Structural and resting-state connection abnormalities of habenula in obsessive-compulsive disorder.

BACKGROUND: Previous studies have suggested that the habenula (Hb) may be involved in the mechanism of obsessive-compulsive disorder (OCD). However, the specific role of Hb in OCD remains unclear. This study aimed to explore the structural and functional abnormalities of Hb in OCD and their relationship with the clinical symptoms. METHODS: Eighty patients with OCD and 85 healthy controls (HCs) were recruited as the primary dataset. The grey matter volume, resting-state functional connectivity (FC), and effective connectivity (EC) of the Hb were calculated and compared between OCD group and HCs. An independent replication dataset was used to verify the stability and robustness of the results. RESULTS: Patients with OCD exhibited smaller Hb volume and increased FC of right Hb-left hippocampus than HCs. Dynamic causal model revealed an increased EC from left hippocampus to right Hb and a less inhibitory causal influence from the right Hb to left hippocampus in the OCD group compared to HCs. Similar results were found in the replication dataset. CONCLUSIONS: This study suggested that abnormal structure of Hb and hippocampus-Hb connectivity may contribute to the pathological basis of OCD.

Neural functional network of early Parkinson's disease based on independent component analysis.

This work explored neural network changes in early Parkinson's disease: Resting-state functional magnetic resonance imaging was used to investigate functional alterations in different stages of Parkinson's disease (PD). Ninety-five PD patients (50 early/mild and 45 early/moderate) and 37 healthy controls (HCs) were included. Independent component analysis revealed significant differences in intra-network connectivity, specifically in the default mode network (DMN) and right frontoparietal network (RFPN), in both PD groups compared to HCs. Inter-network connectivity analysis showed reduced connectivity between the executive control network (ECN) and DMN, as well as ECN-left frontoparietal network (LFPN), in early/mild PD. Early/moderate PD exhibited decreased connectivity in ECN-LFPN, ECN-RFPN, ECN-DMN, and DMN-auditory network, along with increased connectivity in LFPN-cerebellar network. Correlations were found between ECN-DMN and ECN-LFPN connections with UPDRS-III scores in early/mild PD. These findings suggest that PD progression involves dysfunction in multiple intra- and inter-networks, particularly implicating the ECN, and a wider range of abnormal functional networks may mark the progression of the disease.

Promising preclinical patient-derived organoid (PDO) and xenograft (PDX) models in upper gastrointestinal cancers: progress and challenges.

Gastrointestinal (GI) cancers (gastric cancer, oesophageal cancer, liver cancer, colorectal cancer, etc.) are the most common cancers with the highest morbidity and mortality in the world. The therapy for most GI cancers is difficult and is associated with a poor prognosis. In China, upper GI cancers, mainly gastric cancer (GC) and oesophageal cancer (EC), are very common due to Chinese people's characteristics, and more than half of patients are diagnosed with distant metastatic or locally advanced disease. Compared to other solid cancers, such as lung cancer and breast cancer, personalized therapies, especially targeted therapy and immunotherapy, in GC and EC are relatively lacking, leading to poor prognosis. For a long time, most studies were carried out by using in vitro cancer cell lines or in vivo cell line-derived xenograft models, which are unable to reproduce the characteristics of tumours derived from patients, leading to the possible misguidance of subsequent clinical validation. The patient-derived models represented by patient-derived organoid (PDO) and xenograft (PDX) models, known for their high preservation of patient tumour features, have emerged as a very popular platform that has been widely used in numerous studies, especially in the research and development of antitumour drugs and personalized medicine. Herein, based on some of the available published literature, we review the research and application status of PDO and PDX models in GC and EC, as well as detail their future challenges and prospects, to promote their use in basic and translational studies or personalized therapy.

Characteristics of neonatal hypoxic-ischemic encephalopathy at high altitude and early results of therapeutic hypothermia.

