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This article, titled "A comparative study of prenatal ultrasound diagnosis and postnatal pathology of fetal pulmonary dysplasia," explores the clinical value of prenatal ultrasound in diagnosing abnormal fetal lung development. The study conducted a retrospective analysis on 78 cases of fetal lung dysplasia and compared the prenatal ultrasound diagnosis results with postoperative pathological findings. The results showed that prenatal ultrasound had a high accuracy rate of 94.8% in diagnosing abnormalities of fetal lung development. However, there were difficulties in diagnosing certain malformations and compound malformations. [Extracted from the article]

Protein disulphide isomerase (PDI) plays an important role in a variety of physiological processes through its oxidoreductase activity and molecular chaperone activity. In this study, we cloned two PDI family members, AccPDIA1 and AccPDIA3, from Apis cerana cerana. AccPDIA1 and AccPDIA3 had typical sequence features of PDI family members and were constitutively expressed in A. cerana cerana. The expression levels of AccPDIA1 and AccPDIA3 were generally upregulated after treatment with a variety of environmental stress factors. Inhibition assays showed that E. coli expressing recombinant AccPDIA1 and AccPDIA3 proteins was more resistant to oxidative stress than control E. coli. In addition, silencing AccPDIA1 or AccPDIA3 in A. cerana cerana resulted in significant changes in the expression levels of several antioxidant‐related genes as well as the enzymatic activities of peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT) and reduced the survival rate of A. cerana cerana under oxidative stress caused by high temperature. In conclusion, our results suggest that AccPDIA1 and AccPDIA3 may play important roles in the antioxidant activities of A. cerana cerana. [ABSTRACT FROM AUTHOR]

Background and purpose: Post‐stroke fatigue (PSF) is a common neuropsychiatric affective symptom occurring after stroke. Evidence indicates activated inflammatory pathways are involved in modulating the stroke and fatigue. High‐sensitivity C‐reactive protein (hs‐CRP) is one of the most sensitive indicators of inflammation. Our aim was to estimate the association between plasma hs‐CRP and PSF after acute ischaemic stroke. Methods: In all, 212 acute ischaemic stroke patients were consecutively recruited within the first 14 days after stroke onset and followed up for 6 months. Plasma hs‐CRP levels were assayed by enzyme linked immunosorbent assay. Fatigue severity was assessed using the Fatigue Scale for Motor and Cognitive Functions. A score ≥ 43 is defined as PSF. Results: Sixty‐eight stroke patients (32.1%) were diagnosed with PSF at 6 months' follow‐up. In the patients with PSF, plasma hs‐CRP levels were significantly higher compared with those in non‐PSF patients (t = −8.524, P ≤ 0.001). In multivariate analyses, plasma levels of hs‐CRP were independently associated with PSF at 6 months (odds ratio 3.435, 95% confidence interval 2.222–5.309; P ≤ 0.001) after adjusting other recorded variables. Based on the receiver operating characteristic curve, the optimal cut‐off value of plasma hs‐CRP levels as an indicator for the prediction of PSF was projected to be 0.52 mg/dl, which yielded a sensitivity of 77.9% and a specificity of 74.3%, with the area under the curve 0.794 (95% confidence interval 0.725–0.864; P ≤ 0.001). Conclusion: Elevated plasma hs‐CRP levels at admission were associated with PSF 6 months after stroke, suggesting that these alterations might predict the development of PSF in stroke patients. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to determine the maximum tolerated dose (MTD, the dose of causing 10% respiratory depression) of intranasal sufentanil (SUF) and midazolam (MID) for sedation during gastroscopy by continual reassessment method (CRM).Methods: Patients (18-65 years old) scheduled for gastroscopy were recruited in this study. Subjects received intranasal SUF and MID for sedation. The dose of MID (5 mg) was fixed, while the dose of SUF was increased progressively (six incremental doses ranging from 0-0.60 μg/kg, n = 3 for each dose). The first cohort received a conservative, predetermined dose of 5 mg MID and 0 μg/kg SUF, subsequent cohorts received doses of SUF that were determined by the responses of all previous patients using Bayesian-based software. The dose allocated to the next cohort is the one with an updated posterior response probability closest to 10%.Results: Thirty Chinese patients scheduled for gastroscopy were included. Probability of respiratory depression at each dose was as follows: 5 mg MID + 0 μg/kg SUF, 0.4%; 5 mg MID + 0.1 μg/kg SUF, 0.8%; 5 mg MID + 0.2 μg/kg SUF, 1.8%; 5 mg MID + 0.3 μg/kg SUF, 3.7%; 5 mg MID + 0.4 μg/kg SUF, 9.9%; 5 mg MID + 0.5 μg/kg SUF, 17.8%; 5 mg MID + 0.6 μg/kg SUF, 36.0%.Conclusion: The MTD of intranasal MID and SUF for sedation during gastroscopy causing 10% respiratory depression is 5 mg MID + 0.4 μg/kg SUF, based on CRM. [ABSTRACT FROM AUTHOR]

Aim To evaluate in vitro the physicochemical properties, cytotoxicity and calcium phosphate nucleation of an experimental light-curable pulp capping material composed of a resin with antibacterial monomer ( MAE- DB) and Portland cement ( PC). Methodology The experimental material was prepared by mixing PC with a resin containing MAE- DB at a 2 : 1 ratio. Cured pure resin containing MAE- DB served as control resin. ProRoot MTA and Dycal served as commercial controls. The depth of cure, degree of monomer conversion, water absorption and solubility of dry samples, calcium release, alkalinizing activity, calcium phosphate nucleation and the cytotoxicity of materials were evaluated. Statistical analysis was carried out using anova followed by Tukey's HSD test (equal variance assumed) or Tamhane test (equal variance not assumed) and independent-samples t-tests. Results The experimental material had a cure depth of 1.19 mm, and the mean degree of monomer conversion was 70.93% immediately post-cure and 88.75% at 24 h post-cure. The water absorption of the experimental material was between those of MTA and Dycal, and its solubility was significantly less ( P < 0.05) than that of Dycal and higher than that of MTA. The experimental material exhibited continuous calcium release and an alkalinizing power between those of MTA and Dycal throughout the test period. Freshly set experimental material, control resin and all 24-h set materials had acceptable cytotoxicity. The experimental material, MTA and Dycal all exhibited the formation of apatite precipitates after immersion in phosphate-buffered saline. Conclusions The experimental material possessed adequate physicochemical properties, low cytotoxicity and good calcium phosphate nucleation. [ABSTRACT FROM AUTHOR]

