[Identification and visual analysis of ginsenosides in multi-steamed roots of Panax quinquefolium based on UPLC-Q-TOF-MS/MS and MALDI-MSI].

This study aims to investigate the component variations and spatial distribution of ginsenosides in Panax quinquefolium roots during repeated steaming and drying. Ultra performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to identify the ginsenosides in the root extract. Matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) was employed to visualize the spatial distribution and spatiotemporal changes of prototype ginsenosides and metabolites in P. quinquefolium roots. The UPLC results showed that 90 ginsenosides were identified during the steaming process of the roots, and polar ginsenosides were converted into low polar or non-polar ginsenosides. The content of prototype ginsenosides decreased, while that of rare ginsenosides increased, which included 20(S/R)-ginsenoside Rg_3, 20(S/R)-ginsenoside Rh_2, and ginsenosides Rk_1, Rg_5, Rs_5, and Rs_4. MALDI-MSI results showed that ginsenosides were mainly distributed in the epidermis and phloem. As the steaming times increased, ginsenosides were transported to the xylem and medulla. This study provides fundamental information for revealing the changes of biological activity and pharmacological effect of P. quinquefolium roots that are caused by repeated steaming and drying and gives a reference for expanding the application scope of this herbal medicine.

Identification of raffinose family oligosaccharides in processed Rehmannia glutinosa Libosch using matrix-assisted laser desorption/ionization mass spectrometry image combined with machine learning.

RATIONALE: Currently, research on oligosaccharides primarily focuses on the physiological activity and function, with a few studies elaborating on the spatial distribution characterization and variation in the processing of Rehmannia glutinosa Libosch. Thus, imaging the spatial distributions and dynamic changes in oligosaccharides during the steaming process is significant for characterizing the metabolic networks of R. glutinosa. It will be beneficial to characterize the impact of steaming on the active ingredients and distribution patterns in different parts of the plant. METHODS: A highly sensitive matrix-assisted laser desorption/ionization mass spectrometry image (MALDI-MSI) method was used to visualize the spatial distribution of oligosaccharides in processed R. glutinosa. Furthermore, machine learning was used to distinguish the processed R. glutinosa samples obtained under different steaming conditions. RESULTS: Imaging results showed that the oligosaccharides in the fresh R. glutinosa were mainly distributed in the cortex and xylem. As steaming progressed, the tetra- and pentasaccharides were hydrolyzed and diffused gradually into the tissue section. MALDI-MS profiling combined with machine learning was used to identify the processed R. glutinosa samples accurately at different steaming intervals. Eight algorithms were used to build classification machine learning models, which were evaluated for accuracy, precision, recall, and F1 score. The linear discriminant analysis and random forest models performed the best, with prediction accuracies of 0.98 and 0.97, respectively, and thus can be considered for identifying the steaming durations of R. glutinosa. CONCLUSIONS: MALDI-MSI combined with machine learning can be used to visualize the distribution of oligosaccharides and identify the processed samples after steaming for different durations. This can enhance our understanding of the metabolic changes that occur during the steaming process of R. glutinosa; meanwhile, it is expected to provide a theoretical reference for the standardization and modernization of processing in the field of medicinal plants.

σ-Alkynyl Adsorption Enables Electrocatalytic Semihydrogenation of Terminal Alkynes with Easy-Reducible/Passivated Groups over Amorphous PdSx Nanocapsules.

Highly chemo- and regioselective semihydrogenation of alkynes is significant and challenging for the synthesis of functionalized alkenes. Here, a sequential self-template method is used to synthesize amorphous palladium sulfide nanocapsules (PdSx ANCs), which enables electrocatalytic semihydrogenation of terminal alkynes in H2O with excellent tolerance to easily reducible groups (e.g., C-I/Br/Cl, C═O) and the metal center deactivating skeletons (e.g., quinolyl, carboxyl, and nitrile). Mechanistic studies demonstrate that specific σ-alkynyl adsorption via terminal carbon and negligible alkene adsorption on isolated Pd2+ sites ensure successful synthesis of various alkenes with outstanding time-irrelevant selectivity in a wide potential range. The key hydrogen and carbon radical intermediates are validated by electron paramagnetic resonance and high-resolution mass spectrometry. Gram-scale synthesis of 4-bromostyrene and expedient preparation of deuterated alkene precursors and drugs with D2O show promising applications. Impressively, PdSx ANCs can be applied to the prevailing thermocatalytic semihydrogenation of functionalized alkyne using H2.

