Investigation of the causal association between Parkinson's disease and autoimmune disorders: a bidirectional Mendelian randomization study.

Background: To date, an increasing number of epidemiological evidence has pointed to potential relationships between Parkinson's disease (PD) and various autoimmune diseases (AIDs), however, no definitive conclusions has been drawn about whether PD is causally related to AIDs risk. Methods: By employing summary statistics from the latest and most extensive genome-wide association studies (GWAS), we performed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal associations between PD and a variety of 17 AIDs, encompassing multiple sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis, asthma, inflammatory bowel disease, Crohn's disease, ulcerative colitis, irritable bowel syndrome, celiac disease, primary biliary cirrhosis, primary sclerosing cholangitis, type 1 diabetes, ankylosing spondylitis, rheumatoid arthritis, systemic lupus erythematosus, psoriasis and vitiligo. Inverse-variance weighted (IVW) was adopted as the main statistical approach to obtain the causal estimates of PD on different AIDs, supplemented by a series of complementary analyses (weighted median, MR Egger regression, and MR-PRESSO) for further strengthening the robustness of results. Results: Our MR findings suggested that genetically predicted higher liability to PD was causally associated with a decreased risk of irritable bowel syndrome (OR = 0.98; 95% CI: 0.96-0.99; P = 0.032). On the contrary, IVW analysis showed a potential positive correlation between genetically determined PD and the incidence of type 1 diabetes (OR = 1.10; 95%CI: 1.02-1.19; P = 0.010). Subsequent MR tests ended up in similar results, confirming our findings were reliable. Additionally, in the reverse MR analyses, we did not identify any evidence to support the causal relationship of genetic predisposition to AIDs with PD susceptibility. Conclusion: In general, a bifunctional role that PD exerted on the risk of developing AIDs was detected in our studies, both protecting against irritable bowel syndrome occurrence and raising the incidence of type 1 diabetes. Future studies, including population-based observational studies and molecular experiments in vitro and in vivo, are warranted to validate the results of our MR analyses and refine the underlying pathological mechanisms involved in PD-AIDs associations.

Transient dataset of household appliances with Intensive switching events.

With the development of Non-Intrusive Load Monitoring (NILM), it has become feasible to perform device identification, energy consumption decomposition, and load switching detection using Deep Learning (DL) methods. Similar to other machine learning problems, the research and validation of NILM necessitate substantial data support. Moreover, different regions exhibit distinct characteristics in their electricity environments. Therefore, there is a need to provide open datasets tailored to different regions. In this paper, we introduce the Transient Dataset of Household Appliances with Intensive Switching Events (TDHA25). This dataset comprises switch instantaneous data from 10 typical household appliances in China. The TDHA dataset features a high sampling rate, accurate labelling, and realistic representation of actual appliance start-up waveforms. Additionally, appliance switching is achieved through precise control of relay switches, thus mitigating interference caused by mechanical switches. By furnishing such a dataset, we aim not only to enhance the recognition accuracy of existing NILM algorithms but also to facilitate the application of NILM algorithms in regions sharing similar electricity consumption characteristics to those of China.

