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Potentiometric ion-selective electrodes (ISEs), which rely on selective and lipophilic ionophores, are commonly employed in clinical diagnostics. However, there are very limited specific ionophores for the detection of creatinine, a critical biomarker for renal function assessment. In the present research, we designed and synthesized an endo-functionalized cage, which is able to selectively bind the creatininium cation (K a = 8.6 × 105 M-1) through the formation of multiple C-Hâ¯O and N-Hâ¯N hydrogen bonds and cationâ¯π interactions. ISEs prepared with this host show a Nernstian response to creatinine and exhibit excellent selectivity and a low detection limit of 0.95 µM. In addition, the creatinine levels in urine or plasma samples determined by our sensor are consistent with those analyzed using enzymatic assay on a Cobas c702. The method is simple, fast and accurate, and amenable to clinical detection of creatinine levels.
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BACKGROUND: Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide. Neoadjuvant chemoradiotherapy (nCRT) is standard for locally advanced rectal cancer (LARC). Except for pathological examination after resection, it is not known exactly whether LARC patients have achieved pathological complete response (pCR) before surgery. To date, there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes. AIM: To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC. METHODS: Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed. Patients were categorized into pCR and non-pCR groups. Univariate analysis (using the χ 2 test or Fisher's exact test) and logistic multivariate regression analysis were used to study clinical predictors affecting pCR. The 5-year disease-free survival (DFS) and overall survival (OS) rates were calculated using Kaplan-Meier analysis, and differences in survival curves were assessed with the log-rank test. RESULTS: Univariate analysis showed that pretreatment carcinoembryonic antigen (CEA) level, lymphocyte-monocyte ratio (LMR), time interval between neoadjuvant therapy completion and total mesorectal excision, and tumor size were correlated with pCR. Multivariate results showed that CEA ≤ 5 ng/mL (P = 0.039), LMR > 2.73 (P = 0.023), and time interval > 10 wk (P = 0.039) were independent predictors for pCR. Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates (94.7% vs 59.7%, P = 0.002) and 5-year OS rates (95.8% vs 80.1%, P = 0.019) compared to the non-pCR group. Tumor deposits (TDs) were significantly correlated with shorter DFS (P = 0.002) and OS (P < 0.001). CONCLUSION: Pretreatment CEA, LMR, and time interval contribute to predicting nCRT efficacy in LARC patients. Achieving pCR demonstrates longer DFS and OS. TDs correlate with poor prognosis.
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OBJECTIVES: To study chest computed tomography (CT) manifestations in neonates with chronic granulomatous disease (CGD) to provide clues for early diagnosis of this disease. METHODS: A retrospective analysis was conducted on the clinical data and chest CT scan results of neonates diagnosed with CGD from January 2015 to December 2022 at Anhui Provincial Children's Hospital. RESULTS: Nine neonates with CGD were included, with eight presenting respiratory symptoms as the initial sign. Chest CT findings included: consolidation in all 9 cases; nodules in all 9 cases, characterized by multiple, variably sized scattered nodules in both lungs; masses in 4 cases; cavities in 3 cases; abscesses in 6 cases; bronchial stenosis in 2 cases; pleural effusion, interstitial changes, and mediastinal lymphadenopathy each in 1 case. CT enhancement scans showed nodules and masses with uneven or ring-shaped enhancement; no signs of pulmonary emphysema, lung calcification, halo signs, crescent signs, bronchiectasis, or scar lesions were observed. There was no evidence of rib or vertebral bone destruction. Fungal infections were present in 8 of the 9 cases, including 6 with Aspergillus infections; three of these involved mixed infections with Aspergillus, with masses most commonly associated with mixed Aspergillus infections (3/4). CONCLUSIONS: The primary manifestations of neonatal CGD on chest CT are consolidation, nodules, and/or masses, with Aspergillus as a common pathogen. These features can serve as early diagnostic clues for neonatal CGD.
Subject(s)
Granulomatous Disease, Chronic , Tomography, X-Ray Computed , Humans , Granulomatous Disease, Chronic/diagnostic imaging , Infant, Newborn , Male , Female , Retrospective Studies , Thorax/diagnostic imagingABSTRACT
Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer, accounting for approximately 90% of liver cancer cases. It currently ranks as the fifth most prevalent cancer worldwide and represents the third leading cause of cancer-related mortality. As a malignant disease with surgical resection and ablative therapy being the sole curative options available, it is disheartening that most HCC patients who undergo liver resection experience relapse within five years. Microvascular invasion (MVI), defined as the presence of micrometastatic HCC emboli within liver vessels, serves as an important histopathological feature and indicative factor for both disease-free survival and overall survival in HCC patients. Therefore, achieving accurate preoperative noninvasive prediction of MVI holds vital significance in selecting appropriate clinical treatments and improving patient prognosis. Currently, there are no universally recognized criteria for preoperative diagnosis of MVI in clinical practice. Consequently, extensive research efforts have been directed towards preoperative imaging prediction of MVI to address this problem and the relative research progresses were reviewed in this article to summarize its current limitations and future research prospects.
