using the penalized spline method. The piecewise association was estimated using segmented linear splines in weighted Cox proportional hazards regression models. RESULTS: Of 47 885 adults (53.2% women) with a median age of 40 years, 1836 developed type 2 diabetes after a 5-year median follow-up. In women, higher pSMI was associated with a lower risk of incident type 2 diabetes (Pnonlinearity = 0.09, hazard ratio [HR] per standard deviation increment in pSMI: 0.79 [95% confidence interval {CI} 0.68, 0.91]). A nonlinear association of pSMI with incident type 2 diabetes was detected in men (Pnonlinearity < 0.001). In men with pSMI lower than 8.1, higher pSMI was associated with a lower risk of incident type 2 diabetes (HR 0.58 [95% CI 0.40, 0.84]), whereas pSMI was not significantly associated with incident diabetes in men with pSMI equal to or greater than 8.1 (HR 1.08 [95% CI 0.93, 1.25]). CONCLUSIONS: In females, a larger muscular mass is associated with a lower risk of type 2 diabetes. For males, this association is significant only among those with diminished muscle mass.

Methylation and Demethylation of Emerging Contaminants in Plants.

Many contaminants of emerging concern (CECs) have reactive functional groups and may readily undergo biotransformations, such as methylation and demethylation. These transformations have been reported to occur during human metabolism and wastewater treatment, leading to the propagation of CECs. When treated wastewater and biosolids are used in agriculture, CECs and their transformation products (TPs) are introduced into soil-plant systems. However, little is known about whether transformation cycles, such as methylation and demethylation, take place in higher plants and hence affect the fate of CECs in terrestrial ecosystems. In this study, we explored the interconversion between four common CECs (acetaminophen, diazepam, methylparaben, and naproxen) and their methylated or demethylated TPs in Arabidopsis thaliana cells and whole wheat seedlings. The methylation-demethylation cycle occurred in both plant models with demethylation generally taking place at a greater degree than methylation. The transformation rate of demethylation or methylation was dependent on the bond strength of R-CH3, with demethylation of methylparaben or methylation of acetaminophen being more pronounced. Although not explored in this study, these interconversions may exert influences on the behavior and biological activity of CECs, particularly in terrestrial ecosystems. The study findings demonstrated the prevalence of transformation cycles between CECs and their methylated or demethylated TPs in higher plants, contributing to a more complete understanding of risks of CECs in the human-wastewater-soil-plant continuum.

Promotive Effects of Chloride and Sulfate on the Near-Complete Destruction of Perfluorocarboxylates (PFCAs) in Brine via Hydrogen-tuned 185-nm UV Photolysis: Mechanisms and Kinetics.

Hydrogen-tuned 185 nm vacuum ultraviolet (VUV/H2) photolysis is an emerging technology to destroy per- and polyfluoroalkyl substance (PFAS) in brine. This study discovered the promotive effects of two major brine anions, i.e., chloride and sulfate in VUV/H2 photolysis on the hydrated electron (eaq-) generation and perfluorocarboxylates (PFCAs) destruction and established a kinetics model to elucidate the promotive effects on the steady-state concentration of eaq- ([eaq-]ss). Results showed that VUV/H2 achieved near-complete defluorination of perfluorooctanoic acid (PFOA) in the presence of up to 1000 mM chloride or sulfate at pH 12. The defluorination rate constant (kdeF) of PFOA peaked with a chloride concentration at 100 mM and with a sulfate concentration at 500 mM. The promotive effects of chloride and sulfate were attributed to an enhanced generation of eaq- via their direct VUV photolysis and conversion of additionally generated hydroxyl radical to eaq- by H2, which was supported by a linear correlation between the predicted [eaq-]ss and experimentally observed kdeF. The kdeF value increased from pH 9 to 12, which was attributed to the speciation of the H·/eaq- pair. Furthermore, the VUV system achieved >95% defluorination and ≥99% parent compound degradation of a concentrated PFCAs mixture in a synthetic brine, without generating any toxic perchlorate or chlorate.

Imaging features of pediatric meningiomas: emphasis on unusual locations.