Rhizoma Alismatis Decoction improved mitochondrial dysfunction to alleviate SASP by enhancing autophagy flux and apoptosis in hyperlipidemia acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas, especially hyperlipidemia acute pancreatitis (HLAP) is the third leading cause of acute pancreatitis which is more severe with a greater incidence of persistent multiorgan failure. HLAP inflicts injury upon the organelles within the acinar cell, particularly mitochondria, the endolysosomal-autophagy system, and is accompanied by senescence-associated secretory phenotype (SASP). RAD, only two consists of Rhizoma Alismatis and Atractylodes macrocephala Rhizoma, which is best known for its ability to anti-inflammatory and lipid-lowering. Nevertheless, the mechanism by which RAD alleviates HLAP remains obscure, necessitating further investigation. PURPOSE: The study aimed to assess the effects of the RAD on HLAP and to elucidate the underlying mechanism in vivo and in vitro, offering a potential medicine for clinical treatment for HLAP. STUDY DESIGN AND METHODS: C57BL/6 mice with hyperlipidemia acute pancreatitis were induced by HFD and CER, then administrated with RAD. AR42J were stimulated by cerulein or conditioned medium and then cultured with RAD. Serums were analyzed to evaluate potential pancreas and liver damage. Furthermore, tissue samples were obtained for histological, and protein investigations by H&E, Oil red staining, and Western blot. In addition, western blot and immunofluorescent staining were utilized to estimate the effect of RAD on mitochondrial function, autophagy flux, and SASP. RESULTS: In vivo, RAD considerably alleviated systemic inflammation while attenuating TC, TG, AMY, LPS, inflammatory cytokines, histopathology changes, oxidative damage, mitochondrial fission, and autophagy markers in HLAP mice. Impaired autophagy flux and mitochondrial dysfunction resulted in a significant enhancement of NLRP3 and IL-1ß in the pancreas. RAD could reverse these changes. In vitro, RAD significantly restored mitochondrial membrane potential and oxidative phosphorylation levels. RAD decreased Beclin-1 and LC3-II expression and increased LAMP-1 and Parkin-Pink expression, which showed that RAD significantly ameliorated HLAP-induced damage to the mitochondria function by suppressing mitochondrial oxidative damage and enhancing autophagy flux and mitophagy to remove the damaged mitochondria. In addition, we found that RAD could up-regulate the expression of BAX, and Bad and down-regulate the expression of p16, and p21, indicating that RAD could promote damaged cell apoptosis and alleviate SASP. CONCLUSIONS: This study revealed that RAD ameliorates mitochondrial function to alleviate SASP through enhancing autophagy flux, mitophagy, and apoptosis which provided a molecular basis for the advancement and development of protection strategies against HLAP.

Identifying piRNAs that regulate BaP-induced lung injuries: A bottom-up approach from toxicity pathway investigation to animal validation.

PIWI-interacting RNAs (piRNAs) is an emerging class of small non-coding RNAs that has been recently reported to have functions in infertility, tumorigenesis, and multiple diseases in humans. Previously, 5 toxicity pathways were proposed from hundreds of toxicological studies that underlie BaP-induced lung injuries, and a "Bottom-up" approach was established to identify small non-coding RNAs that drive BaP-induced pulmonary effects by investigating the activation of these pathways in vitro, and the expression of the candidate microRNAs were validated in tissues of patients with lung diseases from publications. Here in this study, we employed the "Bottom-up" approach to identifying the roles of piRNAs and further validated the mechanisms in vivo using mouse acute lung injury model. Specifically, by non-coding RNA profiling in in vitro BaP exposure, a total of 3 suppressed piRNAs that regulate 5 toxicity pathways were proposed, including piR-004153 targeting CYP1A1, FGFR1, ITGA5, IL6R, NGRF, and SDHA, piR-020326 targeting CDK6, and piR-020388 targeting RASD1. Animal experiments demonstrated that tail vein injection of respective formulated agomir-piRNAs prior to BaP exposure could all alleviate acute lung injury that was shown by histopathological and biochemical evidences. Immunohistochemical evaluation focusing on NF-kB and Bcl-2 levels showed that exogenous piRNAs protect against BaP-induced inflammation and apoptosis, which further support that the inhibition of the 3 piRNAs had an important impact on BaP-induced lung injuries. This mechanism-driven, endpoint-supported result once again confirmed the plausibility and efficiency of the approach integrating in silico, in vitro, and in vivo evidences for the purpose of identifying key molecules.

A novel stochastic resonance based deep residual network for fault diagnosis of rolling bearing system.

Rolling bearings constitute one of the most vital components in mechanical equipment, monitoring and diagnosing the condition of rolling bearings is essential to ensure safe operation. In actual production, the collected fault signals typically contain noise and cannot be accurately identified. In the paper, stochastic resonance (SR) is introduced into a spiking neural network (SNN) as a feature enhancement method for fault signals with varying noise intensities, combining deep learning with SR to enhance classification accuracy. The output signal-to-noise ratio(SNR) can be enhanced with the SR effect when the noise-affected fault signal input into neurons. Validation of the method is carried out through experiments on the CWRU dataset, achieving classification accuracy of 99.9%. In high-noise environments, with SNR equal to -8 dB, SRDNs achieve over 92% accuracy, exhibiting better robustness and adaptability.

