Structure of crude polysaccharides from Atractylodes lancea rhizome and treatment of diarrhea owing to spleen deficiency through intestinal flora.

To optimize the extraction process of crude polysaccharides from Atractylodes and elaborate the mechanism of Atractylodes polysaccharides in treating diarrhea owing to spleen deficiency, so as to lay a foundation for further development and utilization of Atractylodes lancea, we used an orthogonal test to optimize the extraction process and established a model of spleen deficiency. It was further combined with histopathology and intestinal flora to elaborate the mechanism of Atractylodes polysaccharides in the treatment of spleen-deficiency diarrhea. The optimized extraction conditions were as follows: the ratio of material to liquid was 1:25; the rotational speed was 150 rpm; the extraction temperature was 60°C; the extraction time was 2 h; and the extraction rate was about 23%. The therapeutic effect of Atractylodes polysaccharides on a spleen-deficiency diarrhea model in mice showed that the water content of stools and diarrhea grade in the treatment group were alleviated, and the levels of gastrin, motilin and d-xylose were improved. The analysis results based on gut microbiota showed that the model group had a higher diversity of gut microbiota than the normal group and treatment group, and the treatment group could correct the diversity of gut microbiota in model mice. Analysis based on the level of phylum and genus showed that the treatment group could inhibit the abundance of Helicobacter pylori genus and increase beneficial bacteria genera. The conclusion was that the optimized extraction process of Atractylodes polysaccharides was reasonable and feasible, and had a good therapeutic effect on spleen deficiency diarrhea.

[Design of nonlinear locking mechanism for shape memory alloy archwire of miniature orthodontic device].

The locking mechanism between bracket and shape memory alloy (SMA) archwire in the newly developed domestic orthodontic device is the key to controlling the precise alignment of the teeth. To meet the demand of locking force in clinical treatment, the tightening torque angle of the locking bolt and the required torque magnitude need to be precisely designed. For this purpose, a design study of the locking mechanism is carried out to analyze the correspondence between the tightening torque angle and the locking force and to determine the effective torque value, which involves complex coupling of contact, material and geometric nonlinear characteristics. Firstly, a simulation analysis based on parametric orthogonal experimental design is carried out to determine the SMA hyperelastic material parameters for the experimental data of SMA archwire with three-point bending. Secondly, a two-stage fine finite-element simulation model for bolt tightening and archwire pulling is established, and the nonlinear analysis is converged through the optimization of key contact parameters. Finally, multiple sets of calibration experiments are carried out for three tightening torsion angles. The comparison results between the design analysis and the calibration experiments show that the deviation between the design analysis and the calibration mean value of the locking force in each case is within 10%, and the design analysis method is valid and reliable. The final tightening torque angle for clinical application is determined to be 10° and the rated torque is 2.8 N∙mm. The key data obtained can be used in the design of clinical protocols and subsequent mechanical optimization of novel orthodontic devices, and the research methodology can provide a valuable reference for force analysis of medical devices containing SMA materials.

Quantitative prediction of the hydraulic performance of free water surface constructed wetlands by integrating numerical simulation and machine learning.

Quantitative prediction of the design parameter-influenced hydraulic performance is significant for optimizing free water surface constructed wetlands (FWS CWs) to reduce point and non-point source pollution and improve land utilization. However, owing to limitations of the test conditions and data scale, a quantitative prediction model of the hydraulic performance under multiple design parameters has not yet been established. In this study, we integrated field test data, mechanism model, statistical regression, and machine learning (ML) to construct such quantitative prediction models. A FWS CW numerical model was established by integrating 13 groups of trace data from field tests. Subsequently, training, test and extension datasets comprising 125 (5^3), 25 (L25(56)) and 16 (L16(44)) data points, respectively, were generated via numerical simulation of multi-level value combination of three quantitative design parameters, namely, water depth, hydraulic loading rate (HLR), and aspect ratio. The short circuit index (φ10), Morrill dispersion index (MDI), hydraulic efficiency (λ) and moment index (MI) were used as representative hydraulic performance indicators. Training set with large samples were analyzed to determine the variation rules of different hydraulic indicators. Based on the control variable method, φ10, λ, and MI grew exponentially with increasing aspect ratio whereas MDI showed a decreasing trend; with increasing water depth, φ10, λ, and MI showed polynomial decreases whereas MDI increased; with increasing HLR, φ10, λ, and MI slowly increased linearly whereas MDI showed the opposite trend. Finally, we constructed models based on multivariate nonlinear regression (MNLR) and ML (random forest (RF), multilayer perceptron (MLP), and support vector regression. The coefficients of determination (R2) of the MNLR and ML models fitting the training and test sets were all greater than 0.9; however, the generalization abilities of different models in the extension set were different. The most robust MLP, MNLR without interaction term, and RF models were recommended as the preferred models to hydraulic performance prediction. The extreme importance of aspect ratio in hydraulic performance was revealed. Thus, gaps in the current understanding of multivariate quantitative prediction of the hydraulic performance of FWS CWs are addressed while providing an avenue for researching FWS CWs in different regions according to local conditions.