BACKGROUND: Altitude hypoxia and limited socioeconomic conditions may result in distinctive features of neonatal hypoxic-ischemic encephalopathy (HIE). Therapeutic hypothermia (TH) has not been used at altitude. We examined characteristics of HIE and early outcomes of TH in 3 centers at two high altitudes, 2 at 2,261 m and 1 at 3,650 m. METHODS: The incidence of HIE at NICUs was noted. TH was conducted when personnel and devices were available in 2019~2020. Standard inclusion criteria were used, with the addition of admission age >6 hours and mild HIE. Demographic and clinical data included gestational age, gender, weight, Apgar score, ethnics, age on admission, age at TH and clinical degree of HIE. EEG was monitored for 96 hours during hypothermia and rewarming. MRI was performed before discharge. RESULTS: There was significant difference in ethnics, HIE degree, age at TH across 3 centers. The overall NICU incidence of HIE was 4.0%. Among 566 HIE patients, 114 (20.1%) received TH. 63 (55.3%) patients had moderate/severe HIE. Age at TH >6 hours occurred in 34 (29.8%) patients. EEG discharges showed seizures in 7~11% of patients, whereas spikes/sharp waves in 94~100%, delta brushes in 50~100%. After TH, MRI showed moderate to severe brain injury in 77% of patients, and correlated with center, demographic and clinical variables (Ps≤0.0003). Mortality was 5% during hospitalization and 11% after discharge until 1 year. CONCLUSIONS: At altitude, the incidence of HIE was high and brain injury was severe. TH was limited and often late >6 hours. EEG showed distinct patterns attributable to altitude hypoxia. TH was relatively safe. TRIAL REGISTRATION: The study was registered on February 23, 2019 in Chinese Clinical Trial Register (ChiCTR1900021481).

miRNAs derived from plasma small extracellular vesicles predict organo-tropic metastasis of gastric cancer.

BACKGROUND: Peritoneum, liver and lymph node are the most common metastatic sites of gastric cancer (GC). Biomarkers for GC's organo-tropic metastasis remained largely unknown, which was investigated in this study from the perspective of small extracellular vesicle (sEV)-derived miRNAs. METHODS: Plasma from treatment-naïve GC patients including no metastasis (M0), peritoneal metastasis (PM), hepatic metastasis (HM) and distant lymph node metastasis (dLNM)) were divided into one discovery (N = 40), one training (N = 40) and one validating cohort (N = 86), then assessed by sEV-miRNA-sequencing and sEV-miRNA-qPCR. Functional explorations were also performed for verification. RESULTS: The expression profiles of sEV-miRNAs varied greatly across different metastatic patterns. Based on logistic regression models, we constructed signatures for M0 (hsa-miR-186-5p/hsa-miR-200c-3p/hsa-miR-429/hsa-miR-5187-5p/hsa-miR-548ae-5p), PM (hsa-miR-200c-3p/hsa-miR-429), HM (hsa-miR-200c-3p/hsa-miR-429) and dLNM (hsa-miR-324-5p/hsa-miR-374a-5p/hsa-miR-429/hsa-miR-548ae-5p). These signatures vigorously characterized organo-tropic metastasis (all displaying AUC > 0.8, consistency ≥ 75%), and effectively conjectured the risk of future metastasis within 5 years (accuracy 45.5% for occurrence, 70% for organotropism, P = 0.002 for prognostic diversity). Additionally, we explored these seven biomarker miRNAs' impact on GC's in vitro motility and discussed their potential involvement in cancer-related biological processes and pathways. CONCLUSIONS: Our work highlighted that plasma sEV-miRNAs powerfully characterized and predicted the organo-tropic metastasis of GC and provided new insight into the applications of sEV-based liquid biopsy in clinical practice.

Increased functional interaction within frontoparietal network during working memory task in major depressive disorder.