PURPOSE: This article aims to analyze pediatric meningioma's imaging characteristics, especially those in unusual locations. METHODS: Pediatric patients with pathologically confirmed meningiomas at our hospital from January 2010 to January 2024 were enrolled. Meningiomas located in the cerebral convexity, parasagittal falcine region, anterior skull base, middle skull base, sphenoid ridge, cerebellopontine angle (CPA), olfactory groove, or juxtasella were considered in usual locations. Meningiomas found in other areas were considered in unusual locations. Clinical information, pathology results, and imaging features of pediatric meningiomas in usual and usual locations were analyzed and compared. RESULTS: A total of 18 patients (19 meningiomas) were enrolled, including 14 males and 4 females, with an average age of 14 years (ranging from 6 to 18 years). A total of 12 (63.2%) meningiomas were in the unusual location, including four (33.3%) were intraparenchymal, four (33.3%) were intraventricular, two (16.7%) were intraosseous, one (8.3%) case was in the paranasal sinus, and one (8.3%) was intraspinal. The meningiomas in unusual locations usually lacked the meningeal tail sign, and the misdiagnosis rate on preoperative imaging was significantly higher than that of meningiomas in usual locations. CONCLUSION: Pediatric meningiomas are prone to occur in unusual locations. When they occur in usual locations, they often lack typical radiographic features of meningiomas, leading to potential misdiagnosis before surgery. Recognition of the imaging characteristics of meningiomas in unusual locations in children may facilitate accurate preoperative imaging diagnosis.

Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials.

BACKGROUND: Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs. METHODS: This systematic review and network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled trials of weight-lowering drugs in adults with overweight and obesity. We performed frequentist random-effect network meta-analyses to summarise the evidence and applied the Grading of Recommendations Assessment, Development, and Evaluation frameworks to rate the certainty of evidence, calculate the absolute effects, categorise interventions, and present the findings. The study was registered with PROSPERO, CRD 42021245678. FINDINGS: 14 605 citations were identified by our search, of which 143 eligible trials enrolled 49 810 participants. Except for levocarnitine, all drugs lowered bodyweight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification. High to moderate certainty evidence established phentermine-topiramate as the most effective in lowering weight (odds ratio [OR] of ≥5% weight reduction 8·02, 95% CI 5·24 to 12·27; mean difference [MD] of percentage bodyweight change -7·97, 95% CI -9·28 to -6·66) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·76, 95% CI -6·30 to -5·21). Naltrexone-bupropion (OR 2·69, 95% CI 2·11 to 3·43), phentermine-topiramate (2·40, 1·69 to 3·42), GLP-1 receptor agonists (2·17, 1·71 to 2·77), and orlistat (1·72, 1·44 to 2·05) were associated with increased adverse events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed substantially larger benefits than other drugs with a similar risk of adverse events as other drugs for both likelihood of weight loss of 5% or more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD -11·41, 95% CI -12·54 to -10·27). INTERPRETATION: In adults with overweight and obesity, phentermine-topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might be the most effective. FUNDING: 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University.

Azvudine and nirmatrelvir-ritonavir in hospitalized patients with moderate-to-severe COVID-19: Emulation of a randomized target trial.

To examine the effectiveness of azvudine and nirmatrelvir-ritonavir in treating hospitalized patients with moderate-to-severe COVID-19. We emulated a target trial with a multicenter retrospective cohort of hospitalized adults with moderate-to-severe COVID-19 without contraindications for azvudine or nirmatrelvir-ritonavir between December 01, 2022 and January 19, 2023 (during the Omicron BA.5.2 variant wave). Exposures included treatment with azvudine or nirmatrelvir-ritonavir for 5 days versus no antiviral treatment during hospitalization. Primary composite outcome (all-cause death and initiation of invasive mechanical ventilation), and their separate events were evaluated. Of the 1154 patients, 27.2% were severe cases. In the intent-to-treat analyses, azvudine reduced all-cause death (Hazard ratio [HR]: 0.31; 95% CI: 0.12-0.78), and its composite with invasive mechanical ventilation (HR: 0.47; 95% CI: 0.24-0.92). Nirmatrelvir-ritonavir reduced invasive mechanical ventilation (HR: 0.42; 95% CI: 0.17-1.05), and its composite with all-cause death (HR: 0.38; 95% CI: 0.18-0.81). The study did not identify credible subgroup effects. The per-protocol analyses and all sensitivity analyses confirmed the robustness of the findings. Both azvudine and nirmatrelvir-ritonavir improved the prognosis of hospitalized adults with moderate-to-severe COVID-19.

