Targeting Fatty Acid Desaturase I Inhibits Renal Cancer Growth Via ATF3-mediated ER Stress Response.

Monounsaturated fatty acids (MUFAs) play a pivotal role in maintaining endoplasmic reticulum (ER) homeostasis, an emerging hallmark of cancer. However, the role of polyunsaturated fatty acid (PUFAs) desaturation in persistent ER stress driven by oncogenic abnormalities remains elusive. Fatty Acid Desaturase 1 (FADS1) is a rate-limiting enzyme controlling the bioproduction of long-chain PUFAs. Our previous research has demonstrated the significant role of FADS1 in cancer survival, especially in kidney cancers. We explored the underlying mechanism in this study. We found that pharmacological inhibition or knockdown of the expression of FADS1 effectively inhibits renal cancer cell proliferation and induces cell cycle arrest. The stable knockdown of FADS1 also significantly inhibits tumor formation in vivo. Mechanistically, we show that while FADS1 inhibition induces ER stress, its expression is also augmented by ER-stress inducers. Notably, FADS1-inhibition sensitized cellular response to ER stress inducers, providing evidence of FADS1's role in modulating the ER stress response in cancer cells. We show that, while FADS1 inhibition-induced ER stress leads to activation of ATF3, ATF3-knockdown rescues the FADS1 inhibition-induced ER stress and cell growth suppression. In addition, FADS1 inhibition results in the impaired biosynthesis of nucleotides and decreases the level of UPD-N-Acetylglucosamine, a critical mediator of the unfolded protein response. Our findings suggest that PUFA desaturation is crucial for rescuing cancer cells from persistent ER stress, supporting FADS1 as a new therapeutic target.

Targeting pro-inflammatory T cells as a novel therapeutic approach to potentially resolve atherosclerosis in humans.

Atherosclerosis (AS), a leading cause of cardio-cerebrovascular disease worldwide, is driven by the accumulation of lipid contents and chronic inflammation. Traditional strategies primarily focus on lipid reduction to control AS progression, leaving residual inflammatory risks for major adverse cardiovascular events (MACEs). While anti-inflammatory therapies targeting innate immunity have reduced MACEs, many patients continue to face significant risks. Another key component in AS progression is adaptive immunity, but its potential role in preventing AS remains unclear. To investigate this, we conducted a retrospective cohort study on tumor patients with AS plaques. We found that anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) significantly reduces AS plaque size. With multi-omics single-cell analyses, we comprehensively characterized AS plaque-specific PD-1+ T cells, which are activated and pro-inflammatory. We demonstrated that anti-PD-1 mAb, when captured by myeloid-expressed Fc gamma receptors (FcγRs), interacts with PD-1 expressed on T cells. This interaction turns the anti-PD-1 mAb into a substitute PD-1 ligand, suppressing T-cell functions in the PD-1 ligands-deficient context of AS plaques. Further, we conducted a prospective cohort study on tumor patients treated with anti-PD-1 mAb with or without Fc-binding capability. Our analysis shows that anti-PD-1 mAb with Fc-binding capability effectively reduces AS plaque size, while anti-PD-1 mAb without Fc-binding capability does not. Our work suggests that T cell-targeting immunotherapy can be an effective strategy to resolve AS in humans.

IRF5 governs macrophage adventitial infiltration to fuel abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease characterized by the expansion of the aortic wall. One of the most significant features is the infiltration of macrophages in the adventitia, which drives vasculature remodeling. The role of macrophage-derived interferon regulatory factor 5 (IRF5) in macrophage infiltration and AAA formation remains unknown. RNA sequencing of AAA adventitia identified Irf5 as the top significantly increased transcription factor that is predominantly expressed in macrophages. Global and myeloid cell-specific deficiency of Irf5 reduced AAA progression, with a marked reduction in macrophage infiltration. Further cellular investigations indicated that IRF5 promotes macrophage migration by direct regulation of downstream phosphoinositide 3-kinase γ (PI3Kγ, Pik3cg). Pik3cg ablation hindered AAA progression, and myeloid cell-specific salvage of Pik3cg restored AAA progression and macrophage infiltration derived from Irf5 deficiency. Finally, we found that IRF5 and PI3Kγ expression in the adventitia is significantly increased in patients with AAA. These findings reveal that the IRF5-dependent regulation of PI3Kγ is essential for AAA formation.

