Construction of CDs@ß-CD@CCM ratiometric fluorescence probe for FRET-based ClO--sensing.

ß-Cyclodextrin (ß-CD) -functionalized carbon quantum dots (CDs) loaded with curcumin (CCM) were used for ClO--sensing with high sensitivity and selectivity. This fluorescence resonance energy transfer (FRET)-based sensor was created through attaching CCM to the CDs via ß-CD linker. CCM could get into the interior of ß-CD triggering the FRET from CDs to CCM, providing an "off" state of the CDs. However, the effect of FRET was weakened by the ClO-, because the o- methoxyphenol structure from CCM was oxidized to be benzoquinone. The fluorescence intensity of CDs@ß-CD@CCM at 440 nm can be heightened and 520 nm from CCM can decrease along with the increased ClO-. Therefore, a ratiometric fluorescence probe for ClO--sensing is successfully constructed. It conforms to a polynomial curve equation which is I440/I520 = -0.0268+0.0315 CClO-+0.0055[CClO-]2 (R2= 0.9958) between 0-18.4 µM ClO-. Furthermore, we also obtain excellent results using this spectrophotometric method for ClO-- sensing in pure water and commercial disinfectants, which afford potential in the environment monitoring area. We expect this sensing platform could be helpful in other analogous probes in relevant fields.

Study on the Efficacy and Safety of the Huangqi Guizhi Wuwu Decoction in the Prevention and Treatment of Chemotherapy-Induced Peripheral Neuropathy: Meta-Analysis of 32 Randomized Controlled Trials.

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) still lacks efficient therapeutic drugs. This study aimed to systematically evaluate the effects of Huangqi Guizhi Wuwu Decoction (HGWD) alone or combined with positive drugs on CIPN prevention and treatment. Methods: The PubMed, Embase, Web of Science, Cochrane, China National Knowledge Infrastructure (CNKI), Wan Fang Data, China Science and Technology Journal (VIP) and Chinese Biomedical (CBM) databases were searched for randomized controlled trials (RCTs) of HGWD for CIPN prevention and treatment. The search time ranged from database establishment to October 17, 2023. The Cochrane risk-of-bias assessment tool was used for quality assessment, Review Manager 5.3 and STATA 12.0 were used for meta-analysis, and GRADEprofiler was used for evidence level assessment. Results: A total of 32 RCTs involving 1987 patients were included. The meta-analysis results revealed the following: 1. In terms of the total CIPN incidence, that in the HGWD group was lower than that in the blank control group. The incidence in both the HGWD and HGWD+positive drug groups was lower than that in the monotherapy-positive drug group. 2. In terms of the incidence of severe CIPN, that in the HGWD group was lower than that in the blank control and positive drug groups. There was no statistically significant difference between the HGWD+positive drug and positive drug groups. Sensitivity analysis revealed that the results of severe incidence in the HGWD group was lower than that in the positive drug group were unstable 3. HGWD did not increase the number of chemotherapy-related adverse events. Conclusion: HGWD can safely and effectively prevent CIPN, reduce symptoms, improve quality of life and reduce the impact of chemotherapy drugs on sensory nerve conduction. However, more high-quality RCTs are needed to compare the efficacy of HGWD with that of positive control drugs in preventing severe CIPN.

Caregiving risk perception characteristics and associated factors among informal caregivers of functionally dependent elderly individuals at home: a qualitative study.

BACKGROUND: This study explored risk perception characteristics and influencing factors among informal caregivers of functionally dependent elderly individuals at home, aiming to improve caregivers' caregiving risk perception and coping abilities and ultimately enhance the quality of life for these individuals. METHODS: We used purposive sampling to select 22 informal caregivers from a community in Zhengzhou City, Henan Province, China, between March and September 2023 and conducted face-to-face semi-structured in-depth interviews. The data were analyzed using Colaizzi's seven-step analysis method. RESULTS: We extracted two themes, caregiving risk perception characteristics and caregiving risk perception associated factors, and eight sub-themes, perceived risk possibility, perceived risk anticipation, perceived severity of consequences, past caregiving experiences, health literacy, psychological status, caregiving burden, and family social support. CONCLUSION: There were differences in how informal caregivers perceived the risks associated with caring for functionally dependent elderly individuals at home, which various factors could influence. It was essential to provide training that covered the knowledge and skills needed for caregiving, improve caregivers' awareness of safety risks, and establish a correct perception of caregiving risks. The government must construct and refine a comprehensive framework for caregiver respite services. Simultaneously, healthcare professionals should proactively undertake health education endeavors to augment the recognition of care safety risks among informal caregivers, thereby cultivating an accurate awareness of care risk perception.

