Morphological Changes of Peri-Coronary Adipose Tissue Together with Elevated NLR in Acute Myocardial Infarction Patients in-Hospital.

Background: Inflammation triggers atherosclerotic plaque rupture, leading to acute myocardial infarction (AMI). Following AMI, peri-coronary adipose tissue (PCAT) undergoes a transition from lipid-rich to hydrophilic characteristics due to vascular inflammation. This study investigates PCAT changes and neutrophil-to-lymphocyte ratio levels during AMI. Patients and Methods: 60 AMI patients undergoing coronary computed tomography angiography and angiography (Jan 2020-Jun 2022) were studied 60 age, gender, BMI-matched stable angina, and 60 non-coronary artery disease patients were included. Siemens VB20.0 measured PCAT-volume and fat attenuation index (FAI). Neutrophil-to-lymphocyte ratio levels were calculated by peripheral blood tests. Results: The PCAT volume and PCAT-FAI gradually increased across the control, stable angina, and AMI groups, with a corresponding gradual rise in NLR. NLR exhibited weak positive correlation with PCAT-FAI (r=0.35) and PCAT-volume (r=0.24). Multivariable logistic regression identified increased PCAT-volume, PCAT-FAI and neutrophil-to-lymphocyte ratio as possible independent AMI risk factors. No significant PCAT-volume difference was observed between infarct-related artery (IRA) and non-IRA for all three coronary arteries. Only PCAT-FAI around IRA-LAD was higher than non-IRA-LAD (-74.84±6.93 HU vs -79.04±8.68 HU). PCAT-FAI around culprit vessels in AMI was higher than corresponding lesion related vessel in SA. PCAT-volume around narrowed non-IRA in AMI was higher than that of corresponding LRV in SA. PCAT-FAI of narrowed non-IRA-LADs and non-IRA-LCXs in AMI were elevated compared to LADs (-78.46±8.56HU vs -83.13±8.34 HU) and LCXs (-73.83±10.63 HU vs -81.38±7.88 HU) of lesion related vessel in stable angina. Conclusion: We found an association between AMI and inflammation in the coronary perivascular adipose tissue and systemic inflammatory response.

Prognostic nutritional index during hospitalization correlates with adverse outcomes in elderly patients with acute myocardial infarction: a single-center retrospective cohort study.

BACKGROUND AND AIMS: Acute myocardial infarction (AMI) is one of the most prevalent illnesses endangering the elderly's health. The predictive nutritional index (PNI) has been shown in several studies to be a good predictor of nutritional prognosis. In this study, we explored the correlation between PNI during hospitalization and the outcome of elderly AMI patients. METHODS: Elderly AMI patients in the Cardiac Intensive Care Unit of Huadong Hospital from September 2017 to April 2020 were recruited for analysis. The clinical and laboratory examination data of subjects were retrieved. All enrolled patients were monitored following discharge. The primary clinical endpoints encompass major adverse cardiovascular events (MACEs) and Composite endpoint (MACEs and all-cause mortality). Survival analyses were conducted via the Kaplan-Meier and the log-rank analyses, and the Cox, proportional hazards model, was employed for hazard rate (HR) calculation. RESULTS: 307 subjects were recruited for analysis. The optimal PNI threshold is 40.923. Based on the Kaplan-Meier analysis, the elevated PNI group experienced better prognosis (P < 0.001). Cox analysis demonstrated that the PNI group was a stand-alone predictor for elderly AMI patient prognosis (HR = 1.674, 95% CI 1.076-2.604, P = 0.022). Subgroup analysis showed that the HR of the PNI group was the highest in the ST-segment elevation myocardial infarction (STEMI) subgroup (HR = 3.345, 95% CI 1.889-5.923, P = 0.05), but no discernible difference was observed in the non-ST-segment elevation myocardial infarction (NSTEMI) subgroup. CONCLUSION: Based on our analyses, the PNI during hospitalization can accurately predict the prognosis of elderly STEMI patients but not that of elderly NSTEMI patients.