Preparation and in Vitro Evaluation of Osmotic-Pump Lorcaserin-hydrochloride Controlled-Release Tablets.

Long-term and constant-release osmotic-pump lorcaserin hydrochloride controlled-release tablets (OP LH CRTs) were prepared, to investigate the influencing factors of LH release and optimize the formulation. The mechanism of release of LH from OP LH CRTs in vitro was investigated. By establishing a high-efficiency method for measuring LH release in vitro, and optimizing it by single-factor and orthogonal experiments, the best formulation of OP LH CRTs was determined. Then, the optimal prescription of OP LH CRTs was: LH = 20.8 mg; mannitol = 100 mg, microcrystalline cellulose = 125 mg; magnesium stearate = 5 mg; cellulose acetate = 3%; polyethylene glycol 400 = 10%; dibutyl phthalate = 10%; Wetting agent and binder was 3% polyvinyl pyrrolidone (PVP) K30 ethanol solution; aperture diameter = 0.8 mm; the coating gained 3% weight. And finally, prepared OP LH CRTs were released at a constant rate in vitro and sustained for 16 h with good reproducibility between batches. Using an orthogonal experimental design, OP LH CRTs with remarkable zero-order release characteristics within 16 h were obtained, and formulation optimization was realized.

Purification of Polysaccharides from Orostachys cartilaginous Cell Cultures by Macroporous Resin Absorption and Bioactivities of the Purified Polysaccharides.

Orostachys cartilaginous is a traditional herbal medicine and its cell cultures contain large amounts of polysaccharides. To utilize the cultured O. cartilaginous cells, this study purified the crude polysaccharides of O. cartilaginous cells by macroporous resin absorption and optimized the purification process in the experiment of orthogonal design with four factors (sample concentration and volume, and eluent concentration and volume) and three levels; the antibacterial and anti-cancer effects of the purified polysaccharides (OTP) were further examined. The results showed that polysaccharide purity reached 95 % in the optimized group, i. e., 1.6 mg/mL of sample (crude polysaccharides) concentration, 3.0 bed volume (BV) of sample volume, 65 % eluent (ethanol) concentration, and 3.0 BV of eluent volume. In the antibacterial experiment, the growth of three bacterial species, i. e., Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis was inhibited by OTP, whereas that of Escherichia coli was not affected; the largest diameter of the inhibitory zone was found on B. subtilis; the extracellular alkaline phosphatase activity and the electrical conductivity, nucleic acid, and protein levels of B. subtilis increased after OTP treatment, indicating that the inhibition of B. subtilis growth was caused by the leakage of cell contents. In the anti-cancer experiment, OTP decreased the cell viabilities of the tested human cancer cells, i. e., AGS (gastric cancer), HCT116 (colon cancer), HepG2 (liver cancer), and HeLa (cervical cancer), and the highest inhibitory effect was on HCT116. OTP promoted HCT116 apoptosis and affected the expression of apoptosis-related proteins, i. e., the expression of B-cell lymphoma-2 decreased and that of bcl-2 associated X protein, cytochrome c, caspase 9 and caspase 3 increased. The findings of the present study suggest that O. cartilaginous cell cultures have a potential application in food or drug production.

Utilizing artificial neural network to simulate and predict the hydraulic performance of free water surface constructed wetlands.

