GWAShug: a comprehensive platform for decoding the shared genetic basis between complex traits based on summary statistics.

The shared genetic basis offers very valuable insights into the etiology, diagnosis and therapy of complex traits. However, a comprehensive resource providing shared genetic basis using the accessible summary statistics is currently lacking. It is challenging to analyze the shared genetic basis due to the difficulty in selecting parameters and the complexity of pipeline implementation. To address these issues, we introduce GWAShug, a platform featuring a standardized best-practice pipeline with four trait level methods and three molecular level methods. Based on stringent quality control, the GWAShug resource module includes 539 high-quality GWAS summary statistics for European and East Asian populations, covering 54 945 pairs between a measurement-based and a disease-based trait and 43 902 pairs between two disease-based traits. Users can easily search for shared genetic basis information by trait name, MeSH term and category, and access detailed gene information across different trait pairs. The platform facilitates interactive visualization and analysis of shared genetic basic results, allowing users to explore data dynamically. Results can be conveniently downloaded via FTP links. Additionally, we offer an online analysis module that allows users to analyze their own summary statistics, providing comprehensive tables, figures and interactive visualization and analysis. GWAShug is freely accessible at http://www.gwashug.com.

In situ electro-generated Ni(OH)2 synergistic with Cu cathode to promote direct ammonia oxidation to nitrogen.

To solve the problem of low removal rate and poor N2 selectivity in direct electrochemical ammonia oxidation (EAO), commercial Ni foam and Cu foam were used as anode and cathode of the EAO system, respectively. The coupling effect between the cathode and anode promoted nitrogen cycling during the reaction process, which improved N2 selectivity of the reaction system and promoted it to achieve a high ammonia removal rate. This study showed that the thin Ni(OH)2 with oxygen vacancy formed on the surface of Ni foam anode played an effective role in the dimerization of intermediate products in ammonia oxidation to form N2. This electrochemical system was used to treat real goose wastewater containing 422.5 mg/L NH4+-N and 94.5 mg/L total organic carbon (TOC). After treatment, this electrochemical system achieved good performance with an ammonia removal rate of 87%, N2 selectivity of 77%, and TOC removal rate of 72%. Therefore, this simple and efficient system with Ni foam anode and Cu foam cathode is a promising method for treating ammonia nitrogen wastewater.

Cerebello-cerebral resting-state functional connectivity in spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder characterized by progressive motor and nonmotor deficits concomitant with degenerative pathophysiological changes within the cerebellum. The cerebellum is topographically organized into cerebello-cerebral circuits that create distinct functional networks regulating movement, cognition, and affect. SCA3-associated motor and nonmotor symptoms are possibly related not only to intracerebellar changes but also to disruption of the connectivity within these cerebello-cerebral circuits. However, to date, no comprehensive investigation of cerebello-cerebral connectivity in SCA3 has been conducted. The present study aimed to identify cerebello-cerebral functional connectivity alterations and associations with downstream clinical phenotypes and upstream topographic markers of cerebellar neurodegeneration in patients with SCA3. This study included 45 patients with SCA3 and 49 healthy controls. Voxel-based morphometry and resting-state functional magnetic resonance imaging (MRI) were performed to characterize the cerebellar atrophy and to examine the cerebello-cerebral functional connectivity patterns. Structural MRI confirmed widespread gray matter atrophy in the motor and cognitive cerebellum of patients with SCA3. We found reduced functional connectivity between the cerebellum and the cerebral cortical networks, including the somatomotor, frontoparietal, and default networks; however, increased connectivity was observed between the cerebellum and the dorsal attention network. These abnormal patterns correlated with the CAG repeat expansion and deficits in global cognition. Our results indicate the contribution of cerebello-cerebral networks to the motor and cognitive impairments in patients with SCA3 and reveal that such alterations occur in association with cerebellar atrophy. These findings add important insights into our understanding of the role of the cerebellum in SCA3.