Association of adherence to the enhanced recovery after surgery pathway and outcomes after laparoscopic total gastrectomy.

OBJECTIVE: The current study used a composite outcome to investigate whether applying the ERAS protocol would enhance the recovery of patients undergoing laparoscopic total gastrectomy (LTG). EXPOSURES: Laparoscopic total gastrectomy and perioperative interventions were the exposure. An ERAS clinical pathway consisting of 14 items was implemented and assessed. Patients were divided into either ERAS-compliant or non-ERAS-compliant group according the adherence above 9/14 or not. MAIN OUTCOMES AND MEASURES: The primary study outcome was a composite outcome called 'optimal postoperative recovery' with the definition as below: discharge within 6 days with no sever complications and no unplanned re-operation or readmission within 30 days postoperatively. Univariate logistic regression analysis and multivariate logistic regression analysis were used to model optimal postoperative recovery and compliance, adjusting for patient-related and disease-related characteristics. RESULTS: A total of 252 patients were included in this retrospective study, 129 in the ERAS compliant group and 123 in the non-ERAS-compliant group. Of these, 79.07% of the patients in ERAS compliant group achieved optimal postoperative recovery, whereas 61.79% of patients in non-ERAS-compliant group did (P = 0.0026). The incidence of sever complications was lower in the ERAS-compliant group (1.55% vs. 6.5%, P = 0.0441). No patients in ERAS compliant group had unplanned re-operation, whereas 5.69% (7/123) of patients in non-ERAS-compliant group had (p = 0.006). The median length of the postoperative hospital stay was shorter in the in the ERAS compliant group (5.51 vs. 5.68 days, P = 0.01). Both logistic (OR 2.01, 95% CI 1.21-3.34) and stepwise regression (OR 2.07, 95% CI 1.25-3.41) analysis showed that high overall compliance with the ERAS protocol facilitated optimal recovery in such patients. In bivariate analysis of compliance for patients who had an optimal postoperative recovery, carbohydrate drinks (p = 0.0196), early oral feeding (P = 0.0043), early mobilization (P = 0.0340), and restrictive intravenous fluid administration (P < 0.0001) were significantly associated with optimal postoperative recovery. CONCLUSIONS AND RELEVANCE: Patients with higher ERAS compliance (almost 70% of the accomplishment) suffered less severe postoperative complications and were more likely to achieve optimal postoperative recovery.

Systematic review of melatonin in cerebral ischemia-reperfusion injury: critical role and therapeutic opportunities.

Cerebral ischemia-reperfusion (I/R) injury is the predominant causes for the poor prognosis of ischemic stroke patients after reperfusion therapy. Currently, potent therapeutic interventions for cerebral I/R injury are still very limited. Melatonin, an endogenous hormone, was found to be valid in preventing I/R injury in a variety of organs. However, a systematic review covering all neuroprotective effects of melatonin in cerebral I/R injury has not been reported yet. Thus, we perform a comprehensive overview of the influence of melatonin on cerebral I/R injury by collecting all available literature exploring the latent effect of melatonin on cerebral I/R injury as well as ischemic stroke. In this systematic review, we outline the extensive scientific studies and summarize the beneficial functions of melatonin, including reducing infarct volume, decreasing brain edema, improving neurological functions and attenuating blood-brain barrier breakdown, as well as its key protective mechanisms on almost every aspect of cerebral I/R injury, including inhibiting oxidative stress, neuroinflammation, apoptosis, excessive autophagy, glutamate excitotoxicity and mitochondrial dysfunction. Subsequently, we also review the predictive and therapeutic implications of melatonin on ischemic stroke reported in clinical studies. We hope that our systematic review can provide the most comprehensive introduction of current advancements on melatonin in cerebral I/R injury and new insights into personalized diagnosis and treatment of ischemic stroke.

