Platelet PD-L1 inhibits storage-induced apoptosis by sustaining activation of the AKT signalling pathway.

Platelet apoptosis is irreversible under current storage conditions in blood banks. Studies have shown that programmed cell death ligand 1 (PD-L1) in tumour cells is required for neoplastic progression, tumour recurrence and metastasis by regulating apoptosis. However, whether PD-L1 is involved in storage-induced apoptosis in platelets remains poorly understood. In this study, we explored whether PD-L1 on platelets participated in the regulation of storage-induced apoptosis under blood bank conditions, as well as the underlying mechanism. Several apoptotic events in platelets from humans and PD-L1-knockout mice during storage under blood bank conditions were measured. The mechanism by which storage-induced apoptosis was regulated by platelet-intrinsic PD-L1 signalling was further investigated. Our results showed that PD-L1 in platelets progressively decreased. There was a strong negative correlation between platelet PD-L1 expression and the phosphatidylserine (PS) externalization rate and cleaved caspase-3 level and a positive correlation with anti-apoptosis protein Bcl-xl. Ex vivo, PD-L1-/- platelets stored at 22 °C showed rapid apoptosis via an intrinsic mitochondria-dependent pathway over time. Likewise, inhibiting PD-L1 signalling with BMS-1166 accelerated apoptosis by intrinsic mitochondria-dependent pathway. Coimmunoprecipitation analysis revealed that PD-L1 could bind AKT in platelets, and the binding capacity of both showed a progressive decrease with time. Finally, the decrease in PD-L1 expression levels during storage could be attributed to a complex process of progressive secretion. Therefore, platelet PD-L1 inhibits storage-induced apoptosis by sustaining activation of the AKT signalling pathway, which is expected to become a target for alleviating platelet storage lesions (PSLs) under current blood bank conditions.

Uniportal video-assisted thoracic surgery versus open thoracotomy for chronic pain after surgery: a prospective cohort study.

PURPOSE: The potential of uniportal video-assisted thoracic surgery (U-VATS) to reduce chronic pain after thoracic surgery (CPTS) compared to open thoracotomy (OT) remains unexplored. This prospective study aims to assess the incidence of CPTS following U-VATS or OT and identify associated risk factors. METHODS: Patients undergoing thoracic surgery were recruited from March 2021 to March 2022, categorized by surgical approach (U-VATS vs. OT). Standard clinical protocols for surgery, anesthesia, and analgesia were followed. Pain symptoms were assessed using the Short-form McGill Pain Questionnaire, with follow-ups up to 6 months. Perioperative factors influencing CPTS at 3 months were analyzed through univariate and multivariate methods. RESULTS: A total of 694 patients were analyzed. Acute pain after thoracic surgery (APTS) was significantly less severe in the U-VATS group (p < 0.001). U-VATS patients exhibited a lower incidence of CPTS at 3 months (63.4% vs. 80.1%, p < 0.001), with reduced severity among those experiencing CPTS (p = 0.007) and a decreased occurrence of neuropathic pain (p = 0.014). Multivariate analysis identified OT incision, moderate to severe APTS (excluding moderate static pain at 24 h postoperative), nocturnal surgery, and lung surgery as risk factors for CPTS. CONCLUSION: This study underscores the potential of U-VATS to reduce both the incidence and severity of CPTS at 3 months compared to OT. Furthermore, it highlights risk factors for CPTS, including OT incision, inadequately managed APTS, lung surgery, and nocturnal surgery. These findings emphasize the importance of considering surgical approach and perioperative pain management strategies to mitigate the burden of CPTS.

Supraglottic Jet Oxygenation and Ventilation to Minimize Hypoxia in Patients Receiving Flexible Bronchoscopy Under Deep Sedation: A 3-Arm Randomized Controlled Trial.