COVID-19 imaging, where do we go from here? Bibliometric analysis of medical imaging in COVID-19.

OBJECTIVES: We conducted a systematic and comprehensive bibliometric analysis of COVID-19-related medical imaging to determine the current status and indicate possible future directions. METHODS: This research provides an analysis of Web of Science Core Collection (WoSCC) indexed articles on COVID-19 and medical imaging published between 1 January 2020 and 30 June 2022, using the search terms "COVID-19" and medical imaging terms (such as "X-ray" or "CT"). Publications based solely on COVID-19 themes or medical image themes were excluded. CiteSpace was used to identify the predominant topics and generate a visual map of countries, institutions, authors, and keyword networks. RESULTS: The search included 4444 publications. The journal with the most publications was European Radiology, and the most co-cited journal was Radiology. China was the most frequently cited country in terms of co-authorship, with the Huazhong University of Science and Technology being the institution contributing with the highest number of relevant co-authorships. Research trends and leading topics included: assessment of initial COVID-19-related clinical imaging features, differential diagnosis using artificial intelligence (AI) technology and model interpretability, diagnosis systems construction, COVID-19 vaccination, complications, and predicting prognosis. CONCLUSIONS: This bibliometric analysis of COVID-19-related medical imaging helps clarify the current research situation and developmental trends. Subsequent trends in COVID-19 imaging are likely to shift from lung structure to function, from lung tissue to other related organs, and from COVID-19 to the impact of COVID-19 on the diagnosis and treatment of other diseases. Key Points • We conducted a systematic and comprehensive bibliometric analysis of COVID-19-related medical imaging from 1 January 2020 to 30 June 2022. • Research trends and leading topics included assessment of initial COVID-19-related clinical imaging features, differential diagnosis using AI technology and model interpretability, diagnosis systems construction, COVID-19 vaccination, complications, and predicting prognosis. • Future trends in COVID-19-related imaging are likely to involve a shift from lung structure to function, from lung tissue to other related organs, and from COVID-19 to the impact of COVID-19 on the diagnosis and treatment of other diseases.

Evaluation of liver function using Gd-EOB-DTPA-enhanced MRI with T1 mapping.

PURPOSE: To evaluate the value of MRI T1 mapping with Gd-EOB-DTPA for assessing liver function. METHODS: Seventy-two patients who underwent Gd-EOB-DTPA-enhanced MRI for focal liver lesions at Beijing Friendship Hospital from August 2020 to March 2022 were prospectively enrolled, and variable-flip-angle T1 mapping was performed before and 20 min after enhancement. The Child-Pugh (C-P) score and albumin-bilirubin (ALBI) grade of liver function were assessed using the clinical data of the patients. Correlation analysis was used to evaluate the correlation between T1 mapping parameters and liver function grading and laboratory tests. Nonparametric tests were used to compare the differences among different liver function groups. The liver function classification efficiency of each image index was evaluated with receiver operating characteristic (ROC) curves. RESULTS: T1post was positively correlated with the C-P grade and the ALBI grade (r = 0.717 and r = 0.652). ΔT1 was negatively correlated with the C-P grade and the ALBI grade (r = -0.790 and r = -0.658). T1post and ΔT1 significantly differed among different liver function grades (p < 0.05). For the C-P grade, T1post and ΔT1 were significantly different between each pair of groups (p < 0.05), and ΔT1 had a better diagnostic efficiency than T1post. For the ALBI grade, ΔT1 and T1post were significantly different between the NLF and ALBI1 groups (p < 0.05), and ΔT1 had a better diagnostic efficacy than T1post. T1post significantly differed between the ALBI1 and ALBI2 + 3 groups (p < 0.05), while ΔT1 had a weak ability to differentiate between these two groups. CONCLUSION: T1post and ΔT1 were strongly correlated with the two liver function grades and can be noninvasive imaging indexes for evaluating liver function.

