Fully integrated wearable microneedle biosensing platform for wide-range and real-time continuous glucose monitoring.

Wearable microneedle sensors for continuous glucose monitoring (CGM) have great potential for clinical impact by allowing access to large data sets to provide individualized treatment plans. To date, their development has been challenged by the accurate wide linear range tracking of interstitial fluid (ISF) glucose (Glu) levels. Here, we present a CGM platform consisting of a three-electrode microneedle electrochemical biosensor and a fully integrated radio-chemical analysis system. The long-term performance of the robust CGM on diabetic rats was achieved by electrodepositing Prussian blue (PB), and crosslinking glucose oxidase (GOx) and chitosan to form a 3D network using glutaraldehyde (GA). After redox by GOx, PB rapidly decomposes hydrogen peroxide and mediates charge transfer, while the 3D network and graphite powder provide enrichment and release sites for Glu and catalytic products, enabling a sensing range of 0.25-35 mM. Microneedle CGM has high sensitivity, good stability, and anti-interference ability. In diabetic rats, CGM can accurately monitor Glu levels in the ISF in real-time, which are highly consistent with levels measured by commercial Glu meters. These results indicate the feasibility and application prospects of the PB-based CGM for the clinical management of diabetes. STATEMENT OF SIGNIFICANCE: This study addresses the challenge of continuous glucose monitoring system design where the narrow linear range of sensing due to the miniaturization of sensors fails to meet the monitoring needs of clinical diabetic patients. This was achieved by utilizing a three-dimensional network of glutaraldehyde cross-linked glucose oxidase and chitosan. The unique topology of the 3D network provides a large number of sites for glucose enrichment and anchors the enzyme to the sensing medium and the conductive substrate through covalent bonding, successfully blocking the escape of the enzyme and the sensing medium and shortening the electron transfer and transmission path.

Investigation of the regulatory mechanism of lijie capsules on gut microbiota in rheumatoid arthritis.

Lijie Capsules (LJJN) are a classical Chinese herbal formula adopted to treat rheumatoid arthritis (RA) clinically, yet the regulatory mechanism underlying the protection of LJJN against RA has not been fully elucidated. Here, the animal model of RA was established by complete Freund's adjuvant administration in mice. About 60 mg/ml of LJJN was used for treatment. The histological change of ankle joint was measured by hematoxylin and eosin staining. The inflammatory cytokines were detected using ELISA kits. The protein associated with inflammation and GLUD2 was detected using Western blot. The mice feces were analyzed by 16S rRNA sequencing. The levels of glutamate (Glu) and α-ketoglutarate (α-KG) were detected using their detection kits. In addition, fibroblast-like synoviocytes (FLSs) were stimulated by Glu to induce an injured synoviocytes model in vitro, with or without LJJN treatment for 48 h. It was demonstrated that LJJN alleviated ankle joint swelling and synovial injury in RA mice. Meanwhile, LJJN inactivated nuclear factor kappa B signaling and suppressed inflammation of RA mice. The disordered gut microbiota composition in RA mice was partly restored by LJJN. Bacteroides-mediated Glu metabolism was impacted in RA mice, and LJJN contributed to the conversion of Glu to α-KG in RA mice. In addition, the in vitro results revealed that LJJN could block Glu-induced inflammation in FLSs but had no direct influence on α-KG and GLUD2 levels. In summary, LJJN exerted a protective role against ankle joint injury and inflammation in RA, which might be partly associated with gut microbiota-mediated Glu metabolism.

Assessing the environmental sustainability of different soil disinfestation methods used in solar greenhouse vegetable production systems.

