Differential diagnostic value of simultaneous detection of CD69 and HLA-DR on host T and NK cells in QFT-TB assay for identifying active tuberculosis.

BACKGROUND: Interferon-gamma release assay (IGRA) for tuberculosis (TB) remains limited in its ability to discriminate between active TB (ATB) and latent TB infection (LTBI). Activation markers on host T and NK cells are currently considered to be promising markers in the diagnosis of ATB. METHODS: This prospective observational study enrolled 213 participants and the participants were divided into ATB, LTBI, other lung-related diseases (ORD), and health control (HC) groups. CD69 and HLA-DR on T and NK cells were detected in QFT-TB assay, and a composite scoring system (TB-Flow) was created for the diagnosis of ATB. RESULTS: The expression of activation markers (CD69 and HLA-DR) were significantly increased in ATB. HLA-DR on NK cells, CD69 on T cells, and QFT-TB in the differential diagnosis of ATB and HC were all of good diagnostic value (AUC>0.90). In addition, the TB-Flow greatly improved the efficiency of differential diagnosis between ATB and LTBI (AUC=0.90, 95%CI: 0.84-0.96), with sensitivity and specificity of 79.17 % (95%CI: 64.60%-89.04 %) and 88.68 % (95%CI: 76.28%-95.31 %). CONCLUSIONS: CD69 and HLA-DR on host T and NK cells are promising markers in distinguishing different TB infection status. Our blood-based TB-Flow scoring system can distinguish ATB from LTBI with good diagnostic efficacy.

Effect of negative remodeling of the side branch ostium on the efficacy of a two-stent strategy for distal left main bifurcation lesions: an intravascular ultrasound study.

OBJECTIVES: To investigate whether negative remodeling (NR) detected by intravascular ultrasound (IVUS) of the side branch ostium (SBO) would affect in-stent neointimal hyperplasia (NIH) at the one-year follow-up and the clinical outcome of target lesion failure (TLF) at the long-term follow-up for patients with left main bifurcation (LMb) lesions treated with a two-stent strategy. METHODS: A total of 328 patients with de novo true complex LMb lesions who underwent a 2-stent strategy of percutaneous coronary intervention (PCI) treatment guided by IVUS were enrolled in this study. We divided the study into two phases. Of all the patients, 48 patients who had complete IVUS detection pre- and post-PCI and at the 1-year follow-up were enrolled in phase I analysis, which aimed to analyze the correlation between NR and in-stent NIH at SBO at the 1-year follow-up. If the correlation was confirmed, the cutoff value of the remodeling index (RI) for predicting NIH ≥ 50% was analyzed next. The phase II analysis focused on the incidence of TLF as the primary endpoint at the 1- to 5-year follow-up for all 328 patients by grouping based on the cutoff value of RI. RESULTS: In phase I: according to the results of a binary logistic regression analysis and receiver operating characteristic (ROC) analysis, the RI cutoff value predicting percent NIH ≥ 50% was 0.85 based on the ROC curve analysis, with a sensitivity of 85.7%, a specificity of 88.3%, and an AUC of 0.893 (0.778, 1.000), P = 0.002. In phase II: the TLR rate (35.8% vs. 5.3%, P < 0.0001) was significantly higher in the several NR (sNR, defined as RI ≤ 0.85) group than in the non-sNR group. CONCLUSION: The NR of LCxO is associated with more in-stent NIH post-PCI for distal LMb lesions with a 2-stent strategy, and NR with RI ≤ 0.85 is linked to percent NIH area ≥ 50% at the 1-year follow-up and more TLF at the 5-year follow-up.

Multi-omics analysis and experimental validation of the value of monocyte-associated features in prostate cancer prognosis and immunotherapy.