Absence of a causal link between COVID-19 and deep vein thrombosis: Insights from a bi-directional Mendelian randomisation study.

Background: Several large-scale observational studies have found deep vein thrombosis (DVT) to be related with coronavirus disease 2019 (COVID-19). However, whether there is a clear causal connection between the two is unknown. Methods: Our primary analytical method was the inverse variance-weighted (IVW) approach, complemented by the Mendelian randomisation-Egger (MR-Egger) and weighted median methods. We also used MR-Egger to examine the presence of pleiotropy and the Mendelian randomisation pleiotropy residual sum and outlier (MR-PRESSO) approach to analyse for heterogeneity in the data. Results: We did not observe a direct causal relationship between COVID-19 susceptibility (odds ratio (OR) = 1.023; 95% confidence interval (CI) = 0.828-1.264, standard error (SE) = 0.108, P = 0.833), hospitalisation (OR = 1.030; 95% CI = 0.943-1.125, SE = 0.374, P = 0.720), severity (OR = 0.994; 95% CI = 0.923-1.071, SE = 0.038, P = 0.877), and DVT. The results of the reverse Mendelian randomisation (MR) for DVT and COVID-19 susceptibility exhibited heterogeneity and horizontal pleiotropy. Even after removing outliers, we detected no direct causal relationship between the two (OR = 1.015; 95% CI = 0.954-1.080, SE = 0.032, P = 0.630). Similarly, we found no direct causal relationship between DVT and COVID-19 hospitalisation (OR = 0.999; 95% CI = 0.907-1.102, SE = 0.050, P = 0.999) or severity (OR = 1.014; 95% CI = 0.893-1.153, SE = 0.065, P = 0.826). Conclusions: In this MR study, we identified no direct causal impact in a European population between DVT and the COVID-19 susceptibility, severity, or hospitalisation.

Efficacy and safety of the combination of camrelizumab and apatinib in the treatment of liver cancer: a systematic review and single-arm meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of the combination of camrelizumab and apatinib in the treatment of liver cancer and to furnish clinical recommendations for pharmacological interventions. METHODS: PubMed, Embase, Web of Science and the Cochrane Library were scrutinized for research publications from their inception to 22 December 2023. Bibliographic perusal and data procurement were executed. The quality of the included studies was evaluated employing the MINORS tool. Meta-analysis was conducted utilizing Stata 15.0 software. RESULTS: A total of 10 studies involving 849 patients were included in the meta-analysis. The study revealed that the objective response rate (ORR) of the combined therapy was 28% (95% CI: 23%-34%), the disease control rate (DCR) was 69% (95% CI: 64%-73%), the median progression-free survival (mPFS) was 5.87 months (95% CI: 4.96-6.78), the median overall survival (mOS) was 19.35 months (95% CI: 17.53-21.17), the incidence of any grade adverse events was 90% (95% CI: 85%-95%), and the occurrence of grade 3 or higher adverse events was 49% (95% CI: 27%-71%). CONCLUSION: The combination of camrelizumab and apatinib exhibits commendable effectiveness in the management of liver cancer; nevertheless, vigilance should be exercised concerning potential adverse reactions in clinical applications to enhance the safety of pharmacological interventions.

Radionuclide labeled nanocarrier for imaging guided combined radionuclide, sonodynamic, and photothermal therapy of pancreatic tumours.

