Association of SGLT2i vs DPP4i With Pneumonia, COVID-19, and Other Adverse Respiratory Events in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

OBJECTIVE: Our aim in this study was to systematically assess the association of sodium-glucose cotransporter-2 inhibitors (SGLT2i) vs dipeptidyl peptidase-4 inhibitors (DPP4i) with pneumonia, COVID-19, and adverse respiratory events in patients with type 2 diabetes mellitus (DM). METHODS: PubMed, Embase, and Cochrane Library databases were retrieved to include studies on DM patients receiving SGLT2i (exposure group) or DPP4i (control group). Stata version 15.0 statistical software was used for the meta-analysis. RESULTS: Ten studies were included, all 10 of which were used for the qualitative review and 7 for the meta-analysis. According to the meta-analysis, patients receiving SGLT2i had a lower incidence of pneumonia (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.51 to 0.74) and pneumonia risk (OR 0.63, 95% CI 0.60 to 0.68, p=0.000) compared with those receiving DPP4i. The same situation was seen for mortality for pneumonia (OR 0.49, 95% CI 0.39 to 0.60) and pneumonia mortality risk (OR 0.47, 95% CI 0.42 to 0.51). There was lower mortality due to COVID-19 (OR 0.31, 95% CI 0.28 to 0.34) and a lower hospitalization rate (OR 0.61, 95% CI 0.56 to 0.68, p=0.000) and incidence of mechanical ventilation (OR 0.69, 95% CI 0.58 to 0.83, p=0.000) due to COVID-19 in patients with type 2 DM receiving SGLT2i. Qualitative analysis results show that SGLT2i was associated with a lower incidence of COVID-19, lower risk of obstructive airway disease events, and lower hospitalization rate of health-care-associated pneumonia than DPP4i. CONCLUSION: In patients with type 2 DM, SGLT2i are associated with a lower risk of pneumonia, COVID-19, and mortality than DPP4i.

The modulation effect of lotus (Nelumbo nucifera Gaertn.) seeds oligosaccharides with different structures on intestinal flora and action mode of growth effects on Bifidobacterium in vivo and in vitro.

Natural lotus seed oligosaccharides monomers (LOSs: LOS3-1, LOS3-2, and LOS4) were prepared by preparative chromatography and were hydroxyl-labeled with fluorescein isothiocyanate (FITC). The prebiotic properties of LOSs by the gut microbiota of male Balb/C mice in vivo and in vitro were studied. In vivo experiment results showed that LOS4 could significantly increase the average daily food consumption, weight, liver index and the abundance of Bacteroides and Bifidobacterium for mice (p < 0.05). In addition, LOS4 also had significant proliferation effect on Bifidobacterium adolescentis and longum in vitro (p < 0.05). Laser confocal microscopy observation showed interaction site between LOS4-FITC and Bifidobacterium adolescentis was located outside and inside of cell, which was completed within 1 h. The relationship between structures of LOSs and prebiotics of intestinal flora (especially Bifidobacterium), and expanded the knowledge on the effects of carbohydrate polymerization degree (DP) and glycosidic bond connection with fermentation selectivity of bacteria was studied.

Using Machine Learning to Predict the Requirement for Revascularization in Patients with Chest Pain in the Emergency Department.

Objective: The study aimed to use machine learning algorithms to predict the need for revascularization in patients presenting with chest pain in the emergency department. Methods: We obtained data from 581 patients with chest pain, 264 who underwent revascularization, and the other 317 were treated with medication alone for 3 months. Using standard algorithms, linear discriminant analysis, and standard algorithms, we analyzed 41 features relevant to coronary artery disease (CAD). Results: We identified seven robust predictive features. The combination of these predictors gave an area under the curve (AUC) of 0.830 to predict the need for revascularization. By contrast, the GRACE score gave an AUC of 0.68. Conclusions: This machine learning-based approach predicts the need for revascularization in patients with chest pain.

UPLC-MS/MS method for the determination of voriconazole plasma concentration from pediatric patients with hematologic tumors: An application toward personalized therapy.

Untreated invasive fungal infection is one of the important risk factors affecting the prognosis of pediatric patients with hematologic tumors. Voriconazole (VOR) is the first-line antifungal drug for the treatment of Aspergillus infections. In order to reduce the risk of adverse drug reactions while producing an ideal antifungal effect, therapeutic drug monitoring was performed to maintain the VOR plasma concentration in a range of 1,000-5,500 ng/ml. In the present study, a reliable, accurate, sensitive and quick ultra-high performance liquid chromatograph-tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of the VOR level. Protein precipitation was performed using acetonitrile, and then the chromatographic separation was carried out by UPLC using a C18 column with the gradient mobile phases comprising 0.1% methanoic acid in acetonitrile (A) and 0.1% methanoic acid in water (B). In the selective reaction monitor mode, the mass spectrometric detection was carried out using an TSQ Endura triple quadruple mass spectrometer. The performance of this UPLC-MS/MS method was validated as per the National Medical Products Administration for Bioanalytical Method Validation. Additionally, the plasma concentrations of VOR in pediatric patients with hematologic tumors were detected using this method, and the analyzed results were used for personalized therapy.

Purification and Characterisation of κ-Carrageenan Oligosaccharides Prepared by κ-Carrageenase from Thalassospira sp. Fjfst-332.

