Clinical Value Research Articles

B-204 A Real-time Probe-based PCR Assay for Detection of Pneumocystis Pneumonia

Abstract Background Pneumocystis jirovecii is an atypical opportunistic fungus with lung tropism and worldwide distribution that continues to be one of the major opportunistic pathogens causing severe Pneumocystis pneumonia (PcP) in individuals with acquired immune deficiency syndrome (AIDS) and patients with immunosuppression due to other causes. Widespread prophylaxis and treatment for P. jirovecii with sulfa drugs have decreased the incidence of PcP, but concerns have been raised about the possible emergence of P. jirovecii isolates resistant to these drugs. Point mutations in this gene have been associated with prior exposure to sulfa drugs in other microorganisms, the polymorphic positions 165 and 171, which lead to an amino acid change at positions 55 (Thr55Ala) and 57 (Pro57Ser) of the polypeptide chain, respectively. Fluorescent PCR technology can detect the nucleic acid fragments of P. jirovecii in patients' serum, alveolar perfusion fluid (BALF) and tissue samples, and further identify drug-resistant mutations, which is of great significance for early clinical and accurate initiation of antifungal therapy. MycoMDx Pneumocystis Jirovecii PCR Assay is the use of PCR-fluorescence probe method, combined with other methods to achieve the auxiliary diagnosis of P. jirovecii infection and resistance to sulfonamides (Fig. 1). Methods In this study, we did a performance evaluation of the MycoMDx Pneumocystis Jirovecii PCR Assay (CE-approved), including diagnostic sensitivity and specificity, the limit of detection (LoD), precision and stability. The above PCR assay reagents were developed and produced by Dynamiker Biotechnology (Tianjin) Co., Ltd. Results The sensitivity and specificity of the PCR assay reagents were above 90%, the LoD was 1000 copies/mL, and the precision and stability were in accordance with the requirements (CV≤5%). Conclusions The MycoMDx Pneumocystis Jirovecii PCR Assay has great clinical value by providing a rapid and reliable test to aid in early diagnosis.

Associations of 2 Established Methods of Measuring Gait Speed and Sit-To-Stand Performance With Frailty and Life-Space Mobility in Community-Dwelling Older Adults

ObjectivesThe 4-m gait speed (4mGS) and 10-m gait speed (10mGS) tests and the 30-second sit-to-stand (30sSTS) and 5-times sit-to-stand (5xSTS) tests are commonly used and advocated in consensus recommendations. We compared these tests on their predictive and clinical value concerning the risk of prefrailty/frailty and restricted life-space mobility (RLSM). DesignCross-sectional study. Setting and ParticipantsA sample of 1235 community-dwelling adults (mean ± SD, 68 ± 7 years) participated in this prospective cohort study. MethodsAt baseline assessment, participants completed a survey and functional assessment, from which gait speed, sit-to-stand performance, self-reported mobility limitation, 40-item Frailty Index, and Life Space Assessment were measured. Participants with a 40-item Frailty Index >0.15 and a Life Space Assessment <60 points were classified as having prefrailty/frailty and RLSM, respectively. At 1-year follow-up assessment, prefrailty/frailty and RLSM were evaluated. ResultsCorrelations between gait speed and sit-to-stand measures were high (ρ values >0.80). In multivariable ordinal models, these measures added incremental prognostic value beyond a base model comprising demographics and self-reported mobility limitation variables in predicting baseline and 1-year outcomes. Between 10mGS and 4mGS, models with 10mGS had higher concordance indices (differences, 0.005-0.009), and these differences translated to generally greater net benefit in decision curve analyses. Between 30sSTS and 5xSTS measures, no one measure consistently outperformed the other, with small net benefit differences between measures (<0.2%). Conclusions and ImplicationsIn community-dwelling older adults, gait speed and sit-to-stand measures meaningfully predicted prefrailty/frailty and RLSM. 10mGS provided more robust prognostic information than the 4mGS, whereas 5xSTS and 30sSTS measures showed near equivalence of performance. These findings could guide the choice of functional measures in clinical and research settings.