BACKGROUND: Hypoxia often occurs due to shared airway and anesthetic sedation-induced hypoventilation in patients receiving flexible bronchoscopy (FB) under deep sedation. Previous evidence has shown that supraglottic jet oxygenation and ventilation (SJOV) via Wei nasal jet tube (WNJ) reduces the incidence of hypoxia during FB. This study aimed to investigate the extent to which SJOV via WNJ could decrease the incidence of hypoxia in patients under deep sedation as compared to oxygen supplementation via WNJ alone or nasal catheter (NC) for oxygen supplementation during FB. METHODS: This was a single-center 3-arm randomized controlled trial (RCT). Adult patients scheduled to undergo FB were randomly assigned to 3 groups: NC (oxygen supplementation via NC), low-pressure low-flow (LPLF) (low-pressure oxygen supplementation via WNJ alone), or SJOV (high-pressure oxygen supplementation via WNJ). The primary outcome was hypoxia (defined as peripheral saturation of oxygen [Sp o2 ] <90% lasting more than 5 seconds) during FB. Secondary outcomes included subclinical respiratory depression or severe hypoxia, and rescue interventions specifically performed for hypoxia treatment. Other evaluated outcomes were sore throat, xerostomia, nasal bleeding, and SJOV-related barotraumatic events. RESULTS: One hundred and thirty-two randomized patients were included in 3 interventions (n = 44 in each), and all were included in the final analysis under intention to treat. Hypoxia occurred in 4 of 44 patients (9.1%) allocated to SJOV, compared to 38 of 44 patients (86%) allocated to NC, with a relative risk (RR) for hypoxia, 0.11; 98% confidence interval (CI), 0.02-0.51; P < .001; or to 27 of 44 patients (61%) allocated to LPLF, with RR for hypoxia, 0.15; 95% CI, 0.04-0.61; P < .001, respectively. The percentage of subclinical respiratory depression was also significantly diminished in patients with SJOV (39%) compared with patients with NC (100%) or patients with LPLF (96%), both P < .001. In SJOV, no severe hypoxia event occurred. More remedial interventions for hypoxia were needed in the patients with NC. Higher risk of xerostomia was observed in patients with SJOV. No severe adverse event was observed throughout the study. CONCLUSIONS: SJOV via WNJ effectively reduces the incidence of hypoxia during FB under deep sedation.

Recent advances in the analysis of electronic cigarette liquids and aerosols: Sample preparation and chromatographic characterization.

Electronic cigarette (e-cigarette) usage has risen dramatically worldwide in recent years. It has been publicized as a safer alternative to the conventional combustible cigarette. This, however, has not yet been supported by robust toxicological research evidence. Analysis of the chemical compositions of e-liquids and generated aerosols is an important step in evaluating the toxicity effects of e-cigarettes. Currently, a broad spectrum of analytical methods have been employed for qualitative and quantitative analysis of chemical compositions of e-cigarette liquids and aerosols. The aim of this article is to review the advances in the chromatographic characterization of chemical composition of the latter in the recent five years. In addition, sample preparation methods for e-liquids and aerosols are surveyed and discussed. A study of the relevant literature indicates that, expectedly, gas chromatography and liquid chromatography with a variety of detection systems, particularly mass spectrometry, have been the main analytical techniques used in this field. Sample preparation procedures primarily include headspace sampling, dilute-and-shoot approach, liquid-liquid extraction and sorbent-based extraction for e-liquids and for aerosols (the latter usually with laboratory-built collection devices). Some challenges of current e-cigarette analytical research, and an overview on prospective work are also presented.

Comparison of supercritical fluid chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry for the stereoselective analysis of chlorfenvinphos and dimethylvinphos in tobacco.