Penthorum chinense Pursh compound flavonoids supplementation alleviates Aflatoxin B1-induced liver injury via modulation of intestinal barrier and gut microbiota in broiler.

Aflatoxin B1 (AFB1) is a commonly occurring toxicant in animal and human diets, leading to hazardous effects on health. AFB1 is known to be a hepato-toxicant, and the intestinal barrier may play a crucial role in reversing AFB1-induced liver injury. This study aimed to optimize the extraction conditions of Penthorum chinense Pursh Compound Flavonoids (PCPCF) by the response surface method with a Box-Behnken design and investigate the effects of PCPCF on AFB1-induced liver injury in broilers. A total of 164 one-day-old broilers were divided into seven groups, including Control, PCPCF (400 mg PCPCF/kg feed), AFB1 (3 mg AFB1/kg feed), and YCHT (Yin-Chen-Hao-Tang extract, 3 mg AFB1 +10 mL YCHT/kg feed) and low, medium, and high dose groups (PCPCF at 3 mg AFB1 +200, 400, 600 mg respectively). Samples of serum, liver, duodenum, and cecum contents were collected at 14th and 28th days for further analysis. The results showed that the maximum extraction rate of PCPCF was 8.15 %. PCPCF was rich in rutin, quercetin, liquiritin and kaempferol, and significantly inhibited the growth of Aspergillus flavus. The addition of PCPCF improved the growth performance of AFB1-injury broilers, modulated liver function, and increased serum immunoglobulin levels. PCPCF also alleviated liver pathological and oxidative stress damages caused by AFB1 and decreased AFB1-DNA and AFB1-lysine content in the liver. Furthermore, PCPCF supplementation ameliorated intestinal pathological damage, improved intestinal permeability of duodenum in the AFB1-induced broilers, and repaired the intestinal mucosal and mechanical barrier associated with the Notch signaling pathway. Meanwhile, PCPCF improved the intestinal flora structure of AFB1-damaged broilers and increased the abundance of beneficial bacteria. In conclusion, PCPCF ameliorated the adverse effects of AFB1 on growth performance and alleviated liver damage by repairing the intestinal barrier and improving intestinal health of broiler chicken.

Inhibition of macrophage migration inhibitory factor alleviates LPS-induced inflammation response of HEI-OC1 cells via suppressing NF-κB signaling.

BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is acute and unexplained. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine in several inflammatory diseases. However, its role in SSNHL remains elusive. METHODS: Lipopolysaccharide (LPS) was used to induce the inflammatory response of murine auditory cells, HEI-OC1. Silencing of MIF in HEI-OC1 cells was achieved by transfection of short hairpin RNA against MIF. 740Y-P and IMD0354 were used to stimulate the PI3K pathway and suppress the NF-κB pathway, respectively. RT-qPCR and western blotting were used to examine MIF and cyclooxygenase 2 (COX2) expression in LPS-treated HEI-OC1 cells. ELISA was employed to assess prostaglandin E2 (PGE2) concentrations. RESULTS: MIF was upregulated in LPS-treated HEI-OC1 cells. MIF knockdown reduced PGE2 synthesis and COX2 expression in LPS-treated HEI-OC1 cells. Moreover, MIF knockdown suppressed activation of the PI3K/AKT and NF-κB pathway in LPS-treated HEI-OC1 cells. Additionally, inhibition of MIF decreased PGE2 production and COX2 expression via inactivation of the NF-κB pathway. CONCLUSION: Inhibition of MIF alleviated LPS-induced inflammation in HEI-OC1 cells via inactivating the NF-κB signaling, which might provide a better understanding for SSNHL development.

Comparison between postauricular steroid injection and intratympanic steroid perfusion for refractory severe and profound sudden sensorineural hearing loss.