Screening and validation of an alkaline-tolerant biomimetic affinity chromatography A5-87 resin for purification of discarded bovine serum Immunoglobulin G.

It is important to recycle the bovine blood discarded at slaughter and develop it into high value-added bovine serum products. Biomimetic affinity chromatography (BiAC) resins have been developed to specifically purify bovine serum immunoglobulin G (Bs-IgG). The BiAC strategy was used to screen the resins with the best purification effect on Bs-IgG. Four resins with specificity for Bs-IgG adsorption were selected from 90 BiAC resins. Finally, BiAC-A5-87 was selected and used to purify Bs-IgG based on the results of SDS-PAGE and BCA protein quantification analysis. The adsorption capacity and purity of BiAC-A5-87 were 32.79 ± 3.57 mg/mL and 85.9 ± 1.21 % for Bs-IgG, respectively. The total protein recovery rate of Bs-IgG purified by BiAC-A5-87 was 89.78±3.52 %. The resin of BiAC-A5-87 column was recycled in 40 breakthrough cycles, and its Bs-IgG adsorption efficiency decreased by less than 10 %. After soaking BiAC-A5-87 in 1.0 moL NaOH solution for 64 h, its adsorption capacity for Bs-IgG was almost the same as that before soaking. The development of waste bovine serum not only realizes the utilization of blood resources and produces high economic benefits but also reduces the pollution of the environment.

[Development of Vital Signal Monitoring System Based on Accelerometer].

OBJECTIVE: Reduce the number of false alarms and measurement time caused by movement interference by the sync waveform of the movement. METHODS: Vital signal monitoring system based on motion sensor was developed, which collected and processed the vital signals continuously, optimized the features and results of vital signals and transmitted the vital signal results and alarms to the interface. RESULTS: The system was tested in many departments, such as digestive department, cardiology department, internal medicine department, hepatobiliary surgery department and emergency department, and the total collection time was 1 940 h. The number of false electrocardiograph (ECG) alarms decreased by 82.8%, and the proportion of correct alarms increased by 28%. The average measurement time of non-invasive blood pressure (NIBP) decreased by 16.1 s. The total number of false respiratory rate measurement decreased by 71.9%. CONCLUSIONS: False alarms and measurement failures can be avoided by the vital signal monitoring system based on accelerometer to reduce the alarm fatigue in clinic.

Transcriptional Analysis of lncRNA and Target Genes Induced by Influenza A Virus Infection in MDCK Cells.

BACKGROUND: The MDCK cell line is the primary cell line used for influenza vaccine production. Using genetic engineering technology to change the expression and activity of genes that regulate virus proliferation to obtain high-yield vaccine cell lines has attracted increasing attention. A comprehensive understanding of the key genes, targets, and molecular mechanisms of viral regulation in cells is critical to achieving this goal, yet the post-transcriptional regulation mechanism involved in virus proliferation-particularly the effect of lncRNA on influenza virus proliferation-is still poorly understood. Therefore, this study used high-throughput RNA-seq technology to identify H1N1 infection-induced lncRNA and mRNA expression changes in MDCK cells and explore the regulatory relationship between these crucial lncRNAs and their target genes. RESULTS: In response to H1N1 infection in MDCK cells 16 h post-infection (hpi) relative to uninfected controls, we used multiple gene function annotation databases and initially identified 31,501 significantly differentially expressed (DE) genes and 39,920 DE lncRNAs (|log2FC| > 1, p < 0.05). Among these, 102 lncRNAs and 577 mRNAs exhibited predicted correlations with viral response mechanisms. Based on the magnitude of significant expression differences, related research, and RT-qPCR expression validation at the transcriptional level, we further focused on 18 DE mRNAs and 32 DE lncRNAs. Among these, the differential expression of the genes RSAD2, CLDN1, HCLS1, and IFIT5 in response to influenza virus infection was further verified at the protein level using Western blot technology, which showed results consistent with the RNA-seq and RT-qPCR findings. We then developed a potential molecular regulatory network between these four genes and their six predicted lncRNAs. CONCLUSIONS: The results of this study will contribute to a more comprehensive understanding of the molecular mechanism of host cell non-coding RNA-mediated regulation of influenza virus replication. These results may also identify methods for screening target genes in the development of genetically engineered cell lines capable of high-yield artificial vaccine production.