Background: Monocytes play a critical role in tumor initiation and progression, with their impact on prostate adenocarcinoma (PRAD) not yet fully understood. This study aimed to identify key monocyte-related genes and elucidate their mechanisms in PRAD. Method: Utilizing the TCGA-PRAD dataset, immune cell infiltration levels were assessed using CIBERSORT, and their correlation with patient prognosis was analyzed. The WGCNA method pinpointed 14 crucial monocyte-related genes. A diagnostic model focused on monocytes was developed using a combination of machine learning algorithms, while a prognostic model was created using the LASSO algorithm, both of which were validated. Random forest and gradient boosting machine singled out CCNA2 as the most significant gene related to prognosis in monocytes, with its function further investigated through gene enrichment analysis. Mendelian randomization analysis of the association of HLA-DR high-expressing monocytes with PRAD. Molecular docking was employed to assess the binding affinity of CCNA2 with targeted drugs for PRAD, and experimental validation confirmed the expression and prognostic value of CCNA2 in PRAD. Result: Based on the identification of 14 monocyte-related genes by WGCNA, we developed a diagnostic model for PRAD using a combination of multiple machine learning algorithms. Additionally, we constructed a prognostic model using the LASSO algorithm, both of which demonstrated excellent predictive capabilities. Analysis with random forest and gradient boosting machine algorithms further supported the potential prognostic value of CCNA2 in PRAD. Gene enrichment analysis revealed the association of CCNA2 with the regulation of cell cycle and cellular senescence in PRAD. Mendelian randomization analysis confirmed that monocytes expressing high levels of HLA-DR may promote PRAD. Molecular docking results suggested a strong affinity of CCNA2 for drugs targeting PRAD. Furthermore, immunohistochemistry experiments validated the upregulation of CCNA2 expression in PRAD and its correlation with patient prognosis. Conclusion: Our findings offer new insights into monocyte heterogeneity and its role in PRAD. Furthermore, CCNA2 holds potential as a novel targeted drug for PRAD.

Comparison between MRI-negative and positive results and the predictors for a poor prognosis in patients with idiopathic acute transverse myelitis.

BACKGROUND: Idiopathic acute transverse myelitis (IATM) is a focal inflammatory disorder of the spinal cord that results in motor, sensory, and autonomic dysfunction. However, the comparative analysis of MRI-negative and MRI-positive in IATM patients were rarely reported. OBJECTIVES: The purpose of this study was to compare MRI-negative with MRI-positive groups in IATM patients, analyze the predictors for a poor prognosis, thus explore the relationship between MRI-negative and prognosis. METHODS: We selected 132 patients with first-attack IATM at the First Affiliated Hospital of Nanchang University from May 2018 to May 2022. Patients were divided into MRI-positive and MRI-negative group according to whether there were responsible spinal MRI lesions, and good prognosis and poor prognosis based on whether the EDSS score ≥ 4 at follow-up. The predictive factors of poor prognosis in IATM patients was analyzed by logistic regression models. RESULTS: Of the 132 patients, 107 first-attack patients who fulfilled the criteria for IATM were included in the study. We showed that 43 (40%) patients had a negative spinal cord MRI, while 27 (25%) patients were identified as having a poor prognosis (EDSS score at follow-up ≥ 4). Compared with MRI-negative patients, the MRI-positive group was more likely to have back/neck pain, spinal cord shock and poor prognosis, and the EDSS score at follow-up was higher. We also identified three risk factors for a poor outcome: absence of second-line therapies, high EDSS score at nadir and a positive MRI result. CONCLUSIONS: Compared with MRI-negative group, MRI-positive patients were more likely to have back/neck pain, spinal cord shock and poor prognosis, with a higher EDSS score at follow-up. The absence of second-line therapies, high EDSS score at nadir, and a positive MRI were risk factors for poor outcomes in patients with first-attack IATM. MRI-negative patients may have better prognosis, an active second-line immunotherapy for IATM patients may improve clinical outcome.

Reflectance confocal microscopy for plaque psoriasis therapeutic follow-up during an anti-interleukin-17A monoclonal antibody: an observational study.