Analysis of Rice Blast Fungus Genetic Diversity and Identification of a Novel Blast Resistance OsDRq12 Gene.

The rice blast fungus Magnaporthe oryzae poses a significant challenge to maintaining rice production. Developing rice varieties with resistance to this disease is crucial for its effective control. To understand the genetic variability of blast isolates collected between 2015 and 2017, the 27 monogenic rice lines that carry specific resistance genes were used to evaluate blast disease reactions. Based on criteria such as viability, virulence, and reactions to resistance genes, 20 blast isolates were selected as representative strains. To identify novel resistance genes, a quantitative trait locus analysis was carried out utilizing a mixture of the 20 representative rice blast isolates and a rice population derived from crossing the blast-resistant cultivar 'Cheongcheong' with the blast-susceptible cultivar 'Nagdong'. This analysis revealed a significant locus, RM1227-RM1261 on chromosome 12, that is associated with rice blast resistance. Within this locus, 12 disease resistance-associated protein genes were identified. Among them, OsDRq12, a member of the nucleotide-binding, leucine-rich repeat disease resistance family, was chosen as the target gene for additional computational investigation. The findings of this study have significant implications for enhancing rice production and ensuring food security by controlling rice blast and developing resistant rice cultivars.

Dispel some mist on circulating biopterins: measurement, physiological interval and pathophysiological implication.

BACKGROUND AND AIMS: Biopterins, including tetrahydrobiopterin (BH4), dihydrobiopterin (BH2), and biopterin (B), were crucial enzyme cofactors in vivo. Despite their recognized clinical significance, there remain notable research gaps and controversies surrounding experimental outcomes. This study aims to clarify the biopterins-related issues, including analytical art, physiological intervals, and pathophysiological implications. MATERIALS AND METHODS: A novel LC-MS/MS method was developed to comprehensively profile biopterins in plasma, utilizing chemical derivatization and cold-induced phase separation. Subsequently, apparently healthy individuals were enrolled to investigate the physiological ranges. And the relationships between biopterins and biochemical indicators were analyzed to explore the pathophysiological implications. RESULTS: The developed method was validated as reliable for detecting biopterins across the entire physiological range. Timely anti-oxidation was found to be essential for accurate assessment of biopterins. The observed overall mean ± SDs levels were 3.51 ± 0.94, 1.54 ± 0.48, 2.45 ± 0.84 and 5.05 ± 1.14 ng/mL for BH4, BH2, BH4/BH2 and total biopterins. The status of biopterins showed interesting correlations with age, gender, hyperuricemia and overweight. CONCLUSION: In conjunction with proper anti-oxidation, the newly developed method enables accurate determination of biopterins status in plasma. The observed physiological intervals and pathophysiological implications provide fundamental yet inspiring support for further clinical researches.

A high stable sample loading for analysis of adult alpha-thalassemia via the improved microarray isoelectric focusing of Hb species.