Preoperative supine time for adrenal venous sampling: a prospective randomized controlled trial.

BACKGROUND: Primary aldosteronism (P.A.) is the most common form of secondary hypertension, accounting for 5% of hypertensive patients and 17-23% of patients with resistant hypertension. Compared to primary hypertension, P.A. is more prone to cause severe organ damage and even early death. Adrenal venous sampling (AVS) is a practical confirmatory test for subtyping aldosterone-producing adenoma and bilateral adrenal hyperplasia, helping physicians to make an accurate decision between surgery or medication. According to guidelines, supine in bed before AVS is recommended for a desirable result of AVS. However, investigations about the most optimal preoperative supine time before AVS are lacking. METHODS/DESIGN: This is a multi-center prospective randomized controlled study. One hundred twenty patients diagnosed as P.A. and willing for AVS examination will be included. Participants will be randomly allocated to a 15-min supine time group or 2-h supine time group. The primary outcome is the degree of biochemical remission (serum potassium and orthostatic ARR). The secondary outcomes are degrees of clinical remission (blood pressure, type and dose of antihypertensive drugs), the technical success rate, and the adverse event of AVS (selective index ≥ 2 is considered successful surgery without corticotropin stimulation). DISCUSSION: P.A. is an intractable public health problem, and many techniques including AVS have been developed to identify this disease correctly. This study will help to understand whether the length of preoperative supine time would affect the diagnostic efficacy of AVS and thus help to formulate a more reasonable AVS procedure. TRIAL REGISTRATION: ClinicalTrials.gov NCT05658705. Registered on 10 September 2022.

Comprehensive bioinformatics analysis revealed potential key genes and pathways underlying abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a permanent, asymptomatic segmental dilatation of the abdominal aorta, with a high mortality risk upon rupture. Identification of potential key genes and pathways may help to develop curative drugs for AAA. We conducted RNA-seq on abdominal aortic tissues from both AAA patients and normal individuals as a control group. Integrated bioinformatic analysis was subsequently performed to comprehensively reveal potential key genes and pathways. A total of 1148 differential expressed genes (DEGs) (631 up-regulated and 517 down-regulated) were identified in our study. Gene Ontology (GO) analysis revealed enrichment in terms related to extracellular matrix organization, while KEGG analysis indicated enrichment in hematopoietic cell lineage and ECM-receptor interaction. Protein-protein interaction (PPI) network analysis revealed several candidate key genes, and differential expression of 6 key genes (CXCL8, CCL2, PTGS2, SELL, CCR7, and CXCL1) was validated by Gene Expression Omnibus (GEO) datasets. Receiver operating characteristic curve (ROC) analysis demonstrated these genes' high discriminatory ability between AAA and normal tissues. Immunohistochemistry indicated that several key genes were highly expressed in AAA tissues. Single-cell RNA sequencing revealed differential distribution patterns of these identified key genes among various cell types. 26 potential drugs linked to our key genes were found through DGIdb. Overall, our study provides a comprehensive evaluation of potential key genes and pathways in AAA, which could pave the way for the development of curative pharmacological therapies.

Trapping and diffusion of hydrogen in iron-doped Y2O3.

Y2O3 is a promising material for use as a tritium permeation barrier (TPB) coating and as dispersed particles in oxide dispersion strengthened steels for experimental fusion reactors. By using first-principles approaches, we found that substituting Fe for Y in Y2O3 is the most energetically favourable under O-deficient and H-rich conditions, leading to easier formation of the nearby O vacancies. These O vacancies serve as effective trapping sites for H atoms with a formation energy of -2.36 eV. The presence of Fe defects also makes it more difficult for H atoms to migrate in Y2O3 from three possible H-related defects. These findings suggest that incorporating Fe into Y2O3 could yield a better TPB and provide insight into the improved H trapping ability of Y2O3 with Fe dopants.

