Simultaneous analysis of 29 synthetic cannabinoids and metabolites,amphetamines, and cannabinoids in human whole blood by liquid chromatography–tandem mass spectrometry – A New Zealand perspective of use in 2018

We describe the validation of a method for the simultaneous analysis of 29 synthetic cannabinoids (SCs) and metabolites, 4 amphetamines, and 2 cannabinoids in human whole blood. This method enables one analysis to cover what previously required multiple analyses for these classic and novel drugs‐of‐abuse with diverse physicochemical properties. The scope of targeted analytes was based on the most prevalent drugs‐of‐abuse and SCs encountered at the New Zealand border in 2017 and included parent compounds and metabolites belonging to the indole and indazole carboxamide, quinolinyl indole carboxylate, and naphthoylindole classifications. Samples were prepared by supported‐liquid‐extraction (SLE) followed by liquid chromatography?tandem mass spectrometry (LC?MS/MS) analysis with positive electrospray ionization (ESI). The method was validated with respect to selectivity, matrix effects, process efficiency, sensitivity, repeatability, extract stability, and carryover for qualitative confirmation. Linearity as well as accuracy and precision data at target decision concentrations were also evaluated. The limits of detection and confirmation ranged from 0.1 to 6.0 ng/mL and 1.0 to 6.0 ng/mL, respectively. The described method was successfully applied to the analysis of 564 ante‐ and post‐mortem blood samples in 2018. There were 132 cases (23%) with positive findings of at least one SC, with the five most commonly detected SCs being AMB‐FUBINACA and/or acid (61%), 5F‐ADB and/or acid (40%), ADB‐FUBINACA (11%), 5F‐MDMB‐PICA acid (6%), and MDMB‐FUBINACA acid (6%). The results also demonstrate the predominant presence of metabolites at higher levels than the unchanged parent SCs in blood, highlighting the need to maintain forensic screening methods capable of the simultaneous detection of both parent compounds and metabolites.     

A new prenatal sonographic sign of epidermolysis bullosa

We report on the prenatal sonographic appearance of epidermolysis bullosa (EB). The third viable pregnancy of a consanguineous couple was found at 23 weeks to have dysplastic external ears and nose. The neonate was born at 33 weeks and was found to have junctional EB with pyloric atresia. On reviewing the 23‐week ultrasound images, skin denudation was evident. This is a report of visualization of skin denudation in EB. When EB is suspected prenatally, special attention should be given to the visualization of skin surfaces.     

Rapid Changes in Serum Testosterone in Men With Newly Diagnosed Type 2 Diabetes With Intensive Insulin and Metformin

OBJECTIVETo investigate the effect of metformin on testosterone levels in men with type 2 diabetes mellitus (T2DM).RESEARCH DESIGN AND METHODSSeventy men with newly diagnosed drug-naive T2DM and HbA_1c >9.0% (75 mmol/mol) were treated with intensive insulin pump therapy for 5 days to achieve glucose normalization. They were randomized to control (continued on intensive insulin only) and metformin (plus metformin) groups (1:1) for 1 month. Testosterone was measured at baseline, randomization, and after 1-month treatment.RESULTSTotal, free, and bioavailable testosterone increased significantly within 5 days (all P < 0.001). After 1 month, compared with the control group, the metformin group had lower total (12.7 vs. 15.3 nmol/L), free (0.20 vs. 0.24 nmol/L), and bioavailable (4.56 vs. 5.31 nmol/L) testosterone (all P < 0.05).CONCLUSIONSIn men with T2DM, 1-month oral metformin may decrease serum testosterone levels independent of blood glucose control. The effects of long-term metformin on testosterone in men need further study.     