Interleukin-17A therapeutic inhibitors are among the most effective treatment methods for moderate-to-severe plaque psoriasis (PP). Reflectance confocal microscopy is a non-invasive imaging technique already documented to be beneficial in evaluating the follow-up of PP under treatment with topical actives and phototherapy. This study aimed to assess the epidermal and dermal changes associated with psoriasis and its treatment with RCM during systemic secukinumab treatment in patients with moderate-to-severe PP. A pilot study was conducted to evaluate RCM as a non-invasive tool for monitoring secukinumab treatment in patients with PP. For patients receiving secukinumab treatment, lesional skin was selected for RCM imaging, which were recorded at all scheduled times. The RCM evaluation criteria were established based on the histopathological diagnostic criteria for psoriasis. The clinical severity of psoriasis was assessed utilizing the psoriasis area severity index. A total of 23 patients with PP were included in the study. Each patient received 300 mg of subcutaneous secukinumab as induction therapy at baseline and weeks 1-4, followed by maintenance therapy every four weeks. Microscopic confocal changes were observed during the treatment. The results identified early microscopic evidence of the anti-inflammatory activity of secukinumab, which was not detected during the clinical examination. RCM findings correlating with the PASI were used to observe the patient's response to treatment and were identified as follows: acanthosis and parakeratosis, presence of epidermal and dermal inflammatory cells, presence of non-edge dermal papillae, and vascularization in the papillary dermis. This study is the first to demonstrate the use of RCM as an effective tool for non-invasive monitoring of secukinumab therapeutic response at a cellular level in a clinical or research setting. Early detection of RCM parameters associated with secukinumab activity may facilitate the identification of an early treatment response. RCM appears to be capable of providing practical and helpful information regarding follow-up in patients with PP undergoing secukinumab treatment. RCM may also provide novel perspectives on the subclinical evaluation of PP's response to biological therapy.

Single-cell transcriptome dissecting the microenvironment remodeled by PD1 blockade combined with photodynamic therapy in a mouse model of oral carcinogenesis.

Oral squamous cell carcinoma (OSCC) stands as a predominant and perilous malignant neoplasm globally, with the majority of cases originating from oral potential malignant disorders (OPMDs). Despite this, effective strategies to impede the progression of OPMDs to OSCC remain elusive. In this study, we established mouse models of oral carcinogenesis via 4-nitroquinoline 1-oxide induction, mirroring the sequential transformation from normal oral mucosa to OPMDs, culminating in OSCC development. By intervening during the OPMDs stage, we observed that combining PD1 blockade with photodynamic therapy (PDT) significantly mitigated oral carcinogenesis progression. Single-cell transcriptomic sequencing unveiled microenvironmental dysregulation occurring predominantly from OPMDs to OSCC stages, fostering a tumor-promoting milieu characterized by increased Treg proportion, heightened S100A8 expression, and decreased Fib_Igfbp5 (a specific fibroblast subtype) proportion, among others. Notably, intervening with PD1 blockade and PDT during the OPMDs stage hindered the formation of the tumor-promoting microenvironment, resulting in decreased Treg proportion, reduced S100A8 expression, and increased Fib_Igfbp5 proportion. Moreover, combination therapy elicited a more robust treatment-associated immune response compared with monotherapy. In essence, our findings present a novel strategy for curtailing the progression of oral carcinogenesis.

LASSO-derived nomogram for early identification of pediatric monogenic lupus.