Total tanshinones protect against acute lung injury through the PLCγ2/NLRP3 inflammasome signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge is a widely used traditional Chinese medicine with anticholinesterase, antitumor, and anti-inflammatory. Total Tanshinones (TTN), the most significant active ingredient of Salvia miltiorrhiza Bunge, exerts anti-inflammatory activity. However, the protective mechanism of total Tanshinones on acute lung injury (ALI) still needs to be explored. AIM OF THIS STUDY: In this study, the underlying mechanisms of TTN to treat with ALI were investigated in vitro and in vivo. MATERIALS AND METHODS: Cell experiments established an in vitro model of LPS-induced J774A.1 and MH-S macrophages to verify the mechanism. The levels of inflammatory cytokines (TNF-α, IL-6 and IL-1ß) were estimated by ELISA. The changes of ROS, Ca2+ and NO were detected by flow cytometry. The expression levels of proteins related to the NLRP3 inflammasome were determined by Western blotting. The effect of TTN on NLRP3 inflammasome activation was examined by immunofluorescence analysis of caspase-1 p20. Male BALB/c mice were selected to establish the ALI model. The experiment was randomly divided into six groups: control, LPS, LPS + si-NC, LPA + si-Nek7, LPS + TTN, and DEX. Pathological alterations were explored by H&E staining. The expression levels of proteins related to the NLRP3 inflammasome were analyzed by Western blotting. RESULTS: TTN decreased pro-inflammatory cytokines levels like TNF-α, IL-6, IL-1ß, NO, and ROS in alveolar macrophages. TTN bound to NIMA-related kinase 7 (NEK7), a new therapeutic protein to modulate NLRP3 inflammasome and PLCγ2-PIP2 signaling pathway. In ALI mice, LPS enhanced IL-1ß levels in the serum, lung tissues, and bronchoalveolar lavage fluid (BALF),which were reversed by TTN. TTN decreased cleaved-caspase-1 and NLRP3 expressions in lung tissues. When Nek7 was knocked down in mice by siRNA, the syndrome of ALI in mice was significantly suppressed, of which the effect was similar to that of TTN. CONCLUSIONS: This research demonstrates that TTN alleviated ALI by binding to NEK7 in vitro and in vivo to modulate NLRP3 inflammasome activation and PLCγ2-PIP2 signaling pathways.

Application evaluation of mixed-reality holographic imaging technology in the surgical treatment of spinal cord glioma.

Objectives: To investigate the application effect of mixed reality (MR) holographic imaging technology in the clinical surgical treatment of spinal cord glioma. Methods: The clinical data of 53 patients with spinal cord glioma who underwent surgical treatment in the Neurosurgery Department of our hospital from January 2017 to May 2020 were retrospectively studied. All the patients were divided into two groups according to different assistive technologies during the surgery: the observation group and the control group, with 30 cases and 23 cases respectively. Patients in the observation group received MR holographic imaging technology intraoperatively, while those in the control group received ultrasound. The surgical conditions of the two groups: the rate of complete resection of tumor lesions and the evaluation accuracy of complete resection were compared. Patients were followed up for 12 months in the outpatient department after surgery, and the recovery of postoperative spinal physiological function was evaluated based on imaging review and MMS scale grading, and the recurrence was obtained. Results: There was no statistical significance in the basic clinical conditions between the two groups (P>0.05), and the total tumor resection rate in the experimental group was 96.67%, and that in the control group was 82.61%, showing a statistically significant difference (P<0.05). Based on enhanced MRI examination as the standard, the evaluation accuracy of intraoperative complete tumor resection in the experimental group was 93.33%, significantly higher than that in the control group (73.54%), with a statistical significance (P<0.05). The incidence of postoperative complications was 3.33% in the experimental group and 21.74% in the control group, with a statistically significant difference (P<0.05). Postoperative follow-up showed that good recovery rate of spinal cord function in the experimental group was 56.70%, and that in the control group was 41.09%, with a statistically significant difference (P<0.05). The recurrence rate was 0 in the experimental group and 4.34% in the control group at follow-up, with no statistically significant difference (P>0.05). Conclusions: With the application of MR holographic imaging technology in the surgical treatment of spinal cord glioma, critical clinical value can be realized. Specifically, the resection degree of spinal cord glioma can be displayed in real time, accurately, and three-dimensionally, the effect of surgical resection can be improved, surgical complications can be diminished, and the recovery of spinal cord function can be accelerated.

