Biochar-bacteria-plant combined potential for remediation of oil-contaminated soil.

Oil pollution is a common type of soil organic pollution that is harmful to the ecosystem. Bioremediation, particularly microbe-assisted phytoremediation of oil-contaminated soil, has become a research hotspot in recent years. In order to explore more appropriate bioremediation strategies for soil oil contamination and the mechanism of remediation, we compared the remediation effects of three plants when applied in combination with a microbial agent and biochar. The combined remediation approach of Tagetes erecta, microbial agent, and biochar exhibited the best plant growth and the highest total petroleum hydrocarbons degradation efficiency (76.60%). In addition, all of the remediation methods provided varying degrees of restoration of carbon and nitrogen contents of soils. High-throughput sequencing found that microbial community diversity and richness were enhanced in most restored soils. Some soil microorganisms associated with oil degradation and plant growth promotion such as Cavicella, C1_B045, Sphingomonas, MND1, Bacillus and Ramlibacter were identified in this study, among which Bacillus was the major component in the microbial agent. Bacillus was positively correlated with all soil remediation indicators tested and was substantially enriched in the rhizosphere of T. erecta. Functional gene prediction of the soil bacterial community based on the KEGG database revealed that pathways of carbohydrate metabolism and amino acid metabolism were up-regulated during remediation of oil-contaminated soils. This study provides a potential method for efficient remediation of oil-contaminated soils and thoroughly examines the biochar-bacteria-plant combined remediation mechanisms of oil-contaminated soil, as well as the combined effects from the perspective of soil bacterial communities.

Metabolomics analysis reveals characteristic metabolites in different levels of oxaliplatin-induced neurotoxicity.

Oxaliplatin (L-OHP), a third-generation platinum-based anti-tumor drug, finds widespread application in the first-line treatment of metastatic colorectal cancer. Despite its efficacy, the drug's usage is curtailed by a litany of side effects, with L-OHP-induced peripheral neuropathy (OIPN) being the most debilitating. This condition can be classified into varying degrees of severity. Employing serum metabolomics, a high-sensitivity, high-throughput technique, holds promise as a method to identify biomarkers for clinical assessment and monitoring of OIPN patients across different severity levels. In our study, we analyzed serum metabolites in patients with different OIPN levels using ultra-performance liquid chromatography-high resolution mass spectrometry. By employing statistical analyses and pathway enrichment studies, we aimed to identify potential biomarkers and metabolic pathways. Our findings characterized the serum metabolic profiles of patients with varying OIPN levels. Notably, pathway analysis revealed a significant correlation with lipid metabolism, amino acid metabolism, and energy metabolism. Multivariate statistical analysis and receiver operator characteristic curve evaluation pointed to anhalamine and glycochenodeoxycholic acid as potential biomarkers for OIPN C and A, which suggest that serum metabolomics may serve as a potent tool for exploring the metabolic status of patients suffering from diverse diseases and for discovering novel biomarkers.

Biomarker Identification and Risk Prediction Model Development for Differentiated Thyroid Carcinoma Lung Metastasis Based on Primary Lesion Proteomics.

PURPOSE: The rising global high incidence of differentiated thyroid carcinoma (DTC) has led to a significant increase in patients presenting with lung metastasis of DTC (LMDTC). This population poses a significant challenge in clinical practice, necessitating the urgent development of effective risk stratification methods and predictive tools for lung metastasis. EXPERIMENTAL DESIGN: Through proteomic analysis of large samples of primary lesion and dual validation employing parallel reaction monitoring and IHC, we identified eight hub proteins as potential biomarkers. By expanding the sample size and conducting statistical analysis on clinical features and hub protein expression, we constructed three risk prediction models. RESULTS: This study identified eight hub proteins-SUCLG1/2, DLAT, IDH3B, ACSF2, ACO2, CYCS, and VDAC2-as potential biomarkers for predicting LMDTC risk. We developed and internally validated three risk prediction models incorporating both clinical characteristics and hub protein expression. Our findings demonstrated that the combined prediction model exhibited optimal predictive performance, with the highest discrimination (AUC: 0.986) and calibration (Brier score: 0.043). Application of the combined prediction model within a specific risk threshold (0-0.97) yielded maximal clinical benefit. Finally, we constructed a nomogram based on the combined prediction model. CONCLUSIONS: As a large sample size study in LMDTC research, the identification of biomarkers through primary lesion proteomics and the development of risk prediction models integrating clinical features and hub protein biomarkers offer valuable insights for predicting LMDTC and establishing personalized treatment strategies.