Changes in coagulation markers in children with Mycoplasma pneumoniae pneumonia and their predictive value for Mycoplasma severity.

BACKGROUND: This study investigates the correlation between coagulation levels and the severity of Mycoplasma pneumoniae pneumonia (MPP) in children. In addition, the study analyses the predictive value of coagulation abnormalities in MPP combined with necrotising pneumonia (NP). METHODS: A total of 170 children with MPP who underwent treatment between June 2021 and February 2022 were selected for this study. The study population was divided into groups according to the severity of the disease to compare differences in the incidence of coagulation abnormalities between the groups. The participants were also divided into groups according to imaging manifestations to compare the differences in coagulation function among the different groups. All data information was processed for statistical analysis using SPSS Statistics 25.0 and GraphPad Prism 7.0 statistical analysis software. RESULTS: The incidence of coagulation abnormalities in the children in the severe MPP (SMPP) group was significantly higher than that in the normal MPP (NMPP) group (P < 0.05). The multi-factor logistic regression analysis revealed that the D-dimer level is an independent risk factor for the development of NP in SMPP (P < 0.05). The receiver operating characteristic curve analysis revealed statistically significant differences (P < 0.05) in D-dimer, fibrinogen degeneration products (FDP), neutrophils, lactate dehydrogenase and serum ferritin for predicting SMPP combined with NP. Bronchoscopic manifestations of coagulation indicators (D-dimer and FDP levels) were significantly higher in the mucus plug group than in the non-mucus plug group, while the activated partial thromboplastin time levels were lower in the former than in the latter (P < 0.05). CONCLUSION: The degree of elevated D-dimer and FDP levels was positively correlated with the severity of MPP, with elevated serum D-dimer levels (> 3.705 mg/L) serving as an independent predictor of MPP combined with NP in children.

UV-based solvent system screening for high-speed counter-current chromatography fractionation of compounds with similar UV absorption from complex samples followed by preparative HPLC purification: Flavonoids from barley seedlings as sample.

This article proposes a solvent system screening strategy for compounds with similar UV absorption in complex samples by UV spectrophotometer. There is no need to calculate the partition coefficient value of each compound, only the partition coefficient of the whole sample. The partition coefficient value should be close to 1 in order to obtain as many high-speed counter-current chromatography fractions as possible. Then, preparative HPLC was used to purify the high-speed counter-current chromatography fractions. Based on the above strategy, seven c-glycosyl flavonoids and an amino acid were successfully obtained from barley seedlings through high-speed counter-current chromatography fractionation with ethyl acetate/n-butanol/water (8:2:10, v:v:v) system followed by preparative HPLC purification. The research shows that high-speed counter-current chromatography could be well developed as a tool for fractionation before purification, and greatly improves the separation efficiency.

Study on the function of Huazhuo Jiedu Decoction in promoting the homing of bone marrow mesenchymal stem cells and contributing to the treatment of ulcerative colitis.