BACKGROUND: Monogenic lupus is defined as systemic lupus erythematosus (SLE)/SLE-like patients with either dominantly or recessively inherited pathogenic variants in a single gene with high penetrance. However, because the clinical phenotype of monogenic SLE is extensive and overlaps with that of classical SLE, it causes a delay in diagnosis and treatment. Currently, there is a lack of early identification models for clinical practitioners to provide early clues for recognition. Our goal was to create a clinical model for the early identification of pediatric monogenic lupus, thereby facilitating early and precise diagnosis and treatment for patients. METHODS: This retrospective cohort study consisted of 41 cases of monogenic lupus treated at the Department of Pediatrics at Peking Union Medical College Hospital from June 2012 to December 2022. The control group consisted of classical SLE patients recruited at a 1:2 ratio. Patients were randomly divided into a training group and a validation group at a 7:3 ratio. A logistic regression model was established based on the least absolute shrinkage and selection operator to generate the coefficient plot. The predictive ability of the model was evaluated using receiver operator characteristic curves and the area under the curve (AUC) index. RESULTS: A total of 41 cases of monogenic lupus patients and 82 cases of classical SLE patients were included. Among the monogenic lupus cases (with a male-to-female ratio of 1:1.05 and ages of onset ranging from birth to 15 years), a total of 18 gene mutations were identified. The variables included in the coefficient plot were age of onset, recurrent infections, intracranial calcifications, growth and developmental delay, abnormal muscle tone, lymphadenopathy/hepatosplenomegaly, and chilblain-like skin rash. Our model demonstrated satisfactory diagnostic performance through internal validation, with an AUC value of 0.97 (95% confidence interval = 0.92-0.97). CONCLUSIONS: We summarized and analyzed the clinical characteristics of pediatric monogenic lupus and developed a predictive model for early identification by clinicians. Clinicians should exercise high vigilance for monogenic lupus when the score exceeds - 9.032299.

Fibroblast growth factor receptor 4 deficiency in macrophages aggravates experimental colitis by promoting M1-polarization.

OBJECTIVE AND DESIGN: Compelling evidence indicates that dysregulated macrophages may play a key role in driving inflammation in inflammatory bowel disease (IBD). Fibroblast growth factor (FGF)-19, which is secreted by ileal enterocytes in response to bile acids, has been found to be significantly lower in IBD patients compared to healthy individuals, and is negatively correlated with the severity of diarrhea. This study aims to explore the potential impact of FGF19 signaling on macrophage polarization and its involvement in the pathogenesis of IBD. METHODS: The dextran sulfate sodium (DSS)-induced mouse colitis model was utilized to replicate the pathology of human IBD. Mice were created with a conditional knockout of FGFR4 (a specific receptor of FGF19) in myeloid cells, as well as mice that overexpressing FGF19 specifically in the liver. The severity of colitis was measured using the disease activity index (DAI) and histopathological staining. Various techniques such as Western Blotting, quantitative PCR, flow cytometry, and ELISA were employed to assess polarization and the expression of inflammatory genes. RESULTS: Myeloid-specific FGFR4 deficiency exacerbated colitis in the DSS mouse model. Deletion or inhibition of FGFR4 in bone marrow-derived macrophages (BMDMs) skewed macrophages towards M1 polarization. Analysis of transcriptome sequencing data revealed that FGFR4 deletion in macrophages significantly increased the activity of the complement pathway, leading to an enhanced inflammatory response triggered by LPS. Mechanistically, FGFR4-knockout in macrophages promoted complement activation and inflammatory response by upregulating the nuclear factor-κB (NF-κB)-pentraxin3 (PTX3) pathway. Additionally, FGF19 suppressed these pathways and reduced inflammatory response by activating FGFR4 in inflammatory macrophages. Liver-specific overexpression of FGF19 also mitigated inflammatory responses induced by DSS in vivo. CONCLUSION: Our study highlights the significance of FGF19-FGFR4 signaling in macrophage polarization and the pathogenesis of IBD, offering a potential new therapeutic target for IBD.

Chromothripsis is a novel biomarker for prognosis and differentiation diagnosis of pancreatic neuroendocrine neoplasms.

This study aimed to identify the role of chromothripsis as a novel biomarker in the prognosis and differentiation diagnosis of pancreatic neuroendocrine neoplasms (pNENs). We conducted next-generation gene sequencing in a cohort of 30 patients with high-grade (G3) pNENs. As a reference, a similar analysis was also performed on 25 patients with low-grade (G1/G2) pancreatic neuroendocrine tumors (pNETs). Chromothripsis and its relationship with clinicopathological features and prognosis were investigated. The results showed that DNA damage response and repair gene alteration and TP53 mutation were found in 29 and 11 patients, respectively. A total of 14 out of 55 patients had chromothripsis involving different chromosomes. Chromothripsis had a close relationship with TP53 alteration and higher grade. In the entire cohort, chromothripsis was associated with a higher risk of distant metastasis; both chromothripsis and metastasis (ENETS Stage IV) suggested a significantly shorter overall survival (OS). Importantly, in the high-grade pNENs group, chromothripsis was the only independent prognostic indicator significantly associated with a shorter OS, other than TP53 alteration or pathological pancreatic neuroendocrine carcinomas (pNECs) diagnosis. Chromothripsis can guide worse prognosis in pNENs, and help differentiate pNECs from high-grade (G3) pNETs.