This experiment investigated the effects of supplementing the maternal diet with linseed oil ( LSO) and soya bean oil ( SBO) on immunoglobulins, the fatty acid composition and hepatic expression of lipid metabolism-related genes in piglets. Multiparous sows (twenty-four per diet) were fed on diets containing a supplement of either SBO or LSO during last week of gestation and lactation. The results indicated that supplementation of maternal diet with LSO could improve the weaning weight of piglets and average daily gain ( ADG) (p < 0.05). The concentration of immunoglobulin G (IgG) and immunoglobulin A (IgA) was enhanced in sow plasma, colostrum and milk by the addition of LSO (p < 0.05). In addition, the concentration of 18: 3n-3 fatty acids was higher in the milk of LSO sows. Meanwhile, maternal supplementation with LSO increased the levels of plasma IgG, IgA and the tissues n-3 polyunsaturated fatty acid ( PUFA) in piglets (p < 0.05). Correspondingly, the mRNA expression levels of hepatic ∆5-desaturase (D5D) and ∆6-desaturase (D6D) were higher, and fatty acid synthase ( FAS) was lower in piglets from LSO-fed sows when compared with that in the SBO group. In conclusion, LSO supplementation of the maternal diet increases immunoglobulins, modifies the fatty acid composition and affects the gene of D5D and D6D expression of piglets. [ABSTRACT FROM AUTHOR]

Difficulty during placement of the tracheal tube is a known problem when intubating with the GlideScope® , which may lead to subglottic airway injury. This randomised, controlled clinical trial was designed to compare the resistance to passage of PVC (polyvinyl chloride), reinforced or BlockBuster tracheal tubes during intubation with the GlideScope. Secondary outcomes included the time taken to intubate and assessment of subglottic airway injury. One-hundred and seventy-seven patients were included in the data analysis. There was difficult tracheal tube passage (moderate or severe resistance) in 15 (21.4%) patients using the PVC tube compared with 4 (7.4%) and 1 (1.9%) using the reinforced and BlockBuster tubes, respectively (p = 0.003 for PVC vs. BlockBuster). The median (IQR [range]) time taken to intubate was 35 (27-45 [15-115]) s, 25 (20-27 [15-110]) s and 25 (22-30 [16-90]) s, respectively, (p < 0.001 for PVC vs. reinforced as well as PVC vs. BlockBuster). Subglottic airway injury, assessed using a fibreoptic bronchoscope after extubation, was higher with the PVC tube (p < 0.001) and the reinforced tube (p = 0.012) compared with the BlockBuster tube. We conclude that the BlockBuster tracheal tube is a better choice for orotracheal intubation with the GlideScope than PVC or reinforced tubes. [ABSTRACT FROM AUTHOR]

Autophagy is a highly conserved lysosomal degradation process which can recycle unnecessary or dysfunctional cell organelles and proteins, thereby playing a crucial regulatory role in cell survival and maintenance. It has been widely accepted that autophagy regulates various pathological processes, among which cancer attracts much attention. Autophagy may either promote cancer cell survival by providing energy during unfavourable metabolic circumstance or can induce individual cancer cell death by preventing necrosis and increasing genetic instability. Thus, dual roles of autophagy may determine the destiny of cancer cells and make it an attractive target for small-molecule drug discovery. Collectively, key autophagy-related elements as potential targets, oncogenes mTORC1, class I PI3K and AKT, as well as tumour suppressor class III PI3K, Beclin-1 and p53, have been discussed. In addition, some small molecule drugs, such as rapamycin and its derivatives, rottlerin, PP242 and AZD8055 (targeting PI3K/AKT/ mTORC1), spautin-1, and tamoxifen, as well as oridonin and metformin (targeting p53), can modulate autophagic pathways in different types of cancer. All these data will shed new light on targeting the autophagic process for cancer therapy, using small-molecule compounds, to fight cancer in the near future. [ABSTRACT FROM AUTHOR]

Ubiquitously distributed in different plant species, plant lectins are highly diverse carbohydrate-binding proteins of non-immune origin. They have interesting pharmacological activities and currently are of great interest to thousands of people working on biomedical research in cancer-related problems. It has been widely accepted that plant lectins affect both apoptosis and autophagy by modulating representative signalling pathways involved in Bcl-2 family, caspase family, p53, PI3K/Akt, ERK, BNIP3, Ras-Raf and ATG families, in cancer. Plant lectins may have a role as potential new anti-tumour agents in cancer drug discovery. Thus, here we summarize these findings on pathway- involved plant lectins, to provide a comprehensive perspective for further elucidating their potential role as novel anti-cancer drugs, with respect to both apoptosis and autophagy in cancer pathogenesis, and future therapy. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to explore mechanisms by which fructus Schisandrae chinensis (Wuweizi) is able to reveal its protective capacity against hepatocyte injury. Materials and methods Identification of candidate small molecular compounds was performed by text-mining, extraction and isolation, reverse-docking, network construction, molecular docking and molecular dynamics ( MD) simulation. In vitro cytological examination and western blotting were used to validate efficacy of selected compounds. Results We analyzed chemical composition of fructus Schisandrae chinensis and constructed protein-protein networks of key targets. Networks of mi RNA-protein were constructed. Molecular docking and MD simulation results supported good interaction between selected compound 11/12 and GBA3/ SHBG. Further in vitro examination divulged molecular mechanisms involved. Conclusions In silico analysis and experimental validation together demonstrated that compound 11/12 of fructus Schisandrae chinensis targetted GBA3/ SHBG in hepatocytes. Hopefully this will shed light on exploration of its complex molecular mechanisms. [ABSTRACT FROM AUTHOR]

