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Background: Increasing evidence indicates a close relationship between alterations in human immune cells and plasma metabolites with Rheumatoid Arthritis (RA). However, limited studies have left the causal relationships behind these links unclear. Methods: A bidirectional Mendelian Randomization (MR) study was conducted, combined with mediation analysis, using data from genome-wide association study database covering 731 immune cell phenotypes and 1,400 plasma metabolite traits to explore their causal relationships with RA and potential mediating effects. The primary method used for MR analysis was inverse-variance weighted and False Discovery Rate (FDR) correction was applied to verify the robustness of our results. Results: HLA DR on CD33- HLA DR+ (myeloid cell group) (OR, 1.422; 95% CI, 1.194-1.694; P < 0.001; PFDR = 0.012) increased the risk of developing RA. CD19 on IgD+ CD38- naive (B cell group) (OR, 0.969; 95% CI, 0.954-0.985; P < 0.001; PFDR = 0.021) reduced the risk of developing RA. RA was a risk factor for HLA DR on CD14- CD16+ monocytes (monocyte group) (OR, 1.242; 95% CI, 1.102-1.401; P < 0.001; PFDR = 0.047). RA was a protective factor for memory B cell %lymphocyte (B cell group) (OR, 0.861; 95% CI, 0.795-0.933; P < 0.001; PFDR = 0.050), CD4+ CD8dim T cell %lymphocyte (TBNK group) (OR, 0.802; 95% CI, 0.711-0.904; P < 0.001; PFDR = 0.043), CD4+ CD8dim T cell %leukocyte (TBNK group) (OR, 0.814; 95% CI, 0.726-0.913; P < 0.001; PFDR = 0.046), CD24 on IgD+ CD24+ B cells (B cell group) (OR, 0.857; 95% CI, 0.793-0.927; P < 0.001; PFDR = 0.038), and CD24 on unswitched memory B cells (B cell group) (OR, 0.867; 95% CI, 0.797-0.942; P < 0.001; PFDR = 0.050). Increasing levels of docosatrienoate (22:3n3) (OR, 0.886; 95% CI, 0.838-0.936; P < 0.001; PFDR = 0.023) significantly reduced the risk of developing RA. The mediating effect of plasma metabolites in this context was not established. Conclusion: This study provides genetic evidence for the intricate relationships between immune cells, plasma metabolites, and RA, highlighting the potential mechanisms involved. This will contribute to future directions in precision medicine and research.

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Perfluorinated and polyfluoroalkyl substances (PFASs) are compounds characterized by at least one perfluorinated carbon atom in an alkyl chain linked to side-chain groups. Owing to their unique chemical properties, these compounds are widely used in industrial production and daily life. However, owing to anthropogenic activities, sewage discharge, surface runoff, and atmospheric deposition, PFASs have gradually infiltrated the environment and aquatic resources. With their gradual accumulation in environmental waters, PFASs have been detected in fishes and several fish-feeding species, suggesting that they are bioconcentrated and even amplified in aquatic organisms. PFASs exhibit high intestinal absorption efficiencies, and they bioaccumulate at higher trophic levels in the food chain. They can be bioconcentrated in the human body via food (e. g., fish) and thus threaten human health. Therefore, establishing an efficient analytical technique for use in analyzing PFASs in typical fish samples and providing technical support for the safety regulation and risk assessment of fish products is necessary. In this study, by combining solvent extraction and magnetic dispersion-solid phase extraction (d-SPE), an improved QuEChERS method with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed for the determination of 13 PFASs in fish samples. Fe3O4-TiO2 can be used as an ideal adsorbent in the removal of sample matrix interference and a separation medium for the rapid encapsulation of other solids to be isolated from the solution. Based on the matrix characteristics of the fish products and structural properties of the target PFASs, Fe3O4-TiO2 and N-propyl ethylenediamine (PSA) were employed as adsorbents in dispersive purification. The internal standard method was used in the quantitative analyses of the PFASs. To optimize the sample pretreatment conditions of analyzing PFASs, the selection of the extraction solvent and amounts of Fe3O4-TiO2 and PSA were optimized. Several PFASs contain acidic groups that are non-dissociated in acidic environments, thus favoring their entry into the organic phase. In addition, acidified acetonitrile can denature and precipitate the proteins within the sample matrix, facilitating their removal. Finally, 2% formic acid acetonitrile was used as the extraction solvent, and 20 mg Fe3O4-TiO2, 20 mg PSA and 120 mg anhydrous MgSO4 were used as purification adsorbents. Under the optimized conditions, the developed method exhibited an excellent linearity (R≥0.9973) in the range of 0.01-50 µg/L, and the limits of detection (LODs) and quantification (LOQs) ranged from 0.001-0.023 and 0.003-0.078 µg/L, respectively. The recoveries of the 13 PFASs at low, medium, and high spiked levels (0.5, 10, and 100 µg/kg) were 78.1%-118%, with the intra- and inter-day precisions of 0.2%-11.1% and 0.8%-8.7%, respectively. This method was applied in analyzing real samples, and PFASs including perfluorooctanesulfonic acid, perfluorooctanoic acid, perfluoroundecanoic acid, perfluorododecanoic acid, and perfluorotridecanoic acid, were detected in all 11 samples evaluated. This method is simple, sensitive, and suitable for use in analyzing PFASs in fish samples.