Tunable multicolour S/N co-doped carbon quantum dots synthesized from waste foam and application to detection of Cr3+ ions.

In this study, by adjusting sulfuric acid concentrations, tunable multicolour S/N-carbon quantum dots (CQDs) were synthesized from waste foam as the raw material. The S/N-CQDs presented blue, blue-green, green, green-yellow and yellow emission with an emission peak shifting from 475 to 589 nm and with optimum excitation wavelengths of 385, 405, 440, 450, and 500 nm, respectively. Using transmission electron microscopy, the S/N-CQDs were seen to be spherical in morphology with a size around 6-8 nm. Fourier transform infrared spectra and X-ray photoelectron spectroscopy indicated that the surface of the S/N-CQDs was highly oxidized and sulfur doped. The fluorescence mechanism of multicolour S/N-CQDs emission was mainly related to a band gap change caused by the surface state. Blue-emitting S/N-CQDs were used as a fluorescent probe that was highly selective and sensitive to Cr3+ ions, with a low detection limit of 6 µM. The waste foam-derived S/N-CQDs exhibited promising potential for ion detection in real water samples due to its excellent fluorescence activity.

Effects of several in-feed antibiotic combinations on the abundance and diversity of fecal microbes in weaned pigs.

To characterize the effects of several subtherapeutic antibiotic combinations on the abundance and diversity of fecal microbes, 400 weaned pigs were selected and randomly assigned to 8 groups, where they were continuously fed different antibiotic combinations for 28 days. Then, a total of 48 pigs were randomly selected to collect feces samples for DNA extraction and 16S rRNA high-throughput sequencing. Compared with that of pigs without antibiotic administration, the diversities of fecal microbes were decreased in the pigs fed chlortetracycline (CTC), olaquindox (OLA), and either enramycin (ER) or virginiamycin (VIR), and the relative abundances of members of the phylum Bacteroidetes and the genus Prevotella were increased. Compared with that of pigs without antibiotic administration, the relative abundances of members of the phylum Proteobacteria and the genus Succinivibrio were decreased in the pigs fed CTC, a mixture of zinc bacitracin (ZB) + colistin sulfate (COL), a mixture of CTC+ZB+COL, a mixture of CTC+OLA, or a mixture of CTC+OLA+ER. α-Diversity and ß-diversity were decreased (P < 0.05) in the pigs fed ZB+COL or a mixture of CTC+OLA+ER or CTC+OLA+VIR. This study provides experimental data to deepen our understanding on the effects of antibiotic combinations on intestinal microbes.

The effects of gliclazide, metformin, and acarbose on body composition in patients with newly diagnosed type 2 diabetes mellitus.

BACKGROUND: Although numerous clinical trials have evaluated the body weight change achieved using diabetes medications alone or in combinations, the composition of body weight change in these clinical trials has rarely been assessed. OBJECTIVE: We aimed to evaluate the effects of gliclazide, metformin, and acarbose monotherapy on body composition, fat distribution, and other cardiometabolic risk factors in patients with newly diagnosed type 2 diabetes. METHODS: A total of 86 patients with newly diagnosed type 2 diabetes mellitus were randomly assigned to receive gliclazide, metformin, or acarbose for 6 months. Dual-energy x-ray absorptiometry; abdominal computed tomography scans; and measurements of adiponectin, leptin, and lipid levels were performed before and after 6-month monodrug therapy. RESULTS: Blood glucose and glycosylated hemoglobin levels significantly improved after 6 months of monodrug therapy. During the 6 months of use of the 3 antidiabetes medications, the majority of participants experienced fat mass loss and lean mass gain. Metformin monotherapy in patients with newly diagnosed type 2 diabetes led to a significant decrease in percent body fat (P = 0.029) and body fat mass (P = 0.038). Levels of serum total cholesterol (P = 0.004), triglycerides (P = 0.014), and adiponectin (P = 0.001) took a favorable turn after metformin treatment. The 3 antidiabetes medications caused no significant change in abdominal fat distribution, waist circumstance, and blood pressure during the 6 months. CONCLUSIONS: Our results suggest metformin therapy in patients with newly diagnosed type 2 diabetes can improve cardiometabolic risk markers. Moreover, body composition change induced by gliclazide and acarbose was not likely to be simple fat deposition.