This study used reversed-phase liquid chromatography-tandem mass spectrometry and supercritical fluid chromatography-tandem mass spectrometry for determination of the stereoisomers of chlorfenvinphos and dimethylvinphos in tobacco. Tobacco samples were extracted and purified with a modified quick, easy, cheap, effective, rugged, and safe technique using spherical carbon. The performance of both methodologies was comprehensively compared in terms of methods validation parameters (separation efficiency, linearity, selectivity, recovery, repeatability, sensitivity, matrix effect, etc.). Under optimized conditions, the calibration curves of the stereoisomers of chlorfenvinphos and dimethylvinphos in the range of 10-500 ng/mL showed excellent linearity with R2 ≥ 0.997 in both methods. The adequate recoveries of analytes from three different spiked tobaccos were obtained using reversed-phase liquid chromatography-tandem mass spectrometry (86.1-95.7%) as well as supercritical fluid chromatography-tandem mass spectrometry (86.5-94.0%). The relative standard deviations for spiked samples were all below 7.0%. Compared with supercritical fluid chromatography-tandem mass spectrometry, lower matrix effects and LODs can be obtained in reversed-phase liquid chromatography-tandem mass spectrometry.

A Bibliometric Analysis of Mesenchymal Stem Cell-Derived Exosomes in Acute Lung Injury/Acute Respiratory Distress Syndrome from 2013 to 2022.

Background: Mesenchymal stem cell-derived exosomes (MSC-exosomes) have been found to effectively improve the systemic inflammatory response caused by acute lung injury and acute respiratory distress syndrome (ALI/ARDS), regulate systemic immune disorders, and help injured cells repair. The purpose of this study was to take a holistic view of the current status and trends of MSC-exosomes research in ALI/ARDS. Methods: Bibliometrix, Citespace and VOSviewer software were used for bibliometric analysis of the data. We analysed the world trends, country distribution, institution contribution, most relevant journals and authors, research hotspots, and research hotspots related to Coronavirus Disease 2019 (COVID-19) based on the data collected. Results: China possessed the largest number of publications, while the USA had the highest H-index and the number of citations. Both China and the USA had a high influence in this research field. The largest number of publications in the field of MSC-exosomes and ALI/ARDS were mainly from the University of California system. Stem Cell Research & Therapy published the largest number of papers in this scope. The author with the greatest contribution was LEE JW, and ZHU YG published an article in Stem Cell with the highest local citation score. The most frequent keyword and the latest research hotspot were "NF-κB" and "Coronavirus Disease 2019". Furthermore, our bibliometric analysis results demonstrated that MSC-exosomes intervention and treatment can effectively alleviate the inflammatory response caused by ALI/ARDS. Conclusion: Our bibliometric study suggested the USA and China have a strong influence in this field. COVID-19-induced ALI/ARDS had become a hot topic of research.

Research trends in ferroptosis since the origin of the concept: A bibliometric analysis.

Ferroptosis is a newly characterized form of regulated cell death. This bibliometric analysis identified the scientific output, leading institutions and research teams, current research hotspots and trends in research on ferroptosis since the origin of the concept. We searched the Science Citation Index Expanded of Web of Science Core Collection for papers on ferroptosis up to 3 June 2022. The acquired data were analysed and visualized by Bibliometrix package and VOSviewer. The study ultimately included 3511 relevant papers, and annual production in this field has grown rapidly in recent years. Institutions and scholars from China contributed the most work, but the impact of their research was much less than that of the United States. Prof. Brent R. Stockwell's team from Columbia University in the United States has a very strong academic influence in the field. Front Cell Dev Biol published the most papers in the field of ferroptosis. As the keywords of the papers in this field changed from the most numerous 'oxidative stress', 'cell-death', 'iron', 'expression', and 'lipid-peroxidation', to 'prognosis', 'immunotherapy', 'progression', 'tumour microenvironment', and 'colorectal cancer', the hotspot of ferroptosis research is gradually shifting from basic research to clinical translational research. The mechanism of tumour formation and treatment will become the frontier in the field of ferroptosis research in the future.

A portable smartphone-based detection of glyphosate based on inhibiting peroxidase-like activity of heptanoic acid/Prussian blue decorated Fe3O4 nanoparticles.