Harnessing hyperuricemia to atherosclerosis and understanding its mechanistic dependence

Atherosclerosis is regarded as the disease of the arterial vasculature. The main characteristics of atherosclerosis are the abnormal accumulation of lipids, increased inflammatory cells, matrix deposits, and proliferation of smooth muscle cells. Diabetes mellitus, obesity, and hyperlipidemia are the most studied risk factors of atherosclerosis. One least studied risk factor is the uric acid (UA), a high UA in circulation is interlinked with many pathological processes. Several epidemiological studies suggest elevated UA levels as an essential biomarker in the forecast of several cardiovascular diseases. Available evidence claims that UA upholds the atherosclerosis process via disturbing lipid metabolism, reducing the nitric oxide synthesis in endothelial cells, promoting the proliferation of vascular smooth muscle cells, and overwhelms inflammation. In endothelial dysfunction and coronary artery lesions, UA is considered as an independent predictor. The updated studies on the involvement of hyperuricemia in atherosclerosis prove that treatment with xanthine oxidase (XO) inhibitors not just benefits the treatment of hyperuricemia but also reduces the burden of atherosclerosis to a greater extent. In this review, we highlight how the hyperuricemia affects vascular integrity, causes atherosclerosis, and the mechanism of action of XO inhibitors on atherosclerosis.     

Retrieval of fractured dialysis catheter through phlebotomy of internal jugular vein: a case report

A central venous catheter is the most common access for initiating hemodialysis. Prolonged access through a central venous catheter increases the risk of infection and dysfunction of the catheter with potential development of catheter-induced thrombosis and embolism. However, fracture and dislodgement of the catheter with subsequent embolization is an unexpected complication. Endovascular treatment is a promising method to remove intravascular foreign bodies. We herein report a case of a 58-year-old woman undergoing prolonged hemodialysis who required central venous catheter removal because of mechanical fracture of the tunneled cuffed catheter and its migration in the internal jugular vein. An urgent chest X-ray showed that the two free ends of the fractured tunneled cuffed catheter were located in the right atrium and right internal jugular vein. Phlebotomy of the internal jugular vein was successfully performed to retrieve the fractured tunneled cuffed catheter and the associated thrombi. In this case, phlebotomy for retrieval of the embolized catheter fragment extending into the right atrium was a safe alternative to an endovascular technique of catheter fragment retrieval. Phlebotomy preserved the integrity of the catheter fragment and its associated thrombus and was both cost-effective and safe.     

Clinical outcomes and survival analysis in patients with psycho-cardiological disease: a retrospective analysis of 132 cases

ObjectivesThe deleterious effects of psychological problems on coronary heart disease (CHD) are not satisfactorily explained. We explored influential factors associated with mortality in psycho-cardiological disease in a Chinese sample.MethodsOf 7460 cardiac patients, we selected 132 patients with CHD and mental illness. Follow-up was conducted via telephone. We analyzed clinical characteristics, clinical outcomes, and survival.ResultsThe clinical detection rate of psycho-cardiological disease in the overall patient population was 1.8%. Of these, 113 patients completed follow-up; 18 died owing to cardiovascular diseases during follow-up. Kaplan–Meier analysis showed dysphagia, limb function, self-care ability, percutaneous coronary intervention, low-density lipoprotein, total cholesterol, pro-brain natriuretic peptide and high-sensitivity (hs) troponin T had significant associations with cumulative survival. Cox regression analysis showed total cholesterol (hazard ratio [HR]: 2.765, 95% confidence interval [CI]: 1.001–7.641), hs troponin T (HR: 4.668, 95% CI: 1.293–16.854), and percutaneous coronary intervention (HR: 3.619, 95% CI: 1.383–9.474) were independently associated with cumulative survival.ConclusionsThe clinical detection rate of psycho-cardiological disease was far lower than expected. Normal total cholesterol and hs troponin T were associated with reduced cardiovascular disease mortality over 2 years. Percutaneous coronary intervention is a prognostic risk factor in patients with psycho-cardiological disease.     

Effects of Ethanol Extract of Radix Sophorae Flavescentis on Activity of Colon Cancer HT29 Cells

This paper mainly studied the inhibitory effect of total ethanol extract of Radix Sophorae Flavescentis on proliferation of colon cancer HT29 cells. By reflux extraction method and with ethanol as extraction solvent, different extracts were obtained at different ethanol concentrations, different solid-liquid ratios, and at different times. And their inhibitory activities against HT29 cells were compared using MTT assay. The experimental results showed that the extraction processes under three conditions can all draw relatively high inhibition rates. The optimum ethanol extraction process conditions were as follows: a solid-liquid ratio of 1:9, 80 min of heat reflux extraction with 95% ethanol.     