Objective: To study the function of Huazhuo Jiedu Decoction (HZJD) in promoting the homing of bone marrow mesenchymal stem cells (BMSCs) and contributing to the reconstruction of the intestinal mucosal barrier in ulcerative colitis. Methods: Bone mesenchymal stem cells derived from mice were isolated and cultured, osteogenic and adipogenic assays to study the differentiation ability of BMSCs, and flow cytometry was used to detect the surface marker of the third generation cells. 30 mice were selected and divided into blank group, model group, HZJD group, BMSCs group, and HZJD combined with BMSCs group. Mouse colon length, body weight, and DAI score were used to assess efficacy. The levels of IL-6, IL-1ß, TNF-α, and IFN-γ in serum were measured by ELISA. BMSCs transfected with GFP were used to mark the homing of BMSCs in mice. The BMSCs tagging protein CD90+/CD29+ was detected by immunofluorescence. H&E staining detects damage to the colon and the inflammatory response. The expression levels of claudin-2, claudin-4, occludin, and ZO-1 in colon tissues were detected by Western blot. Results: After subculture, the cell grew with adherence. Flow cytometry showed that the cells were CD73+/CD90+/CD29+/CD45-/CD34-, which belonged to bone mesenchymal stem cells. ELISA showed that the treatment with HZJD and BMSCs suppressed the DSS-induced inflammatory response. BMSCs carrying GFP can be detected in intestinal tissues. Immunofluorescence showed that the HZJD combined with the BMSCs group had more BMSCs homing to the colonic tissue. The results of H&E and Western blot showed that DSS-induced intestinal mucosal damage in UC mice was repaired by HZJD and BMSCs, and the abnormal tight junction proteins claudin-2, claudin-4, occludin, and ZO-1 were normalized. Conclusion: HZJD has a therapeutic effect on ulcerative colitis by promoting the migration of BMSCs to ulcers of the colon and contributing to the reconstruction of the intestinal mucosal barrier in ulcerative colitis.

HIF-1α-PPARγ-mTORC1 signaling pathway-mediated autophagy induces inflammatory response in pancreatic cells in rats with hyperlipidemic acute pancreatitis.

OBJECTIVE: The incidence of hyperlipidemic acute pancreatitis (HLAP) has rapidly increased in recent years in China. Autophagy has been implicated in the inflammatory response of pancreatic cells in HLAP, but the molecular mechanisms remain unclear. METHODS: In this study, the role of HIF-1α-PPARγ-mTORC1 pathway-mediated autophagy in the inflammatory response of pancreatic cells and the underlying molecular mechanism were investigated in a rat model of HLAP using immunohistochemistry, ELISA, electron microscopy, and western blot analysis. RESULTS: The results revealed that autophagy was significantly increased and pancreatic injury was exacerbated in HLAP rats, and the inflammatory response was further exacerbated by treatment with rapamycin but relieved by treatment with 3-MA. Hyperlipidemia induced upregulation of HIF-1α and downregulation of PPARγ, which in turn led to an increase in autophagy and consequently exacerbation of the inflammatory response of pancreatic cells. CONCLUSIONS: HIF-1α-PPARγ-mTORC1 pathway-mediated autophagy plays a critical role in the inflammatory response of pancreatic cells in HLAP, and interference with the HIF-1α-PPARγ-mTOR pathway can serve as a new strategy for the prevention and treatment of HLAP.

Development of MDCK-based quadrivalent split seasonal influenza virus vaccine with high safety and immunoprotection: A preclinical study.

Vaccination remains the best prevention strategy against influenza. The MDCK-based influenza vaccine prompted the development of innovative cell culture manufacturing processes. In the present study, we report the effects of multiple administrations of a candidate, seasonal, MDCK-based, quadrivalent split influenza virus vaccine MDCK-QIV in Sprague-Dawley (SD) rats. Moreover, the effects of the vaccine were evaluated in terms of fertility and early embryonic development, embryo-fetal development, and perinatal toxicity in the SD rats and immunogenicity in Wistar rats and BALB/c mice. Regarding the safety profile, MDCK-QIV demonstrated tolerance in local stimulation with repeated dose administration and presented no significant effect on the development, growth, behavior, fertility, and reproductive performance of the adult male rats, maternal rats, and their offspring. MDCK-QIV elicited strong hemagglutination inhibition neutralizing antibody response and protection against the influenza virus in the mouse model. Thus, data supported that MDCK-QIV could be further evaluated in human clinical trial, which is currently underway.

Changes in early postoperative outcomes and complications observed in a single center during the 2022 COVID-19 pandemic wave in China: A single-center ambispective cohort study.