The isoelectric focusing has realized various improvements, including the protocols and creation of mIEF (microcolumn isoelectric focusing) instruments with excellent sensitivity for screening of diabetes and beta thalassemia. However, the problem of manual sample loading and hydration for the mIEF limits the operational capacity for stably detecting and quantitating most abnormal hemoglobin (Hb). Herein, we provided a high stable sample loading protocol for analysis of alpha thalassemia and Hb variants. In contrast to the previous volume of 20 µl, a 100 µl blood sample solution in this protocol was optimized with mixture of 6.4-7.5 and 3-10 pH carrier ampholytes, pI markers and loaded for 30 mins IPG microcolumn hydration. The hydrated microcolumn was then automatically loaded onto the mIEF chip array to which CH3COOH and NH4OH act as anodic and cathodic solutions. Lastly, the IEF was run for 9 mins. Hb H, Barts, A1c, F, A2 and CS were simultaneously separated and focused with higher resolution and sensitivity in quantifying H and Barts as low as 0.6 and 0.5 % respectively. Accordingly, there was an enhanced stability and linearity with a rapid assay time of 45 secs per sample. Moreover, analysis showed a fitting linear relationship with conventional technology at R2 = 0.9803 for H and R2 = 0.9728 for Barts thereby indicating greater accuracy confirmed by the AUC. Hence, the developed protocol could simply be employed for high stable and throughput batch sample loading of hydration, and accurate separation and quantitation of Hb variants for alpha and beta thalassemia.

A bibliometric study on research trends and hotspots of recurrent aphthous stomatitis.

Background/purpose: Recurrent aphthous stomatitis (RAS) is a common oral mucosal disease. Despite a variety of scientific articles have been available till date, merely a few scientometric analyses have been systematically carried out in this field. The objective of this study was to recognize the hotspots and research trends related to RAS via bibliometric approach. Materials and methods: The Elsevier's Scopus database was searched to retrieve qualified literature through an advanced search strategy on 9 Feb 2023. The basic information was collected as following: article type, publication year, journals, impact factor, the count of citations, citation density, keywords, authors, contributing institutions and country. Results: A list of 986 publications were identified from 1933 to 2022, and the number of citations for each paper varied from 0 to 283. A steady increasing trend in the number of documents could be observed each decade with the summit in 2010s. Controlled study (n = 334) and major clinical study (n = 192) were the most common types of study design. Scully C (n = 26) was identified as the most productive author. United States (n = 166) and Turkey (n = 101) top the list of dedicating countries. Conclusion: This report would offer profound insight into the current status of RAS research and serve as a reference source for anyone planning to enhance the quality of future work.

Diagnosis and management of benign recurrent intrahepatic cholestasis and psychosocial stressors in an adolescent: A case report.

BACKGROUND: Benign recurrent intrahepatic cholestasis (BRIC) is a rare autosomal recessive disorder, characterized by episodes of intense pruritus, elevated serum levels of alkaline phosphatase and bilirubin, and near-normal -glutamyl transferase. These episodes may persist for weeks to months before spontaneously resolving, with patients typically remaining asymptomatic between occurrences. Diagnosis entails the evaluation of clinical symptoms and targeted genetic testing. Although BRIC is recognized as a benign genetic disorder, the triggers, particularly psychosocial factors, remain poorly understood. CASE SUMMARY: An 18-year-old Chinese man presented with recurrent jaundice and pruritus after a cold, which was exacerbated by self-medication involving vitamin B and paracetamol. Clinical and laboratory evaluations revealed elevated levels of bilirubin and liver enzymes, in the absence of viral or autoimmune liver disease. Imaging excluded biliary and pancreatic abnormalities, and liver biopsy demonstrated centrilobular cholestasis, culminating in a BRIC diagnosis confirmed by the identification of a novel ATP8B1 gene mutation. Psychological assessment of the patient unveiled stress attributable to academic and familial pressures, regarded as potential triggers for BRIC. Initial relief was observed with ursodeoxycholic acid and cetirizine, followed by an adjustment of the treatment regimen in response to elevated liver enzymes. The patient's condition significantly improved following a stress-related episode, thanks to a comprehensive management approach that included psychosocial support and medical treatment. CONCLUSION: Our research highlights genetic and psychosocial influences on BRIC, emphasizing integrated diagnostic and management strategies.

Concept-based Lesion Aware Transformer for Interpretable Retinal Disease Diagnosis.