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Objectives: The technique of guided bone regeneration (GBR) has been widely used in the field of reconstructive dentistry to address hard tissue deficiency. The objective of this research was to manufacture a novel bi-layered asymmetric membrane that incorporates demineralized dentin matrix (DDM), a bioactive bone replacement derived from dentin, in order to achieve both soft tissue isolation and hard tissue regeneration simultaneously. Methods: DDM particles were harvested from healthy, caries-free permanent teeth. The electrospinning technique was utilized to synthesize bi-layered DDM-loaded PLGA/PLA (DPP) membranes. We analyzed the DPP bilayer membranes' surface topography, physicochemical properties and degradation ability. Rat skull critical size defects (CSDs) were constructed to investigate in vivo bone regeneration. Results: The synthesized DPP bilayer membranes possessed suitable surface characteristics, acceptable mechanical properties, good hydrophilicity, favorable apatite forming ability and suitable degradability. Micro-computed tomography (CT) showed significantly more new bone formation in the rat skull defects implanted with the DPP bilayer membranes. Histological evaluation further revealed that the bone was more mature with denser bone trabeculae. In addition, the DPP bilayer membrane significantly promoted the expression of the OCN matrix protein in vivo. Conclusions: The DPP bilayer membranes exhibited remarkable biological safety and osteogenic activity in vivo and showed potential as a prospective candidate for GBR applications in the future.

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It is a common practice among farmers to utilize high-grain diets with the intention of promoting ruminant growth. However, this approach bears the risk of inducing rumen disorders and nutrient metabolism diseases. Yeast culture (YC) showed advantages in ruminant applications. The objective of this study was to evaluate the effects of adding two different types of YC to high-grain conditions on production performance, rumen fermentation profile, microbial abundance, and immunity in goats. A total of 30 male goats with similar body condition were randomly distributed into 3 dietary treatments with 10 replicates per treatment as follows: basic diet group (CON); basic diet + 0.5% yeast culture 1 (YC1) group; basic diet + 0.5% yeast culture 2 (YC2) group. The trial lasted for 36 days. The results demonstrated that dietary YC supplementation led to an increase in the average daily gain and a reduction in feed intake and weight gain ratio in goats. It increased the apparent digestibility of crude protein, NDF, and ADF (p < 0.05). The serum concentrations of interleukin (IL)-1ß, IL-6, and Tumor Necrosis Factor-α in the control group were significantly higher than those of the YC groups (p < 0.05). The serum concentrations of Immunoglobulin (Ig)A and IgG in the control group were significantly lower than those in the YC groups (p < 0.05). The rumen concentration of microbial protein (MCP) in the control group was significantly lower than that in the YC groups (p < 0.05). There was a negative correlation between the concentration of IL-10 and Bacteroidota, Spirochaetota, and Succinivibrio, while there was a positive correlation between concentrations of IL-10 and Firmicutes. Nevertheless, discrepancies were observed in the impact of the two different types of YC on the physiological and biochemical indicators of the animals. The concentration of triglyceride in the YC1 group was significantly higher than that of the CON and YC2 groups, while the concentration of urea in the YC2 group was significantly higher than that of the CON and YC1 groups (p < 0.05). At the phylum level, the addition of YC2 to the diet significantly increased the relative abundance of Bacteroidota and Fibrobacterota and significantly decreased Firmicutes compared to the control. At the genus level, the addition of YC1 to the HGD significantly reduced the relative abundance of Rikenellaceae_RC9_gut_group, while the addition of YC2 to the HGD significantly increased the relative abundance of Prevotellace-ae_UCG-001, Fibrobacter, and Prevotellaceae_UCG-003 (p < 0.05). The addition of YC significantly improved growth performance, increased nutrient digestibility, beneficially manipulated ruminal fermentation and microbial diversity, and improved immune function. The choice of yeast cultures can be customized according to specific production conditions.