Comparison between endovascular aneurysm repair-selected and endovascular aneurysm repair-only strategies for the management of ruptured abdominal aortic aneurysms: An 11-year experience at a Chinese tertiary hospital.

Objectives: The aim of this study was to review our management experience of ruptured abdominal aortic aneurysms (RAAAs) using an endovascular aneurysm repair (EVAR)-only strategy, and discuss the feasibility of this strategy. Materials and methods: A retrospective analysis of clinical data was performed in patients with RAAAs from January 2009 to October 2020. Our strategy toward operative treatment for RAAAs evolved from an EVAR-selected (from January 2009 to April 2014) to an EVAR-only (from May 2014 to October 2020) strategy. Baseline characteristics, thirty-day mortality, perioperative complications, and long-term outcomes of patients were compared between the two periods. Results: A total of 93 patients undergoing emergent RAAA repair were eventually included. The overall operation rate in RAAAs at our centre was 70.5% (93/132). In the EVAR-only period, all 53 patients underwent ruptured endovascular aneurysm repair (rEVAR). However, only 47.5% (19/40) of patients in the EVAR-selected period underwent rEVAR, and the remaining 21 patients underwent emergent open surgery. Thirty-day mortality in the EVAR-only group was 22.6% (12/53) compared with 25.0% (10/40) for the EVAR-selected group (P = 0.79). Systolic blood pressure ≤70 mmHg [adjusted odds ratio (OR) 4.99, 95% confidence interval (CI), 1.13-22.08, P = 0.03] and abdominal compartment syndrome (adjusted OR 3.72, 95% CI, 1.12-12.32, P = 0.03) were identified as independent risk factors responsible for 30-day mortality. After 5 years, 47.5% (95% CI, 32.0-63.0%) of patients in the EVAR-selected group were still alive versus 49.1% (95% CI, 32.3-65.9%) of patients in the EVAR-only group (P = 0.29). Conclusion: The EVAR-only strategy has allowed rEVAR to be used in nearly all the RAAAs with similar mortality comparing with the EVAR-selected strategy. Due to the avoidance of operative modality selection, the EVAR-only strategy was associated with a more simplified algorithm, less influence on haemodynamics, and a shorter operation and recovery time.

Pregnancy tailors endotoxin-induced monocyte and neutrophil responses in the maternal circulation.

OBJECTIVE: To comprehensively characterize monocyte and neutrophil responses to E. coli and its product [lipopolysaccharide (LPS) or endotoxin] in vitro during pregnancy. MATERIAL OR SUBJECTS: Peripheral blood was collected from pregnant women during the third trimester (n = 20) and from non-pregnant women (n = 20). METHODS: The number, phagocytic activity, and reactive oxygen species (ROS) production of peripheral monocytes and neutrophils were investigated using flow cytometry. The phenotypes of peripheral monocytes and neutrophils after acute or chronic LPS stimulation were also determined using flow cytometry. Cytokine profiles were quantified for LPS-stimulated peripheral blood mononuclear cells (PBMCs) and a whole blood TruCulture® system using a multiplex immunoassay. RESULTS: Increased number, phagocytic activity, and ROS production capacity of monocytes and neutrophils were found in pregnant compared to non-pregnant women. Additionally, specific subsets of pro-inflammatory monocytes (IL-6+CD14+ or MIP-1α+CD14+ cells) and neutrophils (IL-1ß+CD15+ or MIP-1ß+CD15+ cells) were increased in pregnant women in response to acute LPS stimulation. Moreover, distinct subsets of intermediate-activated monocytes expressing CD142, IL-6, and IL-1RA were increased in pregnant women upon chronic LPS stimulation. Last, pregnant women displayed a different cytokine profile than non-pregnant women in LPS-stimulated PBMCs and in whole blood. CONCLUSIONS: Pregnancy tailors the immune responses of circulating monocytes and neutrophils to endotoxin, a Gram-negative bacterial product.