Mitochondrial DNA Copy Number Is Associated with the Severity of Irritable Bowel Syndrome

Background and Objectives: Irritable bowel syndrome (IBS), as a gastrointestinal disorder, presents with abdomen pain and alterations in the bowel habits. Its pathogenesis remains unclear. Here, we examined mitochondrial DNA copy number (mtCN) in IBS and its clinical value. Materials and Methods: mtCN was analyzed in 43 IBS patients using quantitative real-time polymerase chain reaction. Furthermore, data on the clinical characteristics of patients and symptom severity of IBS were collected, and their association with mtCN was analyzed. Results: mtCN was higher in patients with IBS (p = 0.008) and those with a drinking habit (p = 0.004). Smoking and the presence of a sleep partner showed a possible association with mtCN; however, it did not reach significance. The severity of IBS symptoms tended to positively correlate with mtCN (r = 0.279, p = 0.070). Conclusions: Overall, we demonstrated a potential association between mtCN and the clinicopathologic characteristics of patients with IBS. Further studies considering genetic and clinical factors are required.

The clinical value of serum long non-coding RNA human leukocyte antigen complex group 11/microRNA-532-3p in the diagnosis and prognosis of patients with acute myocardial infarction undergoing percutaneous coronary intervention

The clinical value of serum long non-coding RNA human leukocyte antigen complex group 11/microRNA-532-3p in the diagnosis and prognosis of patients with acute myocardial infarction undergoing percutaneous coronary intervention

New ultrasound features in diagnosing fetal anal atresia: a multicenter prospective cohort study

This research aimed to assess the validity of ultrasound scans with new features in detecting fetal anal atresia and verify the effectiveness of these new features. Additionally, we aimed at investigating the perinatal incidence of anal atresia. This multicenter prospective study recruited 94,617 normal gravidas and 84 gravidas with anal atresia fetuses. The gold standard for diagnosing perinatal anal atresia is routine neonatal anus examinations. The incidence calculation was based on the results of the gold standard. The validity of our new approach was evaluated via a diagnostic test involving all 94,701 subjects. The effectiveness of our new features was assessed through an ablation study in a randomly established new dataset, with the ratio of anal atresia to non-anal atresia cases of 1:4. The annual perinatal incidence of anal atresia between 2019 and 2023 ranges from 0.57‰ to 1.29‰. Our new method performed great regarding the Youden index, diagnostic odds ratio (DOR), area under the curve (AUC) of the receiver operating characteristic curve (ROCC), AUC of the precision-recall curve (PRC), F1-score, and Cramer’s V. In the ablation study, our new approach surpassed its competitors concerning Youden index, DOR, AUC of the ROCC, and AUC of the PRC. Ultrasound scans show high validity and clinical value in detecting fetal anal atresia. Our new ultrasound features significantly promote the detection of fetal anal atresia.

Evaluation of the clinical application value of artificial intelligence in diagnosing head and neck aneurysms

ObjectiveTo evaluate the performance of a semi-automated artificial intelligence (AI) software program (CerebralDoc® system) in aneurysm detection and morphological measurement.MethodsIn this study, 354 cases of computed tomographic angiography (CTA) were retrospectively collected in our hospital. Among them, 280 cases were diagnosed with aneurysms by either digital subtraction angiography (DSA) and CTA (DSA group, n = 102), or CTA-only (non-DSA group, n = 178). The presence or absence of aneurysms, as well as their location and related morphological features determined by AI were evaluated using DSA and radiologist findings. Besides, post-processing image quality from AI and radiologists were also rated and compared.ResultsIn the DSA group, AI achieved a sensitivity of 88.24% and an accuracy of 81.97%, whereas radiologists achieved a sensitivity of 95.10% and an accuracy of 84.43%, using DSA results as the gold standard. The AI in the non-DSA group achieved 81.46% sensitivity and 76.29% accuracy, as per the radiologists’ findings. The comparison of position consistency results showed better performance under loose criteria than strict criteria. In terms of morphological characteristics, both the DSA and the non-DSA groups agreed well with the diagnostic results for neck width and maximum diameter, demonstrating excellent ICC reliability exceeding 0.80. The AI-generated images exhibited superior quality compared to the standard software for post-processing, while also demonstrating a significantly reduced processing time.ConclusionsThe AI-based aneurysm detection rate demonstrates a commendable performance, while the extracted morphological parameters exhibit a remarkable consistency with those assessed by radiologists, thereby showcasing significant potential for clinical application.