[Corrigendum] Ophiopogonin B suppresses the metastasis and angiogenesis of A549 cells in vitro and in vivo by inhibiting the EphA2/Akt signaling pathway.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that, for the scratch­wound assay experiments shown in Fig. 3C, two images appeared to overlap [specifically, the '0 h / Control' and 0 h / OP­B (5 µmol/l) data panels], albeit with different magnification and after a 180° rotation. The authors have examined their original data, and realize that an inadvertent error was made in assembling the images in the figure; specifically, the images of 5 and 10 µmol/l OP­B treatment for 0 h were both misused. The corrected version of Fig. 3, showing all the correct data for Fig. 3C, is shown on the next page. Note that these errors did not affect the overall conclusions reported in the paper. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this. They also apologize to the readership for any inconvenience caused. [Oncology Reports 40: 1339­1347, 2018; DOI: 10.3892/or.2018.6531].

Single-cell RNA sequencing reveals that NRF2 regulates vascular smooth muscle cell phenotypic switching in abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a life-threatening disease characterized by extensive membrane destruction in the vascular wall that is closely associated with vascular smooth muscle cell (VSMC) phenotypic switching. A thorough understanding of the changes in regulatory factors during VSMC phenotypic switching is essential for managing AAA therapy. In this study, we revealed the impact of NRF2 on the modulation of VSMC phenotype and the development of AAA based on single-cell RNA sequencing analysis. By utilizing a murine model of VSMC-specific knockout of nuclear factor E2-related factor 2 (NRF2), we observed that the absence of NRF2 in VSMCs exacerbated AAA formation in an angiotensin II-induced AAA model. The downregulation of NRF2 promoted VSMC phenotypic switching, leading to an enhanced inflammatory response. Through genome-wide transcriptome analysis and loss- or gain-of-function experiments, we discovered that NRF2 upregulated the expression of VSMC contractile phenotype-specific genes by facilitating microRNA-145 (miR-145) expression. Our data identified NRF2 as a novel regulator involved in maintaining the VSMC contractile phenotype while also influencing AAA formation through an miR-145-dependent regulatory mechanism.

The impact of female sex hormones on cardiovascular disease: from mechanisms to hormone therapy.

Cardiovascular disease remains the leading cause of mortality in women, yet it has not raised the awareness from the public. The pathogenesis of cardiovascular disease differs significantly between females and males concerning the effect of sex hormones. Estrogen and progestogen impact cardiovascular system through genomic and non-genomic effects. Before menopause, cardiovascular protective effects of estrogens have been well described. Progestogens were often used in combination with estrogens in hormone therapy. Fluctuations in sex hormone levels, particularly estrogen deficiency, were considered the specific risk factor in women's cardiovascular disease. However, considerable heterogeneity in the impact of hormone therapy was observed in clinical trials. The heterogeneity is likely closely associated with factors such as the initial time, administration route, dosage, and formulation of hormone therapy. This review will delve into the pathogenesis and hormone therapy, summarizing the effect of female sex hormones on hypertension, pre-eclampsia, coronary heart disease, heart failure with preserved ejection fraction, and cardiovascular risk factors specific to women.

Genomic and Phenotypic Analysis of bla KPC-2 Associated Carbapenem Resistance in Klebsiella aerogenes: Insights into Clonal Spread and Resistance Mechanisms Across Hospital Departments in Beijing.