Evaluation of Molecular Residual Disease by a Fixed Panel in Resectable Colorectal Cancer.

Purpose: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. Materials and Methods: 75 patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and pre-operative and post-operative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. Results: The tumor-informed fixed assay had a higher pre-operative positive rate than the tumor-agnostic assay (73.3% vs 57.3%). The pre-op ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined post-op ctDNA positivity was significantly associated with worse DFS (HR, 20.74, 95%CI 7.19-59.83; p<0.001), which was an independent predictor by multivariable analysis (HR, 28.57, 95%CI 7.10-114.9; p<0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest pre-operative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in post-op landmark (HR, 26.34, 95%CI, 6.01-115.57; p<0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04, 95%CI, 0.94-9.89; p=0.052). Conclusion: Our study confirmed the prognostic value of the ctDNA positivity at post-op day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

Role of sodium/iodide symporter overexpression in inhibiting thyroid cancer cell invasion and stem cell maintenance by inhibiting the ß-catenin/LEF-1 pathway.

Background: In thyroid cancers, a reduction in the expression of the sodium/iodide symporter (NIS) is observed concomitant with a diminution in cancer cell differentiation. The ß-catenin/LEF-1 pathway emerges as a crucial regulatory pathway influencing the functional expression of NIS in human thyroid cancer cells. Further research is required to comprehensively elucidate the role of NIS overexpression in impeding the progression of thyroid cancer cells. Methods: Human papillary thyroid carcinoma (PTC) cell lines, specifically PTC-1 and KTC-1, were subjected to Scratch and Transwell assays, colony formation, and tumor sphere formation tests to investigate invasion and migration, focusing on the impact of NIS overexpression. The assessment involved the use of western blot to analyze the expression levels of ß-catenin, NIS, CD133, SRY-related HMG box2 (Sox2), lymphoid enhancer-binding factor 1 (LEF-1), NANOG, octamer-binding transcription factor 4 (Oct4), aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), and epithelial cellular adhesion molecule (EpCAM). Statistical analysis was conducted using SPSS version 20.0, and the graphs were developed using GraphPad Prism 7 (GraphPad Software, Inc.). Results: Our observations revealed that Nthy-ori-3-1 cell lines exhibited notably higher average expression levels of NIS, yet significantly lower levels of LEF-1 and ß-catenin compared to PTC-1 and KTC-1 cell lines. Furthermore, the overexpression of ß-catenin resulted in reduced binding of LEF-1 to NIF promotion but concurrently increased the expression of NIS. The downregulation of NIS markedly enhanced the expression of ALDH1A1, CD133, OCT4, Nanog, SOX2, and EpCam-all of which are targets within the Wnt/ß-catenin signaling pathway. Conversely, the upregulation of NIS suppressed the expression of these proteins. Moreover, cells treated with ß-catenin activators demonstrated an increased capability to form more spheroids and displayed heightened aggressiveness. Conversely, the NIS overexpression (OE) group exhibited suppressed abilities in invasion and colony formation. Conclusion: Thyroid cancer cells exhibit diminished expression of NIS, and the invasion and maintenance of stem cells in thyroid cancer cells were hindered by NIS OE through the inhibition of the ß-catenin/LEF-1 pathway. Further research is warranted to comprehensively assess this outcome, which holds promise as a potential targeted treatment for thyroid cancer.