Existing deep learning methods have achieved remarkable results in diagnosing retinal diseases, showcasing the potential of advanced AI in ophthalmology. However, the black-box nature of these methods obscures the decision-making process, compromising their trustworthiness and acceptability. Inspired by the concept-based approaches and recognizing the intrinsic correlation between retinal lesions and diseases, we regard retinal lesions as concepts and propose an inherently interpretable framework designed to enhance both the performance and explainability of diagnostic models. Leveraging the transformer architecture, known for its proficiency in capturing long-range dependencies, our model can effectively identify lesion features. By integrating with image-level annotations, it achieves the alignment of lesion concepts with human cognition under the guidance of a retinal foundation model. Furthermore, to attain interpretability without losing lesion-specific information, our method employs a classifier built on a cross-attention mechanism for disease diagnosis and explanation, where explanations are grounded in the contributions of human-understandable lesion concepts and their visual localization. Notably, due to the structure and inherent interpretability of our model, clinicians can implement concept-level interventions to correct the diagnostic errors by simply adjusting erroneous lesion predictions. Experiments conducted on four fundus image datasets demonstrate that our method achieves favorable performance against state-of-the-art methods while providing faithful explanations and enabling conceptlevel interventions. Our code is publicly available at https://github.com/Sorades/CLAT.

[Chemical composition and pharmacological effects of Cinnamomum camphora chvar. borneol essential oil: a review].

Cinnamomum camphora chvar. borneol, a rare camphor tree variant recently identified in China, is distinguished by its high concentration of D-borneol, also known as " plant gold" due to its significant value. The essential oil extracted from this variant,rich in monoterpenes and sesquiterpenes, demonstrates a broad spectrum of pharmacological activities, including analgesic, antiinflammatory, antioxidant, cognition-enhancing, anti-bacterial, and insecticidal effects. These properties, underscored by extensive research, highlight the oil's potential in the biomedical, chemical, and food sectors as a valuable commodity. Nonetheless, the safety profile of this valuable oil remains poorly characterized, with its chemical composition and therapeutic efficacy subject to variations in the factors like geographic origin, harvesting timing, part used for extraction, and processing techniques. Such variability poses challenges to its clinical application and hampers the efficient exploitation of this resource. This review synthesizes current studies on C. camphora chvar. borneol essential oil and provides a detailed examination of its chemical and pharmacological profiles. In this study, we discuss existing research gaps and propose strategies for advancing its clinical use and industrial application, aiming to provide a foundational reference for future investigations and the resolution of its commercial and therapeutic challenges.

Integrated cell wall and transcriptomic analysis revealed the mechanism underlying zinc-induced alleviation of cadmium toxicity in Cosmos bipinnatus.

Plant growth is severely harmed by cadmium (Cd) contamination, while the addition of zinc (Zn) can reduce the toxic effects of Cd. However, the interaction between Cd and Zn on the molecular mechanism and cell wall of Cosmosbipinnatus is unclear. In this study, a transcriptome was constructed using RNA-sequencing. In C. bipinnatus root transcriptome data, the expression of 996, 2765, and 3023 unigenes were significantly affected by Cd, Zn, and Cd + Zn treatments, respectively, indicating different expression patterns of some metal transporters among the Cd, Zn, and Cd + Zn treatments. With the addition of Zn, the damage to the cell wall was reduced, both the proportion and content of polysaccharides in the cell wall were changed, and Cd accumulation was decreased by 32.34%. In addition, we found that Cd and Zn mainly accumulated in pectins, the content of which increased by 30.79% and 61.4% compared to the CK treatment. Thus, Zn could alleviate the toxicity of Cd to C. bipinnatus. This study revealed the interaction between Cd and Zn at the physiological and molecular levels, broadening our understanding of the mechanisms of tolerance to Cd and Zn stress in cosmos.

Identification and immunological characterization of genes associated with ferroptosis in Alzheimer's disease and experimental demonstration.