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The objective of this experiment was to delve into the impacts of transportation on goats. Sixteen healthy goats were selected as experimental animals; these goats were transported at a speed ranging from 35 to 45 km/h for 20 h. The changes in the physiological indexes, blood physiological indexes, biochemical indexes, rumen fermentation indexes, and rumen microbial structure composition of goats before and after transportation were measured. The results showed that after transportation, the contents of IgM, IgA, IgG, and Thyroxine decreased very significantly, while the contents of propionic acid, Hemoglobin and Epinephrine significantly increased, and the contents of VFA, acetic acid, butyric acid, isobutyric acid, isovaleric acid, LPS, IL-1ß, IL-6, TNF-α, Major Acute Phase Protein, protein carbonyl, and cortisol increased very significantly. There was no significant difference in α-diversity and ß-diversity, and the relative abundance of rumen microorganisms was not significantly different at either phylum or genus levels. The experimental findings revealed that continuous transportation for a duration of 20 h can induce a severe stress response in goats, leading to compromised immune function, diminished antioxidant capacity, escalated inflammatory response, and altered rumen fermentation indices. However, the experiment did not reveal any significant impact on the structure and composition of the rumen microbiota.

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BACKGROUND: It is possible that this condition will lead to urosepsis and progressive deterioration of renal function in the absence of surgical intervention. Several recent clinical studies have shown that multi-tract percutaneous nephrolithotomy (M-PCNL) has a similar stone free rate (SFR) as standard percutaneous nephrolithotomy (S-PCNL). As a result, M-PCNL was also recommended as a treatment option for staghorn calculi. AIM: To examine the perioperative and long-term results of ultrasonography-guided single- and M-PCNL. METHODS: This was a retrospective cohort study. Between March 2021 and January 2022, the urology department of our hospital selected patients for the treatment of staghorn calculi using percutaneous nephrolithotomy. The primary outcomes were complication rate and SFR, and the characteristics of patients, operative parameters, laboratory measurements were also collected. RESULTS: In total, 345 patients were enrolled in the study (186 in the S-PCNL group and 159 in the M-PCNL group). The SFR in the M-PCNL group was significantly higher than that in the S-PCNL group (P = 0.033). Moreover, the incidence rates of hydrothorax (P = 0.03) and postoperative infection (P = 0.012) were higher in the M-PCNL group than in the S-PCNL group. Logistic regression analysis demonstrated that post-operative white blood cell count (OR = 2.57, 95%CI: 1.90-3.47, P < 0.001) and stone size (OR = 1.59, 95%CI: 1.27-2.00, P < 0.001) were associated with a higher overall complication rate in the S-PCNL group. Body mass index (OR = 1.22, 95%CI: 1.06-1.40, P = 0.004) and stone size (OR = 1.70, 95%CI: 1.35-2.15, P < 0.001) were associated with increased overall complications in the M-PCNL group. CONCLUSION: Multiple access tracts can facilitate higher SFR while slightly increasing the incidence of acceptable complications.