Radionuclide therapy (RNT) is an effective method for the clinical precise treatment of cancer. However, the uneven dose distribution and rapid metabolism of nuclides limit the effective killing of tumors. To overcome the limitations of radionuclide therapeutic approaches, combining different therapeutic strategies to treat cancer has manifested great promise in basic and clinical research. Here, a new combination therapy strategy was developed to combine radionuclide therapy, sonodynamic therapy and photothermal therapy (RNT-SDT-PTT) under radionuclide imaging guided achieve highly effective combination therapy. We prepared a polydopamine-modified Au nanostar (AN), then loaded with the acoustic sensitizer protoporphyrin (IX) and labeled with diagnostic (99mTc) or therapeutic (131I) radionuclides (131I/99mTc-AN@D/IX) for the precise diagnosis and treatment of pancreatic cancer. After intratumor administration, single photon emission computed tomography imaging showed that the nanocarriers were mostly retained in the tumor compared to free radionuclide. As well as using near-infrared light to trigger PTT and ultrasound with high penetration depth to activate IX to generate reactive oxygen species achieved SDT of tumor. The ultimate significantly improved the inhibitory effects by the RNT-SDT-PTT combined therapy for pancreatic cancer. Therefore, this study proposes an effective radionuclide combination therapy regimen consisting of three widely used treatments, offering promising prospects for the future of oncology.

Different spatiotemporal dynamics, ecological drivers and assembly processes of bacterial, archaeal and fungal communities in brackish-saline groundwater.

The presence of brackish-saline groundwater (BSG) poses great harms for human health, agricultural and industrial activity. Understanding how the major environmental features in BSG determine microbiota coalescence is crucial for groundwater monitoring optimization. Based on metabarcoding analysis of 242 PCR-amplified samples, we provided the first blueprints about distinct spatiotemporal distributions, ecological drivers and assembly processes of bacterial, archaeal and fungal communities in BSG obtained from new-constructed wells at Xiong'an New Area, China. Our study demonstrated that bacterial and archaeal communities exhibited significant spatial turnovers, while fungal community displayed the most obvious seasonal variation. Environmental filtering drove bacterial compositions more than those of archaea and fungi. Total dissolved solids (TDS), one of the most critical hydrochemical factors for salinization, had a stronger effect on bacterial spatiotemporal turnover than on those of the other two taxonomic groups, while chemical oxygen demand (CODMn) was more significantly associated with prokaryotic community variations. Bacterial and archaeal taxa dominated the metacommunity network and connected closely, and TDS was mostly related to archaeal subnetwork topological features, suggesting a significant influence of TDS on species association patterns within archaea. Specific functional guilds like bacterial nitrite oxidation, anammox, and archaeal methanogenesis were enriched in lower-TDS habitats, while higher TDS favored bacterial communities involved in dark oxidation of sulfur compounds, fumarate respiration, and cellulolysis. Finally, we confirmed that bacterial and archaeal assembly processes were governed by determinism in each season, and that of fungi was more regulated by stochasticity. Higher TDS was speculated to lead bacterial assembly more deterministic and that of fungi more random. Together, these findings provided an integrate theoretical framework about the unique responses of the three life domains to brackish-saline stress, and had important implications for microbial ecological prediction in groundwater.

Association of Pericardiac Adipose Tissue With Coronary Artery Disease.

Background and Aim: Coronary artery disease (CAD) poses a worldwide health threat. Compelling evidence shows that pericardial adipose tissue (PAT), a brown-like adipose adjacent to the external surface of the pericardium, is associated with CAD. However, the specific molecular mechanisms of PAT in CAD are elusive. This study aims to characterize human PAT and explore its association with CAD. Methods: We acquired samples of PAT from 31 elective cardiac surgery patients (17 CAD patients and 14 controls). The transcriptome characteristics were assessed in 5 CAD patients and 4 controls via RNA-sequencing. Cluster profile R package, String database, Cytoscape were applied to analyze the potential pathways and PPI-network key to DEGS, whereas the hubgenes were predicted via Metascape, Cytohubba, and MCODE. We use Cibersort, ENCORI, and DGIDB to predict immunoinfiltration, mRNA-miRNA target gene network, and search potential drugs targeting key DEGs. The predictable hubgenes and infiltrating inflammatory cells were validated in 22 patients (12 CAD samples and 10 control samples) through RT-qPCR and immunohistochemistry. Results: A total of 147 different genes (104 up-regulated genes and 43 down-regulated genes) were identified in CAD patients. These different genes were associated with immunity and inflammatory dysfunction. Cibersort analysis showed monocytes and macrophages were the most common subsets in immune cells, whereas immunohistochemical results revealed there were more macrophages and higher proportion of M1 subtype cells in PAT of CAD patients. The PPI network and module analysis uncovered several crucial genes, defined as candidate genes, including Jun, ATF3, CXCR4, FOSB, CCl4, which were validated through RT-qPCR. The miRNA-mRNA network implicated hsa-miR-185-5p as diagnostic targets and drug-gene network showed colchicine, fenofibrate as potential therapeutic drugs, respectively. Conclusion: This study demonstrates that PAT is mainly associated with the occurrence of CAD following the dysfunction of immune and inflammatory processes. The identified hubgenes, predicted drugs and miRNAs are promising biomarkers and therapeutic targets for CAD.