Accurate birth weight prediction from fetal biometry using the Gompertz model

ObjectivesMonitoring of fetal growth and estimation of birth weight is of clinical importance. During pregnancy, ultrasound fetal biometry values including femur length, head circumference, abdominal circumference, biparietal diameter are measured and used to place fetuses on “growth charts”. There is no simple growth-model-based, predictive formula in use for fetal biometry. Estimation of fetal weight at birth currently depends on ultrasound data taken a short time before birth. Study designOur cohort (“Seethapathy cohort”) consists of ultrasound biometry measurements and other data for 774 pregnant women in Chennai, India, 2015-2017. We use the Gompertz model, a standard model for constrained growth, with just three intuitive parameters, to model the growth of fetal biometry, and a machine learning (ML) model trained on these parameters to predict birth weight (BW). ResultsThe Gompertz model convincingly fits the growth of fetal biometry values. Two Gompertz parameters—t0 (inflection time) and c (rate of decrease of growth rate)—seem universal to all fetuses, while the third, A, is an overall scale specific to each fetus, capturing individual variation. On the Seethapathy cohort we can infer A for each fetus from ultrasound data available by the 24 or 35 weeks. Our ML model predicts birth weight with < 8% error, outperforming published methods that have access to late-term ultrasound data. The same model gives an 8.4% error in BW prediction on an independent validation cohort of 365 women. ConclusionsThe Gompertz model fits fetal biometry growth and enables birth weight estimation without need of late-term ultrasounds. Aside from its clinical predictive value, we suggest its use for future growth standards, with almost all variation described by a single scale parameter A.

STAT6/LINC01637 axis regulates tumor growth via autophagy and pharmacological targeting STAT6 as a novel strategy for uveal melanoma

Compelling evidence has revealed a novel function of the STAT pathway in the pathophysiology of uveal melanoma (UM); however, its regulatory mechanisms remain unclear. Here, we analyzed the clinical prognostic value of STAT family genes in UM patients using bioinformatics approaches and found that high STAT6 expression is associated with poor prognosis. Furthermore, cellular experiments and a nude mouse model demonstrated that STAT6 promotes UM progression through the autophagy pathway both in vivo and in vitro. Next, RIP-PCR revealed that STAT6 protein binds to LINC01637 mRNA, which in turn regulates STAT6 expression to promote UM growth. Finally, molecular docking indicated that STAT6 is a target of Zoledronic Acid, which can delay UM tumorigenicity by inhibiting STAT6 expression. Taken together, our results indicate that the STAT6/LINC01637 axis promotes UM progression via autophagy and may serve as a potential therapeutic target for UM.

Photoresponsive protamine ionic complex towards a smart hemostatic biomaterial

Protamine (PA) is the only licensed antidote for reversing heparin anticoagulation by electrostatically binding with heparin. Efforts have been made on designing various heparin-scavengers, while, it remains a great challenge for gaining the external-stimuli responsive PA-release material. In this study, a generic strategy is developed for fabricating photoresponsive protein materials with the designed azobenzene-containing surfactant. For the first time, based on the isomerization of azobenzene, both cationic and anionic proteins could be phase change biomaterials which are capable of transiting to isotropic state under UV irradiation at room temperature. The formation of isotropic state could set the proteins free from the binding state, activating their intrinsic biological functions. Employing this mechanism, one smart PA material for inhibiting heparin is developed, which could effectively photo-modulate the heparin concentration by turning on-and-off the free state of PA from the binding state. With good biocompatibility, the PA material addresses photoresponsive hemostatic activity in biological studies, confirming its great potential clinical values. This work provides a new designing strategy for gaining photocontrollable hemostasis materials, also opening new opportunities for developing photoresponsive protein drugs and biomedical materials.

Application of Whole-Exome Sequencing in the Prenatal Diagnosis of Foetuses With Central Nervous System Abnormalities.

To investigate the clinical value of whole-exome sequencing (WES) in the diagnosis of foetuses with central nervous system (CNS) abnormalities but having a normal karyotyping and chromosomal microarray result. During the period of 2016-2022, there were a total of 149 foetuses with CNS abnormalities but having negative karyotyping and chromosomal microarray analysis results; WES was performed on these foetuses and their parents. Variants were classified according to ACMG guidelines, and the association of pathogenic variants with specific types of CNS abnormalities was explored. Among these 149 foetuses, three categories of abnormalities, namely, single CNS abnormality, multiple CNS abnormalities, CNS abnormalities along with other organ system abnormalities were identified, for which the detection rate of P/LP variants is 17.4% (12/69), 28.6% (14/49) and 54.8% (17/31), respectively. WES brought about an increase of 28.9% in diagnostic yield in the prenatal evaluation of foetuses with CNS abnormalities but having negative karyotyping and chromosome array results. WES may also be of benefit for the diagnosis of foetuses with isolated CNS abnormalities, as well as for making more informed interpretations of imaging findings and for providing better genetic counselling.