Optimizing the hydraulic performance of free water surface constructed wetlands (FWS CWs) is of great economic and ecological value. However, there is a complex nonlinear relationship between the hydraulic performance and design parameters of FWS CWs. In this study, an artificial neural network (ANN) was applied to simulate and predict the hydraulic performance corresponding to different combinations of design parameters, and orthogonal design L9 (34) was used to determine the optimal combination of the important hyperparameters of the ANN. Based on the convenient scenario prediction ability of ANN, sensitivity analysis of different design parameters was carried out by the control variate method and full factor experiment. The results showed that the combination of 3 hidden layers, 15 neural nodes in each hidden layer, 0.001 learning rate, and 8 batch sizes was optimal for the established ANN model, achieving a coefficient of determination of 0.828 in the validation set and a satisfactory prediction effect in the test set. The narrow feature distribution interval in the training set restricted the generalization ability of the ANN model to some extent. Of the four continuous design parameters, the water depth and aspect ratio had an important influence on the effective volume ratio. The layout of inlet and outlet was the most influential design parameter, as confirmed by the full factor experiment of five factors and four levels. The established ANN allowed real-time implementation in an extended scenario at a low cost. This study suggests that the ANN can simultaneously project complex and uncertain effects of several design parameters on wetland performance. In future research, acquiring further comprehensive, impartial, and unbiased experimental datasets is necessary to establish a more robust and generalizing ANN model that can guide the optimal design of FWS CWs.

Optimization of fermentation conditions and medium compositions for the production of chrysomycin a by a marine-derived strain Streptomyces sp. 891.

Chrysomycin A is one of the valuable drug leads used to treat infectious diseases such as tuberculosis and methicillin-resistant Staphylococcus aureus. In order to increase its yield, this work firstly focuses on optimization of fermentation conditions and medium compositions of a wild-type chrysomycin A-producing strain Streptomyces sp. 891 from marine sediment. By single-factor experiment, effects of fermentation conditions (fermentation time, seed age, initial pH, inoculum amount, liquid loading, shaking speed) and medium composition (carbon sources, nitrogen sources, inorganic salts) on the yield of chrysomycin A were carefully evaluated and analyzed followed by optimization at shake-flask level. The results indicated its optimal fermentation conditions for producing chrysomycin A were as follows: fermentation time 168 h, seed age 48 h, initial pH 6.5, inoculum amount 5.0%, liquid loading 30 mL in 250-mL Erlenmeyer flask and shaking speed 220 rpm. By orthogonal test, the optimal fermentation medium constitutes 40 g/L glucose, 20 g/L corn starch, 25 g/L hot-pressed soybean flour, 3 g/L CaCO3. Verification tests suggested the yield of chrysomycin A under optimized conditions reaches up to 3648 ± 119 mg/L, which is increased by almost 5 times. These findings definitely pave the way for scale-up preparation of chrysomycin A and application in the pharmaceutical industry.

Protoplast fusion between Blakeslea trispora 14,271 (+) and 14,272 (-) enhanced the yield of lycopene and ß-carotene.

Blakeslea trispora, a heterothallic Zygomycota with two mating types (termed "plus" and "minus"), is an ideal source of lycopene and ß-carotene. The lycopene and ß-carotene yields when the two type strains are used for fermentation separately are lower than those when they are joint together. To enhance the yield of lycopene and ß-carotene in B. trispora, protoplast fusion technology was carried out between ATCC 14,271 (+) and ATCC 14,272 (-). After protoplast preparation, protoplast fusion, fusion sorting, fusion regeneration, and high-throughput screening, two fusions (Fu-1and Fu-2) with high lycopene and ß-carotene yields were obtained. The lycopene yields of Fu-1 and Fu-2 were increased to 0.60 mg/gDW and 0.90 mg/gDW, which were respectively 3.62- and 5.44-fold those of 14,271 and 1.76- and 2.64-fold those of 14,272. The ß-carotene yields of Fu-1 and Fu-2 were increased to 22.07 mg/gDW and 36.93 mg/gDW, which were respectively 1.72- and 2.89-fold those of 14,271 and 1.23- and 2.06-fold those of 14,272. In this study, the protoplast fusion technique was successfully used in Blakeslea trispora, providing new ideas for improving lycopene and ß-carotene production.

[Optimizing experimental conditions of graphite furnace atomic absorption spectrometer using orthogonal design for determination of cobalt in urine].