Determination of acyclovir in renal microdialysis fluid and confirmation of renal function index.

Acyclovir (ACV) is a nucleoside antivirus-free agent that was developed and marketed by Burroughs Well-come of the United States. Renal damage from ACV has been a major factor limiting its clinical application. Thus, the renal toxicity mechanism of ACV requires systematic study. In our previous study, we speculated that the nephrotoxicity of ACV may be associated with oxidative stress. In addition to the study of ACV's toxic effect in vivo, it is also necessary to explore the absorption and distribution of ACV in the body to further investigate the changes to ACV in the body. In this study, the toxicokinetics ACV in the kidney of the rat were explored using microdialysis, and the renal function of rats was measured. The results showed that high-dose ACV is associated with renal toxicity after a single intravenous injection or successive administration.

Apoptotic effects of rhein through the mitochondrial pathways, two death receptor pathways, and reducing autophagy in human liver L02 cells.

Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid) is a major component of many medicinal herbs such as Rheum palmatum L. and Polygonum multiflorum. Despite being widely used, intoxication cases associated with rhein-containing herbs are often reported. Currently, there are no available reports addressing the effects of rhein on apoptosis in human liver L02 cells. Thus, the aim of this study is to determine the cytotoxic effects and the underlying mechanism of rhein on human normal liver L02 cells. In the present study, the methyl thiazolyl tetrazolium assay demonstrated that rhein decreased the viability of L02 cells in dose-dependent and time-dependent ways. Rhein was found to trigger apoptosis in L02 cells as shown by Annexin V-fluoresceine isothiocyanate (FITC) apoptosis detection kit and cell mitochondrial membrane potential (MMP) assay, with nuclear morphological changes demonstrated by Hoechst 33258 staining. Detection of intracellular superoxide dismutase activity, lipid oxidation (malondialdehyde) content, and reactive oxygen species (ROS) levels showed that apoptosis was associated with oxidative stress. Moreover, it was observed that the mechanism implicated in rhein-induced apoptosis was presumably via the death receptor pathway and the mitochondrial pathway, as illustrated by upregulation of TNF-α, TNFR1, TRADD, and cleaved caspase-3, and downregulation of procaspase-8, and it is suggested that rhein may increase hepatocyte apoptosis by activating the increase of TNF-α level. Meanwhile, rhein upregulates the expression of Bax and downregulates the expression of procaspase-9 and -3, and it is suggested that the mitochondrial pathway is activated and rhein-induced apoptosis may be involved. In addition, we also want to explore whether rhein-induced apoptosis is related to the autophagic changes induced by rhein. The results showed that rhein treatment increased P62 and decreased LC3-II and beclin-1, which means that autophagy was weakened. The results of our studies indicated that rhein induced caspase-dependent apoptosis via both the Fas death pathway and the mitochondrial pathway by generating ROS, and meanwhile the autophagy tended to weaken.