Diagnostic and screening potential of plasma exosome miR‑99b‑5p and its combination with other miRNAs for colorectal cancer.

Extracellular vesicles (EVs) secreted by tumor cells have been documented to hold viable biomarker potential. Therefore, the present study evaluated the potential clinical value of EV-microRNAs (miRNAs or miRs) in the plasma exosomes of patients with colorectal cancer (CRC) for the early diagnosis and screening of CRC. In total, 95 plasma samples were collected at The Third Affiliated Hospital of Guangzhou Medical University (Guangzhou, China) between 2017 and 2019. Specifically, 68 samples were from patients with CRC and 27 were from healthy control (HC) donors. High-throughput sequencing was used to detect the expression of miRNAs in the isolated plasma EVs, which was subsequently verified by reverse transcription-quantitative PCR. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic potential of single and combined miRNAs for CRC. Bioinformatics analysis was employed to predict the target genes of candidate miRNAs. Compared with those in the HC group, the CRC group expressed higher levels of miR-99b-5p and miR-409-3p, especially during the early stages of CRC. Clinicopathological analysis confirmed the higher expression levels of miR-99b-5p during the early stages, as well as higher expression levels in the colon compared with those in the rectum. ROC curve analysis revealed that the area under the curve (AUC) of miR-99b-5p for the diagnosis of early CRC was 73.5% (P=0.007). The early diagnostic capability of miR-99b-5p combined with miR-409-3p for CRC was evaluated, and the AUC was found to be 74.1% (P=0.006). In addition, the AUC of the combination of miR-99b-5p, miR-409-3p and carcinoembryonic antigen was 81.2% (P<0.001), indicating that this three-parameter combination displayed higher diagnostic power compared with any single miRNA for early CRC screening. The results from the present study suggest that the expression of miR-99b-5p in plasma exosomes is significantly upregulated in CRC, which holds potential for the early diagnosis of this cancer type. Such potential can be enhanced further by combining it with other miRNAs. Therefore, the present study provides a comprehensive but preliminary insight for the viability of miR-99b-5p (alone or combined with other miRNAs) for CRC diagnosis, which requires further exploration in the future.

Comparison of three-dimensional vs. two-dimensional assisted thoracoscopy for recurrent laryngeal nerve lymph nodes dissection in esophagectomy: a retrospective study

BackgroundThis study aimed to explore the clinical value of 3D video-assisted thoracoscopic surgery in dissecting recurrent laryngeal nerve lymph nodes in patients undergoing minimally invasive esophagectomy.MethodsA retrospective cohort study was conducted on 205 patients, including 120 males, who underwent esophagectomy from May 2018 to May 2020 in the Department of Thoracic Surgery at the Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University. Perioperative parameters, including intraoperative blood loss, operation time, the number of dissected recurrent laryngeal nerve lymph nodes, the incidence and degree of postoperative recurrent laryngeal nerve injury, the volume of postoperative thoracic drainage, and postoperative complications, were compared between the 3D and 2D groups.ResultsThere were no significant differences in the preoperative baseline data between these two groups (P > 0.05). The number of dissected recurrent laryngeal nerve lymph nodes in the 3D group was significantly higher than in the 2D group (P < 0.05). The operation times were significantly shorter in the 3D group than in the 2D group (P < 0.05). The volume of thoracic drainage in the first 2 days was significantly less in the 3D group than in the 2D group (P < 0.05).ConclusionsCompared to the 2D system, the application of 3D video-assisted thoracoscopic surgery in minimally invasive esophagectomy can increase the number of dissected recurrent laryngeal nerve lymph nodes and ensure safety. Additionally, it can reduce the duration of the operation, decrease early postoperative thoracic drainage volume, and promote patient recovery.