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The problems with the current food distribution system are laid forth in this study. Getting high-quality agricultural and food products to consumers is the goal of what is known as the "agri-food supply chain." Agri-food supply chain knowledge exchange and risk management culture are being studied, as is the effect of supply chain management methods on business success. We are seeing an increase in the regularity of supply chain interruptions. The recent supply chain interruptions and their associated consequences highlight the necessity for robust supply systems. The primary goal of this research is to examine the interplay between critical antecedents of the agri-food supply chain; supply chain resilience (including risk management culture); supply chain connectivity, visibility, collaboration, and agility; and the effect these factors have on supply chain resilience and, ultimately, firm performance. With the same foundational elements and backing from the literature, an empirical model has been suggested. From September 2020 to June 2021, 245 random samples were collected throughout Indonesia for this investigation. The suggested model and the interdependencies among the crucial antecedents have been verified using partial least squares-structural equation modeling (PLS-SEM). Findings from this study support the notion that agri-food supply chains benefit from increased emphasis on traceability, transparency, information sharing, and a culture of risk management. One major takeaway from this study is that by adopting the suggested methodology, businesses may build and strengthen their supply chain resilience capabilities by institutionalizing a risk management culture, raising employee risk awareness, and holding regular risk assessment drills. The study also suggests that businesses that want to strengthen their supply chains can do so by adopting information and communications technologies and visibility tools to improve their supply chain connectivity and visibility, allowing them to respond to and recover from disruptions in the supply chain more quickly. The model is validated using data from Indonesia's industrial sector. In order to establish supply chain resilience, the suggested model provides a comprehensive perspective that defines the interconnections between key antecedents. We conclude with some thoughts and suggestions for further study.

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Eight well-known herbals in Zhejiang Province, Zhebawei, are commonly used as traditional Chinese herbal medicines owing to their rich active ingredients. However, the unavoidable use of pesticides during agricultural production has led to pesticide residue problems in these herbs. In this study, a simple, rapid, and accurate method was established to determine 22 triazole pesticide residues in Zhebawei. An improved QuEChERS method was used for sample pretreatment, and Rhizoma Atractylodis Macrocephalae was used as a representative sample. The sample was extracted with acetonitrile to eliminate some polar and nonpolar compounds, pigments, and other impurities, and the purification effects of multiwalled carbon nanotubes (MWCNTs), amino-modified multiwalled carbon nanotubes (MWCNTs-NH2), carboxylated multiwalled carbon nanotubes (MWCNTs-COOH), crosslinked polyvinylpyrrolidone (PVPP), zirconium dioxide (ZrO2), 3-(N,N-diethylamino)-propyltrimethoxysilane (PSA), octadecyl (C18), and graphitized carbon black (GCB) were compared. MWCNTs-COOH and C18 were selected as the purification adsorbents, and their dosages were systematically optimized. The combination of 10 mg of MWCNTs-COOH and 20 mg of C18 was eventually selected as the purification adsorbents. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for analysis, and box graphs were plotted to present the dispersion of each group of recoveries, thus enabling the identification of the data outliers, dispersion distribution, and data symmetry. The established method was systematically verified and showed good linearity over the concentration range of 1-200 µg/L (except for bromuconazole, epoxiconazole, and etaconazole) with correlation coefficients >0.99. The average recoveries of the 22 pesticides at spiked levels of 10, 20, 100, and 200 µg/kg were in the range of 77.0%-115% with relative standard deviations (RSDs) <9.4%. The limits of detection and quantification were 1-2.5 µg/kg and 10-20 µg/kg, respectively. The applicability of the developed method to other herbals was investigated at 100 µg/kg, and the average recoveries of the target pesticides in different matrices ranged from 76.4% to 123% with RSDs <12.2%. Finally, the method established was used to detect triazole pesticide residues in 30 actual Zhebawei samples. The results showed that triazole pesticides were present in Bulbus Fritillariae Thunbergii and Dendranthema Morifolium. Difenoconazole was detected in Bulbus Fritillariae Thunbergii at contents ranging from 41.4 µg/kg to 110 µg/kg, while difenoconazole, myclobutanil, triadimenol and propiconazole were detected in Dendranthema Morifolium at contents ranging from 16.1 µg/kg to 250 µg/kg. The established method can meet the requirements for the accurate quantitative analysis of triazole fungicides in Zhebawei.

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Although previous studies have identified several autonomous pathway components that are required for the promotion of flowering, little is known about how these components cooperate. Here, we identified an autonomous pathway complex (AuPC) containing both known components (FLD, LD and SDG26) and previously unknown components (EFL2, EFL4 and APRF1). Loss-of-function mutations of all of these components result in increased FLC expression and delayed flowering. The delayed-flowering phenotype is independent of photoperiod and can be overcome by vernalization, confirming that the complex specifically functions in the autonomous pathway. Chromatin immunoprecipitation combined with sequencing indicated that, in the AuPC mutants, the histone modifications (H3Ac, H3K4me3 and H3K36me3) associated with transcriptional activation are increased, and the histone modification (H3K27me3) associated with transcriptional repression is reduced, suggesting that the AuPC suppresses FLC expression at least partially by regulating these histone modifications. Moreover, we found that the AuPC component SDG26 associates with FLC chromatin via a previously uncharacterized DNA-binding domain and regulates FLC expression and flowering time independently of its histone methyltransferase activity. Together, these results provide a framework for understanding the molecular mechanism by which the autonomous pathway regulates flowering time.