Methylation and Demethylation of Emerging Contaminants Changed Bioaccumulation and Acute Toxicity in Daphnia magna.

Contaminants of emerging concern (CECs) in the environment undergo various transformations, leading to the formation of transformation products (TPs) with a modified ecological risk potential. Although the environmental significance of TPs is increasingly recognized, there has been relatively little research to understand the influences of such transformations on subsequent ecotoxicological safety. In this study, we used four pairs of CECs and their methylated or demethylated derivatives as examples to characterize changes in bioaccumulation and acute toxicity in Daphnia magna, as a result of methylation or demethylation. The experimental results were further compared to quantitative structure-activity relationship (QSAR) predictions. The methylated counterpart in each pair generally showed greater acute toxicity in D. magna, which was attributed to their increased hydrophobicity. For example, the LC50 values of methylparaben (34.4 ± 4.3 mg L-1) and its demethylated product (225.6 ± 17.3 mg L-1) differed about eightfold in D. magna. The methylated derivative generally exhibited greater bioaccumulation than the demethylated counterpart. For instance, the bioaccumulation of methylated acetaminophen was about 33-fold greater than that of acetaminophen. In silico predictions via QSARs aligned well with the experimental results and suggested an increased persistence of the methylated forms. The study findings underline the consequences of simple changes in chemical structures induced by transformations such as methylation and demethylation and highlight the need to consider TPs to achieve a more holistic understanding of the environmental fate and risks of CECs.

Breast cancer organoids and their applications for precision cancer immunotherapy.

Immunotherapy is garnering increasing attention as a therapeutic strategy for breast cancer (BC); however, the application of precise immunotherapy in BC has not been fully studied. Further studies on BC immunotherapy have a growing demand for preclinical models that reliably recapitulate the composition and function of the tumor microenvironment (TME) of BC. However, the classic two-dimensional in vitro and animal in vivo models inadequately recapitulate the intricate TME of the original tumor. Organoid models which allow the regular culture of primitive human tumor tissue are increasingly reported that they can incorporate immune components. Therefore, organoid platforms can be used to replicate the BC-TME to achieve the immunotherapeutic reaction modeling and facilitate relevant preclinical trial. In this study, we have investigated different organoid culture methods for BC-TME modeling and their applications for precision immunotherapy in BC.

Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Heart Failure : A Systematic Review and Meta-analysis.

BACKGROUND: Randomized controlled trials established the cardiac protection of sodium-glucose cotransporter-2 (SGLT2) inhibitors among adults with type 2 diabetes. New evidence suggests that these results could extend to people without diabetes. PURPOSE: To evaluate the effect of SGLT2 inhibitors in patients with heart failure, regardless of the presence of type 2 diabetes. DATA SOURCES: PubMed, Web of Science, Cochrane Library, and Embase (OVID interface). STUDY SELECTION: Eligible trials randomly assigned adults with heart failure to SGLT2 inhibitors or control. DATA EXTRACTION: Time-to-event individual patient data were reconstructed from published Kaplan-Meier plots; time-varying risk ratios (RRs) were calculated in half-, 1-, and 2-year time frames; and anticipated absolute benefits were calculated using simple models applying relative effects to baseline risks. DATA SYNTHESIS: Sodium-glucose cotransporter-2 inhibitors reduce hospitalization for heart failure by 37% (95% CI, 25% to 47%) at 6 months, 32% (CI, 20% to 42%) at 1 year, and 26% (CI, 10% to 40%) at 2 years (all high certainty) and reduce cardiovascular death by 14% (CI, 1% to 25%) at 1 year (high certainty). Nevertheless, low-certainty evidence did not indicate protection against all-cause death, kidney disease progression, or kidney failure. Anticipated absolute benefits are greater for patients treated in the first year and for those with poorer prognoses, such as those newly diagnosed with heart failure in the hospital. In addition, SGLT2 inhibitors doubled the risk for genital infections (RR, 2.69 [CI, 1.61 to 4.52]; high certainty). LIMITATION: Covariates were unavailable in meta-analyses with reconstructed individual patient data. CONCLUSION: Among people with heart failure, SGLT2 inhibitors reduce hospitalizations for heart failure regardless of the presence of diabetes; absolute benefits are most pronounced in first-year treatment and vary with prognostic factors. Clinicians should note the increased risk for genital infection in patients receiving SGLT2 inhibitors. PRIMARY FUNDING SOURCE: 1.3.5 Project for Disciplines of Excellence, West China Hospital of Sichuan University. (PROSPERO: CRD42021255544).