Clinical value of plasma pTau181 to predict Alzheimer's disease pathology in a large real-world cohort of a memory clinic

BackgroundThe identification of patients with an elevated risk of developing Alzheimer’s disease (AD) dementia and eligible for the disease modifying treatments (DMTs) in the earliest stages is one of the greatest challenges in the clinical practice. Plasma biomarkers has the potential to predict these issues, but further research is still needed to translate them to clinical practice. Here we evaluated the clinical applicability of plasma pTau181 as a predictive marker of AD pathology in a large real-world cohort of a memory clinic. MethodsThree independent cohorts (modelling [n=991, 59.7% female], testing [n=642, 56.2% female] and validation [n=441, 55.1% female]) of real-world patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD dementia, and other dementias were included. Paired cerebrospinal fluid (CSF) and plasma samples were used to measure AT(N) CSF biomarkers and plasma pTau181. FindingsCSF and plasma pTau181 showed correlation in all phenotypes except in SCD and other dementias. Age significantly influenced the biomarker’s performance. The general Aβ(+) vs Aβ(-) ROC curve showed an AUC = 0.77 [0.74 to 0.80], whereas the specific ROC curve of MCI due to AD vs non-AD MCI showed an AUC = 0.89 [0.85 to 0.93]. A cut-off value of 1.30 pg/ml of plasma pTau181 exhibited a sensitivity of 93.57% [88.72 to 96.52], specificity of 72.38 % [62.51 to 79.01], VPP of 77.85% [70.61 to 83.54], and 8.30% false negatives in the subjects with MCI of the testing cohort.The HR of cox regression showed that patients with MCI up to this cut-off value exhibited a HR = 1.84 [1.05 to 3.22] higher risk to convert to AD dementia than patients with MCI below the cut-off value. InterpretationPlasma pTau181 has the potential to be used in the memory clinics as a screening biomarker of AD pathology in subjects with MCI, presenting a valuable prognostic utility in predicting the MCI conversion to AD dementia. In the context of a real-world population, a confirmatory test employing gold-standard procedures is still advisable.Funding: this study has been mainly funded by Ace Alzheimer Center Barcelona, Instituto de Salud Carlos III (ISCIII), Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Spanish Ministry of Science and Innovation, Fundación ADEY, Fundación Echevarne and Grífols S.A.

A novel long non-coding RNA connects obesity to impaired adipocyte function

BackgroundLong non-coding RNAs (lncRNAs) can perform tasks of key relevance in fat cells, contributing, when defective, to the burden of obesity and its sequelae. Here, scrutiny of adipose tissue transcriptomes before and after bariatric surgery (GSE53378) granted identification of 496 lncRNAs linked to the obese phenotype. Only expression of linc-GALNTL6-4 displayed an average recovery over 2-fold and FDR-adjusted p-value <0.0001 after weight loss. The aim of the present study was to investigate the impact on adipocyte function and potential clinical value of impaired adipose linc-GALNTL6-4 in obese subjects. MethodsWe employed transcriptomic analysis of public dataset GSE199063, and cross validations in two large transversal cohorts to report evidence of a previously unknown association of adipose linc-GALNTL6-4 with obesity. We then performed functional analyses in human adipocyte cultures, genome-wide transcriptomics, and untargeted lipidomics in cell models of loss and gain of function to explore the molecular implications of its associations with obesity and weight loss. ResultsThe expression of linc-GALNTL6-4 in human adipose tissue is adipocyte-specific and co-segregates with obesity, being normalized upon weight loss. This co-segregation is demonstrated in two longitudinal weight loss studies and two cross-sectional samples. While compromised expression of linc-GALNTL6-4 in obese subjects is primarily due to the inflammatory component in the context of obesity, adipogenesis requires the transcriptional upregulation of linc-GALNTL6-4, the expression of which reaches an apex in terminally differentiated adipocytes. Functionally, we demonstrated that the knockdown of linc-GALNTL6-4 impairs adipogenesis, induces alterations in the lipidome, and leads to the downregulation of genes related to cell cycle, while propelling in adipocytes inflammation, impaired fatty acid metabolism, and altered gene expression patterns, including that of apolipoprotein C1 (APOC1). Conversely, the genetic gain of linc-GALNTL6-4 ameliorated differentiation and adipocyte phenotype, putatively by constraining APOC1, also contributing to the metabolism of triglycerides in adipose. ConclusionsCurrent data unveil the unforeseen connection of adipocyte-specific linc-GALNTL6-4 as a modulator of lipid homeostasis challenged by excessive body weight and meta-inflammation.