[T follicular helper cells and their related molecules in rheumatoid arthritis: A review].

Abnormal T follicular helper (Tfh) cells in patients with rheumatoid arthritis (RA) is related to the occurrence and development of RA. At present, the mechanism of Tfh cells regulating RA is still unclear. In addition, Tfh cell surface molecules C-X-C motif chemokine receptor 5 (CXCR5), inducible costimulatory molecule (ICOS) and programmed death factor 1 (PD-1) and its secreted interleukin 21 (IL-21), B-cell lymphoma 6 (BCL6) have been shown to be involved in the development of RA. We mainly reviewied the mechanism of RA regulation from the perspective of Tfh cell surface molecules and their secreted factors, analyzed the effects of various molecules related to Tfh cells on RA, and explored the significance of each molecule in the clinical diagnosis of RA and the potential ways of treating RA with each molecule as a target.

[IgG4-related diseases: A comprehensive review].

IgG4-related disease (IgG4-RD) is an inflammatory disorder with slow progression in multiple organs, characterized by abundant infiltration of IgG4-positive plasmacytes and fibrosis in the involved organs. The precise pathogenic mechanism of IgG4-RD still remains unclear. Currently, the abnormal regulation of acquired immunity and adaptive immunity is considered as the main pathogenesis of IgG4-RD, and its clinical manifestations are diverse. IgG4-RD can affect any tissue and organ. Inflammatory pseudotumor and diffuse enlargement are the common manifestations, which are easily misdiagnosed as tumor or inflammation. The treatment of glucocorticoid-based drugs is effective. However, the symptoms of IgG4-RD are variable and the prognosis is poor. We mainly summarized the research progress in the pathogenesis, clinical features, diagnosis and treatment of IgG4-RD.

Oxymatrine Causes Hepatotoxicity by Promoting the Phosphorylation of JNK and Induction of Endoplasmic Reticulum Stress Mediated by ROS in LO2 Cells.

Oxymatrine (OMT) often used in treatment for chronic hepatitis B virus infection in clinic. However, OMT-induced liver injury has been reported. In this study, we aim to investigate the possible mechanism of OMT-induced hepatotoxicity in human normal liver cells (L02). Exposed cells to OMT, the cell viability was decreased and apoptosis rate increased, the intracellular markers of oxidative stress were changed. Simultaneously, OMT altered apoptotic related proteins levels, including Bcl-2, Bax and pro-caspase-8/-9/-3. In addition, OMT enhanced the protein levels of endoplasmic reticulum (ER) stress makers (GRP78/Bip, CHOP, and cleaved-Caspase-4) and phosphorylation of c-Jun N-terminal kinase (p-JNK), as well as the mRNA levels of GRP78/Bip, CHOP, caspase-4, and ER stress sensors (IREI, ATF6, and PERK). Pre-treatment with Z-VAD-fmk, JNK inhibitor SP600125 and N-acetyl-l-cysteine (NAC), a ROS scavenger, partly improved the survival rates and restored OMT-induced cellular damage, and reduced caspase-3 cleavage. SP600125 or NAC reduced OMT-induced p-JNK and NAC significantly lowered caspase-4. Furthermore, 4-PBA, the ER stress inhibitor, weakened inhibitory effect of OMT on cells, on the contrary, TM worsen. 4-PBA also reduced the levels of p-JNK and cleaved-caspase-3 proteins. Therefore, OMT-induced injury in L02 cells was related to ROS mediated p-JNK and ER stress induction. Antioxidant, by inhibition of p-JNK or ER stress, may be a feasible method to alleviate OMT-induced liver injury.

[Paeoniflorin ameliorates liver injury of MRL/lpr mice through inhibition of NF-κB pathway].