Natural products are chemical compounds or substances produced naturally by living organisms. With the development of modern technology, more and more plant extracts have been found to be useful to medical practice. Both micromolecules and macromolecules have been reported to have the ability to inhibit tumour progression, a novel weapon to fight cancer by targeting its 10 characteristic hallmarks. In this review, we focus on summarizing plant natural compounds and their derivatives with anti-tumour properties, into categories, according to their potential therapeutic strategies against different types of human cancer. Taken together, we present a well-grounded review of these properties, hoping to shed new light on discovery of novel anti-tumour therapeutic drugs from known plant natural sources. [ABSTRACT FROM AUTHOR]

Autophagy, the cell process of self-digestion, plays a pivotal role in maintaining energy homoeostasis and protein synthesis. When required, it causes degradation of long-lived proteins and damaged organelles, indicating that it may play a dual role in cancer, by both protecting against and promoting cell death. The autophagy-related gene (Atg) family, with more than 35 members, regulates multiple stages of the process. Serine/threonine protein kinase Atg1 in yeast, for example, can interact with other ATG gene products, functioning in autophagosome formation. One mammalian homologue of Atg1, UNC-51-like kinase 1 (ULK1) and its related complex ULK1-mAtg13-FIP200 can mediate autophagy under nutrientdeprived conditions, by protein-protein interactions and post-translational modifications. Although specific mechanisms of how ULK1 and its complex transduces upstream signals to the downstream central autophagy pathways is not fully understood, past studies have indicated that ULK1 can both suppress and promote tumour growth under different conditions. Here, we summarize some properties of ULK1 which can regulate autophagy in cancer, which may shed new light on future cancer therapy strategies, utilizing ULK1 as a potential new target. [ABSTRACT FROM AUTHOR]

Introduction The aim of this study was to investigate the contribution of the perioperative cell salvage process to the changes in erythrocyte 2,3-disphosphoglycerate (2,3- DPG) and glucose-6-phosphate dehydrogenase ( G-6- PD) levels and phosphatidylserine ( PS) expression using a self-control study comparing washed blood with venous blood. Methods Thirty patients undergoing elective heart and blood vessel surgery were enrolled. Blood was collected and processed using a Fresenius continuous autotransfusion system device. 2,3- DPG and G-6- PD activities, as well as PS expression, from both venous and washed red blood cells ( RBC) were measured. We also compared these indicators among washed RBC at 6 h, washed RBC at 0 h, and venous RBC. Results 2,3- DPG and G-6- PD activities in washed blood at 0 h were significantly higher than in venous RBC (2,3- DPG, venous vs. washed blood P < 0.05; G-6- PD, venous vs. washed blood P < 0.05). Flow cytometry results showed no differences between venous blood and washed RBC at 0 h ( n = 23, P > 0.05). 2,3- DPG activity in washed RBC that were allowed to stand for 6 h decreased compared with that in venous blood ( venous vs. washed blood at 6 h P < 0.01), whereas no significant difference was observed in G-6- PD activity ( venous. vs. washed blood at 6 h P > 0.05). Conclusion Compared with venous RBC, washed RBC from intraoperative cell salvage exhibited good oxygen-carrying and antioxidant capacities. However, the oxygen-carrying capacity of washed RBC that were allowed to stand for 6 h was not as good as that of venous RBC. Thus, we suggest that washed RBC that were left to stand for more than 6 h should not be reinfused. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background: Accurate estimation of glomerular filtration rate (GFR) allows early detection of renal disease and maximizes opportunity for intervention. Aim: To assess the accuracy of estimated GFR (eGFR) in an Australian and New Zealand cohort with chronic kidney disease using the 4-variable Modification of Diet in Renal Disease equation (MDRD4V), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, and the Cockcroft and Gault equation with actual and ideal body weight. Methods: Retrospective review of patients who had measured GFR (mGFR) by 51Cr-EDTA clearance and simultaneous measurements of serum biochemistry and anthropometrics. eGFR was compared with mGFR using the concordance correlation coefficient (CCC) and Bland-Altman measures of agreement. Results: 178 patients had 441 radioisotope measurements of GFR. Mean mGFR of was 22.6 mL/min per 1.73 m2. The MDRD4V equation using the 'black' correction factor was most accurate with a mean eGFR of 19.74 (CCC 0.733, bias −2.86). The CKD-EPI equations also using the 'black' correction factors were almost as good at 19.11 (CCC 0.719, bias −3.49). The Cockcroft-Gault creatinine clearance values had the poorest agreement with mGFR. In the 18 nonwhite non-Asian patients, the MDRD4V and CKD-EPI equations were generally less accurate although the use of the 'black' correction factor resulted in greater accuracy for both equations. Conclusion: The MDRD4V equation was the most accurate. However, its accuracy might be less for nonwhite non-Asian patients if the 'black' correction factor is omitted. Further study of the estimation of GFR in Australian and New Zealand ethnic subgroups would be helpful. [ABSTRACT FROM AUTHOR]