BACKGROUND: To analyze the clinical efficacy of intratympanic steroid perfusion (ISP) and postauricular steroid injection (PSI) for refractory severe and profound sudden sensorineural hearing loss (SSNHL). METHODS: SSNHL patients who failed a conventional treatment with severe to profound hearing loss [pure tone average (PTA, 0.25-8 kHz) > 60 dB] were treated with ISP or PSI plus antioxidant and neurotrophin for 10 consecutive days. Antioxidant and neurotrophin were administrated either intravenously and/or orally. All patients were assigned into the ISP group or the PSI group and followed up for more than three months. The changes in PTA, effective rate and side effects were analyzed in the two groups. RESULTS: Similar hearing improvements and effective rates were observed in the two groups. However, a slightly better efficacy was observed in the PSI group compared to the ISP group. Patients with shorter intervals from onset to treatment had significantly more hearing improvements. The route of antioxidant and neurotrophin administration had no impact on treatment effects. CONCLUSION: Both ISP and PSI could be used as salvage treatments for refractory SSNHL. These salvage treatments should be started as soon as possible once SSNHL patients fail a conventional treatment.

Performance of Diagnostic Model for Differentiating Between COVID-19 and Influenza: A 2-Center Retrospective Study.

BACKGROUND COVID-19 and influenza share many similarities, such as mode of transmission and clinical symptoms. Failure to distinguish the 2 diseases may increase the risk of transmission. A fast and convenient differential diagnosis between COVID-19 and influenza has significant clinical value, especially for low- and middle-income countries with a shortage of nucleic acid detection kits. We aimed to establish a diagnostic model to differentiate COVID-19 and influenza based on clinical data. MATERIAL AND METHODS A total of 493 patients were enrolled in the study, including 282 with COVID-19 and 211 with influenza. All data were collected and reviewed retrospectively. The clinical and laboratory characteristics of all patients were analyzed and compared. We then randomly divided all patients into development sets and validation sets to establish a diagnostic model using multivariate logistic regression analysis. Finally, we validated the diagnostic model using the validation set. RESULTS We preliminarily established a diagnostic model for differentiating COVID-19 from influenza that consisted of 5 variables: age, dry cough, fever, white cell count, and D-dimer. The model showed good performance for differential diagnosis. CONCLUSIONS This initial model including clinical features and laboratory indices effectively differentiated COVID-19 from influenza. Patients with a high score were at a high risk of having COVID-19, while patients with a low score were at a high risk of having influenza. This model could help clinicians quickly identify and isolate cases in the absence of nucleic acid tests, especially during the cocirculation of COVID-19 and influenza. Owing to the study's retrospective nature, further prospective study is needed to validate the accuracy of the model.

A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus-A possible reference for coronavirus disease-19 treatment option.

In the past few decades, coronaviruses have risen as a global threat to public health. Currently, the outbreak of coronavirus disease-19 (COVID-19) from Wuhan caused a worldwide panic. There are no specific antiviral therapies for COVID-19. However, there are agents that were used during the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) epidemics. We could learn from SARS and MERS. Lopinavir (LPV) is an effective agent that inhibits the protease activity of coronavirus. In this review, we discuss the literature on the efficacy of LPV in vitro and in vivo, especially in patients with SARS and MERS, so that we might clarify the potential for the use of LPV in patients with COVID-19.

Hematoporphyrin monomethyl ether-mediated photodynamic therapy inhibits the growth of keloid graft by promoting fibroblast apoptosis and reducing vessel formation.