Objective To investigate the effects of paeoniflorin (PF) on liver injury of MRL/lpr mice and its underlying mechanisms. Methods The research included 10 normal control C57BL/6 mice and 40 MRL/lpr mice. MRL/lpr mice were randomly assigned equally to a blank control group, a dexamethasone (1.5 mg/kg) group, and two PF (20, 40 mg/kg) groups. The serum levels of alanine transaminase (ALT) and aspartate transaminase (AST) were tested with microplate assay. Inflammatory cytokines in the serum and liver were also detected using ELISA. Liver pathological changes were observed using HE staining. The protein levels of receptor interacting protein140 (RIP140), Toll-like receptor 4 (TLR4), p-NF-κBp65, NF-κBp65, p-IκBα and IκBα in the liver were detected by Western blot analysis. Results PF significantly decreased the serum levels of AST and ALT, obviously decreased the expressions of the inflammatory cytokines IL-1ß, IL-6 and TNF-α in the serum and liver, alleviated liver pathological changes and inhibited the expressions of RIP140, TLR4, p-NF-κBp65, p-IκBα proteins in the MRL/lpr mice. Conclusion PF has protective effects against liver injury in MRL/lpr mice by inhibiting NF-κB pathway.

[Protection of Rho-associated protein kinase inhibitor Y-27632 in MRL/lpr mice].

Objective To investigate the immunological effect of Rho-associated protein kinase inhibitor Y-27632 on MRL/lpr mice and explore its underlying mechanisms. Methods The study collected 10 wild-type C57BL/6 mice as normal controls and 20 MRL/lpr mice that were randomly assigned to MRL/lpr group and 5 mg/kg Y-27632-treated MRL/lpr group, with 10 mice in each group. Superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA), interleukin 6 (IL-6), IL-1ß and tumor necrosis factor α (TNF-α) in the serum or spleen were detected by ELISA. The protein levels of thioredoxin-interacting protein/thioredoxin (Txnip/Trx), MAPK-associated protein ERK, JNK, p38 and NF-κB were detected by Western blot analysis. T lymphocytes were isolated and cultured from the groups, and then subjected to Western blotting for evaluating the levels of Txnip/Trx, MAPK, NF-κB proteins and to ELISA for determining the levels of IL-6, IL-1ß, TNF-α in the supernatants. Results Compared with the MRL/lpr group, the level of SOD increased and MDA decreased in the serum and spleen; the levels of IL-6, IL-1ß, TNF-α were reduced in the serum, spleen and the supernatant of T cells from the spleen; the protein levels of Txnip/Trx, MAPK, NF-κB from the spleen were inhibited and the level of Trx in the spleen was raised in MRL/lpr mice treated with Y-27632. Conclusion Ros kinase inhibitor Y-27632 has protective effects on MRL/lpr lupus mice.

[Protective effects of glycyrrhizic acid against lupus nephritis in MRL/lpr mice].

OBJECTIVE: To investigate protective effect of glycyrrhizic acid (GA) against lupus nephritis in MRL/lpr mice and explore its underlying mechanisms. METHODS: Forty MRL/lpr mice were randomized equally into blank control group, dexamethasone (1.5 mg/kg) group, GA (20 mg/kg) group, and GA (40 mg/kg) group with corresponding treatments for 7 days, with 10 wild-type mice as the control group. Serum levels of uric acid and creatinine and inflammatory cytokines in the serum and kidney were tested after the treatments using enzyme-linked immunosorbent assays (ELISA). The pathological changes in the kidneys were detected using HE staining, and the protein expressions of NLRP3, ASC, caspase-1, IL-1ß, p-NF-κB, NF-κB, p-IκBα, and IκBα were detected with Western blotting. RESULTS: GA obviously decreased serum levels of uric acid and creatinine, decreased inflammatory cytokines in the serum and kidney, ameliorated renal pathologies and inhibited the expressions of NLRP3, ASC, caspase-1, IL-1ß, p-NF-κB, and p-IκBα proteins in MRL/lpr mice. CONCLUSION: GA has protective effects against lupus nephritis in MRL/lpr mice.