Overuse of fertilizers and irrigation and continuous monocropping is increasingly jeopardizing vegetable production in solar greenhouses as it causes serious soil degradation and the spread of soil-borne diseases. As a countermeasure, the practice of anaerobic soil disinfestation (ASD) has been recently introduced, which is carried out during the summer fallow period. However, ASD may increase N leaching and greenhouse gas (GHG) emissions when large amounts of chicken manure are applied. This study assesses how the use of different amounts of chicken manure (CM) combined with rice shells (RS) or maize straw (MS) affects soil O2 availability, N leaching, and GHG emissions during and following the ASD period. Application of RS or MS alone effectively stimulated long-lasting soil anaerobiosis without major stimulating effects on N2O emissions and N leaching. Seasonal N leaching and N2O emissions were in the ranges of 144-306 and 3-44 kg N ha-1, respectively, and were strongly increasing with increasing rates of manure application. Combining high rates of manure application with the additional incorporation of crop residues further increased N2O emissions by 56 %-90 % as compared to the standard practice of farmers (1200 kg N ha-1 CM). About 56 %-91 % of seasonal N2O emissions occurred during the ASD period, whereas N leaching mainly occurred in the cropping period (75 %-100 %). Our study shows, that for priming ASD incorporation of crop residue is sufficient and that the addition of chicken manure for ASD is not needed and should be reduced or even prohibited as it does not improve yields but stimulates the emission of the strong GHG N2O.

The effects and significance of gut microbiota and its metabolites on the regulation of osteoarthritis: Close coordination of gut-bone axis.

Osteoarthritis (OA) is a common chronic degenerative disease of articular cartilage in middle-aged and older individuals, which can result in the joint pain and dysfunction, and even cause the joint deformity or disability. With the enhancing process of global aging, OA has gradually become a major public health problem worldwide. Explaining pathogenesis of OA is critical for the development of new preventive and therapeutic interventions. In recent years, gut microbiota (GM) has been generally regarded as a "multifunctional organ," which is closely relevant with a variety of immune, metabolic and inflammatory functions. Meanwhile, more and more human and animal researches have indicated the existence of gut-bone axis and suggested that GM and its metabolites are closely involved in the pathogenic process of OA, which might become a potential and promising intervention target. Based on the close coordination of gut-bone axis, this review aims to summarize and discuss the mechanisms of GM and its metabolites influencing OA from the aspects of the intestinal mucosal barrier modulation, intestinal metabolites modulation, immune modulation and strategies for the prevention or treatment of OA based on perspectives of GM and its metabolites, thus providing a profound knowledge and recognition of it.

Case report of double superior vena cava and double odd vein with hypoplastic left brachiocephalic vein.

Persistent left superior vena cava (PLSVC) is a common venous variation that is usually accompanied by an absence of the left brachiocephalic vein, and displays a higher incidence in patients with congenital heart disease. Here, the case of a 57-year-old male patient who was found to have PLSVC on chest computed tomography (CT) during screening for gastric cancer metastasis at the Affiliated Hospital of Qinghai University, is described. Further coronal CT and three-dimensional reconstruction of the chest revealed the patient's double superior vena cava (DSVC), double odd veins, and left brachiocephalic vein dysplasia. The patient did not have congenital heart disease and the case was associated with dysplasia of the left brachiocephalic vein, indicating an unusual and rare venous abnormality. At the time of writing, the patient was receiving antitumour therapy.

Heavy metal and nutrient concentrations in top- and sub-soils of greenhouses and arable fields in East China - Effects of cultivation years, management, and shelter.

Although greenhouse vegetable production in China is rapidly changing, consumers are concerned about food quality and safety. Studies have shown that greenhouse soils are highly eutrophicated and potentially contaminated by heavy metals. However, to date, no regional study has assessed whether greenhouse soils differ significantly in their heavy metal and nutrient loads compared to adjacent arable land. Our study was conducted in Shouguang County, a key region of greenhouse vegetable production in China. Soil samples down to soil depths of 3 m were taken from 60 greenhouse vegetable fields of three different ages (5, 10, and 20 years) and from 20 adjacent arable fields to analyze the concentrations of heavy metals, nutrients, and soil physio-chemical parameters. A comparison of greenhouse soils with adjacent arable fields revealed that for greenhouses, (a) micro (heavy metals: Cu, Zn, and Mn) and macronutrients (Nmin, Olsen-P, available K) were significantly higher by a factor of about five, (b) N:P:K ratios were significantly imbalanced towards P and K, and (c) topsoil (0-30 cm) concentrations of the above-mentioned micro- and macronutrients increased with years of vegetable cultivation. In contrast, the soil concentrations of the heavy metals Cr and Pb were lower in greenhouse soils. Heavy metal concentrations did not vary significantly with soil depth, except for the micronutrients Cu and Zn, which were between 1- and 3-fold higher in the topsoil (0-30 cm) than in the subsoil (30-300 cm). The Nemerow pollution index (PN) was 0.37, which was below the recommended environmental threshold value (PN < 1). Structural equation model analysis revealed that soil nutrient concentrations in greenhouse soils are directly related to the input of fertilizers and agrochemicals. Lower values of soil Pb and Cr concentrations in greenhouses were due to the sheltering effect of the greenhouse roof, which protected soils from atmospheric deposition due to emissions from nearby industrial complexes.

