L-GrAFT7 has High Accuracy in Predicting Early Allograft Failure after Liver Transplantation: A Multicenter Cohort Study in China.

Background and Aims: Increasing utilization of extended criteria donor leads to an increasing rate of early allograft failure after liver transplantation. However, consensus of definition of early allograft failure is lacking. Methods: A retrospective, multicenter study was performed to validate the Liver Graft Assessment Following Transplantation (L-GrAFT) risk model in a Chinese cohort of 942 adult patients undergoing primary liver transplantation at three Chinese centers. L-GrAFT (L-GrAFT7 and L-GrAFT10) was compared with existing models: the Early Allograft Failure Simplified Estimation (EASE) score, the model of early allograft function (MEAF), and the Early Allograft Dysfunction (EAD) model. Univariate and multivariate logistic regression were used to find risk factors of L-GrAFT high-risk group. Results: L-GrAFT7 had an area under the curve of 0.85 in predicting 90-day graft survival, significantly superior to MEAF [area under the curve (AUC=0.78, p=0.044)] and EAD (AUC=0.78, p=0.006), while there was no statistical significance between the predicting abilities of L-GrAFT7 and EASE (AUC=0.84, p>0.05). Furthermore, L-GrAFT7 maintains good predicting ability in the subgroup of high-donor risk index (DRI) cases (AUC=0.83 vs. MEAF, p=0.007 vs. EAD, p=0.014) and recipients of donors after cardiac death (AUC=0.92 vs. EAD, p<0.001). Through multivariate analysis, pretransplant bilirubin level, units of packed red blood cells, and the DRI score were selected as independent risk factors of a L-GrAFT7 high-risk group. Conclusions: The accuracy of L-GrAFT7 in predicting early allograft failure was validated in a Chinese multicenter cohort, indicating that it has the potential to become an accurate endpoint of clinical practice and transitional study of machine perfusion.

Interaction research of resveratrol and phosvitin based on fluorescence spectroscopy and molecular docking analysis.

Phosvitin (PV) is the main phosphoprotein in egg yolk, with the highest degree of phosphorylation known in nature. The PV and resveratrol (Res) can form a complex, thus effectively improve the solubility of Res. In this work, the interaction between Res and PV was investigated by the fluorescence spectroscopy and molecular docking. The fluorescence emission intensity of PV became weak along with a red shift when it interacted with Res and the antioxidant activity was enhanced. The quenching constants of the interaction systems were 1.12×104  M-1 and 9.40×103  M-1 at 25°C and 35°C, respectively, which indicated the presence of static quenching phenomena between them. The binding constant was 1.80×104  M-1 , and the number of corresponding binding sites was approximately equal to one. The thermodynamic results revealed the combination was spontaneous, and the change of enthalpy and entropy was ∆H = 53.50 kJ/mol, ∆S = 261.00 J/mol·K, respectively. It indicated that the interaction forces between Res and PV were mainly hydrophobic interaction and hydrogen bonding. Molecular docking showed the binding mode, which was consistent with the experiment results. The research on the interaction between Res and PV provided theoretical guidance for the application of Res in food. PRACTICAL APPLICATION: PV is the most highly phosphorylated protein in nature and has pro-calcium absorption effects. Res is a polyphenol with strong antioxidant and anti-inflammatory activity, but its poor solubility limits its application. In this study, the solubility of Res was considerably enhanced by compounding Res and PV, and the antioxidant activity of Res was well retained. It increases the value of Res in food and other applications and opens up new possibilities for processing and utilization of PV.

Acupuncture Analgesia in Patients with Postoperative Neck Pain: A Protocol for Systematic Review and Meta-Analysis.