Abnormal fronto-parietal activation has been suggested as a neural underpinning of the working memory (WM) deficits in major depressive disorder (MDD). However, the potential interaction within the frontoparietal network during WM processing in MDD remains unclear. This study aimed to examine the role of abnormal functional interactions within frontoparietal network in the neuropathological mechanisms of WM deficits in MDD. A total of 40 MDD patients and 47 demographic matched healthy controls (HCs) were included. Functional magnetic resonance imaging and behavioral data were collected during numeric n-back tasks. The psychophysiological interaction and dynamic causal modelling methods were applied to investigate the connectivity within the frontoparietal network in MDD during n-back tasks. The psychophysiological interaction analysis revealed that MDD patients showed increased functional connectivity between the right inferior parietal lobule (IPL) and the right dorsolateral prefrontal cortex (dlPFC) compared with HCs during the 2-back task. The dynamic causal modelling analysis revealed that MDD patients had significantly increased forward modulation connectivity from the right IPL to the right dlPFC than HCs during the 2-back task. Partial correlation was used to calculate the relationship between connective parameters and psychological variables in the MDD group, which showed that the effective connectivity from right IPL to right dlPFC was correlated negatively with the sensitivity index d' of WM performances and positively with the depressive severity in MDD group. In conclusion, the abnormal functional and effective connectivity between frontal and parietal regions might contribute to explain the neuropathological mechanism of working memory deficits in major depressive disorder.

Childhood trauma is associated with elevated anhedonia and altered core reward circuitry in major depression patients and controls.

Childhood trauma (CT) is a well-established risk factor for major depressive disorder (MDD). However, the underlying mechanism linking CT and MDD remains not fully understood. The present study tested the hypothesis that CT have effects on specific types of anhedonia in depression via reward system. To do so, we evaluated different aspects of anhedonia and resting-state functional connectivity (FC) in reward system among 66 patients with MDD (44 with moderate-to-severe and 22 with no or low CT), and 57 healthy controls (HC; 23 with moderate-to-severe and 34 with no or low CT). Results showed that MDD patients with moderate-to-severe CT suffered more severe state anhedonic depression than patients with no or low level of CT. Individuals with moderate-to-severe CT, irrespective of MDD diagnosis, had elevated physical, social and anticipatory but not consummatory trait anhedonia, and demonstrated decreased left nucleus accumbens (NAcc)-right orbital frontal cortex (OFC) and left ventral caudate-left OFC connectivity compared to those with no or low exposure. Left NAcc-right OFC connectivity mediated relationship between CT and state anhedonia in MDD. The total altered ventral striatum (VS)-OFC connectivity mediated links between CT and physical trait anhedonia in HC. These findings highlight specific types of anhedonia and the core reward system as targets of CT. Blunted hedonic responses via decreased coupling within core reward system may be involved in the mechanism of depression following CT. Implications for clinical interventions are also discussed.

Imaging Diagnosis of Chronic Encapsulated Intracerebral Hematoma, a Comparison of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) characteristics.

BACKGROUND: Chronic encapsulated intracerebral hematoma (CEICH) is a rare type of intracerebral hematoma that is often misdiagnosed.To explore the characteristics of CEICH on computerized tomography (CT) and magnetic resonance imaging (MRI). MATERIAL/METHODS: Clinical, CT, MRI, and susceptibility weighted imaging (SWI) data of 5 patients who were diagnosed with CEICH on surgery and pathology were retrospectively analyzed. RESULTS: CT showed quasi-circular or elliptical lesions with clear borders in all 5 cases and iso-density or low-density in the center of lesions that were surrounded by peripheral edema in 2 cases. CT showed mass effect in 5 patients. On contrast-enhanced CT, 2 cases exhibited mild ring enhancement, and 3 cases exhibited moderate ring enhancement. MRI showed cystic lesions with high uniform signal on T1-weighted images (T1WI) and T2-weighted images (T2WI), a lowsignal ring sign on the coated cystic lesions on T2WI, a lower signal ring sign on SWI, and ring enhancement after administration of contrast. CONCLUSIONS: CT imaging of CEICH did not reveal any typical characteristics in the studied patients. MRI showed an envelope with a "ring" and intra-capsular bleeding features. MRI is an effective imaging modality for the diagnosis of CEICH.

Imaging characteristics of cerebral sparganosis with live worms.