The rapid and onsite detection of glyphosate in tobacco products is still a great challenge. In this study, a novel smartphone-assisted sensing platform for the detection of glyphosate has been successfully proposed through the peroxidase-like activity of Fe3O4-based nanozyme. Heptanoic acid/Prussian blue (PB) decorated Fe3O4 nanoparticles (Fe3O4@C7/PB) could catalyze and oxidize 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS, colorless) into a steel blue colored product in the presence of hydrogen peroxide. Glyphosate could specifically inhibit the peroxidase-like activity of Fe3O4@C7/PB by occupying the active site, thereby the glyphosate detection could be accomplished within 10 min by monitoring the color change of ABTS. This study has developed a smartphone-based portable detection platform for online analysis of glyphosate with a detection limit of 0.1 µg mL-1. The absorbance response curve of glyphosate showed good linearity in the concentration range of 0.125-15 µg mL-1 at 415, 647, and 730 nm. Moreover, by employing a co-precipitation technology and inhibiting the peroxidase-like activity, the glyphosate analysis would be less affected by the tobacco sample matrix. The nanosensor possesses excellent selectivity and anti-interference ability, which has application value in actual samples for onsite screening.

Development of a colloidal gold immunochromatographic test strip for the rapid detection of iprodione.

Iprodione is a dicarboximide fungicide that is widely used in agriculture around the world. A reliable and rapid detection method is needed for the on-site monitoring of iprodione residues in a variety of agricultural products. Herein, a colloidal gold immunochromatographic test strip was developed based on a selected coating antigen and a specific monoclonal antibody against iprodione. The particle size of colloidal gold, the preparation technique of the conjugate pad, the composition of the loading buffer, and the extraction solvent were comprehensively optimized for the test strip. A cut-off value of 0.9 mg kg-1 (50 ng mL-1) and a visual limit of detection of 0.09 mg kg-1 (5 ng mL-1) were achieved in a complex matrix of tobacco. No cross-reactivity was observed for iprodione metabolite and four other widely used pesticides during tobacco growth. Furthermore, the developed colloidal gold immunochromatographic test strip was applied to determine iprodione residues in tobacco samples, and the obtained results were in good agreement with those obtained by liquid chromatography tandem mass spectrometry. Additionally, the test strip was found to be stable afterlong-term storage at 37 °C for two months. The developed colloidal gold immunochromatographic test strip showed excellent accuracy, sensitivity, specificity, and stability, therefore, it is suitable for the rapid detection of iprodione residues in complex matrices.

Differential Lung Protective Capacity of Exosomes Derived from Human Adipose Tissue, Bone Marrow, and Umbilical Cord Mesenchymal Stem Cells in Sepsis-Induced Acute Lung Injury.

Exosomes derived from human mesenchymal stem cells (hMSCs) have the capacity to regulate various biological events associated with sepsis-induced acute respiratory distress syndrome (ARDS), including cellular immunometabolism, the production of proinflammatory cytokines, allowing them to exert therapeutic effects. However, little is known about which type of hMSC-derived exosomes (hMSC-exo) is more effective and suitable for the treatment of sepsis-induced ARDS. The purpose of this study is to compare the efficacy of hMSC-derived exosomes from human adipose tissue (hADMSC-exo), human bone marrow (hBMMSC-exo), and human umbilical cord (hUCMSC-exo) in the treatment of sepsis-induced ARDS. We cocultured lipopolysaccharide- (LPS-) stimulated RAW264.7 macrophage cells with the three kinds of hMSCs and found that all hMSCs reduced the glycolysis level and the content of lactic acid in macrophages. Accordingly, the expression of proinflammatory cytokines also decreased. Notably, the protective effects of hMSCs from adipose tissue were more obvious than those of bone marrow and umbilical cord hMSCs. However, this protective effect was eliminated when an exosome inhibitor, GW4869, was added. Subsequently, we extracted and cocultured hMSC-derived exosomes with LPS-stimulated RAW264.7 cells and found that all three kinds of exosomes exerted a similar protective effect as their parental cells, with exosomes from adipose hMSCs showing the strongest protective effect. Finally, an experimental sepsis model in mice was established, and we found that all three types of hMSCs have obvious lung-protective effects, in reducing lung injury scores, lactic acid, and proinflammatory cytokine levels in the lung tissues and decreasing the total protein content and inflammatory cell count in the bronchoalveolar lavage fluid (BALF), and also can attenuate the systemic inflammatory response and improve the survival rate of mice. Intravenous injection of three types of hMSC-exo, in particular those derived from adipose hADMSCs, also showed lung-protective effects in mice. These findings revealed that exosomes derived from different sources of hMSCs can effectively downregulate sepsis-induced glycolysis and inflammation in macrophages, ameliorate the lung pathological damage, and improve the survival rate of mice with sepsis. It is worth noting that the protective effect of hADMSC-exo is better than that of hBMMSC-exo and hUCMSC-exo.