Background. There is a yearly increase in pain after neck surgery, which is accompanied by high consumption of opioids. However, the opioid addiction epidemic is one of the most serious public health problems worldwide. Therefore, it is important to find suitable alternatives for opioids. Acupuncture therapy has been found effective for some types of pain control. This protocol aims to evaluate the efficacy and safety of acupuncture therapy in the treatment of pain after neck surgery. Methods and Analysis. We will search eight electronic databases from their inception to April 2022. Only randomized controlled trials (RCTs) using manual acupuncture, auricular acupuncture, or electroacupuncture as major therapy will be included, regardless of whether the study was published in Chinese or English. The selection of studies and data extraction will be independently completed by at least two experienced reviewers with a master's degree. The methodological quality of the included studies will be assessed by the Cochrane risk-of-bias tool. For the meta-analysis, Review Manager Statistical (RevMan V.5.3) software will be used. The results will be presented as the risk ratio (RR) for the binary data and the mean difference (MD) or standardized mean difference (SMD) for the continuous data. Ethics and Dissemination. This protocol for a systematic review will be submitted to a peer-reviewed journal for publication and presented at a relevant conference, and there is no need to obtain formal ethical approval. Trial Registration Number. PROSPERO registration number CRD42021281722.

Study on Microwave Absorption Performance Enhancement of Metamaterial/Honeycomb Sandwich Composites in the Low Frequency Band.

With the rapid development of electronic technology and modern radar detection system, there is increasingly urgent demand for microwave absorbing composites working efficiently in the low frequency range (e.g., 1−2 GHz). In this work, a type of metamaterial/honeycomb sandwich composite (MHSC) was proposed and fabricated, which exhibited a light weight structure and excellent wave-absorbing performance in the low frequency band. The relationship between the wave-absorbing properties and the design parameters of the composite, such as the thickness of the wave-transmitting skin, the thickness and dielectric properties of the wave-absorbing honeycomb, was systematically investigated. The electromagnetic coupling interference between the honeycomb absorber and metamaterial resonator proved to be a crucial factor that affects synergistic wave-absorbing performance in the low-frequency band. Under the rational design, the incorporation of subwavelength-sized phase-gradient metamaterial units in the composite can significantly improve low-frequency wave-absorbing performance for greater than 5 dB (an increment larger than 100%); and the obtained MHSC exhibits averaged reflectivity (Ra) less than −10 dB in the low frequency band of 1−2 GHz as well as outstanding performance (Ra < −14.6 dB) over an extremely wide frequency range (1−18 GHz). The MHSC reported in this study could be a promising candidate for the key material in high-performance radar stealth and other related applications.

Single-cell analysis reveals cell communication triggered by macrophages associated with the reduction and exhaustion of CD8+ T cells in COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has become an ongoing pandemic. Understanding the respiratory immune microenvironment which is composed of multiple cell types, together with cell communication based on ligand-receptor interactions is important for developing vaccines, probing COVID-19 pathogenesis, and improving pandemic control measures. METHODS: A total of 102 consecutive hospitalized patients with confirmed COVID-19 were enrolled in this study. Clinical information, routine laboratory tests, and flow cytometry analysis data with different conditions were collected and assessed for predictive value in COVID-19 patients. Next, we analyzed public single-cell RNA-sequencing (scRNA-seq) data from bronchoalveolar lavage fluid, which offers the closest available view of immune cell heterogeneity as encountered in patients with varying severity of COVID-19. A weighting algorithm was used to calculate ligand-receptor interactions, revealing the communication potentially associated with outcomes across cell types. Finally, serum cytokines including IL6, IL1ß, IL10, CXCL10, TNFα, GALECTIN-1, and IGF1 derived from patients were measured. RESULTS: Of the 102 COVID-19 patients, 42 cases (41.2%) were categorized as severe. Multivariate logistic regression analysis demonstrated that AST, D-dimer, BUN, and WBC were considered as independent risk factors for the severity of COVID-19. T cell numbers including total T cells, CD4+ and CD8+ T cells in the severe disease group were significantly lower than those in the moderate disease group. The risk model containing the above mentioned inflammatory damage parameters, and the counts of T cells, with AUROCs ranged from 0.78 to 0.87. To investigate the molecular mechanism at the cellular level, we analyzed the published scRNA-seq data and found that macrophages displayed specific functional diversity after SARS-Cov-2 infection, and the metabolic pathway activities in the identified macrophage subtypes were influenced by hypoxia status. Importantly, we described ligand-receptor interactions that are related to COVID-19 serverity involving macrophages and T cell subsets by communication analysis. CONCLUSIONS: Our study showed that macrophages driving ligand-receptor crosstalk contributed to the reduction and exhaustion of CD8+ T cells. The identified crucial cytokine panel, including IL6, IL1ß, IL10, CXCL10, IGF1, and GALECTIN-1, may offer the selective targets to improve the efficacy of COVID-19 therapy. TRIAL REGISTRATION: This is a retrospective observational study without a trial registration number. Video Abstract.