BACKGROUND AND PURPOSE: The purpose of this study was to analyze the computed tomography (CT) and magnetic resonance imaging (MRI) features of cerebral sparganosis to improve the accuracy of diagnosing cerebral sparganosis with medical imaging modalities. MATERIALS AND METHODS: This was a retrospective study of CT and MRI features of 12 patients with cerebral sparganosis. A comparative analysis between imaging findings, and intraoperative and postoperative pathological findings was performed. RESULTS: A total of 20 lesions were observed in 12 patients with 5 patients having a solitary lesion. CT and MRI imaging showed worm-body sign in 5 patients (41.7%), tunnel-sign in 5 patients (41.7%), migration sign in 7 patients (58.3%), worm-shaped enhancement in 4 patients (33.3%), bead-shaped or ring-shaped enhancement in 5 patients (41.7%), irregular or nodular enhancement in 3 patients (25%), meningeal enhancement in 2 patients (16.6%), intracranial hemorrhage in 2 patients (16.6%), brain parenchymal edema in 10 patients (83.3%), cerebral white matter degeneration in 11 patients (91.7%), negative mass effect in 10 patients (83.3%), and punctuate calcification in 3 patients (25%). Among the 4 patients with live worm, CT and MRI showed worm-body sign in 3 patients (75%), tunnel-sign in 3 patients (75%), migration sign in 3 patients (75%), and worm-shaped enhancement in 2 patients (50%). CONCLUSION: Cerebral sparganosis with live worm exhibits several distinguishing imaging characteristics, which reflect the pathological changes and can improve the diagnosis of cerebral sparganosis.

Application of diffusion tensor imaging for detecting structural changes in the brain of schizophrenic patients.

OBJECTIVE: Schizophrenia is a severe psychiatric illness. Although magnetic resonance imaging has been widely used for detecting brain structural and functional abnormalities in patients with schizophrenia, the findings are highly inconsistent between reports. This study investigates structural changes in the brains of schizophrenic patients. METHODS: The brains of fifty male adults with schizophrenia and fifty age- and gender-matched healthy controls were scanned by diffusion tensor imaging. The differences in fractional anisotropy (FA) values between schizophrenic patients and healthy controls were analyzed. RESULTS: Schizophrenic patients exhibited significantly decreased FA values in the right middle frontal gyrus, right inferior frontal gyrus, right superior temporal gyrus, left sub-temporal gyrus, left middle temporal gyrus, left cingulate gyrus, and left precentral gyrus compared with the control group. We did not find any brain regions with higher FA values in the patient group than in the control group. CONCLUSION: This study suggested that structural abnormalities in the frontal region of gray matter and white matter are present at the same time in patients with schizophrenia.

Altered functional-structural coupling may predict Parkinson's patient's depression.

We aimed to elucidate the neurobiological basis of depression in Parkinson's disease and identify potential imaging markers for depression in patients with Parkinson's disease. We recruited 43 normal controls (NC), 46 depressed Parkinson's disease patients (DPD) and 56 non-depressed Parkinson's disease (NDPD). All participants underwent routine T2-weighted, T2Flair, and resting-state scans on the same 3.0 T magnetic resonance imaging (MRI) scanner at our hospital. Pre-processing includes calculating surface-based Regional Homogeneity (2DReHo) and cortical thickness. Then we defined the correlation coefficient between 2DReHo and cortical thickness as the functional-structural coupling index. Between-group comparisons were conducted on the Fisher's Z-transformed correlation coefficients. To identify specific regions of decoupling, the 2DReHo for each participant were divided by cortical thickness at each vertex, followed by threshold-free cluster enhancement (TFCE) multiple comparison correction. Binary logistic regression analysis was performed with DPD as the dependent variable, and significantly altered indicators as the independent variables. Receiver operating characteristic curves were constructed to compare the diagnostic performance of individual predictors and combinations using R and MedCalc software. DPD patients exhibited a significantly lower whole-brain functional-structural coupling index than NDPD patients and NC. Abnormal functional-structural coupling was primarily observed in the left inferior parietal lobule and right primary and early visual cortices in DPD patients. Receiver operating characteristic analysis revealed that the combination of cortical functional-structural coupling, surface-based ReHo, and thickness had the best diagnostic performance, achieving a sensitivity of 65% and specificity of 77.7%. This is the first study to explore the relationship between functional and structural changes in DPD patients and evaluate the diagnostic performance of these altered correlations to predict depression in Parkinson's disease patients. We posit that these changes in functional-structural relationships may serve as imaging biomarkers for depression in Parkinson's disease patients, potentially aiding in the classification and diagnosis of Parkinson's disease. Additionally, our findings provide functional and structural imaging evidence for exploring the neurobiological basis of depression in Parkinson's disease.