LncRNA MIAT can regulate the proliferation, apoptosis, and osteogenic differentiation of bone marrow-derived mesenchymal stem cells by targeting miR-150-5p.

Osteoporosis (OP) is a systemic bone metabolic disease with complicated pathogenesis and is difficult to cure clinically. The regulatory mechanisms of OP are needed to be further investigated. In the present study, we focused on the role of myocardial infarction-associated transcript (MIAT) in OP development and examined the underlying mechanism. The serum expression levels of MIAT in samples from patients with OP and healthy controls were compared using quantitative reverse transcription-PCR (qRT-PCR). The dual-luciferase reporter assay was used to confirm the relationship between MIAT and its potential target microRNA, i.e., miR-150-5p. Moreover, bone marrow-derived mesenchymal stem cells (BMSCs) were cultured and transfected with MIAT shRNA, with or without miR-150-5p inhibitor. EdU staining and colony formation analysis were performed to determine the proliferation ability of these cells. Furthermore, the TUNEL assay and flow cytometry were used to assess BMSC apoptosis. Finally, RT-PCR and Western blot assays were employed to assess the expression of osteogenic differentiation biomarkers. Compared with controls, the expression of MIAT was significantly increased, whereas that of miR-150-5p was markedly decreased in patients with OP. MIAT and miR-150-5p expression levels exhibited a strong negative correlation. Furthermore, osteogenic differentiation indicators were suppressed in serum of OP patients. MIAT was downregulated, and miR-150-5p was upregulated in induced to osteogenic differentiation BMSCs. Furthermore, downregulation of MIAT dramatically promoted osteogenic differentiation, increased proliferation, and inhibited apoptosis in BMSCs; miR-150-5p inhibitor abrogated the effects of MIAT. In conclusion, lncRNA MIAT can regulate the proliferation, apoptosis, and osteogenic differentiation of BMSCs.

Global Research Trends and Hotspots on Mitochondria in Acute Lung Injury from 2012-2021: A Bibliometric Analysis.

BACKGROUND: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a clinical syndrome associated with mitochondria and lacks effective preventive and therapeutic measures. This bibliometric study aims to gain insight into the scientific findings regarding mitochondria in ALI/ARDS. METHODS: We retrieved the Science Citation Index Expanded (SCIE) of the Web of Science Core Collection (WoSCC) for mitochondria in ALI/ARDS publications from 2012-2021. VOSviewer, CiteSpace (5.8. R3) and Bibliometrix (3.1.4) R package were used for further analysis and visualization. RESULT: A total of 756 English-language articles and reviews were identified. The annual number of publications presented a rapidly developing trend. China was the most productive and cited country, and the USA had the greatest impact. In the keyword co-occurring network, the terms "acute lung injury", "oxidative stress", "inflammation", "mitochondria" and "apoptosis" occurred most frequently. The co-citation network revealed that #1 mesenchymal stromal cell and #3 endothelial cell had the most bursts of citations. In addition, research hotspots have shifted from "potential therapeutic treatments" and "mitochondrial DNA (mtDNA)" to "endothelial cell" and "mesenchymal stromal cell (MSC)". CONCLUSION: This bibliometric analysis reveals the research directions and frontier hotspots of mitochondria in ALI/ARDS, which has shown a rapid growth trend in annual publication numbers. mtDNA, mitophagy, and apoptosis have been the most active research areas, while studies on mitochondrial transfer in stem cells have become a hot topic in recent years.