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Objective: This trial was conducted to explore the impact of different wilting time of Italian ryegrass in the field on the dynamics in nutritional quality and fermentation of its silage. Methods: The harvested Italian ryegrass was directly wilted in the field for 0 day (W0), 1day (W1), 2 days (W2) and 3 days(W3), respectively, and tedded every 6 hours. And the preserved Italian ryegrass was sampled at 1, 2, 3, 5, 10, 20, 30, and 45 days after ensiling and three replicates per treatment. Results: With the extension of wilting, the DM content and pH value of wilted IRG gradually increased (p<0.05). There was a downward trend in; NDF (neutral detergent fiber), ADF (acid detergent fiber) and HEM (hemicellulose) with the increase of wilting time, but only W2 and W3 were significantly different from W0 (p<0.05). CP (crude protein), IVDMD (in vitro dry matter digestibility), TDN (total digestible nutrients) and RFV (relative feed value) decreased significantly with the increase of wilting time (p<0.05), except for W1. After 45 days of ensiling, W1 had the highest CP, TDN, and the lowest ADF and NDF. During ensiling, the increase of acetic acid and the decrease of WSC in W0 and W1 were similar, but the accumulation rate of lactic acid in W0 was faster than that in W1, resulting in the lowest pH value in W0. After 5 days of ensiling, the ratio of lactic acid to acetic acid in W1 stabilized at around 3:1, while W0 kept changing. Conclusion: Italian ryegrass that wilted in the field for 1 day effectively improved the dynamic changes in CP, TDN, ADF and NDF and fermentation quality of silage. Therefore, in practice, W1 was more recommended in production of IRG silage.
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Objective: In this study, we explored the effect of fruit and vegetable waste addition on the quality of corn stalk silage. Method: Corn stalks were ensiled 20 days after ear harvesting and mixed with fruit and vegetable waste (FVW) consisting of apple, orange, broccoli, and Chinese cabbage waste as 3% of fresh matter (FM). Fruit waste consisted of solid residue obtained after juicing, and vegetable waste was collected from farms and cut into small pieces (2-3cm). The materials were stored anaerobically in 20-L silo buckets and opened after 60 days of fermentation. Results: There were significant differences in dry matter (DM), acid detergent fiber (ADF), neutral detergent fiber (NDF), total digestible nutrient (TDN), and relative feed value (RFV) levels in FVW derived from all tested raw materials (P < 0.05). Corn stalk mixed with orange waste (CSOW) had the highest DM content (28.77%), lowest ADF and NDF content (47.78% and 26.62% of DM, respectively), and highest TDN and RFV content (69.21 and 133, respectively). After 60 days, there were significant differences in all chemical parameters examined (P < 0.05). Corn stalk mixed with broccoli waste (CSBW) had the lowest DM loss (2.23%), and the CSOW group had the lowest NDF and ADF content and highest in vitro DM digestibility. CSBW had the lowest pH and ammonia nitrogen content, but the highest lactic acid/acetic acid ratio among the treatment groups. CSOW had the highest lactic acid content (2.27% of DM). The microbial contents of each group differed only in lactic acid bacteria counts before and after ensiling, showing a slight increase (P > 0.05) and significant decreases in yeast and mold counts (P < 0.05) after ensiling. Conclusion: These findings confirmed that mixing various FVW materials, particularly orange waste, with corn stalks improved the nutritional value of silage. Adding broccoli waste resulted in better fermentation quality than the addition of other FVW materials.