Koumine inhibits RANKL-induced ubiquitination and NF-κB activation to prevent ovariectomy and aging-induced bone loss.

Osteoporosis (OP) is a bone remodeling disease characterized by an imbalance between bone resorption and formation. Osteoclasts are the primary therapeutic targets for treating bone destruction. Koumine (KM), the most bioactive component in Gelsemium alkaloids, exhibits antitumor, immunosuppressive, anti-inflammatory, and analgesic properties. However, the effects of bone loss have not been well studied. This study conducted in vitro and in vivo verification experiments on KM. The results showed that KM inhibited bone resorption and tartrate-resistant acid phosphatase positive (TRAP+) osteoclasts development by mature osteoclasts in a dose-dependent manner. Moreover, KM prevented OVX-induced OP in vivo and potentially inhibited ubiquitination, a process closely related to various biological activities, including protein interaction, transcription, and transmembrane signal transduction regulation, especially within the nuclear factor-κB (NF-κB) pathway. Previous studies have demonstrated that several proteins ubiquitination promotes osteoclastogenesis, our study indicated that KM inhibits early NF-κB activation and receptor activator of NF-κB ligand induced ubiquitination, a critical factor in osteoclast differentiation. In conclusion, our research suggests that KM holds potential as an effective therapeutic agent for OP.

Development and Validation of Potential Molecular Subtypes and Signatures of Thyroid Carcinoma Based on Aging-related Gene Analysis.

BACKGROUND/AIM: Thyroid carcinoma (THCA) is a cancer of the endocrine system that most commonly affects women. Aging-associated genes play a critical role in various cancers. Therefore, we aimed to gain insight into the molecular subtypes of thyroid cancer and whether senescence-related genes can predict the overall prognosis of THCA patients. MATERIALS AND METHODS: Thyroid carcinoma (THCA) transcriptome-related expression profiles were obtained from The Cancer Genome Atlas (TCGA) database. These profiles were randomly divided into training and validation subsets at a ratio of 1:1. Unsupervised clustering algorithms were used to compare differences between the two subtypes; prognosis-related senescence genes were used to further construct our prognostic models by univariate and multivariate Cox analyses and construct a nomogram to predict the 1-, 3-, and 5-year overall survival probability of THCA patients. In addition, we performed gene set enrichment analysis (GSEA) to predict the immune microenvironment and somatic mutations between the different risk groups. Finally, real-time PCR was used to verify the expression levels of key model genes. RESULTS: The 'ConsensusClusterPlus' R package was used to cluster thyroid cancer into two categories (Cluster1 and Cluster2) on the basis of 46 differentially expressed aging-related genes (DE-ARGs); patients in Cluster1 demonstrated a better prognosis than those in Cluster2. Cox analysis was used to screen six prognosis-related DE-ARGs. Finally, our real-time PCR results confirmed our hypothesis. CONCLUSION: Differences exist between the two subtypes of thyroid cancer that help guide treatment decisions. The six DE-ARG genes have a high predictive value for risk stratifying THCA patients.

IGF2BP2 promotes ovarian cancer growth and metastasis by upregulating CKAP2L protein expression in an m6 A-dependent manner.

Ovarian cancer (OC) is the second leading cause of gynecological cancer-related death in women worldwide. N6-methyladenosine (m6 A) is the most abundant internal modification in eukaryotic RNA. Human insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an m6 A reader, can enhance mRNA stability and promote translation by recognizing m6 A modifications. Its tumor-promoting effects have been demonstrated in several cancers. However, the roles of m6 A modification and IGF2BP2 in OC remain unclear. Here, by using methylated RNA immunoprecipitation sequencing, we demonstrated that there is widespread dysregulation of m6 A modification in OC tissues. The m6 A modification and the mRNA and protein levels of IGF2BP2 were significantly elevated in OC. Overexpression of IGF2BP2 facilitated OC cell proliferation, migration, and invasion in vitro and accelerated tumor growth and metastasis in vivo. While IGF2BP2-knockdown showed the opposite effect. Mechanistically, we identified cytoskeleton-associated protein 2-like (CKAP2L) as a target of IGF2BP2. IGF2BP2 promoted CKAP2L translation dependent on m6 A modification, rather than affecting mRNA and protein stability. Overexpression of CKAP2L rescued the tumor-suppressive effect of IGF2BP2 knockdown in OC cells. In conclusion, this study revealed the potential role of IGF2BP2 in tumor progression, at least partially via promoting the translation of CKAP2L in an m6 A-dependent manner.