Objective: To select and optimize the conditions of urine cobalt determination by graphite furnace atomic absorption spectroscopy and establish a method for urine cobalt determination. Methods: In April 2020, the matrix modifier and spectrum wavelength were selected by mathematical statistics method, the heating procedure of graphite furnace was optimized, the variance of orthogonal test results was analyzed, and the working curve was quantified by external standard method. Results: The results showed that the diammonium hydrogen phosphate was a matrix modifier with a wavelength of 240.7 nm, and the optimized graphite furnace heating procedure showed a good linear relationship at 5-80 µg/L. The correlation coefficient was 0.9991. The detection limit was 0.9 µg/L, the lowest detection concentration was 1.8 µg/L. The recovery was 94.0%-101.4%, and the precision was 2.6%-5.8%. Conclusion: The orthogonal design method can efficiently and scientifically optimize the optimal combination of the various factor levels of graphite furnace atomic absorption spectrometry. The determination method established based on this has high precision and good accuracy, and can be applied to the determination of cobalt in urine.

Visualized analysis and evaluation of simultaneous controlled release of metformin hydrochloride and gliclazide from sandwiched osmotic pump capsule.

The aim of this study was to develop the Metformin Hydrochloride and Gliclazide (MH-GZ) sandwiched osmotic pump capsule which could overcome the problems associated with short half-life and burst release. The system could deliver drugs with different solubility simultaneously at zero-order rate, in which MH-GZ were filled in both sides of the push layer respectively. The single factor and orthogonal test were employed to obtain the optimized formulation with the evaluation index of similarity factor (ƒ2). R language was used to visualized analyze the main influence factors of drug release and their correlations. Pharmacokinetic study was performed in beagle dogs compared to the marketed conventional product, which showed decreased Cmax, prolonged Tmax, and improved bioavailability, independent of pH and agitational speed but related to osmotic pressure differences across the semi permeable membrane. The designed sandwiched osmotic pump capsule proposed a promising substitute for the marketed product for the treatment of type 2 diabetes.

Preparation of resveratrol dry suspension and its immunomodulatory and anti-inflammatory activity in mice.

Context: Resveratrol is a natural polyphenol compound. It exhibits antitumor, immunostimulatory, and antiviral activities. However, poor water solubility and structural instability limit its administration and storage.Objective: A resveratrol dry suspension (RDS) was prepared and immunomodulatory effect in immunosuppressive mice induced by cyclophosphamide and anti-inflammatory activities in mice were evaluated.Materials and methods: The preparation of RDS was optimized by the orthogonal design method. To evaluate the immunomodulatory effects, SPF Kunming mice were divided into seven groups comprising of nine males and nine females for each group. The RDS supplemented group was administrated doses of 3.33, 1.67, and 0.83 g/kg/d. Then visceral index, lymphocyte proliferation, the ratio of CD3+ CD4+/CD3+ CD8+, and the contents of cytokines in serum were tested. To ameliorate effects of acetic acid induced capillary permeability, xylene-based ear oedema, and cotton pellet granuloma, RDS as anti-inflammatory agent was administered at doses of 1, 0.33, and 0.1 g/kg/d as compared to indomethacin (IM) provided as a positive control at 10 mg/kg.Results: RDS inhibited the degradation of resveratrol and enhanced the CD3+ CD4+/CD3+ CD8+ ratio, spleen index, IL-2 level, and splenic lymphocytes in immunosuppressive mice. RDS (0.1 g/kg/d) significantly inhibited the acetic acid-induced capillary permeability, and at doses of 0.33 and 1 g/kg/d repressed the ear swelling and granuloma formation in immunocompromised mice.Discussion and Conclusion: RDS is a stable, cheaper, and suitable preparation with potent immunoregulatory and anti-inflammatory activities. Keeping in view these remarkable properties, RDS could be an appropriate preparation for clinic use of resveratrol.

Influence of environmental factors on arsenic accumulation and biotransformation using the aquatic plant species Hydrilla verticillata.

Hydrilla verticillata (waterthyme) has been successfully used for phytoremediation in arsenic (As) contaminated water. To evaluate the effects of environmental factors on phytoremediation, this study conducted a series of orthogonal design experiments to determine optimal conditions, including phosphorus (P), nitrogen (N), and arsenate (As(V)) concentrations and initial pH levels, for As accumulation and biotransformation using this aquatic plant species, while also analyzing As species transformation in culture media after 96-hr exposure. Analysis of variance and the signal-to-noise ratio were used to identify both the effects of these environmental factors and their optimal conditions for this purpose. Results indicated that both N and P significantly impacted accumulation, and N was essential in As species transformation. High N and intermediate P levels were critical to As accumulation and biotransformation by H. verticillata, while high N and low P levels were beneficial to As species transformation in culture media. The highest total arsenic accumulation was (197.2 ± 17.4) µg/g dry weight when As(V) was at level 3 (375 µg/L), N at level 2 (4 mg/L), P at level 1 (0.02 mg/L), and pH at level 2 (7). Although H. verticillata is highly efficient in removing As(V) from aquatic environments, its use could be potentially harmful to both humans and the natural environment due to its release of highly toxic arsenite. For cost-effective and ecofriendly phytoremediation of As-contaminated water, both N and P are helpful in regulating As accumulation and transformation in plants.