Maxillary Sinus Mucocele With Fungal Ball.

Mucocele is a benign, expansile, and oppressive lesion, more common in the frontal and ethmoid sinus and less in the maxillary sinus. Sinus mucocele mainly causes cheek swelling pain and nasal obstruction. In some cases, the paranasal mucocele grows large enough to compress periorbital structures and lead to impaired vision. Generally, mucocele is full of simple mucus, but pathogens can be found if co-infected, which means a poor prognosis. Functional endoscopic sinus surgery is an effective treatment for this disease. Here, the authors report a case that a mucocele occurred in the maxillary sinus, and a fungal ball was also found during the operation, which is a result of Paecilomyces farinosus co-infection.

[Ontologies Applied in Clinical Decision Support Systems for Diabetes].

A clinical decision support system (CDSS) integrated with electronic health records helps physicians at the grassroots make patient-appropriate and evidence-based treatment decisions and improves the efficiency of diagnosis and treatment. Furthermore, using ontologies to build up the medical knowledge base and patient data for CDSS enhances the automation and transparency of the reasoning process of CDSS and helps generate interpretable and accurate treatment recommendations. Herein, we reviewed the relevant ontologies in the field of diabetes treatment and the progress and challenges concerning ontology-based CDSSs. Firstly, we elaborated on the current status and challenges of diabetes treatment in China, highlighting the urgent need to improve the efficiency and quality of medical services. Then, we presented background information about ontologies and gave an overview of the framework, methodology, and features of using ontologies to construct CDSS. After that, we reviewed the ontologies and instances of ontology-based CDSS in the field of diabetes treatment in China and abroad and summarized their construction methods and features. Last but not the least, we discussed the future prospects of the field, suggesting that integrating evidence-based medicine with ontologies to build a reliable clinical recommendation system should be the current focus of CDSS development.

'Stress hyperglycemia ratio and in-hospital prognosis in non-surgical patients with heart failure and type 2 diabetes.

OBJECTIVE: To evaluate the impact of stress hyperglycemia on the in-hospital prognosis in non-surgical patients with heart failure and type 2 diabetes. RESEARCH DESIGN AND METHODS: We identified non-surgical hospitalized patients with heart failure and type 2 diabetes from a large electronic medical record-based database of diabetes in China (WECODe) from 2011 to 2019. We estimated stress hyperglycemia using the stress hyperglycemia ratio (SHR) and its equation, say admission blood glucose/[(28.7 × HbA1c)- 46.7]. The primary outcomes included the composite cardiac events (combination of death during hospitalization, requiring cardiopulmonary resuscitation, cardiogenic shock, and the new episode of acute heart failure during hospitalization), major acute kidney injury (AKI stage 2 or 3), and major systemic infection. RESULTS: Of 2875 eligible Chinese adults, SHR showed U-shaped associations with composite cardiac events, major AKI, and major systemic infection. People with SHR in the third tertile (vs those with SHR in the second tertile) presented higher risks of composite cardiac events ([odds ratio, 95% confidence interval] 1.89, 1.26 to 2.87) and major AKI (1.86, 1.01 to 3.54). In patients with impaired kidney function at baseline, both SHR in the first and third tertiles anticipated higher risks of major AKI and major systemic infection. CONCLUSIONS: Both high and low SHR indicates poor prognosis during hospitalization in non-surgical patients with heart failure and type 2 diabetes.

Electronic-Waste-Driven Pollution of Liquid Crystal Monomers: Environmental Occurrence and Human Exposure in Recycling Industrial Parks.