Construction of a TRFIC strip for rapid and sensitive detection of Ralstoniasolanacearum.

The development of a sensitive and rapid screening method for Ralstonia solanacearum is critical for the control of tobacco wilt. In the present study, tissue homogenates of three tobacco varieties (Honda, Yunnan 87 and K326) with different resistance to R. solanacearum, were individually used as additives to the bacteria culture medium. The changes in R. solanacearum secretome were investigated and one of the most abundant secretary proteins with increased expression, polygalacturonase (PG), was selected as a marker for R. solanacearum identification. Then PG gene was cloned into E. coli, and the expressed protein was used as the immunogen to develop monoclonal antibodies. Subsequently, the monoclonal antibody against PG was coupled with synthesized polystyrene microspheres, and a rapid test strip system was developed for the detection of R. solanacearum based on time-resolved fluorescent immunochromatographic (TRFIC) method. Under optimal conditions, the detection limit of the strips could reach 72 cells/mL; while it was 422 cells/mL with a linear range from 4 × 102 to 5.12 × 104 cells/mL when testing tobacco samples, which is 1000 times lower than that of colloidal gold-labeled strips. Notably, no cross-reactivity was observed with nine tobacco-related pathogens. Finally, this TRFIC strips was applied to detect R. solanacearum existed in the tobacco and soils of fields with or without bacterial wilt. The results demonstrated that this TRFIC strips could distinguish the difference in bacterial concentration existed in tobacco and soil between the two fields. In summary, this test strip is suitable for sensitive, quick screening of R. solanacearum in tobacco.

Highly sensitive time-resolved fluoroimmunoassay for the quantitative onsite detection of Alternaria longipes in tobacco.

AIMS: Alternaria longipes is a causal agent of brown spot of tobacco, which remains a serious threat to tobacco production. Herein, we established a detection method for A. longipes in tobacco samples based on the principle of time-resolved fluoroimmunoassay, in order to fulfil the requirement of rapid, sensitive and accurate detection in situ. METHODS AND RESULTS: A monoclonal antibody against A. longipes was generated, and its purity and titration were assessed using western blot and ELISA. The size of europium (III) nanospheres was measured to confirm successful antibody conjugation. The method described here can detect A. longipes protein lysates as low as 0.78 ng ml-1 , with recovery rates ranging from 85.96% to 99.67% in spiked tobacco. The specificity was also confirmed using a panel of microorganisms. CONCLUSIONS: The fluorescent strips allow rapid and sensitive onsite detection of A. longipes in tobacco samples, with high accuracy, specificity, and repeatability. SIGNIFICANCE AND IMPACT OF THE STUDY: This novel detection method provides convenience of using crude samples without complex procedures, and therefore allows rapid onsite detection by end users and quick responses towards A. longipes, which is critical for disease control and elimination of phytopathogens.

Two cGAS-like receptors induce antiviral immunity in Drosophila.

In mammals, cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the cyclic dinucleotide 2'3'-cGAMP in response to cytosolic DNA and this triggers an antiviral immune response. cGAS belongs to a large family of cGAS/DncV-like nucleotidyltransferases that is present in both prokaryotes1 and eukaryotes2-5. In bacteria, these enzymes synthesize a range of cyclic oligonucleotides and have recently emerged as important regulators of phage infections6-8. Here we identify two cGAS-like receptors (cGLRs) in the insect Drosophila melanogaster. We show that cGLR1 and cGLR2 activate Sting- and NF-κB-dependent antiviral immunity in response to infection with RNA or DNA viruses. cGLR1 is activated by double-stranded RNA to produce the cyclic dinucleotide 3'2'-cGAMP, whereas cGLR2 produces a combination of 2'3'-cGAMP and 3'2'-cGAMP in response to an as-yet-unidentified stimulus. Our data establish cGAS as the founding member of a family of receptors that sense different types of nucleic acids and trigger immunity through the production of cyclic dinucleotides beyond 2'3'-cGAMP.