Association of periodontitis and tooth loss with extent of coronary atherosclerosis in patients with type 2 diabetes mellitus.

Aim: The objective was to investigate the association of periodontitis and tooth loss with extent of diabetic coronary atherosclerosis. Materials and methods: 272 patients who were hospitalized at Shanghai East hospital and underwent a coronary artery calcium (CAC) CT scan were enrolled in this study. Individuals were grouped based on their CAC scores into a normal-to-mild coronary atherosclerosis (AS) group (0 ≤ score ≤ 100, n=184) and a moderate-to-severe group (score≥101, n=88). Periodontitis parameters and number of missing teeth were evaluated for every patient. The severity of periodontitis was categorized as mild, moderate, or severe. The taxonomic composition of the microbiota was determined using full-length 16S ribosomal RNA gene sequencing. Salivary inflammatory factors were tested by ELISA. Results: Clinical attachment loss (CAL) (P =0.05) and the number of teeth lost (P = 0.016) were significantly higher in the moderate-to-severe coronary AS group, with these differences being more obvious in younger patients and patients with short-duration diabetes. Multivariate logistic regression analysis revealed that CAL (OR = 1.231, 95% CI = 1.066-1.214, P = 0.047) and having 10-19 missing teeth (OR = 1.604, 95% CI = 1.393-6.555, P = 0.05) were strongly associated with the presence of moderate-to-severe coronary AS. Salivary IL-6 and TNF-α levels, as well as levels of Porphyromonas gingivalis and Neisseria mucosa, were significantly elevated in the moderate-to-severe coronary AS group. Conclusion: It was found that both tooth loss and CAL were related to the extent of diabetic coronary AS. Saliva inflammatory factors and oral bacteremia may be new biomarkers for moderate-to-severe coronary AS.

The patterns and participants of parental histone recycling during DNA replication in Saccharomyces cerevisiae.

Epigenetic information carried by histone modifications not only reflects the state of gene expression, but also participates in the maintenance of chromatin states and the regulation of gene expression. Recycling of parental histones to daughter chromatin after DNA replication is vital to mitotic inheritance of epigenetic information and the maintenance of cell identity, because the locus-specific modifications of the parental histones need to be maintained. To assess the precision of parental histone recycling, we developed a synthetic local label-chasing system in budding yeast Saccharomyces cerevisiae. Using this system, we observed that parental histone H3 can be recycled to their original position, thereby recovering their position information after DNA replication at all tested loci, including heterochromatin boundary, non-transcribed region, and actively transcribed regions. Moreover, the recycling rate appears to be affected by local chromatin environment. We surveyed a number of potential regulatory factors and observed that histone H3-H4 chaperon Asf1 contributed to parental histone recycling, while the eukaryotic replisome-associated components Mcm2 and Dpb3 displayed compounding effects in this process. In addition, the FACT complex also plays a role in the recycling of parental histones and helps to stabilize the nucleosomes.

Boron nitride quantum dots-enhanced laser desorption/ionization mass spectrometry analysis and imaging of bisphenol A.