The incidence of Alzheimer's disease (AD) is rising globally, yet its treatment and prediction of this condition remain challenging due to the complex pathophysiological mechanisms associated with it. Consequently, the objective of the present study was to analyze and characterize the molecular mechanisms underlying ferroptosis­related genes (FEGs) in the pathogenesis of AD, as well as to construct a prognostic model. The findings will provide new insights for the future diagnosis and treatment of AD. First, the AD dataset GSE33000 from the Gene Expression Omnibus database and the FEGs from FerrDB were obtained. Next, unsupervised cluster analysis was used to obtain the FEGs that were most relevant to AD. Subsequently, enrichment analyses were performed on the FEGs to explore biological functions. Subsequently, the role of these genes in the immune microenvironment was elucidated through CIBERSORT. Then, the optimal machine learning was selected by comparing the performance of different machine learning models. To validate the prediction efficiency, the models were validated using nomograms, calibration curves, decision curve analysis and external datasets. Furthermore, the expression of FEGs between different groups was verified using reverse transcription quantitative PCR and western blot analysis. In AD, alterations in the expression of FEGs affect the aggregation and infiltration of certain immune cells. This indicated that the occurrence of AD is strongly associated with immune infiltration. Finally, the most appropriate machine learning models were selected, and AD diagnostic models and nomograms were built. The present study provided novel insights that enhance understanding with regard to the molecular mechanism of action of FEGs in AD. Moreover, the present study provided biomarkers that may facilitate the diagnosis of AD.

Photoinduced Transition-Metal and External Photosensitizer Free Benzylic Fluorination of Unactivated Alkylarenes.

A green and efficient protocol for the direct monofluorination of unactivated alkylarenes under visible-light irradiation has been developed, without any extraneous transition-metal catalysts or photosensitizers. This method is compatible with a broad spectrum of functional groups, including carboxylic and alcoholic scaffolds, under mild reaction conditions. Gram-scale synthesis of a fluorine-containing pharmaceutical analogue was successfully executed, underscoring the strategy's reliability and practicality. Furthermore, mechanistic studies suggest that a single-electron transfer mechanism might be responsible for the generation of the benzylic radicals in initiation step.

Advancing towards practice: A novel LC-MS/MS method for detecting retinol in dried blood spots.

BACKGROUND: To date, clinical laboratories face challenges in quantifying retinol from DBS samples. Disputes arise throughout the whole detection process, encompassing the storage condition, the release strategy as well as the selection of internal standards. METHODS: We incubated DBS with ascorbic acid solution. Then, retinol-d4 in acetonitrile was introduced to incorporate isotopic internal standard and promote protein precipitation. Afterward, sodium carbonate solution was added to ionize cytochromes (such as bilirubin), which amplified the difference of their hydrophobicity to retinol. Subsequently, cold-induced phase separation could be facilitated to separate retinol from the impurities. In the end, the upper layer was injected for LC-MS/MS analysis. RESULTS: By comparing the detected retinol content in whole blood and DBS samples prepared from the same volume, we confirmed the established pretreatment was capable to extract most of retinol from DBS (recovery >90 %). Thereafter, we verified that within DBS, retinol possessed satisfying stability without antioxidation. Indoor-light exposure and storage duration would not cause obvious degradation (<10 %). Following systematic validation, the established method well met the criteria outlined in the relevant guidelines. After comparing with detected DBS results to the paired plasma samples, 54 out of 60 met the acceptance limit for cross-validation of ±20 %. CONCLUSIONS: We realized precise quantification of retinol from one 3.2 mm DBS disc. By circumventing conventional antioxidation, liquid-liquid/solid-phase extraction and organic solvent evaporation, the pretreatment could be completed within 15 min consuming only minimal amounts of low-toxicity chemicals (ascorbic acid, acetonitrile, and sodium carbonate). We expect this contribution holds the potential to significantly facilitate the evaluation of patients' vitamin A status by using DBS samples in the future.

Altered landscape of total RNA, tRNA and sncRNA modifications in the liver and spleen of mice infected by Toxoplasma gondii.

BACKGROUND: Pathogens can impact host RNA modification machinery to establish a favorable cellular environment for their replication. In the present study, we investigated the effect of Toxoplasma gondii infection on host RNA modification profiles and explored how these modifications may influence the host-parasite interaction. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the modification levels of ∼ 80 nt tRNA and 17-50 nt sncRNAs in mouse liver, spleen, and serum using liquid chromatography and tandem mass spectrometry analysis. The results revealed alterations in RNA modification profiles, particularly during acute infection. The liver exhibited more differentially abundant RNA modifications than the spleen. RNA modification levels in serum were mostly downregulated during acute infection compared to control mice. Correlations were detected between different RNA modifications in the liver and spleen during infection and between several RNA modifications and many cytokines. Alterations in RNA modifications affected tRNA stability and protein translation. CONCLUSIONS/SIGNIFICANCE: These findings provide new insight into the role of RNA modifications in mediating the murine host response to T. gondii infection.