Long Non-Coding RNA NEAT1 Promotes the Proliferation, Migration, and Metastasis of Human Breast-Cancer Cells by Inhibiting miR-146b-5p Expression.

BACKGROUND: Breast cancer (BC) is the most commonly diagnosed cancer in women. Tumor recurrence and metastasis are the key causes of death in BC patients. Long non-coding RNA (lncRNA) is closely associated with BC progression. lncRNA nuclear-enriched abundant transcript (NEAT)1 has been reported to regulate the proliferation and mobility of several types of cancer cells. However, how lncRNA NEAT1 affects the proliferation and invasion of BC cells is not known. METHODS: Quantitative real time-polymerase chain reaction (qRT-PCR) was used to measure expression of lncRNA NEAT1 and microRNA (miR)-146b-5p in BC tissues and cell lines. Cell Counting Kit (CCK)-8, cell colony-formation, wound-healing, and Transwell™ assays were undertaken to determine the effects of lncRNA NEAT1 and miR-146b-5p on progression of BC cells. The interaction between lncRNA NEAT1 and miR-146b-5p was examined by luciferase reporter, RNA-binding protein immunoprecipitation (RIP), and RNA-pulldown assays. RESULTS: Expression of lncRNA NEAT1 was upregulated in BC tissues and cell lines. High expression of lncRNA NEAT1 predicted poor overall survival in BC patients. Silencing of expression of lncRNA NEAT1 inhibited epithelial-mesenchymal transition (EMT) and suppressed the proliferation, migration and invasion of BC cells. Ectopic expression of lncRNA NEAT1 induced EMT and promoted BC progression. Mechanistic investigations revealed that miR-146b-5p was a direct target of lncRNA NEAT1, and its expression was correlated negatively with expression of lncRNA NEAT1 in BC tissues. CONCLUSION: lncRNA NEAT1 could (i) serve as a novel prognostic marker for BC and (ii) be a potential therapeutic target for BC.

[Changes of the spectrum on thyroid disease after the ten-year implementation of universal salt iodization in Guangxi Zhuang Autonomous Region].

OBJECTIVE: To reveal the relationship between iodine nutrition and the change of spectrum on thyroid diseases through comparing the different iodine environments pre- and post- the universal salt iodization(USI)campaign. METHODS: To compare the urinary iodine concentration between 1000 normal people and 5998 patients with thyroid disease who had undergone surgical operations, from 4 major cities, including iodine deficient and rich areas of Guangxi Zhuang Autonomous Region. RESULTS: After USI was put into practice, the urinary iodine concentration of patients with thyroid appeared higher than those of normal people(324.3 µg/L vs. 238.5 µg/L, P < 0.05). The urinary iodine concentrations of nodular goiter,Graves disease, toxic nodular goiter, thyroid papillary carcinoma and Hashimoto's thyroiditis were higher than those before the USI was taken(263.8 µg/L vs. 69.75 µg/L, 289.7 µg/L vs. 228.3 µg/L, 346.8 µg/L vs. 268.4 µg/L, 350.3 µg/L vs. 316.2 µg/L and 378.5 µg/L vs. 305.8 µg/L). The proportions of toxic nodular goiter, thyroid papillary carcinoma and Hashimoto's thyroiditis appeared as 7.59% vs. 4.80%, 5.85% vs. 4.02% and 3.88% vs. 2.46%, all higher than those before the implementation of USI, except the nodular goiter which showed a reduction (63.56% vs. 69.75%). CONCLUSION: The spectrum of thyroid diseases appeared an obvious change in Guangxi within the last 10-year implementation of USI. However, the excessive intake of iodine might serve as a risk factor for toxic nodular goiter, thyroid papillary carcinoma and Hashimoto's thyroiditis.

Development and in-vivo assessment of the bioavailability of oridonin solid dispersions by the gas anti-solvent technique.