Real-world treatment patterns and survival for locally advanced esophageal squamous cell carcinoma.

The "real world" treatment mode and clinical efficacy of locally advanced esophageal squamous cell carcinoma (LAESCC) are unclear. Meanwhile, the role of immunotherapy in the clinical practice is also puzzling. We conducted the research to investigate the statue of "real world" LAESCC. The clinical data of patients with locally advanced esophageal squamous cell carcinoma which met the criteria from January 2010 to December 2019 have been retrospectively analyzed, and the distribution of clinical treatment patterns has been analyzed. They cover such aspects as dfferences in survival time and further analysis of the differences in overall survival (OS) and progression-free survival (PFS) between patients who received immunotherapy and those who did not receive immunotherapy. What is more, Cox risk regression model has also been used to evaluate the risk factors affecting the prognosis of LAESCC. The cases of a total of 5328 newly diagnosed patients with esophageal cancer were collected, and a total of 363 patients were included in the study, with a median age of (46.2 ± 7.8) years old; 84 (23.1%) and 279 (76.9%) patients received 1L and ≥ 2L, respectively; Concurrent chemoradiotherapy (74.1%) and paclitaxel combined with platinum-based chemotherapy (14.3%) were the main first-line treatment options; fluorouracil combined with cisplatin regimen-based chemotherapy (63.8%) was the main treatment option for ≥ 2L, of which 69 patients (25.3%) received immunization treatment; OS of patients with 1 line of therapy and ≥ 2L were (22.4 ± 7.2) months and (38.7 ± 8.5) months, respectively, and the comparison between groups was statistically significant (P < .05); among 69 patients with ≥ 2L who received immunotherapy, PFS and The OS was (14.6 ± 6.9) and (45.3 ± 9.7) respectively, and the comparison between the groups was statistically significant (all P < .05). Cox multivariate analysis has shown that clinical stage, immunotherapy, concurrent chemoradiotherapy, and ≥ 2L are the main factors affecting OS. and immunotherapy, concurrent chemoradiotherapy, and ≥ 2L are independent factors affecting PFS. Concurrent chemoradiotherapy is currently one of the standard treatments for LAESCC, and most patients are still willing to receive second-line or above treatments. Adding immunotherapy to standard treatment modalities may further optimize clinical treatment modalities and improve patient outcomes.

Advances in the molecular mechanism and targeted therapy of radioactive-iodine refractory differentiated thyroid cancer.

Most patients with differentiated thyroid cancer have a good prognosis after radioactive iodine-131 treatment, but there are still a small number of patients who are not sensitive to radioiodine treatment and may subsequently show disease progression. Therefore, radioactive-iodine refractory differentiated thyroid cancer treated with radioiodine usually shows reduced radioiodine uptake. Thus, when sodium iodine symporter expression, basolateral membrane localization and recycling degradation are abnormal, radioactive-iodine refractory differentiated thyroid cancer may occur. In recent years, with the deepening of research into the pathogenesis of this disease, an increasing number of molecules have become or are expected to become therapeutic targets. The application of corresponding inhibitors or combined treatment regimens for different molecular targets may be effective for patients with advanced radioactive-iodine refractory differentiated thyroid cancer. Currently, some targeted drugs that can improve the progression-free survival of patients with radioactive-iodine refractory differentiated thyroid cancer, such as sorafenib and lenvatinib, have been approved by the FDA for the treatment of radioactive-iodine refractory differentiated thyroid cancer. However, due to the adverse reactions and drug resistance caused by some targeted drugs, their application is limited. In response to targeted drug resistance and high rates of adverse reactions, research into new treatment combinations is being carried out; in addition to kinase inhibitor therapy, gene therapy and rutin-assisted iodine-131 therapy for radioactive-iodine refractory thyroid cancer have also made some progress. Thus, this article mainly focuses on sodium iodide symporter changes leading to the main molecular mechanisms in radioactive-iodine refractory differentiated thyroid cancer, some targeted drug resistance mechanisms and promising new treatments.