In this paper, we investigate various confidence intervals for the risk ratio under inverse sampling (also known as negative binomial sampling). Three existing confidence intervals (namely, the confidence intervals that are based on Fieller's theorem, the delta method and the F-statistic) are reviewed and three new confidence intervals (namely, the score, likelihood ratio and saddlepoint approximation (SA)-based confidence intervals) are developed. Comparative studies among these confidence intervals through Monte Carlo simulations are evaluated in terms of their coverage probabilities and expected interval widths under different settings. Our simulation results suggest that the SA-based confidence interval is generally more appealing. We illustrate these confidence interval construction methods with real data sets from a drug comparison study and a congenital heart disease study. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Renal replacement therapy is frequently required for critically ill patients with a high risk of bleeding. Conventional heparinization strategies to prevent extracorporeal blood circuit clotting can cause significant haemorrhage in such patients because of systemic anticoagulation. Regional citrate anticoagulation (RCA) is a well-established technique that minimizes this complication by the decalcification of blood in the extracorporeal circuit such that it is incapable of clotting. To date, there are no reports on the use of RCA for sustained low-efficiency dialysis/diafiltration (SLED), a hybrid therapy that involves the use of conventional haemodialysis machinery to deliver lower solute clearances over prolonged periods of time. In preparation for clinical study, an in vitro simulation of SLED was devised (blood substitute flow 250 mL/min, dialysate flow 200 mL/min, predilution haemofiltration 100 mL/min). Blood substitute was decalcified by an infusion of 4% trisodium citrate (TSC) proximally into the extracorporeal blood circuit, with partial restoration of calcium homeostasis from dialysate containing ionized [Ca2+] at 0.9 mmol/L. This simulation was used to establish first the 4% TSC requirement for therapeutic decalcification, and second the associated changes in ionized [Ca2+] and [Mg2+] within the blood substitute from chelation with citrate and subsequent removal of the resulting divalent cation-citrate complex. Serial measurements of blood substitute [Ca2+] from strategic points along the extracorporeal circuit showed therapeutic decalcification was not achieved with 4% TSC infusion rates up to 400 mL/h, and extrapolation of experimental results suggests that 450 mL/h will be required. Under these conditions, ionized [Ca2+] and [Mg2+] in the blood substitute venous return and would be 0.42 and 0.2 mmol/L, respectively, with 0.35 mmol of citrate being returned per minute via the blood substitute venous return. These results were modelled for various changes in SLED operating parameters, and discussed in detail. An appropriate regimen for 4% TSC infusion and divalent cation replacement is proposed for clinical study in the future. [ABSTRACT FROM AUTHOR]

The article presents information on a study which investigated the effects of ethylene inhibitor 1-methylcyclopropene (1-MCP) on the quality attributes of fresh-cut apple slices, and the potential of using this compound as a treatment to extend the shelflife of MP apples. A review of the related literature is given. Variables investigated include respiration, flesh firmness, tissue color and titratable acidity. Findings showed that total sugar and acidity levels were not significantly affected.

Abstract The present study examined temporal changes in activity of large conductance, Ca2+ -activated potassium (BKCa ) channels in postischemic CA1 pyramidal neurons at 2, 6, 24 and 48 h after reperfusion. These changes in activity and possible cellular mechanisms were examined using the inside–out configuration of patch clamp. The unitary conductance of postischemic BKCa channels increased transiently to 119% of the control at 2 h after reperfusion, and recovered to the control level thereafter. A persistent increase in [Ca2+ ]i sensitivity of BKCa channels was observed in postischemic CA1 neurons with the maximal sensitivity to [Ca2+ ]i at 6 h after reperfusion while channel voltage- dependence showed no obvious changes. Kinetic analyses showed that the postischemic enhancement of BKCa channel activity was due to longer open times and shorter closed times as there was no significant changes in opening frequency after ischemia. Glutathione disulphide markedly increased BKCa channel activity in normal CA1 neurons, while reducing glutathione caused a decrease in BKCa channel activity by reducing the sensitivity of this channel to [Ca2+ ]i in postischemic CA1 neurons. Similar modulatory effects on postischemic BKCa channels were also observed with another redox couple, DTNB and DTT, suggesting an oxidation modulation of BKCa channel function after ischemia. The present results indicate that a persistent enhancement in activity of BKCa channels, probably via oxidation of channels, in postischemic CA1 pyramidal neurons may account for the decrease in neuronal excitability and increase in fAHP after ischemia. The ischemia-induced augmentation in BKCa channel activity may be also associated with the postischemic neuronal injury. [ABSTRACT FROM AUTHOR]

The aperture admittance is formulated for a slice dielectric-filled (εr ≥ 1) rectangular waveguide antenna. By considering the specific media discontinuity at the aperture, the formulation is able to predict aperture admittance of the waveguide with various dimension ratios and dielectrics. The summarized results are new in the sense that they have rarely been found in the literature. Calculations and supporting measurements show that the filled dielectric has an important influence, in addition to waveguide height, on the aperture admittance. The proposed approach permits a good simulation of aperture characteristics and impedance matching. [ABSTRACT FROM AUTHOR]

Examines the femtosecond near-field scanning optical microscopy study of molecular thin films. Combination of near-field scanning optical microscope with time resolved measurement; Evaluation of molecular thin films; Uniformity of film composition over a distance of several micrometers.

The article discusses the impact of various polyvinyl chloride (PVC) tracheal tubes, highlighting the subglotic injuries incurred during the Glidescope intubation. It examines the challenges related to the orotracheal intubation with the GlideScope, symptoms of laryngeal trauma, and the importance of muscle relaxation.

7-11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK [ABSTRACT FROM AUTHOR]

Review: 138 refs. [ABSTRACT FROM AUTHOR]

The article presents an abstract of the research paper "Neuroglian, A Drosophila L1-Type Neural Cell Adhesion Molecule, And Its Adhesion-Dependent Interaction With The Membrane Skeleton." The neural cell adhesion molecules Drosophila neuroglian and human L1 cell adhesion molecule directly interact with Drosophila ankyrin. In developing fly nervous system, neuroglian interacts with Dank2 protein, while in non-neuronal cells, Dank1 protein serves as neuroglian's link to the membrane skeleton.