Clinical efficacy of moluodan in the treatment of chronic atrophic gastritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Chronic atrophic gastritis (CAG) is an important stage of precancerous lesions of gastric cancer, and also a key period of drug intervention. However, there is still a lack of drugs to maintain the treatment of CAG until the advent of moluodan. OBJECTIVE: This study was conducted to assess the clinical efficacy of moluodan in the treatment of CAG by meta-analysis and trial sequential analysis. METHODS: China National Knowledge Infrastructure, China Biology Medicine, VIP, Wanfang, Embase, PubMed, the Cochrane Library, and Web of Science databases were searched, all with the time limit from database establishment to July 2022. The published randomized controlled trials of moluodan for CAG were conducted for meta-analysis and trial sequential analysis. RESULTS: 7 studies with a total sample size of 1143 cases were included. Compared to folic acid/vitamins, moluodan alone significantly increased the effective rate of pathological detection (relative risk [RR] = 1.73, 95% confidence interval [95%CI] = [1.48,2.02], P < .00001), and moluodan in combination with folic acid/vitamins significantly increased the effective rates of pathological detection (RR = 1.37, 95%CI = [1.23,1.52], P < .00001), gastroscopy (RR = 1.37, 95%CI = [1.18,1.60], P < .0001) and symptoms (RR = 1.25, 95%CI = [1.13,1.38], P < .0001). Harbord regression showed no publication bias (P = .22). Quality of evidence evaluation demonstrated moderate quality of evidence for all indicators. CONCLUSIONS: Moluodan can improve the effective rates of pathological examination, gastroscopy and symptoms in patients with CAG, and play a role in slowing down the disease progression and reducing clinical symptoms. It may be a potential drug for the treatment of CAG and has the value of further exploration.

Single-stage treatment with iliac vein stenting and stripping of the great saphenous vein for patients with left iliac vein compression syndrome.

BACKGROUND: We sought to evaluate the safety and feasibility of single-stage treatment with left iliac vein stenting and saphenous stripping in patients with left iliac vein compression (LIVC) and left great saphenous vein (GSV) incompetence. METHOD: s: We conducted a prospective cohort study of 72 patients diagnosed with LIVC and left GSV incompetence between June 2012 to Oct 2018. We evaluated the periprocedural, 30-day, and 1-year outcomes of venous clinical severity score (VCSS), Chronic Venous Insufficiency Questionnaire 2 (CIVIQ2), the success rate of stent placement, duration of intervention, length of hospital stay, duplex recurrence, and clinically visible recurrence. RESULTS: There were 43 patients in the two-staged group and 29 patients in the single-staged group. The clinical characteristics of the two groups were similar. There were no differences between the two groups in the technical success rate, perioperative mortality, and surgical morbidity. There was no significant difference in the duplex and clinically visible recurrence. The length of hospital stay was significantly lower in the single-staged group. The single-staged group was associated with a higher complication rate of ecchymosis. There was no death, pulmonary embolism, or contrast-induced nephropathy among the patients. The 1-year primary patency rate was similar. CONCLUSIONS: Both treatment approaches were equally effective and had a high technical success rate. The single-staged group had a higher complication rate of ecchymosis due to heparin applying during the procedure.

Dabigatran Use after Argatroban for Heparin-induced Thrombocytopenia with Thrombosis: A Case Series and Literature Review.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is immune-mediated thrombotic thrombocytopenia following the use of heparin, which contributes to a high limb-amputation rate and mortality if not appropriately handled. There is growing evidence suggesting that novel oral anticoagulants (NOACs) may be effective for treating HIT. METHODS: We described five rare cases of patients with HIT associated with deep vein thrombosis treated with dabigatran, a member of NOACs. We also reviewed representative cases and literature investigating the use of NOACs to treat patients with HIT to further discuss the efficacy and safety. RESULTS AND CONCLUSIONS: Following the treatment of dabigatran after argatroban, the platelet count of patients with HIT gradually elevated and reached the normal range eventually. There was no incidence of new symptomatic, objectively-confirmed arteriovenous thromboembolism observed within the 90-day-period follow up. The patient in case 3 presented with gastric bleeding after dabigatran treatment and died in the end. The results suggested that dabigatran use after argatroban may be effective in the treatment of patients with HIT. However, safety should be reconsidered since severe complications were observed in case 3.