Bisphenol A (BPA) displays harmful effects on the human health, including potent endocrine activity and potential impact on the development of cancer. Analysis BPA residues in water and plastic products attracted considerable attention in the past decades. However, dominantly used conventional analysis techniques are unable to directly and non-destructively identify the correct species of BPA in plastic products. Hence, this study demonstrates the effective utilisation of boron nitride quantum dots (BNQDs) as an inorganic matrix in matrix-assisted laser desorption/ionization mass spectrometry analysis and imaging (MALDI-MS & MSI) for BPA. The presence of abundant hydroxyl and amino groups on the BNQDs' surface is favourable for the formation of hydrogen bonds with BPA, and increases their ionization and chemoselectivity. Intriguingly, the BNQDs matrix offers a distinct signal for phenolic hazardous molecules featuring different hydroxyl groups. The method was applied to detect BPA at nanomolar level in environmental water, and also allowed non-destructive and in situ mapping of BPA in plastics and pacifiers. This research provides a novel strategy for adapting nanomaterials as inorganic matrices for analysis of small molecular pollutants in environmentally relevant samples using MALDI-MS & MSI.

Dietary exposure and risk assessment of chlorinated paraffins in roots and rhizomes of traditional Chinese medicine herbs.

Traditional Chinese medicine (TCM) provides therapeutic and health care effects through dietary intake. Owing to the susceptibility of plants to contaminations, a risk assessment system is urgently needed to ensure the safe use of TCMs. In this study, the contamination levels and risks associated with the dietary intake of short-chain chlorinated paraffins (SCCPs) and medium-chain chlorinated paraffins (MCCPs) were investigated in six kinds of frequently-used TCM herbs. The concentrations varied from 144.4 to 1527.8 ng·g-1 dw for SCCPs and non-detect to 1214.1 ng·g-1 dw for MCCPs, with mean values of 551.5 and 259.8 ng·g-1 dw, respectively. A geographic distribution analysis indicated that the concentrations of CPs in TCMs were mainly associated with their levels of contamination in the ambient environment. Carbon atom-chlorine congener profiles of CPs were dominated by C10Cl7-8 and C14Cl7-8 congeners, accounting for 20.1% and 32.4% of the total SCCP and MCCP concentrations, respectively. Principal component analysis indicated that the TCM species might be the main factor influencing the accumulation of SCCPs congeners. Finally, a risk assessment reveals that the estimated daily intake and margin of exposure were far below levels that might pose a health risk, indicating an acceptable dietary intake of SCCPs and MCCPs in the studied TCMs. This is the first report of CPs in the TCM herbs and the obtained results are expected to aid in future evaluation of the quality of TCMs and ensuring diet and drug safety.

Field-induced reagent concentration and sulfur adsorption enable efficient electrocatalytic semihydrogenation of alkynes.

Efficient electrocatalytic alkyne semihydrogenation with potential/time-independent selectivity and Faradaic efficiency (FE) is vital for industrial alkene productions. Here, sulfur-tuned effects and field-induced reagent concentration are proposed to promote electrocatalytic alkyne semihydrogenation. Density functional theory calculations reveal that bulk sulfur anions intrinsically weaken alkene adsorption, and surface thiolates lower the activation energy of water and the Gibbs free energy for H* formation. The finite element method shows high-curvature structured catalyst concentrates K+ by enhancing electric field at the tips, accelerating more H* formation from water electrolysis via sulfur anion-hydrated cation networks, and promoting alkyne transformations. So, self-supported Pd nanotips with sulfur modifiers are developed for electrochemical alkyne semihydrogenation with up to 97% conversion yield, 96% selectivity, 75% FE, and a reaction rate of 465.6 mmol m-2 hour-1. Wide potential window and time irrelevance for high alkene selectivity, good universality, and easy access to deuterated alkenes highlight the promising potential.

Fluorinated boron nitride nanosheets as an inorganic matrix for the MALDI mass spectrometry analysis of perfluoroalkyl acids.