Phelligridimer A enhances the expression of mitofusin 2 and protects against cerebral ischemia/reperfusion injury.

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress play pivotal roles in the pathology of cerebral ischemia. In this study, we investigated whether phelligridimer A (PA), an active compound isolated from the medicinal and edible fungus Phellinus igniarius, ameliorates ischemic cerebral injury by restoring mitochondrial function and restricting ER stress. An in vitro cellular model of ischemic stroke-induced neuronal damage was established by exposing HT-22 neuronal cells to oxygen-glucose deprivation/reoxygenation (OGD/R). An in vivo animal model was established in rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). The results showed that PA (1-10 µM) dose-dependently increased HT-22 cell viability, reduced OGD/R-induced lactate dehydrogenase release, and reversed OGD/R-induced apoptosis. PA reduced OGD/R-induced accumulation of reactive oxygen species, restored mitochondrial membrane potential, and increased ATP levels. Additionally, PA reduced the expression of the 78-kDa glucose-regulated protein (GRP78) and the phosphorylation of inositol-requiring enzyme-1α (p-IRE1α) and eukaryotic translation-initiation factor 2α (p-eIF2α). PA also inhibited the activation of the mitogen-activated protein kinase (MAPK) pathway in the OGD/R model. Moreover, treatment with PA restored the expression of mitofusin 2 (Mfn-2), a protein linking mitochondria and ER. The silencing of Mfn-2 abolished the protective effects of PA. The results from the animal study showed that PA (3-10 mg/kg) significantly reduced the volume of cerebral infarction and neurological deficits, which were accompanied by an increased level of Mfn-2, and decreased activation of the ER stress in the penumbra of the ipsilateral side after MCAO/R in rats. Taken together, these results indicate that PA counteracts cerebral ischemia-induced injury by restoring mitochondrial function and reducing ER stress. Therefore, PA might be a novel protective agent to prevent ischemia stroke-induced neuronal injury.

Status and influencing factors of returning to work 6 months after discharge from hospital with severe acute pancreatitis-a cross-sectional descriptive-analytical study in China.

Objective: To describe the return to work of patients with severe acute pancreatitis within 6 months after discharge, and to explore the influence of demographic, clinical, and psychosocial factors on their return to work. Research design: Prospective 6 months follow-up study. Setting: A third class hospital in Guizhou Province. Adult of severe acute pancreatitis(18-60years), with a job before admission, in the intensive care unit ≥ 24 h, were included. Main outcome measures: To study return to work and influencing factors one, three and six months severe acute pancreatitis patients discharge. several measurements were used, including General Health Questionnaire (Demographic, disease-related, job-related and health behavior data), Readiness for Return-To-Work Scale and the Hospital Anxiety and Depression Scale. Results: Forty-three severe acute pancreatitis patients were included in our study, with mean age 41.53 years. Twenty-nine (67.44%) patients returned to work within 6 months, and fourteen patients did not return to work. The status of Readiness for Return-To-Work Scale: fourteen severe acute pancreatitis patients who did not return to work were mainly in the precontemplation dimension and prepared for action-self-evaluative dimension both 5 cases (35.71%), and the 29 patients who had returned to work were in the Proactive maintenance stage. The study showed that the independent risk factors for returning to work in SAP patients were chronic disease (OR, 0.095; 95% CI [0.011-0.822]; p=0.008), sepsis (OR, 0.071; 95% CI [0.015-0.339]; p=0.009), low education level (OR, 2.905; 95% CI [0.969-8.710]; p<0.001), and anxiety and depression at 6 months (OR, 1.418; 95% CI [0.996-2.019]; p=0.004). Conclusions: In conclusion, the return to work of patients with severe acute pancreatitis needs to be improved. Chronic diseases, sepsis, low level of education and higher degree of anxiety and depression at 6 months were important factors leading to their failure to return to work.