Background: Some studies confirmed that erythroblast transformation-specific-related gene (ERG) may be a pathogenic factor of oral squamous cell carcinoma (OSCC). However, the undergoing molecular mechanism has not been elucidated yet., Objective: In this study, the investigation will focus on how the transcription factor ERG modulates the biological behaviors of OSCC., Methods: In this study, cancer tissue specimens and corresponding paracancer tissues were collected from 54 patients. Real-time polymerase chain reaction analysis and Western blots were employed to detect the expression of multiple genes. Cell proliferation assays, Transwell, and flow cytometry assay were utilized to detect the proliferation, invasion, and apoptosis of OSCC cell, respectively. Dual luciferase reporter gene and chromatin immunoprecipitation assays were conducted to verify the regulation of ERG on PRDX1., Results: ERG exhibits high expression levels in OSCC. Inhibition of ERG has been shown to effectively suppress the malignant growth of OSCC cells. Moreover, ERG has been found to transcriptionally upregulate the expression of PRDX1. The knockdown of PRDX1 has demonstrated its ability to inhibit the malignant growth of OSCC cells. Interestingly, when PRDX1 is overexpressed, it attenuates the inhibitory effect of si-ERG on the malignant growth of OSCC cells. This suggests that PRDX1 may play a crucial role in mediating the impact of ERG on malignancy in OSCC cells., Conclusion: The transcription factor ERG promotes the expression of PRDX1, which could enhance the proliferation and invasion while inhibiting the apoptosis of OSCC cells., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: This study aimed to investigate the causal relationships between branched-chain amino acids (BCAAs) and the risks of hypertension via meta-analysis and Mendelian randomization analysis., Methods and Results: A meta-analysis of 32 845 subjects was conducted to evaluate the relationships between BCAAs and hypertension. In Mendelian randomization analysis, independent single-nucleotide polymorphisms associated with BCAAs at the genome-wide significance level were selected as the instrumental variables. Meanwhile, the summary-level data for essential hypertension and secondary hypertension end points were obtained from the FinnGen study. As suggested by the meta-analysis results, elevated BCAA levels were associated with a higher risk of hypertension (isoleucine: summary odds ratio, 1.26 [95% CI, 1.08-1.47]; leucine: summary odds ratio, 1.28 [95% CI, 1.07-1.52]; valine: summary odds ratio, 1.32 [95% CI, 1.12-1.57]). Moreover, the inverse variance-weighted method demonstrated that an elevated circulating isoleucine level might be the causal risk factor for essential hypertension but not secondary hypertension (essential hypertension: odds ratio, 1.22 [95% CI, 1.12-1.34]; secondary hypertension: odds ratio, 0.96 [95% CI, 0.54-1.68])., Conclusions: The increased levels of 3 BCAAs positively correlated with an increased risk of hypertension. Particularly, elevated isoleucine level is a causal risk factor for essential hypertension. Increased levels of leucine and valine also tend to increase the risk of essential hypertension, but further verification is still warranted.

Dapagliflozin (DAPA) are clinically effective in improving diabetic nephropathy (DN). However, whether and how chromatin accessibility changed by DN responds to DAPA treatment is unclear. Therefore, we performed ATAC-seq, RNA-seq, and weighted gene correlation network analysis to identify the chromatin accessibility, the messenger RNA (mRNA) expression, and the correlation between clinical phenotypes and mRNA expression using kidney from three mouse groups: db/m mice (Controls), db/db mice (case group), and those treated with DAPA (treatment group). RNA-Seq and ATAC-seq conjoint analysis revealed many overlapping pathways and networks suggesting that the transcriptional changes of DN and DAPA intervention largely occured dependently on chromatin remodeling. Specifically, the results showed that some key signal transduction pathways, such as immune dysfunction, glucolipid metabolism, oxidative stress and xenobiotic and endobiotic metabolism, were repeatedly enriched in the analysis of the RNA-seq data alone, as well as combined analysis with ATAC-seq data. Furthermore, we identified some candidate genes (UDP glucuronosyltransferase 1 family, Dock2, Tbc1d10c, etc.) and transcriptional regulators (KLF6 and GFI1) that might be associated with DN and DAPA restoration. These reversed genes and regulators confirmed that pathways related to immune response and metabolism pathways were critically involved in DN progression., (© 2024 John Wiley & Sons Ltd.)

Background: Accurately diagnosing patients with the vegetative state (VS) and the minimally conscious state (MCS) reached a misdiagnosis of approximately 40%., Methods: A method combined microstate and dynamic functional connectivity (dFC) to study the spatiotemporal variability of the brain in disorders of consciousness (DOC) patients was proposed. Resting-state EEG data were obtained from 16 patients with MCS and 16 patients with VS. Mutual information (MI) was used to assess the EEG connectivity in each microstate. MI-based features with statistical differences were selected as the total feature subset (TFS), then the TFS was utilized to feature selection and fed into the classifier, obtaining the optimal feature subsets (OFS) in each microstate. Subsequently, an OFS-based MI functional connectivity network (MIFCN) was constructed in the cortex., Results: The group-average MI connectivity matrix focused on all channels revealed that all five microstates exhibited stronger information interaction in the MCS when comparing with the VS. While OFS-based MIFCN, which only focused on a few channels, revealed greater MI flow in VS patients than in MCS patients under microstates A, B, C, and E, except for microstate D. Additionally, the average classification accuracy of OFS in the five microstates was 96.2%., Conclusion: Constructing features based on microstates to distinguish between two categories of DOC patients had effectiveness., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Human dihydroorotate dehydrogenase (hDHODH) is a key enzyme that catalyzes the de novo synthesis of pyrimidine. In recent years, various studies have shown that inhibiting this enzyme can treat autoimmune diseases such as rheumatoid arthritis (RA) and cancer. This study designed and synthesized a series of novel thiazolidone hDHODH inhibitors. Through biological activity evaluation, Compound 14 was found to have high inhibitory activity, with an IC 50 value reaching nanomolar level. Preliminary structure-activity relationship studies found that the carboxyl group in R 1 and the naphthalene in R 2 are key factors in improving activity. Through molecular docking, the binding mode between inhibitors and proteins was elucidated. This study provides an important reference for further optimizing hDHODH inhibitors., (© 2023 John Wiley & Sons A/S.)