Additively manufactured biodegradable porous magnesium implants for elimination of implant-related infections: An in vitro and in vivo study.

Magnesium (Mg) alloys that have both antibacterial and osteogenic properties are suitable candidates for orthopedic implants. However, the fabrication of ideal Mg implants suitable for bone repair remains challenging because it requires implants with interconnected pore structures and personalized geometric shapes. In this study, we fabricated a porous 3D-printed Mg-Nd-Zn-Zr (denoted as JDBM) implant with suitable mechanical properties using selective laser melting technology. The 3D-printed JDBM implant exhibited cytocompatibility in MC3T3-E1 and RAW267.4 cells and excellent osteoinductivity in vitro. Furthermore, the implant demonstrated excellent antibacterial ratios of 90.0% and 92.1% for methicillin-resistant S. aureus (MRSA) and Escherichia coli, respectively. The 3D-printed JDBM implant prevented MRSA-induced implant-related infection in a rabbit model and showed good in vivo biocompatibility based on the results of histological evaluation, blood tests, and Mg2+ deposition detection. In addition, enhanced inflammatory response and TNF-α secretion were observed at the bone-implant interface of the 3D-printed JDBM implants during the early implantation stage. The high Mg2+ environment produced by the degradation of 3D-printed JDBM implants could promote M1 phenotype of macrophages (Tnf, iNOS, Ccl3, Ccl4, Ccl5, Cxcl10, and Cxcl2), and enhance the phagocytic ability of macrophages. The enhanced immunoregulatory effect generated by relatively fast Mg2+ release and implant degradation during the early implantation stage is a potential antibacterial mechanism of Mg-based implant. Our findings indicate that 3D-printed porous JDBM implants, having both antibacterial property and osteoinductivity, hold potential for future orthopedic applications.

Modular revision strategy with bispherical augments in severe acetabular deficiency reconstruction.

PURPOSE: Reconstruction of severe acetabular deficiency is extremely challenging in total hip arthroplasty (THA) revisions. Novel bispherical augments were designed to fill acetabular bone loss and facilitate restoration of hip center of rotation (HCOR). Current study aims to compare the outcomes of bispherical augments and tantalum augments. METHODS: Between July 2017 and December 2018, bispherical augments (BA group) were implanted in 25 patients (25 hips) and 22 patients (22 hips) underwent porous tantalum augments (TA group) reconstruction in revision THA. Clinical and radiographic results were evaluated for 25 hips in BA group and 20 hips in TA group at the final follow-up. The mean duration of follow-up was 2.9 years (range, 2.2 ~ 3.7) in BA group and 2.9 years (range, 2.3 ~ 3.8) in TA group. RESULTS: Harris hip scores, HCOR, and leg length discrepancy (LLD) correction did not differ between the treatment groups. The bispherical augments were located more closer to the medial-superior part (zone II) of acetabular shell while the majority of tantalum augments were located at the lateral-superior part (zone I) (P = 0.010). More screws were used in the BA group for augment fixation (mean 2.1 vs. 1.3) (P = 0.000). There was no evidence of loosening or migration in all hips. Only one dislocation occurred in BA group and treated with closed reduction, no recurrence of instability up to the final follow-up. CONCLUSION: The clinical and radiological outcomes of bispherical augments were comparable with tantalum augments; this technique was a reliable alternative method in severe acetabular deficiency reconstruction.

Association of LINC00673 rs11655237 polymorphism with pediatric glioma susceptibility in a Chinese population.