Clinical significance of the CALLY index in patients with gastric cancer undergoing gastrectomy.

The aim of this study was to elucidate the clinical impact of the CALLY index in patients with gastric cancer (GC) undergoing gastrectomy. Between January 2014 and December 2020, 617 patients who underwent gastrectomy for GC at the Osaka City General Hospital were enrolled in this study. The CALLY index was calculated using the following formula: [albumin (g/dL)×lymphocytes (/μl)]/[CRP (mg/dL)×104]. We compared the predictive value of four biomarkers [CALLY index, modified Glasgow prognostic score (mGPS), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR)] for short- and long-term outcomes and focused on the CALLY index to elucidate its clinical value. Receiver operating characteristic analysis showed that the area under the curve for the CALLY index was the highest among the four biomarkers. The 5-year overall survival (OS) and cancer-specific survival (CSS) rates in the low and the high CALLY groups were statistically significant. Multivariate analysis identified the CALLY index as an independent factor for OS and CSS but not NLR or PLR. The mGPS was an independent factor for OS but not for CSS in multivariate analysis. Regarding complications, only the CALLY index was an independent predictor of major complications (≧ Clavien-Dindo grade 3) in multivariate analysis but not others. The CALLY index may have a clinical value in predicting OS, CSS, and major complications in GC patients undergoing gastrectomy.

The clinical predictive value of radiomic features from [68Ga]Ga-PSMA-11 and [18F]F-PSMA-1007 PET in patients with prostate cancer: a preliminary comparative study

The clinical predictive value of radiomic features from [68Ga]Ga-PSMA-11 and [18F]F-PSMA-1007 PET in patients with prostate cancer: a preliminary comparative study

Comparing the diagnostic value of targeted with metagenomic next-generation sequencing in immunocompromised patients with lower respiratory tract infection

BackgroundAccurate identification of the etiology of lower respiratory tract infections (LRTI) is crucial, particularly for immunocompromised patients with more complex etiologies. The advent of next-generation sequencing (NGS) has enhanced the effectiveness of pathogen detection. However, assessments of the clinical diagnostic value of targeted NGS (tNGS) in immunocompromised patients with LRTI are limited.MethodsTo evaluate the diagnostic value of tNGS in immunocompromised patients with LRTI, a total of 88 patients, of whom 54 were immunocompromised, were enrolled. These patients underwent tNGS testing of bronchoalveolar lavage fluid (BALF). Results from both metagenomic next-generation sequencing (mNGS) and conventional microbiological tests (CMT) were also available for all participants. The performance of tNGS was assessed by comparing its findings against mNGS, CMT, and the clinical composite diagnosis.ResultsIn the cohort of 88 patients, tNGS showed comparable diagnostic value to mNGS and was significantly superior to CMT. Compared to CMT and composite reference standard, tNGS showed sensitivity of 94.55% and 90.48%, respectively. In immunocompromised patients, despite a more diverse pathogen variety, tNGS maintained similar sensitivity to mNGS and outperformed CMT. tNGS positively influenced etiologic diagnosis and antibiotic decision-making in 72.72% of cases, leading to a change in antibiotic regimen in 17.05% of cases. We also compared the detection of microbial nucleic acids by tNGS with mNGS and found that tNGS could identify 87.99% of the microbial nucleic acids identified by mNGS.ConclusionIn summary, our study demonstrated that tNGS offers promising clinical diagnostic accuracy in immunocompromised patients, as evidenced by its favorable comparison with CMT, the composite reference standard, and mNGS.