Effect of Health State Sampling Methods on Model Predictions of EQ-5D-5L Values: Small Designs Can Suffice.

OBJECTIVE: The current five-level EQ-5D (EQ-5D-5L) valuation protocol requires the valuation of 86 states. It has been demonstrated that the selection of empirically valued health states affects the extrapolated values in three-level EQ-5D (EQ-3D-3L). In this investigation, we aim to compare the performance of the current EQ-5D-5L valuation design with other designs. STUDY DESIGN: 1603 university students participated in a valuation study using a visual analog scale (VAS) to produce values for all EQ-5D-5L states. Different designs were generated to test their prediction accuracy. METHODS: Subsamples of the dataset were used to mimic data obtained from a particular design; the remaining dataset was used as the validation set. In addition to EuroQol Group Valuation Technology (EQ-VT) design, alternative subsamples and designs were created using random, orthogonal, and "optimizing D-efficiency" sampling methods. The root mean squared error (RMSE) was used as the measure of prediction accuracy. RESULTS: The EuroQol Group Valuation Technology (EQ-VT) design showed an average RMSE of 3.44 on EQ-VAS, for all 3125 health states combined. Notably, a 25-state orthogonal design performed similarly to the EQ-VT design, with a smaller RMSE of 3.40, and was thus the most efficient design. One caveat with respect to the orthogonal design was that it did not predict the mild states well. CONCLUSIONS: Our study supports the EQ-VT design. Smaller designs were identified with similar overall prediction accuracy. It is worth investigating whether issues with misprediction of mild states can be resolved, as the use of smaller size designs would reduce the cost of the valuation of EQ-5D-5L considerably.

Aromatic hydrocarbon compound degradation of phenylacetic acid by indigenous bacterial Sphingopyxis isolated from Lake Taihu.

The aromatic compound phenylacetic acid (PAA) is present in the environment, and released in the catabolism of phenylalanine, 2-phenylethylamine, or environmental contaminants such as ethylbenzene and styrene. PAA was also proposed to be involved in human chronic kidney disease development. Several bacteria and fungi utilize these aromatic acids as sole carbon source either during aerobic or anaerobic conditions. The aromatic structure of PAA makes this compound resistant toward oxidation or reduction, because the stabilizing resonance energy of the aromatic ring system is difficult to overcome. In the case of bacteria that utilize aromatic compounds as growth substrates, the aromatic ring system limits survival due to a lack of carbon source. Sphingopyxis sp. YF1 isolated from Lake Taihu was found to be beneficial in bioremediation of aromatic compounds. This study thus aimed to examine the influence of environmental factors such as temperature, PAA concentration, and pH on the effectiveness of Sphingopyxis sp. YF1 to degrade aromatic compounds using PAA as model compound. Data showed the highest PAA-degrading rate of strain Sphingopyxis sp. YF1 was 7.6 mg/L·h under the condition of 20°C, pH 9 with a 1000 µg/ml concentration of PAA. Evidence indicates that PAA-degrading ability of strain Sphingopyxis sp. YF1 appears to be primarily influenced by the concentration of PAA, followed by temperature and pH. PAA-degrading gene PAAase was identified in this strain using polymerase chain reaction (PCR) method. These results illustrate that the bacteria Sphingopyxis sp. YF1 removes PAA effectively at certain environmental conditions and this proves beneficial in bioremediation of aromatic compounds.

Preparation and in vitro/in vivo evaluation of azilsartan osmotic pump tablets based on the preformulation investigation.