BACKGROUND: Previous researches have suggested that LINC00673 rs11655237 C>T polymorphism might be correlated to cancer susceptibility. However, its correlation with pediatric glioma is unknown. Therefore, this study aimed to determine whether LINC00673 rs11655237 C>T polymorphism is correlated with pediatric glioma. METHODS: In total, we included 399 subjects from South China. The Student's t-test was performed to evaluate age differences between glioma cases and controls. Differences in the categorical variables between the two groups were assessed using the χ2 test. A logistic regression was conducted to calculate the odds ratio (OR) and the 95% confidence interval (CI). RESULTS: We conducted this case-control study to investigate the association between LINC00673 polymorphism and pediatric glioma susceptibility. Our results revealed that LINC00673 rs11655237 C>T polymorphism was not correlated to pediatric glioma susceptibility in a Chinese population (CC/CT compared with TT: adjusted OR =2.49, 95% CI: 0.87-7.15, P=0.091). Furthermore, a stratified analysis also indicated LINC00673 rs11655237 C>T polymorphism did not increase the risk of glioma in different subgroups. CONCLUSIONS: Our study revealed that LINC00673 rs11655237 C>T polymorphism was not correlated to pediatric glioma susceptibility in a Chinese population. In the future, further exploration of this genetic factor in relation to glioma susceptibility will require a larger sample size to verify the current findings.

The correlation between polymorphisms in the XPC gene and glioma susceptibility in a Chinese pediatric population.

BACKGROUND: A previous study revealed that single nucleotide polymorphisms (SNPs) in coding genes play a key role in tumorigenesis, genetic disorders, and drug resistance. Xeroderma pigmentosum group C (XPC) protein is a key DNA damage recognition factor that is required for maintaining the genomic stability. However, the correlation between XPC polymorphisms and glioma susceptibility is still unclear. Hence, this study aimed to investigate the correlation between XPC polymorphisms and pediatric glioma susceptibility. METHODS: A total of 399 participants (171 glioma patients and 228 controls) were enrolled to evaluate the correlation between XPC polymorphism and pediatric glioma susceptibility. The count data of two groups was analyzed by chi-squared (χ2) test. Moreover, logistic regression was used to assess the strength of XPC polymorphisms associated with glioma susceptibility. RESULTS: We identified that XPC rs1870134 G>C reduced pediatric glioma susceptibility. Compared to participants with rs1870134 GG/GC genotypes, those with rs1870134 CC genotype had a significantly lower risk for glioma [adjusted odds ratio (AOR) =0.10, 95% confidence interval (CI): 0.01 to 0.78, P=0.028]. Patients with 4-5 genotypes have higher risk of glioma than those with 0-3 genotypes (AOR =1.59, 95% CI: 1.04 to 2.43, P=0.031). The stratified analysis showed that the risky effects of rs2228000 CT/TT genotypes and rs2229090 GC/CC genotypes were more predominant among children aged ≥60 months, astrocytic tumors, and clinical stage I. CONCLUSIONS: We found for the first time that XPC polymorphisms had a statistically significant correlation with pediatric glioma susceptibility in a Chinese population. The XPC rs2228000 CT/TT and rs2229090 GC/CC genotypes could both increase the risk of pediatric glioma in subgroups with females, astrocytic tumors, and clinical stage I. The XPC polymorphism has potential to be a useful adjunct method to screen pediatric glioma.

Efficacy and Safety of Apatinib for Elderly Patients with Advanced or Metastatic Gastric Cancer After Failure of at Least First-Line Chemotherapy: A Multi-Center, Single-Arm, Phase II Study.