Amyloid-β 1-42 (Aβ 1-42 ) is strongly associated with Alzheimer's disease (AD). The aim of this study is to elucidate whether and how miR-6076 participates in the modulation of amyloid-β (Aβ)-induced neuronal damage. To construct the neuronal damage model, SH-SY5Y cells were treated with Aβ 1-42 . By qRT-PCR, we found that miR-6076 is significantly upregulated in Aβ 1-42 -treated SH-SY5Y cells. After miR-6076 inhibition, p-Tau and apoptosis levels were downregulated, and cell viability was increased. Through online bioinformatics analysis, we found that B-cell lymphoma 6 (BCL6) was a directly target of miR-6076 via dual-luciferase reporter assay. BCL6 overexpression mediated the decrease in elevated p-Tau levels and increased viability in SH-SY5Y cells following Aβ1-42 treatment. Our results suggest that down-regulation of miR-6076 could attenuate Aβ 1-42 -induced neuronal damage by targeting BCL6, which provided a possible target to pursue for prevention and treatment of Aβ-induced neuronal damage in AD., (© 2023 Nantong University. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objective: This study (NCT05588531) aimed to evaluate the safety and pharmacokinetics of cefepime-avibactam (YK-1169) in healthy Chinese subjects and explore the optimal regimen for treating carbapenem-resistant Klebsiella pneumoniae (CRKP) based on the pharmacokinetic/pharmacodynamic evaluation., Methods: YK-1169 single-ascending doses (0.5, 1.25, 2.5 or 3.75 g, 2-h infusion) and multiple doses (2.5 or 3.75 g every 8 h [q8h], 2-h infusion) given for 7 days were evaluated in pharmacokinetic studies. Subjects were randomized to receive cefepime (2 g), avibactam (0.5 g) or YK-1169 (2.5 g) to assess drug-drug interactions. The minimum inhibitory concentrations (MICs) of YK-1169 were determined by the broth microdilution method. Monte Carlo simulation was used to evaluate 10 different dose regimens., Results: Cefepime and avibactam both showed a linear pharmacokinetic profile. No accumulation was found after multiple doses. The cefepime C max,ss and AUC 0-∞,ss were 9.20 and 16.0 μg/mL, 407.2 and 659.45 μg·h/mL in the 2.5 and 3.75 g multiple-dose groups, respectively. The avibactam C max,ss and AUC 0-∞,ss were 0.545 and 0.837 μg/mL, 53.31 and 79.55 μg·h/mL in the 2.5 and 3.75 g multiple-dose groups, respectively. Cefepime and avibactam did not affect each other's pharmacokinetics. No serious adverse events occurred. All regimens achieved 90% probability of target attainment (PTA) goals when the MIC was ≤8 mg/L. The regimens of 2.5 (q8h, 2-h infusion), 3.75 (q8h, 2-, 3- and 4-h infusions) and 7.5 g (24-h continuous infusion) reached a 90% cumulative fraction of response., Conclusion: YK-1169 had good antibacterial activity against CRKP and could be an option for CRKP infections. The regimen of 2.5 g q8h intravenously guttae (ivgtt) 2 h should be considered in future clinical trials., (© 2023 British Pharmacological Society.)

Aims: Recently, human umbilical cord mesenchymal stem cell (HucMSC)-derived exosome is a new focus of research in neurological diseases. The present study was aimed to investigate the protective effects of HucMSC-derived exosome in both in vivo and in vitro TBI models., Methods: We established both mouse and neuron TBI models in our study. After treatment with HucMSC-derived exosome, the neuroprotection of exosome was investigated by the neurologic severity score (NSS), grip test score, neurological score, brain water content, and cortical lesion volume. Moreover, we determined the biochemical and morphological changes associated with apoptosis, pyroptosis, and ferroptosis after TBI., Results: We revealed that treatment of exosome could improve neurological function, decrease cerebral edema, and attenuate brain lesion after TBI. Furthermore, administration of exosome suppressed TBI-induced cell death, apoptosis, pyroptosis, and ferroptosis. In addition, exosome-activated phosphatase and tensin homolog-induced putative kinase protein 1/Parkinson protein 2 E3 ubiquitin-protein ligase (PINK1/Parkin) pathway-mediated mitophagy after TBI. However, the neuroprotection of exosome was attenuated when mitophagy was inhibited, and PINK1 was knockdown. Importantly, exosome treatment also decreased neuron cell death, suppressed apoptosis, pyroptosis, and ferroptosis and activated the PINK1/Parkin pathway-mediated mitophagy after TBI in vitro., Conclusion: Our results provided the first evidence that exosome treatment played a key role in neuroprotection after TBI through the PINK1/Parkin pathway-mediated mitophagy., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Objective: To detail a technique for bonding periodontal splint precisely in a digital workflow., Clinical Considerations: Periodontal splinting can be considered to stabilize the mobile teeth, especially for mandibular anterior teeth. Reliable bonding of periodontal splints is a prerequisite for successful clinical performance. However, when bonding the indirect splint to place or making direct splint intraorally, there is a significant risk of mobile teeth drifting away from the splint. To guide accurate insertion of periodontal splint with no risk of displacement of mobile teeth, a guide device fabricated by digital workflow is introduced in this article., Conclusions: Periodontal compromised teeth can be provisionally fixed during splinting, with the help of the guided device, and precise bonding of the splint is readily accomplished by using such digital workflow. This technique is not only applicable to the lingual splints, but also suitable for the labial ones., Clinical Significance: The use of a guided device, after being digitally designed and fabricated, enables to stabilize the mobile teeth, in case of any displacement during splinting. It is straightforward, and beneficial to reduce the risk of complications, such as debonding of the splint, and secondary occlusal trauma., (© 2023 Wiley Periodicals LLC.)