Tumor-derived extracellular vesicle proteins as new biomarkers and targets in precision oncology.

Extracellular vesicles (EVs) are important carriers of signaling molecules, such as nucleic acids, proteins, and lipids, and have become a focus of increasing interest due to their numerous physiological and pathological functions. For a long time, most studies on EV components focused on noncoding RNAs; however, in recent years, extracellular vesicle proteins (EVPs) have been found to play important roles in diagnosis, treatment, and drug resistance and thus have been considered favorable biomarkers and therapeutic targets for various tumors. In this review, we describe the general protocols of research on EVPs and summarize their multifaceted roles in precision medicine applications, including cancer diagnosis, dynamic monitoring of therapeutic efficacy, drug resistance research, tumor microenvironment interaction research, and anticancer drug delivery.

Alterations in cortical volume and complexity in Parkinson's disease with depression.

AIMS: The aim of this study is to investigate differences in gray matter volume and cortical complexity between Parkinson's disease with depression (PDD) patients and Parkinson's disease without depression (PDND) patients. METHODS: A total of 41 PDND patients, 36 PDD patients, and 38 healthy controls (HC) were recruited and analyzed by Voxel-based morphometry (VBM) and surface-based morphometry (SBM). Differences in gray matter volume and cortical complexity were compared using the one-way analysis of variance (ANOVA) and correlated with the Hamilton Depression Scale-17 (HAMD-17) scores. RESULTS: PDD patients exhibited significant cortical atrophy in various regions, including bilateral medial parietal-occipital-temporal lobes, right dorsolateral temporal lobes, bilateral parahippocampal gyrus, and bilateral hippocampus, compared to HC and PDND groups. A negative correlation between the GMV of left precuneus and HAMD-17 scores in the PDD group tended to be significant (r = -0.318, p = 0.059). Decreased gyrification index was observed in the bilateral insular and dorsolateral temporal cortex. However, there were no significant differences found in fractal dimension and sulcal depth. CONCLUSION: Our research shows extensive cortical structural changes in the insular cortex, parietal-occipital-temporal lobes, and hippocampal regions in PDD. This provides a morphological perspective for understanding the pathophysiological mechanism underlying depression in Parkinson's disease.

Exploring brain asymmetry in early-stage Parkinson's disease through functional and structural MRI.

OBJECTIVE: This study explores the correlation between asymmetrical brain functional activity, gray matter asymmetry, and the severity of early-stage Parkinson's disease (PD). METHODS: Ninety-three early-stage PD patients (ePD, H-Y stages 1-2.5) were recruited, divided into 47 mild (ePD-mild, H-Y stages 1-1.5) and 46 moderate (ePD-moderate, H-Y stages 2-2.5) cases, alongside 43 matched healthy controls (HCs). The study employed the Hoehn and Yahr (H-Y) staging system for disease severity assessment and utilized voxel-mirrored homotopic connectivity (VMHC) for analyzing brain functional activity asymmetry. Asymmetry voxel-based morphometry analysis (VBM) was applied to evaluate gray matter asymmetry. RESULTS: The study found that, relative to HCs, both PD subgroups demonstrated reduced VMHC values in regions including the amygdala, putamen, inferior and middle temporal gyrus, and cerebellum Crus I. The ePD-moderate group also showed decreased VMHC in additional regions such as the postcentral gyrus, lingual gyrus, and superior frontal gyrus, with notably lower VMHC in the superior frontal gyrus compared to the ePD-mild group. A negative correlation was observed between the mean VMHC values in the superior frontal gyrus and H-Y stages, UPDRS, and UPDRS-III scores. No significant asymmetry in gray matter was detected. CONCLUSIONS: Asymmetrical brain functional activity is a significant characteristic of PD, which exacerbates as the disease severity increases, resembling the dissemination of Lewy bodies across the PD neurological framework. VMHC emerges as a potent tool for characterizing disease severity in early-stage PD.