BACKGROUND: Apatinib improves progression-free survival and overall survival with an acceptable safety profile in Chinese patients with chemotherapy-refractory advanced or metastatic gastric cancer. However, the efficacy and safety of apatinib are unclear for elderly patients. This study was undertaken to prospectively investigate the efficacy and safety of apatinib for elderly patients with unresectable advanced or metastatic gastric cancer, who experienced progression to at least one lines of chemotherapy. METHODS: This open-label, single-arm, phase II study enrolled patients aged ≥60 years with advanced gastric cancer, who experienced progression to one or more lines of chemotherapy at five centers in China. Patients received apatinib in an oral dose of 500mg or 250mg daily according to the research physicians' decision. The primary end point was progression-free survival, and the secondary end points were objective response rate, disease control rate, overall survival, and safety. RESULTS: Forty-eight patients were enrolled between June 2017 and September 2019. The median age was 65.5 years (range 60-80 years). Twenty-seven patients (56.3%) started treatment with an initial dose of 500 mg and 21 patients (43.7%) with 250 mg. The median progression-free survival and overall survival were 3.00 months (95% confidence interval, 2.17-3.84) and 8.10 months (95% confidence interval, 4.35-11.85), respectively. The objective response rate and disease control rate assessed by the investigators were 16.7% and 72.9%, respectively. The common side effects were fatigue (58.3%), hypertension (47.9%), abdominal pain (33.3%), proteinuria (29.2%), leukopenia (22.9%), and neutropenia (20.8%). Hypertension (22.9%) was the major grade 3/4 toxicity. CONCLUSION: These data suggest that apatinib is effective and relatively tolerable for elderly patients with unresectable advanced or metastatic gastric cancer who have received at least first-line chemotherapy.

A Social Media-Promoted Educational Community of Joint Replacement Patients Using the WeChat App: Survey Study.

BACKGROUND: Much effort has been made to optimize the results of total hip arthroplasty and total knee arthroplasty. With the rapid growth of social media use, mobile apps, such as WeChat, have been considered for improving outcomes and patient satisfaction after total hip arthroplasty and total knee arthroplasty. OBJECTIVE: We aimed to evaluate the effectiveness of a WeChat-based community as an intervention for overall patient satisfaction. METHODS: The study was conducted among discharged in-hospital patients who received hip or knee procedures in the First Affiliated Hospital of the University of Science and Technology of China from April 2019 to January 2020. An educational online social community was constructed with the WeChat app. Participants willing to join the community were enrolled in a WeChat group and received 3 months of intervention and follow-up. Those who were not willing to use the account were included in a control group and received routine publicity via telephone, mail, and brochures. The Danish Health and Medicine Authority patient satisfaction questionnaire was used to score perioperative patient education and overall satisfaction. The contents in the group chat were analyzed using natural language processing tools. RESULTS: A total of 3428 patients were enrolled in the study, including 2292 in the WeChat group and 1236 in the control group. Participants in the WeChat group had higher overall satisfaction scores than those in the control group (mean 8.48, SD 1.12 vs mean 6.66, SD 1.80, P<.001). The difference between the two groups was significant for primary surgery based on subgroup stratification. To control confounding factors and explore the effects of WeChat participation as a mediating variable between perioperative patient education and overall satisfaction, hierarchical regression was utilized. An interpatient interaction model was found in the community group chat, and it contributed to overall satisfaction. Patients in the group with more interpatient interactions were more likely to have better overall satisfaction. CONCLUSIONS: The social media-promoted educational community using WeChat was effective among joint replacement patients. Provision of more perioperative education is associated with more active patient participation in the community and therefore more patient satisfaction in terms of the overall joint procedure. Community group chat could facilitate interactions among patients and contribute to overall satisfaction.

Drip fertigation with straw incorporation significantly reduces N2O emission and N leaching while maintaining high vegetable yields in solar greenhouse production.