[Effect of CD8+ CD28- T Cells on Acute Graft-Versus-Host Disease after Haploidentical Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To investigate the effect of CD8+ CD28- T cells on acute graft-versus-host disease(aGVHD) after haploidentical hematopoietic stem cell transplantation(haplo-HSCT). METHODS: The relationship between absolute count of CD8+ CD28- T cells and aGVHD in 60 patients with malignant hematological diseases was retrospectively analyzed after haplo-HSCT, and the differences in the incidence rate of chronic graft-versus host disease(cGVHD), infection and prognosis between different CD8+ CD28- T absolute cells count groups were compared. RESULTS: aGVHD occurred in 40 of 60 patients after haplo-HSCT, with an incidence rate of 66.67%. The median occurrence time of aGVHD was 32.5(20-100) days. At 30 days after the transplantation, the absolute count of CD8+ CD28- T cells of aGVHD group was significantly lower than that of non-aGVHD group (P =0.03). Thus the absolute count of CD8+ CD28- T cells at 30 days after transplantation can be used to predict the occurrence of aGVHD to some extent. At 30 days after transplantation, the incidence rate of aGVHD in the low cell count group (CD8+ CD28- T cells absolute count < 0.06/µl) was significantly higher than that in the high cell count group (CD8+ CD28- T cells absolute count ≥0.06/µl,P =0.011). Multivariate Cox regression analysis further confirmed that the absolute count of CD8+ CD28-T cells at 30 days after transplantation was an independent risk factor for aGVHD, and the risk of aGVHD in the low cell count group was 2.222 times higher than that in the high cell count group (P =0.015). The incidence of cGVHD, fungal infection, EBV infection and CMV infection were not significantly different between the two groups with different CD8+ CD28- T cells absolute count. The overall survival, non-recurrent mortality and relapse rates were not significantly different between different CD8+ CD28- T cells absolute count groups. CONCLUSION: Patients with delayed CD8+ CD28- T cells reconstitution after haplo-HSCT are more likely to develop aGVHD, and the absolute count of CD8+ CD28- T cells can be used to predict the incidence of aGVHD to some extent. The absolute count of CD8+ CD28- T cells after haplo-HSCT was not associated with cGVHD, fungal infection, EBV infection, and CMV infection, and was also not significantly associated with the prognosis after transplantation.

Microstrip isoelectric focusing with deep learning for simultaneous screening of diabetes, anemia, and thalassemia.

BACKGROUND: Hemoglobin (Hb) is an important protein in red blood cells and a crucial diagnostic indicator of diseases, e.g., diabetes, thalassemia, and anemia. However, there is a rare report on methods for the simultaneous screening of diabetes, anemia, and thalassemia. Isoelectric focusing (IEF) is a common separative tool for the separation and analysis of Hb. However, the current analysis of IEF images is time-consuming and cannot be used for simultaneous screening. Therefore, an artificial intelligence (AI) of IEF image recognition is desirable for accurate, sensitive, and low-cost screening. RESULTS: Herein, we proposed a novel comprehensive method based on microstrip isoelectric focusing (mIEF) for detecting the relative content of Hb species. There was a good coincidence between the quantitation of Hb via a conventional automated hematology analyzer and the one via mIEF with R2 = 0.9898. Nevertheless, our results showed that the accuracy of disease diagnosis based on the quantification of Hb species alone is as low as 69.33 %, especially for the simultaneous screening of multiple diseases of diabetes, anemia, alpha-thalassemia, and beta-thalassemia. Therefore, we introduced a ResNet1D-based diagnosis model for the improvement of screening accuracy of multiple diseases. The results showed that the proposed model could achieve a high accuracy of more than 90 % and a good sensitivity of more than 96 % for each disease, indicating the overwhelming advantage of the mIEF method combined with deep learning in contrast to the pure mIEF method. SIGNIFICANCE: Overall, the presented method of mIEF with deep learning enabled, for the first time, the absolute quantitative detection of Hb, relative quantitation of Hb species, and simultaneous screening of diabetes, anemia, alpha-thalassemia, and beta-thalassemia. The AI-based diagnosis assistant system combined with mIEF, we believe, will help doctors and specialists perform fast and precise disease screening in the future.