Corrigendum: Cortical gyrification pattern of depression in Parkinson's disease: a neuroimaging marker for disease severity?

[This corrects the article DOI: 10.3389/fnagi.2023.1241516.].

One-Pot Synthesis of 1,2,3-Triarylindoles through Cascade Reactions Using Calcium Carbide, Iodoarenes, and Aromatic Amines.

An efficient method for the construction of 1,2,3-triarylindoles through one-pot multicomponent reactions using calcium carbide, 3 mol of iodoarenes, and aromatic amines as starting materials was described. A series of target products were obtained by the simultaneous formation of five bonds in one step. The main advantages for this protocol are the use of a convenient alkyne source, wide scope of substrates, and simple workup procedure. The method can be extended to the gram scale.

Surface-Based Functional Alterations in Early-Onset and Late-Onset Parkinson's Disease: A Multi-Modal MRI Study.

This study used a surface-based method to investigate brain functional alteration patterns in early-onset Parkinson's disease (EOPD) and late-onset Parkinson's disease (LOPD) to provide more reliable imaging indicators for the assessment of the two subtypes. A total of 58 patients with Parkinson's disease were divided into two groups according to age at onset: EOPD (≤50 years; 16 males and 15 females) and LOPD (>50 years; 17 males and 10 females) groups. Two control groups were recruited from the community: young adults (YC; ≤50 years; 8 males and 19 females) and older adults (OC; >50 years; 12 males and 10 females). No significant differences were observed between the EOPD and YC groups or the LOPD and OC groups in terms of age, sex, education, and MMSE scores (p > 0.05). No statistically significant differences were observed between the EOPD and LOPD groups in terms of education, H-Y scale, UPDRS score, or HAMD score (p > 0.05). Data preprocessing and surface-based regional homogeneity (2D-ReHo) calculations were subsequently performed using the MATLAB-based DPABIsurf software. The EOPD group showed decreased 2D-ReHo values in the left premotor area and right dorsal stream visual cortex, along with increased 2D-ReHo values in the left dorsolateral prefrontal cortex. In patients with LOPD, 2D-ReHo values were decreased in bilateral somatosensory and motor areas and the right paracentral lobular and mid-cingulate. The imaging characterization of surface-based regional changes may serve useful as monitoring indicators and will help to better understand the mechanisms underlying divergent clinical presentations.

Fear of progression, loneliness, and hope in patients with gastrointestinal cancer: a cross-sectional relational study.