Purpose: This study conducted an phenotypic and whole-genome sequencing analysis with Klebsiella aerogenes to elucidate its clinical epidemiological characteristics, antimicrobial resistance (AMR) phenotype, biofilm formation ability and hemolytic activity testing, AMR genes and phylogenetic relationships, so as to provide a further understanding of the intra-hospital strain transmission. Methods: Samples were collected from a hospital in Beijing between 2020 and 2022. All strains underwent bacterial identification, antimicrobial susceptibility testing (AST) using the VITEK-2 compact system. Biofilm formation ability and hemolytic activity were tested. Second-generation sequencing was applied to all strains, with those carrying the bla KPC gene were selected for third-generation sequencing. Whole-genome analysis identified resistance genes, plasmid types, MLST typing, and phylogenetic relationships. Plasmids were assembled to detect plasmid structures and AMR gene location. Results: Among the 42 K. aerogenes isolates, 21 were carbapenem-resistant K. aerogenes (CRKA). All strains exhibited strong biofilm formation and no hemolytic activity. Most were sourced from sputum (83.3%). CRKA demonstrated extensive resistance to antibiotics, particularly ß-lactamase inhibitors and Cefotetan. This resistance pattern was closely associated with the presence of an IncFII(pHN7A8) plasmid, which carried multiple resistance genes, including bla KPC-2, bla CTX-M-65, bla TEM-1, rmtB and a large number of mobile elements. The majority of CRKA strains clustered within the same branch of the phylogenetic tree, exhibiting minimal single nucleotide polymorphism (0-13 SNPs) differences, and they shared the same sequence type (ST292), resistance genes, and plasmids, originating from different departments, suggesting clonal transmission among the hospital. Conclusion: Our research reveals that the clonal transmission of CRKA occurs across various departments within the hospital. The widespread resistance observed in CRKA, attributed to the presence of bla KPC and ESBLs genes, underscores the need for heightened vigilance to prevent the further dissemination of CRKA within the hospital and, potentially, throughout the wider community.

Bidirectional effects of the tryptophan metabolite indole-3-acetaldehyde on colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) has a high incidence and mortality. Recent studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis, progression, and metastasis of CRC. AIM: To investigate the effect of indole-3-acetaldehyde (IAAD) on CRC. METHODS: The effect of IAAD was evaluated in a syngeneic mouse model of CRC and CRC cell lines (HCT116 and DLD-1). Cell proliferation was assessed by Ki-67 fluorescence staining and cytotoxicity tests. Cell apoptosis was analysed by flow cytometry after staining with Annexin V-fluorescein isothiocyanate and propidium iodide. Invasiveness was investigated using the transwell assay. Western blotting and real-time fluorescence quantitative polymerase chain reaction were performed to evaluate the expression of epithelial-mesenchymal transition related genes and aryl hydrocarbon receptor (AhR) downstream genes. The PharmMapper, SEA, and SWISS databases were used to screen for potential target proteins of IAAD, and the core proteins were identified through the String database. RESULTS: IAAD reduced tumorigenesis in a syngeneic mouse model. In CRC cell lines HCT116 and DLD1, IAAD exhibited cytotoxicity starting at 24 h of treatment, while it reduced Ki67 expression in the nucleus. The results of flow cytometry showed that IAAD induced apoptosis in HCT116 cells but had no effect on DLD1 cells, which may be related to the activation of AhR. IAAD can also increase the invasiveness and epithelial-mesenchymal transition of HCT116 and DLD1 cells. At low concentrations (< 12.5 µmol/L), IAAD only exhibited cytotoxic effects without promoting cell invasion. In addition, predictions based on online databases, protein-protein interaction analysis, and molecular docking showed that IAAD can bind to matrix metalloproteinase-9 (MMP9), angiotensin converting enzyme (ACE), poly(ADP-ribose) polymerase-1 (PARP1), matrix metalloproteinase-2 (MMP2), and myeloperoxidase (MPO). CONCLUSION: Indole-3-aldehyde can induce cell apoptosis and inhibit cell proliferation to prevent the occurrence of CRC; however, at high concentrations (≥ 25 µmol/L), it can also promote epithelial-mesenchymal transition and invasion in CRC cells. IAAD activates AhR and directly binds MMP9, ACE, PARP1, MMP2, and MPO, which partly reveals why it has a bidirectional effect.