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BACKGROUND: Studies have revealed the implications of cancer-associated fibroblasts (CAFs) in tumor progression, metastasis, and treatment resistance. Here, in silico analyses were performed to reveal the key genes and pathways by which CAFs affected chemoresistance in ovarian cancer. METHODS: Candidate genes were obtained from the intersected differentially expressed genes in ovarian cancer, ovarian cancer chemoresistance, and ovarian CAF-related microarrays and chemoresistance-related genes from GeneCards databases. Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis were employed to identify the pathways engaged in ovarian cancer chemoresistance and ovarian CAF-related pathways. The top genes with high Degree in the protein-protein interaction network were intersected with the top genes enriched in the key pathways, followed by correlation analyses between key genes and chemotherapeutic response. The expression profiles of key genes were obtained from Human Protein Atlas database and TCGA-ovarian cancer data. RESULTS: p53, cell cycle, PI3K-Akt, and MAPK pathways were the key pathways related to the implication of CAFs in ovarian cancer chemoresistance. 276 candidate genes differentially expressed in CAFs were associated with ovarian cancer chemoresistance. MYC, IGF1, HRAS, CCND1, AKT1, RAC1, KDR, FGF2, FAS, and EGFR were enriched in the key chemoresistance-related ways. Furthermore, MYC, EGFR, CCND1 exhibited close association with chemotherapeutic response to platinum and showed a high expression in ovarian cancer tissues and platinum-resistant ovarian cancer cells. CONCLUSION: The study suggests the key genes (MYC, EGFR, and CCND1) and pathways (p53, cell cycle, PI3K-Akt, and MAPK) responsible for the effect of CAFs on ovarian cancer chemoresistance.

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MicroRNAs are involved in the pathogenesis of various human malignant tumors. This study aims to explore the role of miR-513b-5p in the malignant proliferation of retinoblastoma (RB) cells and its potential molecular mechanisms. The function-gain and function-loss experiments were performed in Weri-RB1 cells using miR-513b-5 mimics and inhibitors. miR-513b-5p mimics inhibited the proliferation and clone formation and promoted apoptosis of Weri-RB1 cells. In contrast, the miR-513b-5p inhibitor promoted the proliferation and clone formation of Weri-RB1 cells and inhibited cell apoptosis. miR-513b-5p can directly bind to the 3'UTR region of TRIB1 mRNA, and inhibit its protein expression. Overexpression of TRIB1 promoted the proliferation and cloning of Weri-RB1 cells but inhibited their apoptosis. The knockdown of TRIB1 inhibited the proliferation and clone formation of Weri-RB1 cells and promoted cell apoptosis. In addition, miR-513b-5p mimics neutralized the effects of TRIB1 overexpression on the proliferation and apoptosis of Weri-RB1 cells. Finally, miR-513b-5p can inhibit the phosphorylation level of AKT, mTOR, and p70, while TRIB1 played the opposite role. miR-513b-5p inhibits the malignant proliferation of Weri-RB1 cells by repressing the expression of TRIB1. miR-513b-5p and TRIB1 may be the biomarkers and/or key targets for clinical diagnosis and treatment of RB.

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Free sulfhydryls are important properties of protein products including monoclonal antibodies (mAbs). Here, a new technology, variable pathlength extension (SoloVPE), is employed to quantify the amount of free sulfhydryl in monoclonal antibodies (mAbs) using the well-known Ellman reagent. Briefly, the unbound thiols (free sulfhydryls) of proteins including mAbs react with Ellman reagent to produce a 2-nitro-5-thiobenzoate (TNB2-) which is detected at visible wavelength of 412 nm and quantified. The method does not require dilution of antibody samples, is simple, reproducible and takes less than one hour to complete. Values obtained by the new method are compared to literature values from traditional UV or fluorescence methods with agreements. Qualification and trending data over two years of method utilization in our labs support that assay variability is minimal with an intermediate precision of relative standard deviation (RSD) ≤ 10 % and a limit of quantification (LOQ) of 0.1 mol/mol, which is sufficient to measure free sulfhydryl content in proteins including mAbs.