BACKGROUND: Currently, the effect of the 2022 nationwide coronavirus disease 2019 (COVID-19) wave on the perioperative prognosis of surgical patients in China is unclear. Thus, we aimed to explore its influence on postoperative morbidity and mortality in surgical patients. METHODS: An ambispective cohort study was conducted at Xijing Hospital, China. We collected 10-day time-series data from December 29 until January 7 for the 2018-2022 period. The primary outcome was major postoperative complications (Clavien-Dindo class III-V). The association between COVID-19 exposure and postoperative prognosis was explored by comparing consecutive 5-year data at the population level and by comparing patients with and without COVID-19 exposure at the patient level. RESULTS: The entire cohort consisted of 3350 patients (age: 48.5 ± 19.2 years), including 1759 females (52.5%). Overall, 961 (28.7%) underwent emergency surgery, and 553 (16.5%) had COVID-19 exposure (from the 2022 cohort). At the population level, major postoperative complications occurred in 5.9% (42/707), 5.7% (53/935), 5.1% (46/901), 9.4% (11/117), and 22.0% (152/690) patients in the 2018-2022 cohorts, respectively. After adjusting for potential confounding factors, the 2022 cohort (80% patients with COVID-19 history) had a significantly higher postoperative major complication risk than did the 2018 cohort (adjusted risk difference [aRD], 14.9% (95% confidence interval [CI], 11.5-18.4%); adjusted odds ratio [aOR], 8.19 (95% CI, 5.24-12.81)). At the patient level, the incidence of major postoperative complications was significantly greater in patients with (24.6%, 136/553) than that in patients without COVID-19 history (6.0% [168/2797]; aRD, 17.8% [95% CI, 13.6-22.1%]; aOR, 7.89 [95% CI, 5.76-10.83]). Secondary outcomes of postoperative pulmonary complications were consistent with primary findings. These findings were verified through sensitivity analyses using time-series data projections and propensity score matching. CONCLUSION: Based on a single-center observation, patients with recent COVID-19 exposure were likely to have a high incidence of major postoperative complications. REGISTRATION: NCT05677815 at https://clinicaltrials.gov/ .

Crosstalk between oxidative stress and neutrophil response in early ischemic stroke: a comprehensive transcriptome analysis.

Background: Ischemic stroke (IS) is the second leading cause of mortality worldwide, continuing to be a serious health concern. It is well known that oxidative stress and neutrophil response play vital roles in the pathophysiology of early IS. However, the complex interactions and critical genes associated with them have not been fully understood. Methods: Two datasets (GSE37587 and GSE16561) from the Gene Expression Omnibus database were extracted and integrated as the discovery dataset. Subsequent GSVA and WGCNA approaches were used to investigate IS-specific oxidative stress-related genes (ISOSGS). Then, we explored IS-specific neutrophil-associated genes (ISNGS) using CIBERSORT analysis. Next, the protein-protein interaction network was established to ascertain candidate critical genes related with oxidative stress and neutrophil response. Furthermore, these candidate genes were validated using GSE58294 dataset and our clinical samples by RT-qPCR method. Finally, functional annotation, diagnostic capability evaluation and drug-gene interactions were performed by using GSEA analysis, ROC curves and DGIDB database. Result: In our analysis of discovery dataset, 155 genes were determined as ISOSGS and 559 genes were defined as ISNGS. Afterward, 9 candidate genes were identified through the intersection of ISOSGS and ISNGS, PPI network construction, and filtration by degree algorithm. Then, six real critical genes, including STAT3, MMP9, AQP9, SELL, FPR1, and IRAK3, passed the validation using the GSE58294 dataset and our clinical samples. Further functional annotation analysis indicated these critical genes were associated with neutrophil response, especially neutrophil extracellular trap. Meanwhile, they had a good diagnostic performance. Lastly, 53 potential drugs targeting these genes were predicted by DGIDB database. Conclusion: We identified 6 critical genes, STAT3, FPR1, AQP9, SELL, MMP9 and IRAK3, related to oxidative stress and neutrophil response in early IS, which may provide new insights into understanding the pathophysiological mechanism of IS. We hope our analysis could help develop novel diagnostic biomarkers and therapeutic strategies for IS.