Urine proteomics identifies biomarkers for diabetic kidney disease at different stages.

BACKGROUND: Type 2 diabetic kidney disease is the most common cause of chronic kidney diseases (CKD) and end-stage renal diseases (ESRD). Although kidney biopsy is considered as the 'gold standard' for diabetic kidney disease (DKD) diagnosis, it is an invasive procedure, and the diagnosis can be influenced by sampling bias and personal judgement. It is desirable to establish a non-invasive procedure that can complement kidney biopsy in diagnosis and tracking the DKD progress. METHODS: In this cross-sectional study, we collected 252 urine samples, including 134 uncomplicated diabetes, 65 DKD, 40 CKD without diabetes and 13 follow-up diabetic samples, and analyzed the urine proteomes with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We built logistic regression models to distinguish uncomplicated diabetes, DKD and other CKDs. RESULTS: We quantified 559 ± 202 gene products (GPs) (Mean ± SD) on a single sample and 2946 GPs in total. Based on logistic regression models, DKD patients could be differentiated from the uncomplicated diabetic patients with 2 urinary proteins (AUC = 0.928), and the stage 3 (DKD3) and stage 4 (DKD4) DKD patients with 3 urinary proteins (AUC = 0.949). These results were validated in an independent dataset. Finally, a 4-protein classifier identified putative pre-DKD3 patients, who showed DKD3 proteomic features but were not diagnosed by clinical standards. Follow-up studies on 11 patients indicated that 2 putative pre-DKD patients have progressed to DKD3. CONCLUSIONS: Our study demonstrated the potential for urinary proteomics as a noninvasive method for DKD diagnosis and identifying high-risk patients for progression monitoring.

Efficacy and safety of rivaroxaban in patients with inferior vena cava filter placement without anticoagulation contraindications (EPICT): a prospective randomised controlled trial study protocol.

INTRODUCTION: Inferior vena cava (IVC) filters are commonly used in patients with venous thromboembolism to prevent fatal pulmonary embolism, but the thrombosis risk increases after filter placement. Warfarin is a widely anticoagulant, but long-term monitoring and dose adjustments are required. Anticoagulation with rivaroxaban is more straightforward as it dose not require laboratory monitoring. This study compares the efficacy and safety of rivaroxaban and warfarin as an in anticoagulation therapy for patients with IVC filter placement. METHODS AND ANALYSIS: This is a multicentre, randomised controlled trial. In total, 200 patients with deep vein thrombosis (DVT) with IVC filter implantation from 10 hospitals will be recruited. The patients will be randomised to the experimental group (rivaroxaban) or the control group (nadroparin overlapped with warfarin). The primary outcomes include death of any cause, pulmonary embolism (PE)-related death, bleeding and recurrent PE/DVT. The secondary outcomes include the percentage of other vascular events, IVC filter retrieval failure and net clinical benefits. This study aims to provide reliable, verification for the efficacy and safety of rivaroxaban antithrombotic therapy after IVC filter placement. ETHICS AND DISSEMINATION: The study was approved by the Human Research Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine (approval number: (2019) 295). The results will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals TRIAL REGISTRATION NUMBER: NCT04066764.

Design and Evaluation of Multiplex One-Step Reverse Transcription PCR-Dipstick Chromatography Method for the Analysis of Seven Respiratory Pathogens.