Introduction: In recent years, fear of disease progression (FoP) has become one of the most common psychological problems in cancer patients. However, there are fewer studies on the FoP in patients with gastrointestinal tumors. We aimed to assess the level of FoP in patients with gastrointestinal tumors and analyze the factors related to FoP. We also aimed to examine the relationship among loneliness, hope and FoP in patients with gastrointestinal cancer. Methods: A cross-sectional survey was conducted on three Grade A hospitals in southwestern China from November 2021 to July 2022. The demographic and clinical characteristics questionnaire, Fear of Disease Progression Scale (FoP-Q-SF), Cancer Loneliness Scale (CLS), and Herth Hope Index (HHI) were included in this study. Data analysis included descriptive statistics, independent samples t-tests, one-way analysis of variance, and multiple linear regression analysis. Results: In total, 245 gastrointestinal cancer patients participated in this study. The average (standard deviation) FoP score in patients was 32.94 ± 10.64. In total, 245 gastrointestinal cancer patients participated in this study. The average (standard deviation) FoP score in patients was 32.94 ± 10.64. The average score of CLS was 17.65 ± 6.71, and that for the HHI was 31.27 ± 7.73. Pearson correlation analysis showed that FoP was negatively significant correlated with hope level (r = -0.522) and FoP was positively significant correlated with loneliness (r = 0.545). Linear regression analysis showed that educational level, age, living condition, hope, and loneliness were the significant predictors of FoP and explained 53.10% of the variability in FoP (F = 16.372). Conclusion: Findings highlight the need to strengthen attention to FoP in gastrointestinal cancer patients. Our study showed that gastrointestinal cancer patients who have a high school education, are age 45 to 59, live alone, high level of loneliness, and low level of hope have higher FoP. Medical staff should enhance clinical screening of FoP and consider the formulation of relevant interventions for high-risk groups to reduce loneliness among patients, raise their hope level, and reduce their FoP.

A new perspective on the potential application of RIPK1 in the treatment of sepsis.

RIPK1 is a global cellular sensor that can determine the survival of cells. Generally, RIPK1 can induce cell apoptosis and necroptosis through TNF, Fas and lipopolysaccharide stimulation, while its scaffold function can sense the fluctuation of cellular energy and promote cell survival. Sepsis is a nonspecific disease that seriously threatens human health. There is some dispute in the literature about the role of RIPK1 in sepsis. In this review, the authors attempt to comprehensively discuss the differential results for RIPK1 in sepsis by summarizing the underlying molecular mechanism and putting forward a tentative idea as to whether RIPK1 can serve as a biomarker for the monitoring of treatment and progression in sepsis.

Sepsis is a syndrome that poses a serious threat to human life and health and is classified as a medical emergency by the WHO. RIPK1 can regulate the onset of apoptosis and necrosis in several ways and is known as a sensor of cell survival status. A series of clinical trials of RIPK1 drugs has been conducted this year and have demonstrated promising efficacy in inflammatory diseases, in particular. In this paper, the authors summarize recent studies on the function and mechanism of RIPK1 in sepsis and combine them with the progress in RIPK1 drug development to provide information for the study of RIPK1 in sepsis.

Diagnostic and predictive values of pyroptosis-related genes in sepsis.

Background: Sepsis is an organ dysfunction syndrome caused by the body's dysregulated response to infection. Yet, due to the heterogeneity of this disease process, the diagnosis and definition of sepsis is a critical issue in clinical work. Existing methods for early diagnosis of sepsis have low specificity. Aims: This study evaluated the diagnostic and predictive values of pyroptosis-related genes in normal and sepsis patients and their role in the immune microenvironment using multiple bioinformatics analyses and machine-learning methods. Methods: Pediatric sepsis microarray datasets were screened from the GEO database and the differentially expressed genes (DEGs) associated with pyroptosis were analyzed. DEGs were then subjected to multiple bioinformatics analyses. The differential immune landscape between sepsis and healthy controls was explored by screening diagnostic genes using various machine-learning models. Also, the diagnostic value of these diagnosis-related genes in sepsis (miRNAs that have regulatory relationships with genes and related drugs that have regulatory relationships) were analyzed in the internal test set and external test. Results: Eight genes (CLEC5A, MALT1, NAIP, NLRC4, SERPINB1, SIRT1, STAT3, and TLR2) related to sepsis diagnosis were screened by multiple machine learning algorithms. The CIBERSORT algorithm confirmed that these genes were significantly correlated with the infiltration abundance of some immune cells and immune checkpoint sites (all P<0.05). SIRT1, STAT3, and TLR2 were identified by the DGIdb database as potentially regulated by multiple drugs. Finally, 7 genes were verified to have significantly different expressions between the sepsis group and the control group (P<0.05). Conclusion: The pyroptosis-related genes identified and verified in this study may provide a useful reference for the prediction and assessment of sepsis.