Toxic effects of Tripterygium glycoside tablets on the reproductive system of male rats by metabolomics, cytotoxicity, and molecular docking.

BACKGROUND: Tripterygium glycoside tablets (TGT) is the most common preparation from Tripterygium wilfordii Hook F, which is widely used in clinical for treating rheumatoid arthritis (RA) and other autoimmune diseases. However, its serious reproductive toxicity limits its application. PURPOSE: This study aimed to elucidate the toxic effects of TGT on the reproductive system of male RA rats and its potential toxic components and mechanism. METHODS: Collagen-induced arthritis (CIA) rat model was established, and TGT suspension was given at low, medium, and high doses. Gonadal index, pathological changes, and the number of spermatogenic cells were used to evaluate the toxic effects of TGT on the reproductive system. Non-targeted metabolomics of testicular tissue was conducted by UHPLC-QTOF/MS. Combined with network toxicology, the key targets of TGT-induced reproductive toxicity were screened and RT-qPCR was used to validation. In vitro toxicity of 19 components of TGT was evaluated using TM3 and TM4 cell lines. Molecular docking was used to predict the interaction between toxic components and key targets. RESULTS: TGT reduced testicular and epididymis weight. Pathology analysis showed a lot of deformed and atrophic spermatogenic tubules. The number of spermatogenic cells decreased significantly (P<0.0001). A total of 58 different metabolites including platelet-activating factor (PAF), lysophosphatidylcholine (Lyso PC), phosphatidylinositol (PI), glutathione (GSH), and adenosine monophosphate (AMP) were identified by testicular metabolomics. Glycerophospholipid metabolism, ether lipid metabolism, and glutathione metabolism were key pathways responsible for the reproductive toxicity of TGT. Ten key reproductive toxicity targets were screened by network toxicology. The cytotoxicity test showed that triptolide, triptonide, celastrol, and demethylzeylasteral could significantly reduce the viability of TM3 and TM4 cells. Alkaloids had no apparent toxic effects. Molecular docking showed that the four toxic components had a good affinity with 10 key targets. All binding energies were less than -7 kcal/mol. The RT-qPCR results showed the Cyp19a1 level was significantly up-regulated. Pik3ca and Pik3cg levels were significantly down-regulated. CONCLUSION: Through testicular metabolomics, we found that TGT may cause reproductive toxicity through CYP19A1, PIK3CA, and PIK3CG three target, which was preliminarily revealed. This study laid the foundation for elucidating the toxicity mechanism of TGT and evaluating its safety and quality.

Large-scale preparation of five polar polyphenols including three isomers from Phyllanthus emblica Linn. by preparative high-speed counter-current chromatography.

The separation of polar compounds is challenging work due to poor retention and insufficient selectivity. In the present study, an efficient strategy for large-scale preparation of five polar polyphenols including three isomers from Phyllanthus emblica Linn has been established by preparative high-speed counter-current chromatography. Macroporous resin column chromatography was used for the enrichment of the polar polyphenols. However, sugar and other ultra-polar impurities were co-washed out with the targets. Liquid-liquid extraction with ethyl acetate/water (1/1, v/v) solvent system was developed to remove the ultra-polar impurities with a clearance rate of 95%. Finally, the targets were introduced to preparative high-speed counter-current chromatography for separation using ethyl acetate/n-butanol/acetic acid/water (2/7/1/10, v/v/v/v) solvent system. As a result, 191 mg of Mucic acid 1,4-lactone 5-O-gallate, 370 mg of ß-Glucogallin, 301 mg of Gallic acid, 195 mg of Mucic acid 1,4-lactone 3-O-gallate and 176 mg of Mucic acid 1,4-lactone 2-O-gallate with purity higher than 98% were obtained from 1.5 g of sample. Mucic acid 1,4-lactone 3-O-gallate, Mucic acid 1,4-lactone 3-O-gallate, and Mucic acid 1,4-lactone 2-O-gallate are isomers. The results showed that high-speed counter-current chromatography could be well developed for the separation of polar compounds from natural products.