We report, for the first time, the application of fluorinated hexagonal boron nitride nanosheets (F-BNNs) as an effective inorganic matrix for matrix-assisted laser desorption and ionization mass spectrometry (MALDI-MS) analysis of perfluoroalkyl acids (PFAAs). Fluoride modification of F-BNNs increases both enrichment ability and ionization efficiency. The method was validated using environmental water, milk, human serum samples, and zebrafish imaging that has been previously exposed to PFAAs. The method provided in this work holds considerable promise in term of rapid analysis, sample requirement, and practicability.

A Matrix Sublimation Device with an Integrated Solvent Nebulizer for MALDI-MSI.

The current matrix deposition methods in MALDI-mass spectrometry imaging (MALDI-MSI) face technical problems related to the inhomogeneous distribution of crystals and the low analyte extraction and cocrystallization efficiency. In this work, an integrated matrix sublimation device with synchronous solvent nebulization was developed for MALDI-MSI. Droplets of solvents were directly introduced into the chamber of the sublimator by using a miniaturized ultrasonic nebulizer unit. The synchronous and asynchronous working modes of solvent nebulization and matrix sublimation were systematically investigated. Imaging of both protein and small metabolite distributions in mouse brain tissue sections was successfully performed using the developed matrix deposition device. The sensitivity and quality of the images were clearly improved in synchronous mode compared with those of the conventional spray and sublimation methods. These results demonstrate that the integrated device with both solvent nebulization and matrix sublimation is a useful tool in MALDI-MSI applications.

[Flow-injection chemiluminescence determination of trace copper on-line separation and enrichment by ion imprinted polymer].

In the present study, Cu(II)-imprinted polymer was prepared and used as an effective method for separation and enrichment of Cu (II) ion in samples. An on-line preconcentration and extraction flow-injection system using solid phase extraction (SPE) column packed with prepared ion imprinted polymer (IIP) was set up. The column was eluted with a mixture of ethanol and H2 SO4 after preconcentration. A sensitive and simple chemiluminescence (CL) method using flow-injection has been developed for the determination of copper. The method is based on the fact that traces of Cu(II) exert a catalytic action on the oxidation between morin by KMnO4 solution. After optimizing the different experimental parameters, a calibration graph was obtained over the concentration range of 0 to 10 microg x mL(-1) for Cu(II) and r = 0.996 8. The detection limit is 0.001 2 microg x mL(-1). The recoveries are between 95% and 105% and the standard relative deviations (RSD) are less than 3% at 4.0 microg x mL(-1) (n = 9) level was obtained. The new chemiluminescence determination for copper has been established. The method can be satisfactorily applied to the determination of copper in sample.

Synthesis of green-emitting carbon quantum dots with double carbon sources and their application as a fluorescent probe for selective detection of Cu2+ ions.

Green-emitting carbon quantum dots (G-CQDs) were prepared using tartaric acid and bran by one-pot solvothermal treatment and had photoluminescence quantum yields (PL QY) as high as 46%. The morphology of the G-CQDs is characterized by TEM, which shows the average diameter of G-CQDs is approximately ∼4.85 nm. The FT-IR spectra display the presence of -OH, C-N, N-H and -COOH on the surface of the G-CQDs. The emission wavelength of the G-CQDs was ∼539 nm in the case of ∼450 nm excitation wavelength, which corresponds to the green fluorescence. Furthermore, the G-CQDs were used as a fluorescent probe for detection Cu2+ ions, and demonstrated a linear distribution between ln(F/F 0) and the Cu2+ ions concentration. Specifically, the Cu2+ ion concentration should fall in the G-CQD concentration range of 0-0.5 mM and the detection limit is 0.0507 µM. Thus, due to the excellent chemical stability and good luminescence performance, these G-CQDs could be excellent probes widely used in detection fields.

TIR generated by continuous glucose monitoring is associated with peripheral nerve function in type 2 diabetes.