1q gain (+1q) is the most common high-risk cytogenetic abnormality (HRCA) in patients with multiple myeloma (MM). However, its prognostic value remains unclear in the era of novel agents. Here, we retrospectively analyzed the impact of +1q on the outcomes of 934 patients newly diagnosed with MM. +1q was identified in 53.1% of patients and verified as an independent variate for inferior overall survival (OS) (hazard ratio, 1.400; 95% confidence interval, 1.097-1.787; p = .007). Concurrence of other HRCAs (particularly t(14;16) and del(17p)) further exacerbated the outcomes of patients with +1q, suggesting prognostic heterogeneity. Thus, a risk-scoring algorithm based on four risk variates (t(14;16), hypercalcemia, ISS III, and high LDH) was developed to estimate the outcomes of patients with +1q. Of the patients, 376 evaluable patients with +1q were re-stratified into low (31.6%), intermediate (61.7%), and high risk (6.7%) groups, with significantly different progression-free survival and OS (p < .0001), in association with early relapse of the disease. The prognostic value of this model was validated in the CoMMpass cohort. While attaining undetectable MRD largely circumvented the adverse impact of +1q, it scarcely ameliorated the outcome of the patients with high risk, who likely represent a subset of patients with extremely poor survival. Hence, patients with +1q are a heterogeneous group of high-risk patients, therefore underlining the necessity for their re-stratification. The proposed simple risk-scoring model can estimate the outcomes of patients with +1q, which may help guide risk-adapted treatment for such patients., (© 2022 Wiley Periodicals LLC.)

Background: Vascular dementia (VaD) is the accumulation of vascular lesions in the subcortical white matter of the brain. These lesions progress and there is no direct medical therapy., Aims: To determine the specific cellular responses in VaD so as to provide molecular targets for therapeutic development., Materials and Methods: Single-nucleus transcriptome analysis was performed in human periventricular white matter (PVWM) samples of VaD and normal control (NC) subjects., Results: Differential analysis shows that cell type-specific transcriptomic changes in VaD are associated with the disruption of specific biological processes, including angiogenesis, immune activation, axonal injury and myelination. Each cell type in the neurovascular unit within white matter has a specific alteration in gene expression in VaD. In a central cell type for this disease, subcluster analysis of endothelial cells (EC) indicates that VaD contains a disease-associated EC subcluster that expresses genes associated with programmed cell death and a response to protein folding. Two other subpopulations of EC in VaD express molecular systems associated with regenerative processes in angiogenesis, and in axonal sprouting and oligodendrocyte progenitor cell maturation., Conclusion: This comprehensive molecular profiling of brain samples from patients with VaD reveals previously unknown molecular changes in cells of the neurovascular niche, and an attempt at regeneration in injured white matter., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Aging is an inevitable process that all individuals experience, of which the extent differs among individuals. It has been recognized as the risk factor of neurodegenerative diseases by affecting gut microbiota compositions, microglia, and cognition abilities. Aging-induced changes in gut microbiota compositions have a critical role in orchestrating the morphology and functions of microglia through the gut-brain axis. Gut microbiota communicates with microglia by its secreted metabolites and neurotransmitters. This is highly associated with age-related cognitive declines. Here, we review the main composition of microbiota in the aged individuals, outline the changes of the brain in age-related cognitive decline from a neuroinflammation perspective, especially the changes of morphology and functions of microglia, discuss the crosstalk between microbiota and microglia in the aged brain and further highlight the role of microbiota-microglia connections in neurodegenerative diseases (Alzheimer's disease and Parkinson's disease)., (© 2022 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Background: The role of H. pylori infection has been reported in various extragastric diseases, particularly, the correlation between H. pylori and atherosclerosis (AS) have received lots of attention. Some scholars demonstrated that the presence of H. pylori-specific DNA in the sclerotic plaques of atheromatous patients provides biological evidences, with indicating that H. pylori infection is a potential factor of AS. However, the underlying mechanism of H. pylori or their products cross the epithelial barriers to enter the blood circulation remains unclear. Recent studies have shown that the extracellular vesicles (EVs) derived from H. pylori-infected gastric epithelial cells encapsulated H. pylori virulence factor cytotoxin-associated gene A (CagA) and existed in the blood samples of patients or mice, which indicating that they can carry CagA into the blood circulation. Based on these findings, some researchers proposed a hypothesis that H. pylori is involved in the pathogenesis of AS via EVs-based mechanisms. In addition, outer membrane vesicles (OMVs) serve as transport vehicles to deliver H. pylori virulence factors to epithelial cells. It is necessary to discuss the role of H. pylori OMVs in the development of AS., Objectives: This review will focus on the correlation between H. pylori infection and AS and tried to unveil the possible role of EVs from H. pylori-infected cells and H. pylori OMVs in the pathogenesis of AS, with a view to providing help in refining our knowledge in this aspect., Methods: All of information included in this review was retrieved from published studies on H. pylori infection in AS., Results: H. pylori infection may be an atherosclerotic risk factor and drives researchers to reevaluate the role of H. pylori in the pathogenesis of AS. Some findings proposed a new hypothesis that H. pylori may be involved in the pathogenesis of AS through EVs-based mechanisms. Besides EVs from H. pylori-infected cells, whether H. pylori OMVs may play some role in the pathogenesis of AS is still remain unclear., Conclusion: Existing epidemiological and clinical evidence had shown that there is a possible association between H. pylori and AS. However, except for the larger randomized controlled trials, more basic research about EVs from H. pylori-infected cells and H. pylori OMVs is the need of the hour to unveil the possible role of H. pylori infection in the pathogenesis of AS., (© 2022 John Wiley & Sons Ltd.)