A Comparative Study of Anti-Gastric Cancer Activity Between Aqueous Extract and Ethanol Extract of Folium Cordylines Fruticosae

The active components in Folium Cordylines Fruticosae were extracted by heat reflux method. The solvents used were distilled water and ethanol. The effects of two types of extracts on gastric cancer cells were compared; dry extract yields were calculated, as well as the inhibition rates of gastric cancer MGC-803 cell proliferation and the colony cell counts. The micro-Kjeldahl method was used to measure the cell protein contents and to make a comprehensive comparison. The results showed that the MGC-803 cell inhibition rates of three different concentrations (32.5, 75 and 150 mg/ml) of ethanol extracts increased with the increase of concentration, which was 48.9% at a concentration of 150 mg/ml; aqueous extract of Folium Cordylines Fruticosae had very low inhibitory activity at a low concentration (32.5 mg/ml), which was remained at about 20%. After being affected by two types of extracts, cells had uneven sizes, with very low brightness, while the normal cells presented a uniform full form, with high definition.     

Using next-generation sequencing as a genetic diagnostic tool in rare autosomal recessive neurologic Mendelian disorders

Next-generation sequencing was used to investigate 9 rare Chinese pedigrees with rare autosomal recessive neurologic Mendelian disorders. Five probands with ataxia-telangectasia and 1 proband with chorea-acanthocytosis were analyzed by targeted gene sequencing. Whole-exome sequencing was used to investigate 3 affected individuals with Joubert syndrome, nemaline myopathy, or spastic ataxia Charlevoix-Saguenay type. A list of known and novel candidate variants was identified for each causative gene. All variants were genetically verified by Sanger sequencing or quantitative polymerase chain reaction with the strategy of disease segregation in related pedigrees and healthy controls. The advantages of using next-generation sequencing to diagnose rare autosomal recessive neurologic Mendelian disorders characterized by genetic and phenotypic heterogeneity are demonstrated. A genetic diagnostic strategy combining the use of targeted gene sequencing and whole-exome sequencing with the aid of next-generation sequencing platforms has shown great promise for improving the diagnosis of neurologic Mendelian disorders.     

Different roles of PD-L1 and FasL in immunomodulation mediated by human placenta-derived mesenchymal stem cells

Mesenchymal stem cells (MSCs) derived from either bone marrow (BMSCs) or placenta (PMSCs) have the capacity to suppress immune responses to mitogenic and allogeneic stimulations. Both cell contact and soluble factor dependent mechanisms have been proposed to explain this immunosuppression. This study explored the roles of some of cell surface molecules expressed on human PMSCs (hPMSCs) in hPMSC mediated immunomodulation. hPMSCs strongly suppressed mitogen and allogeneic peripheral mononuclear cells (PBMCs) induced T cell activation and proliferation. hPMSCs constituently expressed programmed death-ligand 1 (PD-L1) and Fas ligand (FasL) molecules. Neutralising antibodies to-PD-L1 and FasL significantly reduced the suppressive effect of hPMSCs on T cell proliferation. However, only anti-PD-L1 antibody partially restored early T cell activation suppressed by hPMSCs. Anti-FasL antibody but not anti-PD-L1 antibody reduced apoptosis of activated T cell indicating that FasL molecule plays a role in inducing apoptosis of activated T cells, although overall hPMSCs diminished T cell apoptosis. Different effects of PD-L1 and FasL molecules on T cell activation and activated T cell apoptosis suggest that these two molecules influence T cell response at different stages. hPMSCs significantly prevented activated T cells from going into S phase. Both antibodies to PD-L1 and FasL had significant effect on reversing the effect of hPMSCs on cell cycles. hPMSCs reduced INF-γ but increased IL-10 production by mitogen activated T cells. Both antibodies partially abolished the effect of hPMSCs on INF-γ and IL-10 production. These data demonstrated that PD-L1 and FasL molecules play significant roles in immunomodulation mediated by hPMSCs. This study provides a rational basis for modulation of negative costimulators on hPMSCs to increase their immunosuppressive properties in their therapeutic applications.