Liquid crystal monomers (LCMs) in liquid crystal displays (LCDs) may be released into the environment, especially in electronic waste (e-waste) recycling industrial parks with a high pollution risk. However, little has been known about the environmental release and human exposure to LCMs until now. Herein, a total of 45 LCMs were detected in LCDs of commonly used smartphones and computers by high-resolution mass spectrometry with suspect screening analysis. Fluorinated biphenyls and their analogs were the dominant LCMs. Based on available standards of the screening results and previous studies, 55 LCMs were quantified in samples from an e-waste recycling industrial park in Central China. The LCMs were frequently detected in outdoor dust (n = 43), workshop #1 indoor dust (n = 53), and hand (n = 43) and forehead wipes (n = 43), with median concentrations of 6950 ng/g, 67,400 ng/g, 46,100 ng/m2, and 62,100 ng/m2, respectively. The median estimated daily intake values of the LCMs via dust ingestion and dermal absorption were 48.3 and 16.5 ng/kg body weight/day, respectively, indicating a high occupational exposure risk of these compounds. In addition, 16 LCMs were detected in the serum of eight elderly people (≥60 years old) with over 5 years of experience in e-waste dismantling operations, resulting in a total concentration range of 3.9-26.3 ng/mL.

Effects of an environmentally relevant PFAS mixture on dopamine and steroid hormone levels in exposed mice.

In the present study, we investigated the dopaminergic and steroid hormone systems of A/J mice fed environmentally relevant concentrations of a perfluoroalkyl substance (PFAS) mixture over a period of 10 weeks. The PFAS mixture was chosen based on measured PFAS concentrations in earthworms at a Norwegian skiing area (Trondheim) and consisted of eight different PFAS. Dietary exposure to PFAS led to lower total brain dopamine (DA) concentrations in male mice, as compared to control. On the transcript level, brain tyrosine hydroxylase (th) of PFAS exposed males was reduced, compared to the control group. No significant differences were observed on the transcript levels of enzymes responsible for DA metabolism, namely - monoamine oxidase (maoa and maob) and catechol-O methyltransferase (comt). We detected increased transcript level for DA receptor 2 (dr2) in PFAS exposed females, while expression of DA receptor 1 (dr1), DA transporter (dat) and vesicular monoamine transporter (vmat) were not affected by PFAS exposure. Regarding the steroid hormones, plasma and muscle testosterone (T), 11-ketotestosterone (11-KT) and 17ß-estradiol (E2) levels, as well as transcripts for estrogen receptors (esr1 and esr2), gonadotropin releasing hormone (gnrh) and aromatase (cyp19) were unaltered by the PFAS treatment. These results indicate that exposure to PFAS doses, comparable to previous observation in earthworms at a Norwegian skiing area, may alter the dopaminergic system of mice with overt consequences for health, general physiology, cognitive behavior, reproduction and metabolism.

Stage Dependent Enantioselective Metabolism of Bifenthrin in Embryos of Zebrafish (Danio rerio) and Japanese Medaka (Oryzias latipes).

Bifenthrin (BF) is a widely used pyrethroid that has been frequently detected in surface waters. Previous studies indicated that BF had antiestrogenic activity in zebrafish embryos but estrogenic activity in posthatch fish. To determine whether age-related differences in metabolism contribute to the endocrine effects in developing fish, embryos from zebrafish and Japanese medaka were exposed to BF before and after liver development. Since the commercial mixture of BF is an isomer-enriched product containing two enantiomers (1R-cis-BF and 1S-cis-BF), enantioselective metabolism was also evaluated. The estrogenic metabolite, 4-hydroxybifenthrin (4-OH-BF) was identified in zebrafish embryos, and formation was higher in animals after liver development (>48 hpf). Treatments with ß-glucuronidase indicated that 4-OH-BF underwent conjugation in embryos. Formation was reduced by cotreatment of the cytochrome P450 (CYP450) inhibitor, ketoconazole. Formation of 4-OH-BF was greater when treated with 1R-cis-BF compared to the S-enantiomer. However, metabolites were not observed in medaka embryos. These data indicate enantioselective oxidation of BF to an estrogenic metabolite occurs in zebrafish embryos and, since it is increased after liver development, may partially explain estrogenic activity observed in older animals. The lack of activity in medaka suggests species-specific effects with BF metabolism and may influence risk assessment strategies in wildlife.

Ultrasonographic findings and prenatal diagnosis of complete trisomy 17p syndrome: A case report and review of the literature.