Risk prediction of second primary malignant tumor in primary differentiated thyroid cancer patients: a population-based study.

PURPOSE: To investigate the risk factors of second primary malignant tumor (SPMT) in patients with differentiated thyroid cancer (DTC) and establish a competing risk nomogram to predict the probability of SPMT occurrence. METHODS: We retrieved data from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with DTC between 2000 and 2019. The Fine and Gray subdistribution hazard model was employed to identify SPMT risk factors in the training set and develop a competing risk nomogram. Model evaluation was performed using area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: A total of 112,257 eligible patients were included in the study and randomized into a training set (n = 112,256) and a validation set (n = 33,678). The cumulative incidence rate of SPMT was 15% (n = 9528). Age, sex, race, tumor multifocality, and TNM stage were independent risk factors of SPMT. The calibration plots showed good agreement between the predicted and observed SPMT risks. The 10-year AUCs of the calibration plots were 70.2 (68.7-71.6) in the training set and 70.2 (68.7-71.5) in the validation set. Moreover, DCA showed that our proposed model resulted in higher net benefits within a defined range of risk thresholds. The cumulative incidence rate of SPMT differed among risk groups, classified according to nomogram risk scores. CONCLUSION: The competing risk nomogram developed in this study exhibits high performance in predicting the occurrence of SPMT in patients with DTC. These findings may help clinicians identify patients at distinct levels of risk of SPMT and develop corresponding clinical management strategies.

The Value of Percutaneous Ultrasound-Guided Subacromial Bursography for Rotator Cuff Tear in Elderly Patients with Shoulder Pain.

Objective: Based on the analysis of the images of acromial slide, we explored the application of percutaneous ultrasound-guided subacromial bursography (PUSB) on rotator cuff tear (RCT) in diagnosing elderly patients with shoulder pain. Methods: Eighty-five patients who were clinically diagnosed with RCT and underwent PUSB examination in the department of ultrasound in our hospital were enrolled as the subjects. Independent samples t-test was used to analyze the general characteristics. Based on the gold standard of shoulder arthroscopy, the diagnostic efficacy of ultrasound, magnetic resonance imaging (MRI), and PUSB was evaluated. The sensitivity, specificity, positive and negative predictive values, and accuracy were calculated as well. The consistency of these techniques with shoulder arthroscopy in diagnosing the RCT stage was additionally compared using Kappa test. Results: In patients with large full-thickness RCT, the 100% detection rate was achieved by the techniques of ultrasound, MRI, and PUSB. For patients with small full-thickness RCT, the detection rate of PUSB (100%) was evidently higher than those of ultrasound and MRI. Similar results were shown in the detection rates of patients with bursal-side partial-thickness RCT (90.5%) and articular-side partial-thickness RCT (86.9%). More importantly, the sensitivity, specificity, and accuracy of PUSB in patients with both full-thickness RCT and partial-thickness RCT were significantly better than those of ultrasound and MRI. Conclusion: PUSB has a better efficacy in the detection of RCT than ultrasound and MRI, showing its feasibility as an important imaging method to evaluate the degree of RCT.

Icariin synergizes therapeutic effect of dexamethasone on adriamycin-induced nephrotic syndrome.