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AIM: The co-expression network of long non-coding RNA ROR (lncRNA-ROR) and microRNA-185-3p (miR-185-3p) has not been focused on osteosarcoma. Therein, this work was initiated to uncover lncRNA-ROR and miR-185-3p functions in osteosarcoma. METHODS: LncRNA-ROR, miR-185-3p and Yes-associated protein 1 (YAP1) expression in osteosarcoma tissues and cells were detected. The screened cells (MG63 and U2OS) were transfected with decreased and/or increased lncRNA-ROR and miR-185-3p to explore osteosarcoma progression. Tumor growth was detected by tumor xenografts in mice. RESULTS: Up-regulated lncRNA-ROR and YAP1 and down-regulated miR-185-3p were found in osteosarcoma. LncRNA ROR knockdown or miR-185-3p overexpression inhibited osteosarcoma cell progression while lncRNA ROR elevation or miR-185-3p inhibition presented the opposite effects. Function of lncRNA ROR was rescued by miR-185-3p and regulated the growth and metastasis of osteosarcoma cells via modulating YAP1, the target gene of miR-185-3p. CONCLUSION: This work illustrates that lncRNA-ROR down-regulation or miR-185-3p up-regulation inhibits osteosarcoma progression via YAP1 repression.

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In the process of repairing of bone defects, bone scaffold materials need to be implanted to restore the corresponding tissue structure at the injury. At present, the repair materials used for bone defects mainly include autogenous bone, allogeneic bone, metal materials, bioceramics, polymer materials and various composite materials. Different materials have demonstrated strong reconstruction ability in bone repair, but the ideal bone implants in the clinic are still yet to be established. Except for autogenous bone, other materials used in bone defect repair are unable to perfectly balance biocompatibility, bone formation, bone conduction and osteoinduction. Combining the latest advances in materials sciences and clinical application, we believe that composite materials supplementedwith Chinese medicine, tissue cells, cytokines, trace elements, etc. and manufactured using advanced technologies such as additive manufacturing technology may have ideal bone repair performance, and may have profound significance in clinical repair of bone defects of special type. This article reviewed to the domestic and foreign literature in recent years, and elaborates the current status of bone defect repair materials in clinical application and basic research in regard to the advantages, clinical options, shortcomings, and how to improve the autogenous bone, allogeneic bone and artificial bone materials, in order to provide a theoretical basis for clinical management of bone defects.

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A simple and efficient magnetic solid-phase extraction (MSPE) method was established with magnetic covalent organic framework (COF) as adsorbent to enrich organophosphorus pesticides from fatty milk samples, followed by the sensitive determination via LC-MS/MS. The key parameters influencing the MSPE efficiency were comprehensively investigated to afford an optimized procedure. All the target analytes could be captured directly by magnetic COF from milk without protein precipitation, making the pretreatment rapid and convenient. Systematic method validation demonstrated its satisfactory linearity, recoveries (80.0-105 %), and precision (RSDs <12.3 %). The method limits of quantification were 0.2-0.5 µg L-1. A comparison experiment to the reported solid-phase extraction fully verified the present MSPE more rapid, accurate, and environment-friendly. Furthermore, FT-IR and XPS analysis were performed to reveal the adsorption mechanisms of magnetic COF to organophosphorus pesticides, which could offer guidance on the rational design of COF adsorbent for various target analytes.

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A high-throughput and environmentally friendly method based on 96-well plate thin-film microextraction was established to determine 14 fungicides in grapes and grape juice using liquid chromatography-tandem mass spectrometry. The thin-film microextraction optimized method consisted of 60 min of extraction at pH 6.0 with the addition of sodium chloride (2-5%). Acetonitrile/water in the ratio of 8:2 was used for desorption analytes for 60 min. Evaluation of different extractive phases showed that polyacrylonitrile-polystyrene-divinylbenzene was the optimum coating. The linearity of the method was good in the range of 0.01-0.5 µg/mL for 14 fungicides with determination coefficients (R2 ) from 0.990 to 0.999, which indicated good linearity for both the grape juice and grape matrixes. The limit of detection was in the range of 0.002-0.01 µg/mL. The limit of quantitation was in the range of 0.01 mg/kg according to the minimum fortified level. The average absolute recoveries of the 14 fungicides ranged from 75.0 to 118.3%. The intraday relative standard deviation (n = 4) and interday relative standard deviation (n = 4) were 5.6-13.0% and 1.6-6.4%, respectively. This study showed that this method can be used for analyzing 96 samples in parallel, and the sample preparation time was approximately 2.0 min per sample. In addition, this approach offers a green and low-cost sample pretreatment technique for future analyses.