BACKGROUND: Trisomy of the short arm of chromosome 17 is a rare genomic disorder. The clinical features of complete trisomy 17p syndrome have been described. Most cases of this syndrome have been found in infants and children, but only a few cases were found by ultrasound in the prenatal period. METHODS: We report a case of complete trisomy 17p syndrome, which was inherited from paternal balanced translocation t(15;17)(q11.2;q11.2). A pregnant woman underwent an ultrasound examination at 24 weeks of gestation. Amniotic fluid was collected by amniocentesis. Cytogenetic and single nucleotide polymorphism array analyses were performed. We further reviewed the relationship between duplication regions and the clinical phenotype. RESULTS: Ultrasonographic evaluation showed intrauterine growth retardation and a right choroid plexus cyst, but the gallbladder was not observed. The fetal karyotype was 46,XX,der(17)t(15;17)(q11.2;q11.2)pat. The father's karyotype was 46,XY,t(15;17)(q11.2;q11.2). The single nucleotide polymorphism array results showed arr[GRCh37] 17p13.3q11.1(525-25309337)×3, which indicated a 25.309-Mb duplication. CONCLUSION: Complete trisomy 17p syndrome shows severe malformations. Intrauterine growth retardation is the most typical manifestation of this syndrome as shown by ultrasonography in the second trimester of pregnancy. The genotype-phenotype relationships of complete trisomy 17p syndrome are not completely consistent. To further determine these relationships, additional cases are necessary to provide more information from ultrasonographic findings during pregnancy.

Serum metabolomics analysis of patients with polycystic ovary syndrome by mass spectrometry.

Polycystic ovary syndrome (PCOS) is a set of symptoms caused by elevated androgens (male hormones) in females. PCOS is the most common endocrine disorder among women between 18 and 44 years. Currently, the pathogenesis of PCOS remains unclear. Liquid chromatography-mass spectrometry (LC/MS)-based metabolomics is becoming more and more useful for medical research, especially in revealing the mechanism of the disease. The aim of this study was to investigate the difference of serum metabolic profiles in patients with PCOS and healthy control to better understand the mechanism of this disease. Ten patients with PCOS and 10 healthy people were recruited for this study. The serum samples were collected for LC/MS analysis. Multivariate statistical analysis was performed to discover and identify the potential biomarkers. Six biomarkers were found and identified. The biomarkers belonged to different metabolic pathway including lipid metabolism, carnitine metabolism, androgen metabolism, and bile acid metabolism. Those biomarkers also played different roles in disease progression. Metabolomics is a powerful tool used in research of the mechanism involved in this disease to provide useful information for better understanding of PCOS.

Downregulation of α7 nicotinic acetylcholine receptors in peripheral blood monocytes is associated with enhanced inflammation in preeclampsia.

BACKGROUND: Preeclampsia is associated with chronic inflammation. The cholinergic anti-inflammatory pathway regulates systemic inflammation through activating α7 nicotinic acetylcholine receptors (α7nAChR) expressed in monocytes/macrophages. This study aimed to investigate the role of α7nAChR in peripheral blood monocytes in preeclampsia. METHODS: Peripheral blood monocytes were isolated from 30 nonpregnant (NP), 32 normotensive pregnant (NT), and 35 preeclamptic (PE) women. RESULTS: We found that both protein and mRNA expression levels of α7nAChR in monocytes from the PE women were significantly lower than those of the NP and NT women (both p < 0.01). α7nAChR protein expression levels in monocytes were negatively correlated with levels of systolic blood pressure (r = - 0.40, p = 0.04), proteinuria (r = - 0.54, p < 0.01), tumor necrosis factor-alpha (TNF-α, r = - 0.42, p = 0.01), and interleukin (IL)-1ß (r = - 0.56, p < 0.01), while positively correlated with IL-10 levels (r = 0.43, p = 0.01) in the PE women. Both baseline and lipopolysaccharides (LPS)-induced increase of TNF-α, IL-1ß, and IL-6 levels from monocytes were higher in the PE group than the NP and NT groups (all p < 0.01), but IL-10 levels in the PE group was lower than that of the NP and NT groups (p < 0.01). In addition, the NF-κB activity in monocytes from the PE women was higher than the NP and NT women (p < 0.01). Importantly, activation of α7nAChR with its agonist PNU-282987 inhibited NF-κB, decreased TNF-α, IL-1ß, and IL-6 release, and increased IL-10 release in monocytes from the PE women (all p < 0.01). CONCLUSION: In conclusion, these findings suggest that downregulation of α7nAChR may be associated with the development of preeclampsia through increasing pro-inflammatory and decreasing anti-inflammatory cytokine release via the NF-κB pathway.