BACKGROUND: Glomerular damage is a common clinical indicator of nephrotic syndrome. High-dose hormone treatment often leads to hormone resistance in patients. How to avoid resistance and improve the efficiency of hormone therapy draws much attention to clinicians. METHODS: Adriamycin (ADR) was used to induce nephropathy model in SD rats. The rats were treated with dexamethasone (DEX), icariin (ICA), and DEX + ICA combination therapy. The changes in urinary protein (UP), urea nitrogen (BUN), and serum creatinine (SCR) contents in rats were detected by enzyme-linked immunosorbent assay (ELISA), and the degree of pathological injury and the expression level of podocin were detected by HE staining and immunohistochemistry, to test the success of the model and the therapeutic effects of three different ways. The effect of treatments on podocytes autophagy was evaluated via transfection of mRFP-GFP-LC3 tandem adenovirus in vitro. RESULTS: The contents of UP, SCR, and BUN were significantly increased, the glomerulus was seriously damaged, and the expression of Nephrosis2 (NPHS2) was significantly decreased in the ADR-induced nephrotic syndrome rat model compared to that of the control group. DEX, ICA, and the DEX + ICA combined treatment significantly alleviated these above changes induced by ADR. The combined treatment of DEX + ICA exhibited better outcome than single treatment. The combined treatment also restored the podocyte autophagy, increased the expression of microtubule-associated protein light-chain 3II (LC3II), and reduced the expression of p62 in vitro. The combined treatment protects podocytes by mediating the PI3K/AKT/mTOR (rapamycin complex) signaling pathway. CONCLUSION: ICA enhances the therapeutic effect of DEX on the nephrotic syndrome.

Prognostic value of lactate dehydrogenase in non-small cell lung cancer patients with brain metastases: a retrospective cohort study.

Background: At present, although there are some known molecular markers for the prognosis of non-small cell lung cancer (NSCLC) brain metastases, but there are still shortcomings in sensitivity and specificity. Lactate dehydrogenase (LDH) is one of the key enzymes involved in malignancy vital glycolytic pathway. Elevated serum LDH levels are reported significantly associated with a poor prognosis in various malignancies. However, there is currently no consensus regarding the prognostic value of LDH in NSCLC patients with brain metastases. Methods: We retrospectively analyzed 224 patients diagnosed with lung cancer brain metastases between January 2006 and June 2020 after excluding patients meeting combined with other malignancies and inaccurate clinical information. The LDH cutoff values were obtained using a restricted cubic spline (RCS) model, and the patients were divided into two groups according to the optimal cut-off value (180 U/L). 107 patients with LDH ≤180 (47.77%) and 117 patients with LDH >180 (52.23%) were identified. Univariate and multivariate logistic regression analyses were performed to identify the risk factors. The overall survival (OS) time was defined as the time from the first diagnosis of brain metastases to the last follow-up or death. Of the included patients, 147 survived and 77 died. The Kaplan-Meier method was used to illustrate the OS difference between the two groups. Finally, sensitivity analysis was employed to evaluate the robustness of the results. Results: The OS rate was significantly lower in the high LDH group versus the low LDH group (P=0.009). The median survival times of the high and low LDH groups were approximately 16 and 33 months, respectively. Multivariate analysis showed that high LDH was associated with a significantly worse OS [adjusted hazard ratio (aHR), 1.567; 95% confidence interval (CI): 1.058 to 2.32, P=0.025] with adjustment for covariables that P<0.05 in univariate analysis. Sensitivity analysis indicated that the results of this study are robust, despite potential unmeasured confounders. Conclusions: High level of serum LDH indicates poor prognosis for patients with NSCLC brain metastases. This finding may provide useful prognostic information for patients and clinicians to choose more aggressive treatment strategies.

Quality evaluation of clinical practice guidelines for thromboprophylaxis in orthopaedic trauma based on AGREE II and AGREE-REX: a systematic review protocol.