Influenza A, influenza B, severe acute respiratory syndrome coronavirus 2, adenovirus, respiratory syncytial virus, Mycoplasma pneumoniae, and Chlamydophila pneumoniae are common pathogens that can cause severe pneumonia and other symptoms, resulting in acute lower respiratory tract infections. The objective of this study was to design and evaluate a sensitive and specific multiplex one-step reverse transcription PCR (RT-PCR)-dipstick chromatography method for simultaneous rapid detection of these seven pathogens. Streptavidin-coated blue latex particles were used to read out a positive signal. Based on the DNA-DNA hybridization of oligonucleotide sequences (Tag) for forward primer with the complementary oligonucleotide sequence (cTag) on the dipstick and biotin-streptavidin interactions, PCR products were able to be illuminated visually on the dipstick. The specificity and the limit of detection (LOD) were also evaluated. Moreover, the clinical performance of this method was compared with Sanger sequencing for 896 samples. No cross reaction with other pathogens was found, confirming the high specificity of this method. The LOD was 10 copies/µL for each of the tested pathogens, and the whole procedure took less than 40 min. Using 896 samples, the sensitivity and specificity were shown to be no lower than 94.5%. The positive predictive value was higher than 82.1%, and the negative predictive value was higher than 99.5%. The kappa value between the PCR-dipstick chromatography method and Sanger sequencing ranged from 0.869 to 0.940. In summary, our one-step RT-PCR-dipstick chromatography method is a sensitive and specific tool for rapidly detecting multiplex respiratory pathogens.

Application evaluation of intraoperative ultrasound combined with neuro electrophysiological detection in the spinal cord glioma surgery.

OBJECTIVE: To observe application values of intraoperative ultrasound combined with neuro electrophysiological detection in the spinal cord glioma surgery. METHODS: Sixty patients with spinal cord glioma hospitalized in Baoding First Central Hospital from January 2016 to January 2018 were selected, randomly divided into two groups by the random number table method, with 30 cases of each group. PASS software was used to calculate the sample size. The control group was treated with traditional microsurgery, while the experimental group was treated with intraoperative ultrasound combined with neuro electrophysiological testing. The operation time, intraoperative blood loss, postoperative hospital stays, degree of tumor resection, clinical efficacy, recovery of neurological function, recovery of health status, quality of life score, and 2-year recurrence rate of the two groups of patients were observed and compared. RESULTS: The operation time of the experimental group was longer than that of the control group, and the postoperative hospital stay was shorter than that of the control group. The complete tumor resection rate, complete remission rate and postoperative scale scores of the experimental group were significantly higher than those of the control group, while the recurrence rate within two years was significantly lower than that of the control group. The above differences were statistically significant (p<0.05). CONCLUSIONS: Intraoperative ultrasound combined with neuro-electrophysiological detection for spinal glioma has more adequate protection of nerve function, high clinical complete remission rate, more thorough tumor resection, and lower recurrence rate than traditional microsurgery, which is worthy of clinical application.

Tanshinone I exerts cardiovascular protective effects in vivo and in vitro through inhibiting necroptosis via Akt/Nrf2 signaling pathway.

BACKGROUND: Tanshinone I (TI) is a primary component of Salvia miltiorrhiza Bunge (Danshen), which confers a favorable role in a variety of pharmacological activities including cardiovascular protection. However, the exact mechanism of the cardiovascular protection activity of TI remains to be illustrated. In this study, the cardiovascular protective effect and its mechanism of TI were investigated. METHODS: In this study, tert-butyl hydroperoxide (t-BHP)-stimulated H9c2 cells model was employed to investigate the protective effect in vitro. The cell viability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) kit. The reactive-oxygen-species (ROS) level and mitochondrial membrane potential (MMP) were investigated by the flow cytometry and JC-1 assay, respectively. While in vivo experiment, the cardiovascular protective effect of TI was determined by using myocardial ischemia-reperfusion (MI/R) model including hematoxylin-eosin (H&E) staining assay and determination of superoxide dismutase (SOD) and malondialdehyde (MDA). Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) release were detected by Enzyme-linked immunosorbent assay (ELISA). Receptor interacting protein kinase 1 (RIP1), receptor interacting protein kinase 3 (RIP3), receptor interacting protein kinase 3 (MLKL), protein kinase B (Akt), Nuclear factor erythroid 2 related factor 2 (Nrf2), Heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO-1) were determined by western blotting. RESULTS: Our data demonstrated that TI pretreatment attenuated t-BHP and MI/R injury-induced necroptosis by inhibiting the expression of p-RIP1, p-RIP3, and p-MLKL. TI activated the Akt/Nrf2 pathway to promote the expression of antioxidant-related proteins such as phosphorylation of Akt, nuclear factor erythroid 2 related factor 2 (Nrf2), quinone oxidoreductase-1 (NQO-1) and heme oxygenase-1 (HO-1) expression in t-BHP-stimulated H9c2 cells. TI relieved oxidative stress by mitigating ROS generation and reversing MMP loss. In vivo experiment, TI made electrocardiograph (ECG) recovery better and lessened the degree of myocardial tissue damage. The counts of white blood cell (WBC), neutrophil (Neu), lymphocyte (Lym), and the release of TNF-α and IL-6 were reversed by TI treatment. SOD level was increased, while MDA level was decreased by TI treatment. CONCLUSION: Collectively, our findings indicated that TI exerted cardiovascular protective activities in vitro and in vivo through suppressing RIP1/RIP3/MLKL and activating Akt/Nrf2 signaling pathways, which could be developed into a cardiovascular protective agent.