AIMS: Continuous glucose monitoring (CGM)-derived time-in-range (TIR) of 3.9-10 mmol/L is associated with diabetic retinopathy in type 2 diabetes (T2DM), but its relationship to peripheral nerve function has not been previously investigated. To explore the association between the TIR and nerve conduction study parameters in patients with T2DM, we performed a cross-sectional analysis. METHODS: A total of 740 patients with T2DM were enrolled in this study. All of the participants were divided into tertiles according to the TIR (TIR low: ≤53%; TIR medium: 54-76%; TIR high: ≥77%). Composite Z-scores of nerve conduction velocity (CV), latency, and amplitude were calculated. The linear correlation between the TIR and composite nerve function Z-score was evaluated and risk assessment was analysed using binary logistic regression. RESULTS: The composite Z-score of the CV and amplitude increased with higher TIR and the composite Z-score of latency significantly decreased as the TIR tertiles increased (all P trend < 0.05). After adjusting for age, diabetes duration, height, weight and other confounding factors, higher TIR was associated with a higher composite Z-score of CV (ß = 0.230, P < 0.001), amplitude (ß = 0.099, P = 0.010), and lower composite Z-score of latency (ß = -0.172, P < 0.001). The risk of TIR tertiles and low composite Z-score of CV remained significant even after adjustment of HbA1c (TIR medium: OR = 0.48, P = 0.001; TIR high: OR = 0.41, P < 0.001). CONCLUSIONS: Higher TIR tertiles were independently associated with better peripheral nerve function. CGM-derived TIR may be a promising approach to screen patients for further assessment of possible diabetic peripheral neuropathy.

Seasonal variations and inhalation risk assessment of short-chain chlorinated paraffins in PM2.5 of Jinan, China.

Short-chain chlorinated paraffins (SCCPs) were added to the Stockholm Convention on Persistent Organic Pollutants (POPs) at the eighth meeting of the conference of the parties in 2017. As a consequence, increasing environmental attention and international regulation on SCCPs is expected in the future. Inhalation uptake of particulate matter (PM) was an important exposure pathway for POPs into the human body. In the present study, a total of eighty PM2.5 samples were collected in the four seasons of the year at an urban site (Shandong University, Jinan) in Shandong province to investigate the seasonal changes of SCCPs and their inhalation exposure risks to human health. The concentrations of SCCPs ranged from 9.80 to 105 ng m-3, with the mean value of 38.7 ng m-3. The highest concentrations of SCCPs were detected in winter, while the lowest concentrations were in summer. SCCPs concentrations were positively correlated with the mass concentrations of PM2.5 (r = 0.629, p < 0.01), and negatively correlated with the ambient temperature (r = -0.447, p < 0.01). The SCCPs congeners with 10 carbon atoms (C10 congeners) and 7 chlorine numbers (Cl7 congeners) were the predominant congeners, which contributed 35% and 37% of the total SCCPs contamination, respectively. The average inhalation exposure was estimated to be 1.75 × 10-4 mg kg-1 day-1 for adults, which is much lower than the "no observed adverse effect level" (NOAEL) of 100 mg kg-1 day-1 given by European risk assessment for SCCPs.

Peripheral pain is enhanced by insulin-like growth factor 1 and its receptors in a mouse model of type 2 diabetes mellitus.

BACKGROUND: Insulin-like growth factor 1 (IGF1) is a neurotrophic factor with many actions, including a possible hyperalgesic effect. This study investigated the effects of IGF1 on the overall behavior of diabetic mice and explored the possible mechanisms underlying IGF1-induced pain. METHODS: Mice were divided into five groups (db/m, db/db, vehicle-treated db/db, IGF1-treated db/db, and IGF1 + JB1-treated db/db mice). Behavioral studies were conducted using the hot plate and Von Frey tests after intraplantar injection of recombinant (r) IGF1 (50 µg/kg) and the IGF1 receptor (IGF1R) antagonist JB1 (6 µg/mouse). Morphological changes in dorsal root ganglia (DRG) were evaluated using electron microscopy. Immunofluorescence was used to detect IGF1R expression and colocalisation with pain mediators in the DRG. Changes in the expression of IGF1R, extracellular signal-regulated kinase (ERK), and ras-associated factor-1 (c-raf) in the DRG were evaluated using western blotting. RESULTS: Intraplantar injection of rIGF1 resulted in a hyperalgesic effect after 2 hours. This IGF1-induced hypersensitivity was attenuated by prior intraplantar injection of the IGF1R antagonist. There was no significant change in neuronal structure in the db/m group, whereas neuronal structure was impaired in the other four groups. Moreover, IGF1R was colocalised with pain mediators in the DRG of mice. Intraplantar injection of rIGF1 resulted in increased IGF1R, phosphorylated (p-) ERK, and c-raf expression in the DRG; prior intraplantar injection of the IGF1R antagonist attenuated rIGF1-induced increases in p-ERK and c-raf. CONCLUSIONS: The results indicate that IGF1-induced acute hyperalgesia may be associated with the IGF1R/c-raf/ERK pathway. The IGF1-induced hypersensitivity was attenuated by an IGF1R antagonist.