Approximately 1/3 of vegetables in China are produced in solar greenhouses. Most farmers use conventional irrigation with over fertilisation (CIF), thereby applying approximately 2000 kg N ha-1 fertiliser over two cropping seasons per year. Here, we tested the effect of drip irrigation with reduced fertilisation (DIF) combined with straw incorporation on reducing N2O emissions and nitrogen leaching from solar greenhouse vegetable production systems. Over three consecutive tomato cropping seasons, N2O emissions and nitrogen leaching were monitored in high temporal resolution, thereby producing a unique dataset. Compared to CIF, the realised drip fertigation scheme reduces N2O emission and nitrogen leaching of nitrate and dissolved organic nitrogen by approximately a factor of 5-10 (N2O-DIF: 10.3, CIF: 47.5 kg N ha-1 yr-1; N leaching-DIF: 83.6, CIF: 863 kg N ha-1 yr-1). Straw incorporation in CIF, though advantageous for soil health, resulted in pollution swapping as soil N2O emissions increased while NO3- leaching losses decreased. On the contrary, no significant negative environmental N effects of straw incorporation were found for DIF. As crop productivity was not affected by straw incorporation, neither for CIF nor for DIF, our study provides a sound basis for policy advice to recommend farmers to adopt drip fertigation combined with straw application. Wide scale adoption of this technique will result in reductions of environment N losses, alleviate major soil degradation signs, including soil acidity, nutrient imbalance and deterioration of soil microbial community structure, while allowing to maintaining high yields of vegetables in solar greenhouse production systems.

A novel redox-responsive ursolic acid polymeric prodrug delivery system for osteosarcoma therapy.

Ursolic acid (UA), found widely in nature, exerts effective anti-tumoral activity against various malignant tumors. However, the low water solubility and poor bioavailability of UA have greatly hindered its translation to the clinic. To overcome these drawbacks, a simple redox-sensitive UA polymeric prodrug was synthesized by conjugating UA to polyethylene glycol using a disulfide bond. This formulation can self-assemble into micelles (U-SS-M) in aqueous solutions to produce small size micelles (∼62.5 nm in diameter) with high drug loading efficiency (∼16.7%) that exhibit pH and reduction dual-sensitivity. The cell and animal studies performed using the osteosarcoma MG-63 cell line and MG-63 cancer xenograft mice as the model systems consistently confirmed that the U-SS-M formulation could significantly prolong the circulation in blood and favor accumulation in tumor tissue. Targeted accumulation allows the U-SS-M to be effectively internalized by cancer cells, where the rapid release of UA is favored by a glutathione-rich and acidic intracellular environment, and ultimately achieves potent antitumor efficacy.

Integrative Analysis of Genomics and Transcriptome Data to Identify Regulation Networks in Female Osteoporosis.

Background: Osteoporosis is a highly heritable skeletal muscle disease. However, the genetic mechanisms mediating the pathogenesis of osteoporosis remain unclear. Accordingly, in this study, we aimed to clarify the transcriptional regulation and heritability underlying the onset of osteoporosis. Methods: Transcriptome gene expression data were obtained from the Gene Expression Omnibus database. Microarray data from peripheral blood monocytes of 73 Caucasian women with high and low bone mineral density (BMD) were analyzed. Differentially expressed messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) were identified. Differences in BMD were then attributed to several gene modules using weighted gene co-expression network analysis (WGCNA). LncRNA/mRNA regulatory networks were constructed based on the WGCNA and subjected to functional enrichment analysis. Results: In total, 3,355 mRNAs and 999 lncRNAs were identified as differentially expressed genes between patients with high and low BMD. The WGCNA yielded three gene modules, including 26 lncRNAs and 55 mRNAs as hub genes in the blue module, 36 lncRNAs and 31 mRNAs as hub genes in the turquoise module, and 56 mRNAs and 30 lncRNAs as hub genes in the brown module. JUN and ACSL5 were subsequently identified in the modular gene network. After functional pathway enrichment, 40 lncRNAs and 16 mRNAs were found to be related to differences in BMD. All three modules were enriched in metabolic pathways. Finally, mRNA/lncRNA/pathway networks were constructed using the identified regulatory networks of lncRNAs/mRNAs and pathway enrichment relationships. Conclusion: The mRNAs and lncRNAs identified in this WGCNA could be novel clinical targets in the diagnosis and management of osteoporosis. Our findings may help elucidate the complex interactions between transcripts and non-coding RNAs and provide novel perspectives on the regulatory mechanisms of osteoporosis.

YTHDF1 rs6090311 A>G polymorphism reduces Hepatoblastoma risk: Evidence from a seven-center case-control study.