Contribution to energy conservation and quality improvement of frozen pork via contact/contactless immersion freezing in NaCl solution.

High energy consumption and quality deterioration are major challenges in the meat freezing process. In this study, the energy consumption and qualities of frozen pork were investigated using three freezing methods: nonpackaged pork air freezing (NAF), contactless immersion freezing (PIF) and contact immersion freezing (NIF) with NaCl solution as a refrigerant. The results indicated that NIF could improve the energy conservation and freezing efficiency in >4 freezing treatment-times by increasing the unfrozen water content, decreasing the frozen heat load, shortening the freezing time and reducing evaporation loss. NIF could also increase the a* value of the pork and improve the water-holding capacity by facilitating the conversion of free water to immobilized-water. The two immersion freezing methods could reduce freezing-thawing loss and protein loss by alleviating muscle tissue freezing damage. These results provide a suitable application of immersion freezing with energy conservation, high efficiency and good quality of frozen-pork.

Artificial Intelligence-Based Microfluidic Platform for Detecting Contaminants in Water: A Review.

Water pollution greatly impacts humans and ecosystems, so a series of policies have been enacted to control it. The first step in performing pollution control is to detect contaminants in the water. Various methods have been proposed for water quality testing, such as spectroscopy, chromatography, and electrochemical techniques. However, traditional testing methods require the utilization of laboratory equipment, which is large and not suitable for real-time testing in the field. Microfluidic devices can overcome the limitations of traditional testing instruments and have become an efficient and convenient tool for water quality analysis. At the same time, artificial intelligence is an ideal means of recognizing, classifying, and predicting data obtained from microfluidic systems. Microfluidic devices based on artificial intelligence and machine learning are being developed with great significance for the next generation of water quality monitoring systems. This review begins with a brief introduction to the algorithms involved in artificial intelligence and the materials used in the fabrication and detection techniques of microfluidic platforms. Then, the latest research development of combining the two for pollutant detection in water bodies, including heavy metals, pesticides, micro- and nanoplastics, and microalgae, is mainly introduced. Finally, the challenges encountered and the future directions of detection methods based on industrial intelligence and microfluidic chips are discussed.

CircATF6 inhibits hepatocellular carcinoma progression by suppressing calreticulin-mediated Wnt/ß-catenin signaling pathway.

Circular RNAs (circRNAs) are covalently closed, single-stranded RNAs that play critical roles in various biological processes and diseases, including cancers. However, the functions and mechanisms of circRNAs in hepatocellular carcinoma (HCC) need further clarification. Here, we identified and confirmed that circATF6 is downregulated in HCC tissues and negatively associated with the overall survival of HCC patients. Ectopic overexpression of circATF6 inhibits malignant phenotypes of HCC cells in vitro and in vivo, while knockdown of circATF6 had opposite effects. Mechanistically, we found that circATF6 bound to calreticulin (CALR) protein and acted as a scaffold to enhance the interaction of CALR with calpain2 (CAPN2), which promoted the degradation of CALR by its enzymatic activity. Moreover, we found that circATF6 inhibited HCC cells by suppressing CALR-mediated wnt/ß-catenin signaling pathway. Taken together, our findings suggest that circATF6 is a potential prognostic biomarker and therapeutic target for HCC.

Potential increased propofol sensitivity in cognitively impaired elderly: a controlled, double-blind study.