Efficacy and Safety of Premixed Human Insulin Combined with Sulfonylureas in Type 2 Diabetic Patients Previously Poorly Controlled with Insulin.

INTRODUCTION: Some type 2 diabetes (T2DM) patients treated with premixed insulin alone or in combination with oral glucose-lowering agents (without sulfonylureas) cannot reach the required glucose targets. Clinical studies have demonstrated that diabetes patients treated with sulfonylureas achieve stable glycemic control, with a low hypoglycemic rate. The aim of our study was to evaluate the efficacy and safety of therapy with the combination of premixed insulin and sulfonylureas. METHODS: A total of 120 patients with T2DM who were unable to achieve glycemic control on premixed human insulin were randomized into four groups, namely, a control group (premixed human insulin only) and three groups receiving combination therapy with premixed human insulin and one of the following sulfonylureas: gliclazide sustained release tablets [Diamicron], glipizide extended release tablets [Glucotrol XL], and glimepiride medium-to-long-acting tablets [Amaryl], with 30 patients in each group. Hemoglobin A1c, blood glucose, and adverse events were assessed at baseline and at the end of the 12-week treatment period. RESULTS: After treatment for 12 weeks, HbA1c, fasting glucose, and 2-h postprandial glucose levels in the four groups were significantly decreased when compared with baseline (P < 0.05). However, there was no difference between the four groups at the end of the study. In the control group, the daily insulin dose had been significantly increased at the end of the follow-up when compared with baseline (P < 0.05), while there were no significant changes in premixed insulin dose in the three combination therapy groups. There were no significant differences in adverse events among the four groups. CONCLUSION: Insulin combined with sulfonylureas could improve glycemic control without increasing daily insulin dose and adverse events. Based on our results, we consider the combination of premixed insulin and sulfonylureas to be effective and safe for the treatment of T2DM. TRIAL REGISTRATION: This trial was registered as ChiCTR-TRC-14004751. Trial Registration Date: 5 June 2014.

Effects of tail docking and/or teeth clipping on behavior, lesions, and physiological indicators of sows and their piglets.

To evaluate effects of tail docking and/or teeth clipping on sows and their piglets, a total of 24 sows and their 302 piglets at 3 days of age were randomly allocated to one of four treatments: teeth clipping and tail docking (TCTD), teeth clipping (TC), tail docking (TD), or intact teeth and tail (Intact). Behavior of piglets and sows, lesions on the body and tail of piglets and sows' teats were inspected. Heart rates of processed piglets were increased (p < .01) during the procedures. Teeth clipping decreased body surface temperature (p < .01) of piglets during and after the procedures but tail docking did not (p > .01). Processed piglets spent more (p < .05) time lying alone and playing/fighting than sham-processed piglets. Tail docked piglets spent less (p < .01) time standing than tail sham-docked piglets. Intact teeth increased (p < .05) the avoidance behaviors of sows. Teeth clipping decreased (p < .05) the lesion scores on the anterior, middle, and posterior teats. Taken together, piglet teeth clipping had more impact on sows and their piglets than tail docking did in the lactation period based on our findings.