INTRODUCTION: Orthopaedic trauma patients are at high risk of venous thromboembolism (VTE). As VTE prophylaxis has gradually raised public concerns, guidelines related to this topic have increased over time. However, the existing recommendations of thromboprophylaxis guidelines in orthopaedic trauma patients are still inconsistent, and the quality of the guidelines and recommendations for the topic still lacks comprehensive assessments. This review aims to critically appraise clinical practice guidelines for thromboprophylaxis in orthopaedic trauma patients. METHODS AND ANALYSIS: We will conduct a comprehensive literature search up to 31 October 2022 in databases (PubMed, EMBASE, CINAHL, Web of Science, the Cochrane Library, etc), academic websites and guideline repositories. The quality of the guidelines and recommendations will be assessed by five reviewers independently using the Appraisal of Guidelines Research and Evaluation II instrument (AGREE-II) and the AGREE - Recommendation EXcellence (AGREE-REX). We will summarise the characteristics of the guidelines and compare the differences between these recommendations. ETHICS AND DISSEMINATION: This study will follow the Declaration of Helsinki and has received approval from the Ethics Committee on Biomedical Research, West China Hospital, Sichuan University (ethics approval no. 2021-989). The results will be summarised as a paper, disseminated through peer-reviewed journals, and will help guide further research in the future. PROTOCOL REGISTRATION NUMBER: CRD42021273405.

The STING in Non-Alcoholic Fatty Liver Diseases: Potential Therapeutic Targets in Inflammation-Carcinogenesis Pathway.

Non-alcoholic fatty liver disease (NAFLD), an important chronic disease, is one of the major causes of high mortality and creates a substantial financial burden worldwide. The various immune cells in the liver, including macrophages, NK cells, dendritic cells, and the neutrophils involved in the innate immune response, trigger inflammation after recognizing the damage signaled from infection or injured cells and tissues. The stimulator of interferon genes (STING) is a critical molecule that binds to the cyclic dinucleotides (CDNs) generated by the cyclic GMP-AMP synthase (cGAS) to initiate the innate immune response against infection. Previous studies have demonstrated that the cGAS-STING pathway plays a critical role in inflammatory, auto-immune, and anti-viral immune responses. Recently, studies have focused on the role of STING in liver diseases, the results implying that alterations in its activity may be involved in the pathogenesis of liver disorders. Here, we summarize the function of STING in the development of NAFLD and present the current inhibitors and agonists targeting STING.

Astragaloside IV Protects Sepsis-induced Acute Kidney Injury by Attenuating Mitochondrial Dysfunction and Apoptosis in Renal Tubular Epithelial Cells.

BACKGROUND: Acute kidney injury (AKI) is closely linked to the pathogenesis of sepsis. Oxidative stress can affect the development of AKI by increasing damage to renal tubular epithelial cells. Astragaloside IV (AS-IV) is a natural saponin widly verified beneficial for ameliorating sepsis-induced kidney injury. However, the underlying mechanisms of AS-IV on relieving oxidative stress in renal tubular epithelial cells are yet to be established. PURPOSE: We aimed to investigate whether AS-IV could attenuate mitochondrialdysfunction and apoptosis in renal tubular epithelial cells and reveal its underlying mechanisms. METHODS: For the in vivo study, mice were divided into four groups (n=6): sham+saline, CLP+saline, CLP+ASIV- low dosage (5 mg/kg), CLP+AS-IV-high dosage (10 mg/kg), After 6 h or 24 h of treatment, the renal injuries were assessed based on related parameters of blood, protein and histopathological examination. Immunohistochemistry and ELISA were used to examine renal function. The molecular mechanism of AS-IV inhibited apoptosis and mitochondrial damage were monitored by flow cytometry and western blot analysis in HK-2 cells. RESULTS: We found that AS-IV ameliorates renal vacuolization, brush border loss, mitochondrial ultrastructure changes in sepsis-induced AKI, and the apoptosis and oxidative damage were greatly mitigated by AS-IV (10 mg/kg)-treated group. Abnormal changes in mitochondrial morphology and mitochondrial membrane potential were alleviated, and the expression of mitochondrial complex protein I (NDUFB8) and mitochondrial complex protein II (SDHB8) increased with (10 mg/kg)-treated group. Tubular epithelial cell apoptosis in AS-IV (20 µM)-treated cells was reduced by the Bax and cleaved caspase3 pathway. CONCLUSION: These studies demonstrated that AS-IV protects against sepsis-induced kidney tubular injury by alleviating oxidative stress, mitochondrial dysfunction possibly associated with the restored cleaved caspase3 pathway.