Photodynamic therapy (PDT) has been shown to significantly inhibit fibroblast activity. However, the effect of PDT mediated by the photosensitizer hematoporphyrin monomethyl ether (HMME) on keloids is not known well. The aim of our study was to examine the efficacy of HMME-PDT in cellular and animal models of keloids. Keloid fibroblasts (KFbs) were isolated from human keloid specimens and the proliferation, invasion, and migration of KFbs after HMME-PDT treatment was examined in vitro. Apoptosis in cells was measured by flow cytometry. Cysteinyl aspartate specific proteinase 3 (Caspase3) expression was determined by immunofluorescence staining and western blot. HMME-PDT inhibited KFbs proliferation, invasion, migration, increased apoptosis rate and enhanced caspase3 and cleaved caspase3 expression. The keloid graft transplantation was performed by using nude mice. The growth of the graft was monitored every third day. Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) mRNA expression were detected by quantitative real time PCR. It was observed that HMME-PDT attenuated graft growth and reduced vessel density in the keloid grafts. However, HMME-PDT did not alter IL-6 and TNF-α mRNA expression in the keloid grafts. Moreover, HMME-PDT suppressed transforming growth-ß1 (TGF-ß1) and small phenotype and Drosophila Mothers Against Decapentaplegic 3 (Smad3) expression in both KFbs and keloid grafts. Collectively, the evidence suggests that HMME-PDT inhibits the growth of the keloid graft by promoting the apoptosis of fibroblasts and reducing vessel formation of the keloid graft.

MicroRNA-370 functions as a tumor suppressor in hepatocellular carcinoma via inhibition of the MAPK/JNK signaling pathway by targeting BEX2.

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and occurs predominantly in patients with underlying chronic liver disease and cirrhosis. Accumulating studies have revealed that microRNAs (miRNAs) play a critical role in the development and progression of HCC. Through microarray-based gene expression profiling of HCC, miR-370, and BEX2 were identified in HCC. Hence, this study aimed to evaluate their abilities on the cellular processes in HCC. It was determined that BEX2 was highly expressed and miR-370 was poorly expressed in HCC cell lines and tissues. Then, the cell line presenting with the highest BEX2 expression and the lowest miR-370 expression was selected for subsequent gain- and loss-of-function experimentation. The antitumor effect of miR-370 on HCC cell proliferation, invasion, migration, and apoptosis, as well as the MAPK/JNK signaling pathway was examined. Meanwhile, the interaction among miR-370, BEX2, and MAPK/JNK signaling pathway was identified. BEX2 is verified to be a target of miR-370. Moreover, miR-370 exerted antitumor effect on HCC development through suppression of the MAPK/JNK signaling pathway by targeting BEX2. Later, it was further verified by in vivo experiment that overexpression of miR-370 inhibited tumor growth. Above results provide evidence that miR-370 could downregulate BEX2 gene and inhibit activation of MAPK/JNK signaling pathway, thus inhibiting the development of HCC. It provides a worth-trying novel therapeutic target for HCC treatment.

miR-188-5p regulates proliferation and invasion via PI3K/Akt/MMP-2/9 signaling in keloids.

Keloids (KDs) and hypertrophic scars (HSs), two forms of pathological scars, seriously affect the physical and psychological health of patients. Despite many similarities with HSs, KDs are characterized by invasion and a high rate of recurrence after surgery, features they share in common with tumors. The underlying molecular mechanisms of this phenomenon have not been fully elucidated. In this study, we used microRNA (miRNA) array analysis to search for invasion-associated miRNAs in KDs. The expression of miR-188-5p in KDs, HSs, normal skin (NS) tissues, and cell lines was measured by quantitative real-time polymerase chain reaction. Furthermore, cell proliferation, migration, and invasion were detected in KD fibroblasts (KFs) and HS fibroblasts (HSFs), and interrelated proteins were ascertained by western blot analysis. It was found that miR-188-5p was significantly decreased in KD tissue compared with HS and NS tissues. Upregulated expression of miR-188-5p suppressed KF proliferation, migration, and invasion; and decreased expression of miR-188-5p also promoted HSF proliferation, migration, and invasion. The protein levels of MMP-2, MMP-9, PI3K, and p-Akt in miR-188-5p mimic-transfected KFs were repressed. In contrast, after transfection with miR-188-5p inhibitor, the protein levels of MMP-2, MMP-9, PI3K, and p-Akt were higher than the control in HSFs. Treatment with PI3K/Akt inhibitor LY294002 in KFs with miR-188-5p inhibitor did not further reduce their proliferation, migration, and invasion. The upregulation of MMP-2 and MMP-9 by miR-188-5p inhibitor could be abolished by LY294002. These findings together demonstrate a tumor-suppressive role of miR-188-5p in KD proliferation and invasion via PI3K/Akt/MMP-2/9 signaling, indicating that miR-188-5p may be a potential prognostic marker and therapeutic target for KDs.