The objective of this study was to design and evaluate azilsartan osmotic pump tablets. Preformulation properties of azilsartan were investigated for formulation design. Azilsartan osmotic pump tablets were prepared by incorporation of drug in the core and subsequent coating with cellulose acetate and polyethylene glycol 4000 as semi-permeable membrane, then drilled an orifice at the center of one side. The influence of different cores, compositions of semipermeable membrane and orifice diameter on azilsartan release were evaluated. The formulation of core tablet was optimized by orthogonal design and the release profiles of various formulations were evaluated by similarity factor (f2). The optimal formulation achieved to deliver azilsartan at an approximate zero-order up to 14 h. The pharmacokinetic study was performed in beagle dogs. The azilsartan osmotic pump tablets exhibited less fluctuation in blood concentration and higher bioavailability compared to immediate-release tablets. Moreover, there was a good correlation between the in vitro dissolution and in vivo absorption of the tablets. In summary, azilsartan osmotic pump tablets presented controlled release in vitro, high bioavailability in vivo and a good in vitro-in vivo correlation.

[Study on preparation of volatile oil from Acorus tatarinowii self-nanoemulsion dropping pills and its protective effect on acute myocardial ischemia injury].

In this study, solid dispersion technology was used to develop volatile oil from Acorus tatarinowii self-nanoemulsion dropping pills(VOA-SNEDDS-DP) and its protective effect on acute myocardial ischemia injury was evaluated. Taking exterior quality, weight variation and the resolving time as comprehendsive evaluation indexes, the preparation process and formulation of the dropping pills were optimized by orthogonal design, and the dissolution rate in vitro of the optimized VOA-SNEDDS-DP was investigated. The rat model of acute myocardial ischemia was induced by intraperitoneal injection of isoproterenol hydrochloride and the serum levels of superoxide dismutase(SOD), malondialdehyde(MDA), creatine kinase(CK) and pathological changes of myocardial tissue were determined to evaluate therapeutic effect of the dropping pills on acute myocardial ischemia. The results showed that the optimal formulation and preparation process of VOA-SNEDDS-DP were as follows: PEG6000-PEG8000 was 1∶1, proportion of VOA-SNEDDS and matrix was l∶2.5, the temperature of drug fluids was 75 ℃, drop rate was 35 drops/min, drop distance was 5 cm, the condensing agent temperature was 2-10 ℃. The content of ß-asarone in the dropping pills was 42.46 mg·g~(-1). The accumulated dissolution rate of the dropping pills reached 93.85% in 10 min. The results of pharmacodynamic experiments showed that VOA-SNEDDS-DP could significantly increase the SOD content(P<0.05), reduce the levels of MDA and CK(P<0.05) in serum, and effectively improve the pathological morphology of myocardial tissue. These results revealed that the preparation of VOA-SNEDDS-DP by solid dispersion technology was stable and feasible, and VOA-SNEDDS-DP had protective effect on acute myocardial ischemia injury.

Evaluating in Vitro Culture Medium of Gut Microbiome with Orthogonal Experimental Design and a Metaproteomics Approach.

In vitro culture based approaches are time- and cost-effective solutions for rapidly evaluating the effects of drugs or natural compounds against microbiomes. The nutritional composition of the culture medium is an important determinant for effectively maintaining the gut microbiome in vitro. This study combines orthogonal experimental design and a metaproteomics approach to obtaining functional insights into the effects of different medium components on the microbiome. Our results show that the metaproteomic profile respond differently to medium components, including inorganic salts, bile salts, mucin, and short-chain fatty acids. Multifactor analysis of variance further revealed significant main and interaction effects of inorganic salts, bile salts, and mucin on the different functional groups of gut microbial proteins. While a broad regulating effect was observed on basic metabolic pathways, different medium components also showed significant modulations on cell wall, membrane, and envelope biogenesis and cell motility related functions. In particular, flagellar assembly related proteins were significantly responsive to the presence of mucin. This study provides information on the functional influences of medium components on the in vitro growth of microbiome communities and gives insight on the key components that must be considered when selecting and optimizing media for culturing ex vivo microbiotas.

Selecting Health States for EQ-5D-3L Valuation Studies: Statistical Considerations Matter.