Immune-relevant genes of systemic lupus erythematosus by transcriptome profiling analysis.

OBJECTIVE: Our study aimed to reveal the roles of long noncoding RNA (lncRNA) and immune-relevant genes in systemic lupus erythematosus (SLE). METHODS: Expression profiling dataset GSE65391 consisted of 72 healthy blood samples and 924 SLE blood samples was downloaded from the Gene Expression Omnibus. Differentially expressed RNAs (DERs) in SLE samples were identified using the Limma package. Immune-relevant DERs were uncovered after assessing the immune cell infiltration types of different samples. Modules significantly related to the disease were extracted via weighted gene co-expression network analysis (WGCNA), followed by module-trait analysis. LncRNA-mRNA co-expression network was constructed for DERs in immune-relevant modules. Genes related to SLE were further revealed via the Comparative Toxicogenomics Database (CTD). Validation assay was conducted by another independent expression profiling dataset, GSE46907 (consisted of 5 healthy blood samples and 5 SLE blood samples) and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis of 15 healthy blood samples and 15 SLE blood samples. RESULTS: A total of 606 DERs, including 19 lncRNAs and 587 mRNAs, were identified. Obvious differences were observed in the proportions of 20 immune cell types, and 378 immune-relevant DERs were revealed. Genes in the lncRNA-mRNA co-expression network were significantly enriched in primary immunodeficiency, hematopoietic cell lineage, B cell receptor signaling pathway, SLE (up-regulated FCGR3A, down-regulated CD40LG, up-regulated HIST1H2BE, down-regulated human leukocyte antigen [HLA]-DOA, down-regulated HLA-DOB, up-regulated HIST1H3D, and up-regulated HIST1H2BC), and intestinal immune network for IgA production. SLE-related gene, CD40LG, retrieved from CTD has co-expression interactions with seven differentially expressed lncRNAs (HCG27, LINC02555, LINC02210, DHRS4-AS1, MIR600HG, DANCR, and LINC01278). CD40LG and HLA-DOA, were observed down-regulated, and FCGR3A, and HIST1H2BE were up-regulated in validation dataset GES46907. Moreover, CD40LG was validated to be down-regulated using qRT-PCR. CONCLUSIONS: Our results provide new insight in understanding the pathogenesis of SLE and might be helpful for developing new therapeutic approaches of SLE by modulating immune response.

Application of multiplex competitive PCR combined with capillary electrophoresis in carrier screening of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is an autosomal recessive, fatal neurological disorder in children. The pathogenic gene of SMA is survival motor neuron1 (SMN1). There are many methods to detect SMN1 gene copy number, but few techniques are suitable for large-scale population screening. In order to find a rapid and accurate experimental technique for mass screening of SMA carriers in the population, the SMN1 gene copy number of 12 SMA patients and their parents was analyzed by multiplex competitive PCR combined with capillary electrophoresis. Meanwhile, the copy number of SMN1 gene in 151 healthy pregnant women in Jiangsu was screened with the MLPA technology to confirm their copy number of the SMN genes. The results showed that the 12 SMA patients had 0 copy of SMN1 gene, and all their parents had 1 copy of SMN1 gene only. Among 151 healthy subjects, 3 cases (2.0%) had 1 copy of SMN1 gene, and hence designated as SMA carriers. One hundred and thirty-four cases (88.7%) had 2 copies of the SMN1 gene. There were 14 cases (9.3%) with more than 2 copies of the SMN1 gene. Therefore, multiplex competitive PCR combined with capillary electrophoresis is a rapid, simple and accurate method for the detection of SMA carriers; and potentially applicable to mass screening of SMA carriers in the population.