Various factors modulate the risk of hepatoblastoma. In this study, we aimed to investigate whether single nucleotide polymorphisms (SNPs) in the YTHDF1 gene could predispose to hepatoblastoma. We used TaqMan assay to genotype two YTHDF1 SNPs (rs6011668 C>T and rs6090311 A>G) in a Chinese population composed of 313 subjects with hepatoblastoma and 1446 controls from seven hospitals. We then evaluated the associations of these two SNPs with hepatoblastoma risk using unconditional logistic regression. We found that rs6090311 G allele exhibited a significant association with decreased hepatoblastoma risk [AG vs. AA: adjusted odds ratio (OR)=0.75; 95% confidence interval (CI)=0.58-0.98, P=0.033; AG/GG vs. AA: adjusted OR=0.76, 95% CI=0.59-0.97, P=0.029]. Furthermore, the combined analysis of protective genotypes revealed that subjects carrying two protective genotypes were less likely to have hepatoblastoma than those with 0-1 protective genotypes (adjusted OR=0.75, 95% CI=0.59-0.96, P=0.022). Subjects ≥17 months of age had decreased hepatoblastoma risk, in case that they carried rs6090311 AG/GG (adjusted OR=0.63, 95% CI=0.44-0.91, P=0.012), or two protective genotypes (adjusted OR=0.63, 95% CI=0.44-0.91, P=0.012). False-positive report probability analysis validated the reliability of the significant results. Preliminary functional annotations revealed that rs6090311 G was correlated with decreased expression of its surrounding genes in the expression quantitative trait locus (eQTL) analysis. In conclusion, our results indicate that the rs6090311 A>G in the YTHDF1 gene is related to decreased hepatoblastoma risk.

Enhanced oral bioavailability of magnolol via mixed micelles and nanosuspensions based on Soluplus®-Poloxamer 188.

Magnolol, known to have extensive biological activities, is the major bioactive ingredient isolated from the root and stem bark of Magnolia officinalis. However, the clinical application of magnolol is limited by poor aqueous solubility and absorption. The aim of this study is to develop novel mixed micelles and nanosuspensions composed of two biocompatible copolymers, Soluplus® and Poloxamer 188, and to improve the solubility and oral bioavailability of magnolol. The magnolol-loaded mixed micelles (MMs) and magnolol nanosuspensions (MNs) were prepared to use film hydration and antisolvent methods, respectively. The optimal MMs and MNs formulations were prepared to use magnolol, Soluplus®, and Poloxamer 188 in ratios of 1:12:5 and 2:1:1, respectively. The average particle size of MMs was 111.8 ± 14.6, and MNs was 78.53 ± 5.4 nm. The entrapment and drug loading efficiency for MMs were 89.58 ± 2.54% and 5.46 ± 0.65%, correspondingly. The drug loading efficiency of MNs was 42.50 ± 1.57%. In the in vitro release study, MMs showed a slow drug release while that of MNs was fast. The results of the Caco-2 transcellular transport study indicated that both MMs and MNs increased the permeation of magnolol. MMs and MNs markedly promoted gastrointestinal drug absorption by 2.85 and 2.27-fold, respectively, as shown in the pharmacokinetics study. These results indicated that both MMs and MNs formulations prepared with Soluplus® and Poloxamer 188 are promising drug delivery systems for improving the oral absorption of insoluble drugs in the gastrointestinal tract.

[Effectiveness of proximal femur reconstruction combined with total hip arthroplasty for Crowe type â £ developmental dysplasia of hip].