MIF protects against oxygen-glucose deprivation-induced ototoxicity in HEI-OC1 cochlear cells by enhancement of Akt-Nrf2-HO-1 pathway.

Ischemia and oxidative stress play crucial roles in the pathophysiology of sudden sensorineural hearing loss (SSNHL). Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine and serves an important role in hearing function. The present study was designed to evaluate the effect of MIF on oxygen-glucose deprivation (OGD)-induced ototoxicity and to elucidate its molecular mechanism. In HEI-OC1 auditory cells, OGD reduced cell viability and increased supernatant lactate dehydrogenase (LDH) and MIF in a time-dependent manner. However, the reduced cell viability exerted by OGD was attenuated by antioxidant and MIF. Luciferase reporter assay demonstrated that MIF could activate NF-E2-related factor 2 (Nrf2), and real-time PCR showed increased mRNA expressions of Nrf2 and two Nrf2-responsive genes, including heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). MIF also suppressed oxidative stress induced by OGD, as demonstrated by decreased MDA and increased GSH in cellular supernatant. Inhibition of Nrf2 using siRNA suppressed HO-1 protein expression, the protective effect on OGD-induced injury and decrease in oxidative stress by MIF. Moreover, MIF prevented OGD-induced reduction of Akt1 phosphorylation at Ser473. LY294002, an inhibitor of PI3K/Akt signaling, attenuated the enhancement of Nrf2 protein and protective effect of MIF in OGD-treated cochlear cells. We demonstrate that MIF protects cochlear cells against OGD-induced injury through activation of Akt-Nrf2-HO-1 pathway.

Tumor suppressive role of miR-1224-5p in keloid proliferation, apoptosis and invasion via the TGF-ß1/Smad3 signaling pathway.

The molecular mechanism of the pathogenesis of keloids is still not known and the clinical management of keloids remains challenging. MiRNA (microRNA) is a novel class of small regulatory RNAs that has emerged as key post-transcriptional regulators of gene expression. MiRNAs participate in diverse biological processes of various skin diseases and function as key regulators in the occurrence and development of tumors. The purpose of this study was to investigate the involvement of miRNAs in keloid pathogenesis. We performed miRNA microarray analysis to compare miRNA expression between keloid and normal skin samples. We found that 46 miRNAs were upregulated and 28 miRNAs were downregulated in keloid compared with normal skin samples. We focused on miR-1224-5p, which has been reported to function in cancers, although the expression and mechanism of miR-1224-5p in keloids remain to be explored. Overexpression of miR-1224-5p led to inhibition of keloid fibroblast proliferation, promotion of apoptosis and decrease of migration and invasion. Our results suggest that downregulation of miR-1224-5p may be one of the mechanisms involved in the occurrence and development of keloids.

Inflammation marker ESR is effective in predicting outcome of diffuse large B-cell lymphoma.