Ultrasound-Guided Continuous Thoracic Paravertebral Infusion of Methylene Blue in the Treatment of Postherpetic Neuralgia: A Prospective, Randomized, Controlled Study.

INTRODUCTION: Postherpetic neuralgia (PHN) is the most common complication of herpes zoster. Methylene blue (MB) is an inhibitor of nitric oxide synthesis with potentially analgesic and anti-inflammatory properties. Studies have demonstrated that thoracic paravertebral single MB injection is effective in treating chronic pain. However, there are rare reports of the efficacy of continuous thoracic paravertebral infusion of MB for pain management in PHN patients. The purpose of this study was to evaluate the therapeutic effects of continuous thoracic paravertebral infusion of MB on PHN. METHODS: A total of 104 PHN patients were randomly divided into two groups: the control group (continuous thoracic paravertebral infusion of 5% lidocaine in a total volume of 300 ml) and the MB group (continuous thoracic paravertebral infusion of 5% lidocaine plus 0.2% MB in a total volume of 300 ml). All patients were evaluated using the Numerical Rating Scale (NRS), Insomnia Severity Index (ISI), Patient Health Questionnaire-9 (PHQ-9), 36-Item Short-Form Health Survey (SF-36), and medication doses before and after the procedure. The effective treatment rate and adverse complications were recorded 6 months after the procedure. RESULTS: In both groups, the NRS scores, ISI scores, PHQ-9 scores, and rescue medication dosages were significantly decreased at different time points after treatment compared to baseline, while the SF-36 scores were evidently improved at different time points after treatment compared to baseline. Compared with the control group, the MB group had significantly reduced NRS scores, ISI scores, PHQ-9 scores, and rescue medication dosages at each observation time point. Furthermore, the SF-36 scores in the MB group were significantly higher than those in the control group at each observation time point. The total effective treatment rate of the MB group was higher than that of the control group 6 months after the procedure. No severe adverse complications were observed in either group. CONCLUSIONS: Ultrasound-guided continuous thoracic paravertebral infusion with MB is a safe and effective therapy for PHN. Continuous infusion with MB can significantly reduce pain intensity, improve pain-related depression, increase quality of life, and decrease the amount of rescue medicine with no serious adverse complications.

A rapid method for the simultaneous stereoselective determination of the triazole fungicides in tobacco by supercritical fluid chromatography-tandem mass spectrometry combined with pass-through cleanup.

This work presents a simple, rapid and green chiral analysis method for five triazole fungicides (penconazole, tebuconazole, triadimefon, myclobutanil, and triadimenol) in tobacco, by which the samples were cleaned up by the novel pass-through solid phase extraction and subsequently the stereoisomers were separated and determined by the supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS). Optimized separation of the stereoisomers was achieved on an ACQUITY UPC2 Trefoil AMY 1 column within 6 min. Under fortified concentration levels of 0.1, 0.5 and 2.0 mg/kg, the mean recoveries were 82.8-106.6%, the intra-day relative standard deviations (RSDs) were 1.1-6.6%, and the inter-day RSDs were 2.5-5.6%. The correlation coefficient was greater than 0.9926 for all studied analytes within the range of 10-500 ng/mL. The limits of detection (LODs) for all stereoisomers ranged from 0.26 µg/kg to 3.24 µg/kg. The established method was subsequently successfully applied to analyze authentic samples, confirming that this method is a novel, rapid and environmentally friendly method for the stereoselective separation of triazole fungicides in tobacco.

Separation of N'-nitrosonornicotine isomers and enantiomers by supercritical fluid chromatography tandem mass spectrometry.