OBJECTIVE: To investigate the early effectiveness of proximal femur reconstruction combined with total hip arthroplasty (THA) in the treatment of adult Crowe type Ⅳ developmental dysplasia of the hip (DDH). METHODS: Between May 2015 and March 2018, 29 cases (33 hips) suffering from Crowe type Ⅳ DDH were treated with proximal femur reconstruction combined with THA. Of the 29 cases, there were 6 males (7 hips) and 23 females (26 hips), aged from 24 to 74 years with an average age of 44.9 years. The preoperative Harris hip score was 44.0±12.0. Gait abnormalities were found in all of the 33 hips with positive Trendelenburg sign, and the lower limb discrepancy was (3.8±1.6) cm. Preoperative X-ray films and CT both indicated serious anatomical abnormalities, including complete dislocation of the affected hip with significant move-up of the greater trochanter, abnormal development of the femoral neck, abnormal anterversion angle and neck-shaft angle, dysplasia of proximal femur and dysplasia of medullary cavity. The operation time, intraoperative blood loss, transfusion rate, and complications were recorded. The Gruen and DeLee-Charnley zoning methods were used to evaluate the aseptic loosening of the prosthesis on X-ray films. The Harris score was used to evaluate hip function. The lower limb discrepancy was calculated and compared with the preoperative value. RESULTS: The operation time ranged from 80 to 240 minutes, with an average of 124.8 minutes. The intraoperative blood loss ranged from 165 to 1 300 mL, with an average of 568.4 mL. Seventeen patients (51.5%) received blood transfusion treatment. All the incisions healed by first intention without infection or deep vein thrombosis. All patients were followed up 19-53 months, with an average of 33 months. One patient had posterior hip dislocation because of falling from the bed at 4 weeks after operation, and was treated with manual reduction and fixation with abduction brace for 4 weeks, and no dislocation occurred during next 12-month follow-up. Two patients developed sciatic nerve palsy of the affected limbs after operation and were treated with mecobalamin, and recovered completely at 12 weeks later. Trendelenburg sign was positive in 3 patients and mild claudication occurred in 4 patients after operation. X-ray films showed that all the osteotomy sites healed at 3-6 months after operation, and no wire fracture was observed during the follow-up. The Harris score was 89.8±2.8 and lower limb discrepancy was (0.6±0.4) cm at last follow-up, both improved significantly ( t=-22.917, P=0.000; t=11.958, P=0.000). The prosthesis of femur and acetabulum showed no obvious loosening and displacement, and achieved good bone ingrowth except 2 patients who had local osteolysis in the area of Gruen 1 and 7 around the femoral prosthesis, but no sign of loosening and sinking was observed. CONCLUSION: The treatment of Crowe Ⅳ DDH with proximal femur reconstruction and THA was satisfactory in the early postoperative period. The reconstruction technique of proximal femur can effectively restore the anatomical structure of proximal femur, which is one of the effective methods to deal with the deformity of proximal femur.

Investigating an Integrated Sensor Fusion System for Mental Fatigue Assessment for Demanding Maritime Operations.

Human-related issues are currently the most significant factor in maritime causalities, especially in demanding operations that require coordination between two or more vessels and/or other maritime structures. Some of these human-related issues include incorrect, incomplete, or nonexistent following of procedures; lack of situational awareness; and physical or mental fatigue. Among these, mental fatigue is especially dangerous, due to its capacity to reduce reaction time, interfere in the decision-making process, and affect situational awareness. Mental fatigue is also especially hard to identify and quantify. Self-assessment of mental fatigue may not be reliable and few studies have assessed mental fatigue in maritime operations, especially in real time. In this work we propose an integrated sensor fusion system for mental fatigue assessment using physiological sensors and convolutional neural networks. We show, by using a simulated navigation experiment, how data from different sensors can be fused into a robust mental fatigue assessment tool, capable of achieving up to 100 % detection accuracy for single-subject classification. Additionally, the use of different sensors seems to favor the representation of the transition between mental fatigue states.

Cloud scattering influence on satellite laser altimetry data and its correction.

Satellite laser altimetry can obtain submeter or even centimeter-level surface elevation information over a large range. However, the laser will inevitably be affected by clouds during transmission through the atmosphere, which seriously affects the accuracy of altimetry. In this paper, based on laser altimetry data, cloud optical depth inversion was realized by using the Fernald method. The influence of clouds on the echo waveform data was analyzed with actual data, and a method of cloud scattering error correction was proposed. The existing error correction methods are mostly based on the results of semi-analytical Monte Carlo simulations. In observations, it is difficult to synchronously obtain the parameters required for simulation, which significantly limits the method. Therefore, a method for correcting the cloud scattering error of satellite laser altimetry data based on an exponential model is also proposed. The experimental results show that when the cloud optical depth is 0-2, the root mean square error of the model is 0.05, which can correct the height measurement deviation caused by the cloud to within 5 cm and improve the availability of the laser height measurement data affected by the cloud scattering.