BACKGROUND: Systemic inflammation has been implicated in cancer development and progression. This study examined the best cutoff value of erythrocyte sedimentation rate (ESR) in diffuse large B-cell lymphoma (DLBCL) patients. METHODS: The relationship between ESR and clinical characteristics was analyzed in 182 DLBCL patients from 2006 to 2017. The log-rank test, univariate analysis, and Cox regression analysis were applied to evaluate the relationship between ESR and survival. An ESR of more than 37.5 mm/hour was found to be the optimal threshold value for predicting prognosis. RESULTS: ESR was associated with more frequent advanced Ann Arbor stage, poorer performance status, elevated lactate dehydrogenase level, the presence of B symptoms, high-risk International Prognostic Index (IPI 3-5), more extranodal involvement (ENI ≥2), non-germinal-center B-cell (non-GCB) subtypes, and more frequent Myc protein positivity. Shorter overall survival (OS) and progression-free survival (PFS) were found for patients with higher ESRs. Multivariate analysis demonstrated that ESR level is an independent prognostic factor of both OS and PFS. In addition, dynamic changes in ESR are valuable in assessing curative effect and predicting disease recurrence. CONCLUSION: High ESR in DLBCL patients indicated unfavorable prognosis that may require alternative treatment regimens.

[Retracted] MicroRNA­425 is downregulated in nasopharyngeal carcinoma and regulates tumor cell viability and invasion by targeting hepatoma­derived growth factor.

[This retracts the article DOI: 10.3892/ol.2018.8128.].

Association of soluble TREM2 with Alzheimer's disease and mild cognitive impairment: a systematic review and meta-analysis.

Objective: Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is a potential neuroinflammatory biomarker linked to the pathogenesis of Alzheimer's disease (AD) and mild cognitive impairment (MCI). Previous studies have produced inconsistent results regarding sTREM2 levels in various clinical stages of AD. This study aims to establish the correlation between sTREM2 levels and AD progression through a meta-analysis of sTREM2 levels in cerebrospinal fluid (CSF) and blood. Methods: Comprehensive searches were conducted in PubMed, Embase, Web of Science, and the Cochrane Library to identify observational studies reporting CSF and blood sTREM2 levels in AD patients, MCI patients, and healthy controls. A random effects meta-analysis was used to calculate the standardized mean difference (SMD) and 95% confidence intervals (CIs). Results: Thirty-six observational studies involving 3,016 AD patients, 3,533 MCI patients, and 4,510 healthy controls were included. CSF sTREM2 levels were significantly higher in both the AD [SMD = 0.28, 95% CI (0.15, 0.41)] and MCI groups [SMD = 0.30, 95% CI (0.13, 0.47)] compared to the healthy control group. However, no significant differences in expression were detected between the AD and MCI groups [SMD = 0.09, 95% CI (-0.09, 0.26)]. Furthermore, increased plasma sTREM2 levels were associated with a higher risk of AD [SMD = 0.42, 95% CI (0.01, 0.83)]. Conclusion: CSF sTREM2 levels are positively associated with an increased risk of AD and MCI. Plasma sTREM2 levels were notably higher in the AD group than in the control group and may serve as a promising biomarker for diagnosing AD. However, sTREM2 levels are not effective for distinguishing between different disease stages of AD. Further investigations are needed to explore the longitudinal changes in sTREM2 levels, particularly plasma sTREM2 levels, during AD progression. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024514593.

A robust primary liver cancer subtype related to prognosis and drug response based on a multiple combined classifying strategy.

The recurrence or resistance to treatment of primary liver cancer (PLL) is significantly related to the heterogeneity present within the tumor. In this study, we integrated prognosis risk score, mRNAsi index, and immune characteristics clustering to classify patients. The four subtypes obtained from the combined classification are associated with PLC's prognosis and drug response. In these subtypes, we observed mRNAsiH_ICCA subtype, the intersection between high mRNAsi and immune characteristics clustering A, had the worst prognosis. Specifically, immune characteristics clustering B (ICC_B) had high drug sensitivity in most drugs regardless of the value of mRNAsi. On the other hand, patients with low mRNAsi responded better to ten drugs including KU-55933 and NU7441, while patients with high mRNAsi might benefit from drugs like Leflunomide. By matching the specific characteristics of each combined subtype with the drug-induced cell line expression profile, we identified a group of potential therapeutic drugs that might regulate the expression of disease signature genes. We developed a feasible multiple combined typing strategy, hoping to guide therapeutic selection and promote the development of precision medicine.