We developed solid dispersions, using the gas anti-solvent technique (GAS), to improve the oral bioavailability of the poorly water-soluble active component oridonin. The solubility of oridonin in supercritical carbon dioxide was measured under various pressures and temperatures. To prepare oridonin solid dispersions using the GAS technique, ethanol was used as the solvent, CO(2) was used as the anti-solvent and the hydrophilic polymer polyvinylpyrrolidone K17 (PVP K17) was used as the drug carrier matrix. Characterization of the obtained preparations was undertaken using scanning electron microscopy (SEM), X-ray diffraction (XRD) analyses and a drug release study. Oridonin solid dispersions were formed and oridonin was present in an amorphous form in these dispersions. Oridonin solid dispersions significantly increased the drug dissolution rate compared with that of oridonin powder, primarily through drug amorphization. Compared with the physical mixture of oridonin and PVP K17, oridonin solid dispersions gave higher values of AUC and C(max), and the absorption of oridonin from solid dispersions resulted in 26.4-fold improvement in bioavailability. The present study illustrated the feasibility of applying the GAS technique to prepare oridonin solid dispersions, and of using them for the delivery of oridonin via the oral route.

[Determination of vitexin-rhamnoside in Beagle dog plasma and preliminary pharmacokinetics of Yixintong sustained release tablets].

OBJECTIVE: To develop an HPLC method to determine vitexin-rhamnoside in plasma of Beagle dogs and study the pharmacokinetics and bioavailability of Yixintong sustained release tablets in Beagle dogs. METHOD: A newly-developed HPLC method using C18 column and methanol-acetonitrile-tetrahydrogenfuran-0.5% acetic acid (1:1:19.4:78.6) as mobile phase was validated, and then was employed to determine vitexin-rhamnoside in plasma of Beagle dogs after oral administration of Yixintong sustained release tablets and general tablets. The main pharmacokinetic parameters were estimated by pharmacokinetic program 3p87. The non-compartmental pharmacokinetic parameters were also calculated on basis of the statistic moment theory. RESULT: The pharmacokinetic profiles of Yixintong sustained release tablets and the general tablets were fitted to a one-and two-compartment open model, respectively. The T1/2, Tmax, AUC0-infinity and MRT for Yixintong sustained release tablets were 5.22 h, 4.0 h, 6,792.75 ng x h x mL(-1) and 8.4 h, respectively, compared with 8.94 h, 1.0 h, 5,880.4 ng x h x mL(-1) and 6.1 h for the general tablets. The relative bioavailability of the Yixintong sustained release tablets was 115.5% in Beagle dogs. CONCLUSION: The sustained-release characteristic of Yixintong sustained release tablets were confirmed by pharmacokinetic study.

Release-controlling absorption enhancement of enterally administered Ophiopogon japonicus polysaccharide by sodium caprate in rats.

The aim of this study was to improve the intestinal absorption of Ophiopogon japonicus polysaccharide (OJP) by incorporating it together with sodium caprate (SC) into erodible matrices, designed to release OJP and SC at various rates over different periods of time. OJP, a graminan type fructosan with an average molecular weight in number of 3400 Da has been demonstrated to have anti-myocardial ischemic activity. The determination of OJP blood levels was carried out by the fluorescein isothiocyanate (FITC) prelabeling method. Matrix tablets, possessing different erosion rates, were prepared by changing the amounts of sodium alginate and using the two-layer tableting technique. Formulation effectiveness was evaluated by monitoring OJP plasma levels after intra-intestinal administration of each of the tablets to anesthetized rats. The findings indicate that all the SC containing formulations can significantly improve FITC-OJP bioavailability. Compared with the formulations not containing SC, the increase varied from 5.6- to 20.8-fold for the worst and best SC containing formulations studied, respectively. Moreover, there were no statistically significant differences between the C(max) and AUC(0-4) values obtained for three optimized formulations, which synchronously or nonsynchronously released both FITC-OJP and SC within 1-2 h. Their absorption enhancement effects were 2.1- to 3.6-fold higher than those of faster and slower release formulations studied. Fast delivery of the drug and its absorption adjuvant(s) contributes to their high concentrations at the absorption sites. However, at the same time, it leads to their short residence times and fast dilution by intestinal fluids. The better the balance between the two opposite effects for drug absorption, the more effective absorption enhancement would be obtained.