N'-nitrosonornicotine (NNN) is one of the most prevalent and toxic tobacco-specific nitrosoamines. A chiral center at its 2'-position results in R and S enantiomers, the partial double bond character of the NN = O group also results in E and Z isomers, therefore, NNN can form a total of four absolute configurations (E-(R)-NNN, E-(S)-NNN, Z-(R)-NNN, and Z-(S)-NNN). This study investigated the resolution of R/S enantiomers and E/Z isomers of NNN by supercritical fluid chromatography tandem mass spectrometry (SFC-MS/MS). The baseline separation of E/Z-(R,S)-NNN isomers/enantiomers was accomplished through the optimization of chiral columns and co-solvents. Due to the lack of single standard of E/Z isomers, only R-NNN (sum of E-(R)-NNN and Z-(R)-NNN) and S-NNN (sum of E-(S)-NNN and Z-(S)-NNN) were further examined. Through the comprehensive optimization of SFC-MS/MS conditions, R-NNN and S-NNN were separated with a run time of 5 min, the developed method was validated, and its applicability to the determination of NNN enantiomers in burley tobacco samples was demonstrated. This study could be applied to preparative separation of single enantiomer and/or isomer of NNN, and could provide potential benefits to biologic activity studies on these enantiomers and isomers.

A Potential Serum Biomarker, Albumin-to-Glutamyltransferase Ratio, Suggests the Severity of Liver Disease.

BACKGROUND: We aimed to investigate the utility of albumin-to-glutamyltransferase ratio (AGR) as a new biomarker to distinguish hepatic carcinoma from hepatitis, as early disease diagnosis, prognosis or monitoring could improve patient management and outcomes. METHODS: Clinical characteristics of 34 hepatitis (women 19), 88 cirrhosis (women 22) and 52 hepatic carcinoma (women 9) cases were retrospectively reviewed. Patients diagnosed with cirrhosis were classified by Child-Pugh score and the presence of ascites. The differences among groups were evaluated by the Kruskal-Wallis test and Mann-Whitney U. The linear correlation between variables was assessed by Spearman's correlation analysis. The diagnostic value of albumin-to-glutamyltransferase (AGR) was considered using receiver operating characteristic (ROC) curves. Multiple logistic regression analysis and univariate logistic regression analysis were used to identify AGR as an independent predictor in liver disease progression. RESULTS: The significant differences among the hepatitis vs. cirrhosis vs. and hepatic carcinoma were AST (108.50 ± 184.00 vs. 38.00 ± 21.50 vs. 47.00 ± 71.00, p < 0.01), TP/AST (TAR, 0.67 ± 0.69 vs. 1.77 ± 0.87 vs. 1.36 ± 0.95, p < 0.01), and ALB/GGT (AGR, 0.32 ± 0.27 vs. 0.67 ± 0.43 vs. 0.20 ± 0.26, p < 0.05). At the same time, AST (32.00 ± 13.50 vs. 53.00 ± 23.00 vs. 114.50 ± 42.50, p < 0.05) and TAR (2.15 ± 0.72 vs. 1.28 ± 0.74 vs. 0.64 ± 0.39, p < 0.05) were higher but AGR (0.86 ± 0.54 vs. 0.46 ± 0.32 vs. 0.26 ± 0.22, p < 0.05) was lower in Child-Pugh class C group compared with group B and C. TAR (1.92 ± 0.73 vs. 0.98 ± 0.89, p < 0.01) and AGR (0.79 ± 0.52 vs. 0.46 ± 0.28, p < 0.05) were significantly elevated in the serum of cirrhosis with no ascites compared with the cirrhosis patients suffered from ascites, while AST (35.00 ± 14.50 vs. 63.00 ± 44.50, p < 0.01) was reduced in cirrhosis patients with no ascites. Furthermore, AST (r = 0.4490, p<0.01) was positively correlated with AFP, TAR (r = -0.4393, p < 0.01) and AGR (r = -0.4395, p < 0.01) were negatively correlated with AFP. The ROC curve analysis for AST had an area under the curve (AUC) ranging from 0.66 to 0.82, TAR ranged from 0.64 to 0.80 and AGR ranged from 0.54 to 0.72. Multiple logistic regression analysis revealed AGR as an independent parameter to distinguish liver can¬cer to hepatitis, and AGR was associated with the presence of ascites and the progression in cirrhosis patients. CONCLUSIONS: AGR is a potential biomarker for diagnosis of liver disease progression.