BACKGROUND: For many countries, the three-level EuroQol five-dimensional questionnaire (EQ-5D-3L) value sets have been established to estimate health state utilities. To generate these value sets, researchers first collect values for a subset of preselected health states from a panel representing the general public, and then use a prediction algorithm to generate values for all 243 states. High prevalence of a health state in daily practice has historically been a key criterion in selecting a subset of health states as the observed set. More recently, other criteria have been suggested, especially approaches based on statistical criteria such as randomization and orthogonality. OBJECTIVES: To evaluate the validity and accuracy of both the earlier and newer criteria, in terms of prediction of values for all the health states and of the values of common health states in particular. METHODS: We used a pre-existing data set that contained visual analogue scale values from 126 students, each of whom valued all 243 EQ-5D-3L states. Then, we generated a series of designs and subsequently modeled the data with respect to each design. Some of these designs were used in the past; for example, the Measurement and Valuation of Health approach was included. Others were newly generated. The performance of different designs was evaluated in terms of the lowest root mean squared error for all health states taken together, and separately for common and rare states. Classification as common or rare was based on the frequency of the states' occurrence in three patient and population data sets pooled together (N = 5269). RESULTS: The orthogonal design with 54 health states produced the lowest root mean squared errors. Over-representation of common health states in a design did not improve the estimations for these states. The published designs performed the worst, whereas the random selection designs were good on average. Nevertheless, the performance of the random selection designs showed more variance compared with orthogonal designs, because some of the former designs did not display appropriate balance. CONCLUSIONS: The published designs gave rise to large estimation errors for the extrapolated EQ-5D-3L health states. The orthogonal design focusing on statistical efficiency showed its superiority. Overall, when weighing up design properties, increased statistical efficiency outweighs an increased error rate, if any, in rare health states.

Improving the artificial diet for adult of seven spotted ladybird beetle Coccinella septempunctata L. (Coleoptera: Coccinellidae) with orthogonal design.

In this study, an orthogonal array design with 16 factors at two levels (216) was performed to develop an artificial diet rearing the adults of seven spotted ladybird beetle Coccinella septempunctata. The parameters of weight gain and survival rate of adults, preoviposition period, fecundity and hatching rate of diet-fed adults were monitored. The 16 factors were included: pork liver, infant formula, sucrose, olive oil, yolk, corn oil, yeast powder, cholesterol, casein, casein hydrolysate, vitamin powder, 65% juvenile hormone III, protein powder, vitamin E, honey and pumpkin. Results indicated that pork liver, sucrose, yolk, yeast powder, juvenile hormone, pumpkin and honey were the main ingredients of the artificial diet contributing to weight gain and survival rate of adults, preoviposition period, fecundity and hatching rate. A follow-up fed with a selection of improved formulas confirmed the validity of the optimization as predicted by the orthogonal array analysis, indicating the usefulness of this method for selecting artificial diets for C. septempunctata. The weight gain and fecundity of adults reared on the improved artificial diet were 87.46 and 62.70% of those reared on Aphis craccivora; the survival rate and hatch rate were similar between the diet-fed and aphid-fed, while the preoviposition period was significantly shorter for C. septempunctata fed on the diet than on A. craccivora. The latter formula was superior to any formerly developed formulas and may thus have potential for the improved artificial diet mass rearing of C. septempunctata.

Pain management of surgical abortion using transcutaneous acupoint electrical stimulation: An orthogonal prospective study.

AIM: This study aimed to evaluate the optimal combination of parameters for the management of pain during surgical abortion using transcutaneous acupoint electrical stimulation (TEAS). METHODS: This study recruited patients scheduled for surgical abortion between October 2014 and August 2015. The treatment protocol was created using three levels for each factor (stimulating time, acupoints, age, and parity). The primary outcomes were intraoperative visual analog scale (VAS), postoperative VAS, cervical relaxation degree and intraoperative blood loss. The secondary outcomes were the vital signs. RESULTS: Stimulation time was associated with intraoperative VAS scores (P < 0.001), acupoints were associated with postoperative VAS scores (P = 0.037), and age was associated with postoperative VAS scores (P < 0.043). Parity (P = 0.025) was associated with heart rate. A comprehensive analysis of the parameters revealed the best levels for each (stimulation time: from 15 min before operation to immediate postoperative; acupoints: SP 6 and LR 3; patient age 25.1-30.0 years; and parity: G≥2 P0 A≥1 ). Seven patients did not complete follow-up. The remaining 135 subjects did not show continuous vaginal bleeding, abdominal pain, fever or any other adverse effect. CONCLUSION: During surgical abortion, TEAS stimulation from 15 min before operation to immediate postoperative, SP 6 and LR 3, age 25.1-30.0 years and G≥2 P0 A≥1 were associated with the best analgesic effect.