κ-Carrageenan oligosaccharides (KCOs) are promising agents for treating inflammatory diseases. However, the lack of purification and structural elucidation of KCOs has limited structure-function evaluation. In this study, using a system coupling medium pressure liquid chromatography (MPLC) with an evaporative light scattering detector (ELSD), four types of KCOs were separated. The total yield of the four KCO powders was ∼5.02% after purification (KCOs/κ-carrageenan, w/w). Their structural identities were characterised by ESI-MS, CID-MS/MS and NMR, as κ-neocarrabiose (α-DA-1,3-G4Srα/ß), κ-neocarratetraose (α-DA-1,3-ß-G4S-1,4-α-DA-1,3-G4Srα/ß), κ-neocarrahexaose (α-DA-1,3-ß-G4S-1,4-α-DA-1,3-ß-G4S-1,4-α-DA-1,3-G4Srα/ß) and heterozygous κ/ι-neocarrahexaose (α-DA/DA2S-1,3-ß-G4S-1,4-α-DA-1,3-ß-G4S-1,4-α-DA-1,3-G4Srα/ß). KCOs showed no cytotoxicity in RAW264.7 macrophages, and the anti-inflammatory activity was closely correlated with the degree of polymerisation and the number of sulfated groups. κ/ι-Neocarrahexaose exhibited the highest inhibition of ROS (Reactive Oxygen Species) production in LPS-induced RAW264.7 macrophages. The MPLC-ELSD system provides a platform for large-scale fabrication of purified KCOs and affords a route to these compounds that may regulate immune defense.

Enhanced Production of κ-Carrageenase and κ-Carrageenan Oligosaccharides through Immobilization of Thalassospira sp. Fjfst-332 with Magnetic Fe3O4-Chitosan Microspheres.

In this study, immobilized bacteria (IMB) microsphere was prepared by embedding κ-carrageenase-producing Thalassospira sp. Fjfst-332 (TF332) onto a magnetic Fe3O4-chitosan carrier. The performance of Fe3O4-chitosan carrier was optimized by comparing its bacteria immobilization capacity at different Fe3O4:chitosan ratios and temperatures, while the functions of IMB microspheres were characterized by examining their κ-carrageenase production at different temperatures, pH's, and reuse cycles. At the 1:1 (w:w) Fe3O4:chitosan ratio, the Fe3O4-chitosan carriers possessed sufficient anchoring capacity for bacterial immobilization without significant compromise of their magnetism for magnetic separation of IMB from culture media. The spectroscopic analysis of IMB microspheres indicated that the immobilization of TF332 might affect the amide groups in chitosan. Compared to free bacteria, IMB can produce κ-carrageenase at higher temperature, wider pH range, and faster rate. More importantly, the κ-carrageenase-producing activity was sustained for at least seven reuse cycles. The major κ-carrageenan degradation products of IMB-derived κ-carrageenase were the oligosaccharides containing two to six monosaccharide units. Overall, this Fe3O4-chitosan-TF-332 microsphere has the potential to become a stable and reusable platform for large-scale production of κ-carrageenan oligosaccharides.

Separation of Oligosaccharides from Lotus Seeds via Medium-pressure Liquid Chromatography Coupled with ELSD and DAD.

Lotus seeds were identified by the Ministry of Public Health of China as both food and medicine. One general function of lotus seeds is to improve intestinal health. However, to date, studies evaluating the relationship between bioactive compounds in lotus seeds and the physiological activity of the intestine are limited. In the present study, by using medium pressure liquid chromatography coupled with evaporative light-scattering detector and diode-array detector, five oligosaccharides were isolated and their structures were further characterized by electrospray ionization-mass spectrometry and gas chromatography-mass spectrometry. In vitro testing determined that LOS3-1 and LOS4 elicited relatively good proliferative effects on Lactobacillus delbrueckii subsp. bulgaricus. These results indicated a structure-function relationship between the physiological activity of oligosaccharides in lotus seeds and the number of probiotics applied, thus providing room for improvement of this particular feature. Intestinal probiotics may potentially become a new effective drug target for the regulation of immunity.

Stromal cell-derived factor-1α as a novel biomarker for hyperlipidemia.

Stromal cell-derived factor-1 (SDF-1) is expressed in a wide variety of organs, such as heart, and plays a pivotal role in the mobilization of hematopoietic stem and progenitor cells in bone marrow. SDF-1α, a common subtype of SDF-1, may control hematopoiesis and angiogenesis, but its role in the pathogenesis of hyperlipidemia is unknown. The aim of this study was to determine the role of SDF-1α in the pathogenesis of hyperlipidemia. First, log-transformed SDF-1α serum levels (logSDF-1α) were significantly higher in male patients with borderline high lipid profile (BHLP; n=28; 2.15±0.08 ng/ml) compared to control subjects (n=37; 1.94±0.06 ng/ml; P<0.01). The logSDF-1α in male patients with high lipid profile (HLP; n=33; 1.95±0.08 ng/ml) were lower than BHLP patients (P<0.01). The logSDF-1α was positively associated with HDL-C only in female patients (n=125; r=0.379, P=0.016). These results suggest the different pathophysiology in male and female patients with hyperlipidemia. Moreover, flow cytometry analysis showed that expression of the SDF-1α receptor, CXC-chemokine receptor 4, was lower in peripheral blood mononuclear cells of patients with BHLP (n=10) and HLP (n=10), compared to control subjects (n=10; P<0.001). Lastly, peripheral blood leukocyte, neutrophil and lymphocyte counts were higher in BHLP patients (n=62; P<0.05). Taken together, we suggest SDF-1α as a biomarker of hyperlipidemia that may be helpful to uncover the pathogenesis of hyperlipidemia.