Stickler syndrome type I (STL1, MIM 108300) is characterized by ocular, auditory, skeletal and orofacial manifestations. Nonsyndromic ocular STL1 (MIM 609508) characterized by predominantly ocular features is a subgroup of STL1, and it is inherited in an autosomal dominant manner. In this study, a novel variant c.T100>C (p.Cys34Arg) in COL2A1 related to a large nonsyndromic ocular STL1 family was identified through Exome sequencing (ES). Bioinformatics analysis indicated that the variant site was highly conserved and the pathogenic mechanism of this variant may involve in affected structure of chordin-like cysteine-rich (CR) repeats of ColIIA. Minigene assay indicated that this variant did not change alternative splicing of exon2 of COL2A1. Moreover, the nonsyndromic ocular STL1 family with 16 affected members showed phenotype variability and certain male gender trend. None of the family members had hearing loss. Our findings would expand the knowledge of the COL2A1 mutation spectrum, and phenotype variability associated with nonsyndromic ocular STL1. Search for genetic modifiers and related molecular pathways leading to the phenotype variation warrants further studies., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Mycobacterium bovis bacillus Calmette-Guérin (BCG) is an attenuated live vaccine that provides insufficient protection against tuberculosis (TB), the underlying mechanisms for which remain unknown. Assuming that the BCG vaccine inherits immune evasive strategies from virulent parent M. bovis strains, we aimed to identify the associated genes and assess their effects on the vaccine efficacy., Methods: Three genes, BCG&#95;3174, BCG&#95;1782, and BCG&#95;2432c, associated with immune evasion were first identified via bioinformatics analysis and then confirmed in the genome of M. bovis and 12 commercial BCG vaccine substrains using Polymerase Chain Reaction (PCR) and DNA sequencing. These genes were disrupted to develop mutant strains, and their effects on autophagy and their protective efficacy were further compared with the BCG vaccine in vitro and in vivo., Results: Of the three identified genes, only the disruption of BCG&#95;2432c, namely ΔBCG&#95;2432c, conferred stronger protection against intranasal TB in vaccinated mice, when compared with the BCG vaccine. ΔBCG&#95;2432c showed a stronger ability to trigger intracellular ROS-mediated complete autophagic flux in infected THP-1 cells that resulted in higher antigen presentation. The improved protection could be attributed to early and increased IFN-γ + CD4 + T EM and IL-2 + CD4 + T CM cells in the spleens and lungs of ΔBCG&#95;2432c-vaccinated mice., Conclusions: The insufficient efficacy of the BCG vaccine is attributable to the important autophagy-inhibition gene BCG&#95;2432c that blocks the autophagosome-lysosome pathway of antigen presentation. ΔBCG&#95;2432c provides a promising platform to either replace the current BCG vaccine or develop vaccines that are more effective against TB., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Aims: This study aimed to summarize the transthoracic echocardiography (TTE) characteristics of cardiac tumors with different pathologies., Methods: The data of 399 patients with cardiac tumors confirmed by pathology, who had undergone surgical resection were consecutively collected in our hospital between January 1, 2011 and December 31, 2019. The TTE characteristics were summarized and compared with the pathology., Results: Mean patient age was 49.8±15.7 years (22 children and 377 adults), and 62.2% were female. Of the tumors, 90.5% (361) were primary and 9.5% (38) were secondary. Further, 88.7% (354) were benign and 11.3% (45) were malignant. Of the primary tumors (96.1% benign and 3.9% malignant), 84.2% were myxomas, followed by 3.5% lipomas and 1.5% fibromas in adults, while in children, 31.8% were rhabdomyomas and 22.7% were fibromas. The most common type of secondary cardiac tumor was malignant liver carcinoma metastasis (39.5%) and benign intravenous leiomyomatosis with cardiac extension from the uterus (18.4%). TTE features of myxoma showed four variation types among 8.9% of myxomas: liquefaction (anechoic region mostly), calcification (hyperechoic range with a shadow), multiple nodules, and high proliferative activity (a large irregular mass with a wide base and a high Ki67 index). The TTE characteristics of some common benign non-myxoma tumors had specific findings. The TTE features of malignant tumors mostly showed hypoechogenicity, an unclear boundary, a wide basement, and multi-chambers or tissue invasion., Conclusions: Most cardiac tumors have typical ultrasonic manifestations. Preoperative echocardiography could roughly judge cardiac tumor type and may be helpful for guiding clinical treatment decisions., (© 2021 Wiley Periodicals LLC.)

Periodontitis is a major burden of public health, affecting 20%-50% of the global population. It is a complex inflammatory disease characterized by the destruction of supporting structures of the teeth, leading to tooth loss and the emergence or worsening of systematic diseases. Understanding the molecular mechanisms underlying the physiopathology of periodontitis is beneficial for targeted therapeutics. Long non-coding RNAs (lncRNAs), transcripts made up of more than 200 nucleotides, have emerged as novel regulators of many biological and pathological processes. Recently, an increasing number of dysregulated lncRNAs have been found to be implicated in periodontitis. In this review, an overview of lncRNAs, including their biogenesis, characteristics, function mechanisms and research approaches, is provided. And we summarize recent research reports on the emerging roles of lncRNAs in regulating proliferation, apoptosis, inflammatory responses, and osteogenesis of periodontal cells to elucidate lncRNAs related physiopathology of periodontitis. Furthermore, we have highlighted the underlying mechanisms of lncRNAs in periodontitis pathology by interacting with microRNAs. Finally, the potential clinical applications, current challenges, and prospects of lncRNAs as diagnostic and prognostic biomarkers and therapeutic targets for periodontitis disease are discussed., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)