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With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

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BACKGROUND: The predominant method for Manske type IIIB and IV thumb hypoplasia is pollicization. However, for those who are not willing to sacrifice the index finger, a method that could reconstruct a functionally capable and aesthetically acceptable thumb remains desirable. This study aimed to investigate and assess the functional and radiographic outcomes of utilizing a reversed vascularized second metatarsal composite flap for thumb reconstruction as a new alternative. METHODS: From May 2014 to January 2017, 15 patients with Manske type IIIB or IV thumb hypoplasia who were admitted to the Department of Hand Surgery, Beijing Jishuitan Hospital were included in this study. An osteocutaneous flap containing a section of second metatarsal and its distal head was transferred in reversed position to reconstruct carpometacarpal joint. The donor site was reconstructed by a split half of the third metatarsal. Various functional reconstructions were commenced at second stage. The reconstructed thumbs were evaluated using the Kapandji score, pinch force, and the capacities of performing daily activities through a detailed questionnaire. RESULTS: Among these 15 patients (seven type IIIB and eight type IV), there were ten boys and five girls with median age of 4.2 years (range: 2.0-7.0 years). There were seven right, three left, and five bilateral thumbs for whom only the right thumb received surgery. There were 14 metatarsal flaps survived (14/15). With an average follow-up of 19.2 months, the reconstructed thumbs had acceptable functional and aesthetic outcomes and the donor foot presented in decent appearance without signs of impaired function. All 15 children have improved the Kapandji score (from 0 to an average of 6.7), pinch force (from 0 to an average of 1.5 kg), with ability of grip and pen holding. X-ray indicated continuous bone growth. Patients and parents had good acceptance of the new thumb. CONCLUSIONS: Reconstruction of an unstable hypoplastic thumb (Manske type IIIB and IV) with use of a vascularized metatarsal is an effective strategy. It offers an alternative solution for parents insisting on saving the thumb.

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BACKGROUND@#The predominant method for Manske type IIIB and IV thumb hypoplasia is pollicization. However, for those who are not willing to sacrifice the index finger, a method that could reconstruct a functionally capable and aesthetically acceptable thumb remains desirable. This study aimed to investigate and assess the functional and radiographic outcomes of utilizing a reversed vascularized second metatarsal composite flap for thumb reconstruction as a new alternative.@*METHODS@#From May 2014 to January 2017, 15 patients with Manske type IIIB or IV thumb hypoplasia who were admitted to the Department of Hand Surgery, Beijing Jishuitan Hospital were included in this study. An osteocutaneous flap containing a section of second metatarsal and its distal head was transferred in reversed position to reconstruct carpometacarpal joint. The donor site was reconstructed by a split half of the third metatarsal. Various functional reconstructions were commenced at second stage. The reconstructed thumbs were evaluated using the Kapandji score, pinch force, and the capacities of performing daily activities through a detailed questionnaire.@*RESULTS@#Among these 15 patients (seven type IIIB and eight type IV), there were ten boys and five girls with median age of 4.2 years (range: 2.0-7.0 years). There were seven right, three left, and five bilateral thumbs for whom only the right thumb received surgery. There were 14 metatarsal flaps survived (14/15). With an average follow-up of 19.2 months, the reconstructed thumbs had acceptable functional and aesthetic outcomes and the donor foot presented in decent appearance without signs of impaired function. All 15 children have improved the Kapandji score (from 0 to an average of 6.7), pinch force (from 0 to an average of 1.5 kg), with ability of grip and pen holding. X-ray indicated continuous bone growth. Patients and parents had good acceptance of the new thumb.@*CONCLUSIONS@#Reconstruction of an unstable hypoplastic thumb (Manske type IIIB and IV) with use of a vascularized metatarsal is an effective strategy. It offers an alternative solution for parents insisting on saving the thumb.