Ultrasound viscoelastic imaging in the noninvasive quantitative assessment of chronic kidney disease

Background This study aims to evaluate the clinical application value of ultrasound viscoelastic imaging in noninvasive quantitative assessment of chronic kidney disease (CKD). Methods A total of 332 patients with CKD and 190 healthy adults as a control group were prospectively enrolled. Before kidney biopsy, ultrasound viscoelastic imaging was performed to measure the mean stiffness value (Emean), mean viscosity coefficient (Vmean), and mean dispersion coefficient (Dmean) of the renal. CKD patients were divided into three groups based on estimated glomerular filtration rate. The differences in clinic, pathology, ultrasound image parameters between the control and patient groups, or among different CKD groups were compared. The correlation between viscoelastic parameters and pathology were analyzed. Results Emean, Vmean, and Dmean in the control group were less than the CKD group (p < 0.05). In the identification of CKD from control groups, the area under curve of Vmean, Dmean, Emean, and combining the three parameters is 0.90, 0.79, 0.69, 0.91, respectively. Dmean and Vmean were increased with the decline of renal function (p < 0.05). Vmean and Dmean were positively correlated with white blood cell, urea, serum creatinine, and uric acid (p < 0.05). Vmean is positively correlated with interstitial fibrosis and inflammatory cell infiltration grades (p < 0.001). Conclusions Ultrasound viscoelastic imaging has advantages in noninvasive quantitative identification and evaluating renal function of CKD. Emean > 6.61 kPa, Vmean > 1.86 Pa·s, or Dmean > 7.51 m/s/kHz may suggest renal dysfunction. Combining Vmean, Dmean, and Emean can improve the efficiency of identifying CKD.

Therapeutic targets of armored chimeric antigen receptor T cells navigating the tumor microenvironment.

Chimeric antigen receptor (CAR) T cell therapy, which targets tumors with high specificity through the recognition of particular antigens, has emerged as one of the most rapidly advancing modalities in immunotherapy, demonstrating substantial success against hematological malignancies. However, previous generations of CAR-T cell therapy encountered numerous challenges in treating solid tumors, such as the lack of suitable targets, high immunosuppression, suboptimal persistence, and insufficient infiltration owing to the complexities of the tumor microenvironment, all of which limited their efficacy. In this review, we focus on the current therapeutic targets of fourth-generation CAR-T cells, also known as armored CAR-T cells, and explore the mechanisms by which these engineered cells navigate the tumor microenvironment by targeting its various components. Enhancing CAR-T cells with these therapeutic targets holds promise for improving their effectiveness against solid tumors, thus achieving substantial clinical value and advancing the field of CAR-T cell therapy. Additionally, we discuss potential strategies to overcome existing challenges and highlight novel targets that could further enhance the efficacy of CAR-T cell therapy in treating solid tumors.

Association between triglyceride glucose-body mass index and the staging of non-alcoholic steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease

Objective The objective of this study was to thoroughly investigate the clinical value of triglyceride glucose-body mass index (TyG-BMI) in patients diagnosed with non-alcoholic fatty liver disease (NAFLD). Specifically, we aimed to determine its association with non-alcoholic steatohepatitis (NASH) and the progression of liver fibrosis. Methods The study included 393 patients diagnosed with NAFLD after liver biopsy. The patients were divided into two distinct cohorts: a training cohort (N = 320) and a validation cohort (N = 73). The training cohort was further divided into four groups based on TyG-BMI quartiles. The clinical characteristics of the patients in each group were compared in detail, and the association between TyG-BMI and NASH, NAFLD Activity Score (NAS) ≥ 4, at-risk NASH, significant fibrosis, advanced fibrosis, and cirrhosis was analyzed using multiple models. Additionally, we generated receiver operating characteristic (ROC) curves to evaluate the predictive ability of TyG-BMI for NASH and fibrosis staging in patients with NAFLD. Results Patients with higher TyG-BMI values had a significantly higher prevalence of NASH, NAS ≥ 4, at-risk NASH, significant fibrosis, advanced fibrosis, and cirrhosis (all p < .05). TyG-BMI was an independent predictor of these diseases in both unadjusted and adjusted models (all p < .05). ROC curve analysis further revealed the excellent performance of TyG-BMI in predicting NASH, NAS ≥ 4, at-risk NASH, significant fibrosis, advanced fibrosis, and cirrhosis. The validation cohort yielded analogous results. Furthermore, we constructed three multivariate models of TyG-BMI in conjunction with elastography metrics, which demonstrated elevated diagnostic AUC values of 0.782, 0.792, 0.794, 0.785, 0.834, and 0.845, respectively. Conclusion This study confirms a significant association between insulin resistance and NAFLD, including at-risk NASH and fibrosis staging, as assessed using the TyG-BMI index. TyG-BMI and its associated multivariate models can be valuable noninvasive indicators for NAFLD diagnosis, risk stratification, and disease course monitoring.