Background: Cognitive impairment in the elderly may lead to potential increased sensitivity to anesthetic agents targeting receptors associated with cognition. This study aimed to explore the effect of cognitive status on propofol consumption during surgery in elderly patients. Methods: Sixty elderly patients scheduled for laparoscopic radical prostatectomy were allocated to either a cognitively normal [CogN, Montreal Cognitive Assessment (MoCA) score ≥26] or cognitively impaired (CogI, MoCA <26) group. Propofol was administered via target-controlled infusion to maintain a bispectral index (BIS) between 55-65 during surgery. Propofol consumption was recorded at three time points: T1 (abolished eyelash reflex), T2 (BIS = 50), T3 (extubation). BIS values at eyelash reflex abolition were also recorded. Postoperative MoCA, Visual Analogue Scale (VAS) scores, and remifentanil/sufentanil consumption were assessed. Results: BIS values before induction were similar between CogN and CogI groups. However, at eyelash reflex abolition, BIS was significantly higher in CogI than CogN (mean ± SD: 65.3 ± 7.2 vs. 61.1 ± 6.8, p = 0.031). Propofol requirement to reach BIS 50 was lower in CogI vs. CogN (1.24 ± 0.19 mg/kg vs. 1.46 ± 0.12 mg/kg, p = 0.003). Postoperative MoCA, VAS scores, and remifentanil/sufentanil consumption did not differ significantly between groups. Conclusion: Compared to cognitively intact elderly, those with cognitive impairment exhibited higher BIS at eyelash reflex abolition and required lower propofol doses to achieve the same BIS level, suggesting increased propofol sensitivity. Cognitive status may impact anesthetic medication requirements in the elderly.

Novel predictors of intravenous immunoglobulin resistance in patients with Kawasaki disease: a retrospective study.

Objective: The aim of this study was to investigate the predictive value of systemic immune inflammation index (SII), systemic inflammatory response index (SIRI), and pan-immune inflammation value (PIV) in predicting intravenous immunoglobulin (IVIG) resistance in children diagnosed with Kawasaki disease (KD). Methods: The clinical data of pediatric patients diagnosed with Kawasaki disease and admitted to our hospital between January 2006 and December 2022 were retrospectively analyzed. Results: In total, 771 children diagnosed with KD were included in this study, 86 (11.2%) of whom were diagnosed with IVIG resistance. The correlation between SII, SIRI, PIV and IVIG resistance was evaluated using univariate testing, binary logistic regression analysis, and receiver operating characteristic (ROC) curve analysis. Our study found that the SII, SIRI, and PIV were independent risk factors (p=0.001, p<0.001, and p=0.02, respectively). The area under the ROC curve (AUC) values of the SII, SIRI, and PIV were 0.626 (95% confidence interval (CI): 0.553-0.698, p<0.001), 0.571 (95% CI: 0.500-0.642, p=0.032), and 0.568 (95% CI: 0.495-0.641, p=0.040), respectively, and the cutoff values were 2209.66, 3.77, and 1387.825, respectively. Conclusion: The SII, SIRI, and PIV have potential value in predicting IVIG resistance in patients with KD.

Trends in HIV/AIDS-Related Mortality and the Impact of Antiretroviral Treatment Strategies in Lu'an City: A Comprehensive Analysis.

BACKGROUND There are many factors that affect human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)-related deaths, and different antiretroviral therapy (ART) strategies may affect HIV/AIDS-related fatality rates. However, studies on this area are very limited. This study aimed to evaluate the factors associated with HIV/AIDS-related mortality and the impact of different ART strategies in Lu'an City, Anhui Province, China, 1999-2023. MATERIAL AND METHODS Data of HIV/AIDS cases were downloaded from the China HIV/AIDS Comprehensive Response Information Management System, and were assessed to evaluate the impact of different ART strategies on the related fatality rate using interrupted time series (ITS). RESULTS We found that age at diagnosis of 15 years, 25 years, 40 years, and 60 years, as well as receiving ART, were protective factors against death (with P below 0.05), while lower CD4 count at the last CD4 count and the year of diagnosis before 2007 and between 2007 and 2016 were risk factors (with P below 0.05). ITS analysis revealed that in the year of the introduction of free ART in 2006, the fatality rate decreased by 38.60% (P=0.015). The fatality rate trend from 2006 to 2015 was -1.1%, which was not statistically significant (P=0.434). The fatality rate trend from 2016 to 2023 was -0.33%, indicating a decreasing trend (P=0.000). CONCLUSIONS Children under 15 years old and elderly patients had a higher risk of death. The main reasons for the decrease in HIV/AIDS-related fatality rate were ART, especially the "early treatment" strategy.