Computed tomography image fusion, Coaxial guidewire technique, Fast intraprocedural cortisol testing technique improves success rate and decreases radiation exposure, procedure time, and contrast use for adrenal vein sampling.

BACKGROUND: Adrenal vein sampling (AVS) is recommended for discriminating patients with unilateral primary aldosteronism from bilateral disease. However, it is a technically demanding procedure that is markedly underused. We developed a computed tomography image fusion, coaxial guidewire technique, fast intraprocedural cortisol testing (CCF) technique to improve AVS success rate, which combines CT image fusion, coaxial guidewire technique, and fast intraprocedural cortisol testing. OBJECTIVE: To evaluate the effectiveness and safety of the AVS--CCF technique. METHODS: We retrospectively evaluated 105 patients who undervent AVS from June 2016 to October 2020. There were 51 patients in the AVS--CCF group and 54 patients in the AVS group. We compared two groups with technical success rate, procedure time, radiation exposure, volume of contrast medium, and complications (adrenal vein rupture, dissection, infarction, or thrombosis; intraglandular or periadrenal hematoma; and contrast-induced nephropathy). RESULTS: The technical success rate was higher for AVS--CCF than for AVS without CCF (98 vs. 83.3% for bilateral adrenal veins, P = 0.016). AVS--CCF was associated with a shorter procedure time (63.6 ±â€Š24.6 vs. 94.8 ±â€Š40.8 min, P < 0.001), shorter fluoroscopy time (15.6 ±â€Š12.6 vs. 20.4 ±â€Š15.0 min, P = 0.043), and lower contrast medium volume (25.10 ±â€Š21.82 vs. 44.1 ±â€Š31.0 ml, P < 0.001). There were no significant differences between groups with respect to the time for cannulating the left or right adrenal vein or the peak skin radiation dose. Adrenal vein rupture occurred in 14 patients and intraglandular hematoma in 1 patient. CONCLUSION: The CCF technique during AVS not only contributed to improved technical success rates but also associated with decreased procedure time, radiation exposure, and contrast medium volume.

Rotundic acid reduces LPS-induced acute lung injury in vitro and in vivo through regulating TLR4 dimer.

Acute lung injury (ALI) is a serious clinical disease. Rotundic acid (RA), a natural ingredient isolated from Ilex rotunda Thunb, exhibits multiple pharmacological activities. However, RA's therapeutic effect and mechanism on ALI remain to be elucidated. The present study aimed to further clarify its regulating effects on inflammation in vitro and in vivo. Our results indicated that RA significantly inhibited the overproduction of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). RA decreased ROS production and calcium influx. In addition, RA inhibited the activation of PI3K, MAPK, and NF-κB pathways and enhanced the activity of nuclear factor E2-related factor 2 (Nrf2) signaling. The cellular thermal shift assay and docking results indicated that RA bind to TLR4 to block TLR4 dimerization. Furthermore, RA pretreatment effectively inhibited ear edema induced by xylene and LPS-induced endotoxin death and had a protective effect on LPS-induced ALI. Our findings collectively indicated that RA has anti-inflammatory effects, which may serve as a potential therapeutic option for pulmonary inflammation.