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The all-fused-ring acceptor (AFRA) is a success for nonfullerene materials and has attracted considerable attention as its high optical and chemical stability expected to reduce energy loss, and power conversion efficiency (PCE) approaching 15% in constructed all-small-molecule organic solar cells (OSCs). Herein, the intrinsic role of the structure of AFRA F13 and the reason for its high PCE were revealed by comparison with those of typical fused acceptors IDT-IC and Y6. An increased degree of conjugation in F13 leads to broader and red-shifted absorption peaks, facilitating enhancement of the short-circuit current. Multiple charge-transfer mechanisms are mainly attributed to the higher Frenkel exciton (FE) state due to the multiple transition ways for acceptors in the C1-CN:F13 system. The increased number of atoms contributing to the charge-transfer (CT) state facilitated the existence of more superior stacking patterns with easy formation of CT and FE/CT states and a high charge separation rate. It was found using the AFRA is an effective strategy to enhance end-group stacking, enhancing the borrowing of oscillator strength to promote multiple CT mechanisms in the complexes, explaining the high performance of this OSC device. This work is promising to guide designing an efficient AFRA in the future.
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OBJECTIVE: This study aimed to investigate the feasibility of using dual-layer spectral CT multi-parameter feature to predict microvascular invasion of hepatocellular carcinoma. METHODS: This retrospective study enrolled 50 HCC patients who underwent multiphase contrast-enhanced spectral CT studies preoperatively. Combined clinical data, radiological features with spectral CT quantitative parameter were constructed to predict MVI. ROC was applied to identify potential predictors of MVI. The CT values obtained by simulating the conventional CT scans with 70âkeV images were compared with those obtained with 40âkeV images. RESULTS: 50 hepatocellular carcinomas were detected with 30 lesions (Group A) with microvascular invasion and 20 (Group B) without. There were significant differences in AFP,tumer size, IC, NIC,slope and effective atomic number in AP and ICrr in VP between Group A ((1000(10.875,1000),4.360±0.3105, 1.7750 (1.5350,1.8825) mg/ml, 0.1785 (0.1621,0.2124), 2.0362±0.2108,8.0960±0.1043,0.2830±0.0777) and Group B (4.750(3.325,20.425),3.190±0.2979,1.4700 (1.4500,1.5775) mg/ml, 0.1441 (0.1373,0.1490),1.8601±0.1595, 7.8105±0.7830 and 0.2228±0.0612) (all pâ<â0.05). Using 0.1586 as the threshold for NIC, one could obtain an area-under-curve (AUC) of 0.875 in ROC to differentiate between tumours with and without microvascular invasion. AUC was 0.625 with CT value at 70âkeV and improved to 0.843 at 40âkeV. CONCLUSION: Dual-layer spectral CT provides additional quantitative parameters than conventional CT to enhance the differentiation between hepatocellular carcinoma with and without microvascular invasion. Especially, the normalized iodine concentration (NIC) in arterial phase has the greatest potential application value in determining whether microvascular invasion exists, and can offer an important reference for clinical treatment plan and prognosis assessment.
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Atherosclerosis is a significant risk factor for developing cardiovascular disease and a leading cause of death worldwide. The occurrence of atherosclerosis is closely related to factors such as endothelial injury, lipid deposition, immunity, and inflammation. Conventional statins, currently used in atherosclerosis treatment, have numerous adverse side effects that limit their clinical utility, prompting the urgent need to identify safer and more effective therapeutic alternatives. Growing evidence indicates the significant potential of Chinese herbs in atherosclerosis treatment. Herbal monomer components, such as natural flavonoid compounds extracted from herbs like Coptis chinensis and Panax notoginseng, have been utilized for their lipid-lowering and inflammation-inhibiting effects in atherosclerosis treatment. These herbs can be used as single components in treating diseases and with other Chinese medicines to form herbal combinations. This approach targets the disease mechanism in multiple ways, enhancing the therapeutic effects. Thus, this review examines the roles of Chinese herbal medicine monomers and Chinese herbal compounds in inhibiting atherosclerosis, including regulating lipids, improving endothelial function, reducing oxidative stress, regulating inflammation and the immune response, and apoptosis. By highlighting these roles, our study offers new perspectives on atherosclerosis treatment with Chinese herbs and is anticipated to contribute to advancements in related research fields.
Subject(s)
Atherosclerosis , Drugs, Chinese Herbal , Oxidative Stress , Atherosclerosis/drug therapy , Atherosclerosis/immunology , Atherosclerosis/prevention & control , Humans , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Oxidative Stress/drug effects , Immunomodulation , Apoptosis/drug effects , Phytotherapy , Inflammation/drug therapy , Panax notoginseng/chemistry , Endothelium, Vascular/drug effects , Animals , Coptis/chemistry , FlavonoidsABSTRACT
Interferon-induced transmembrane 3 (IFITM3) is a membrane-associated protein that exhibits antiviral activities against a wide range of viruses through interactions with other cellular and viral proteins. However, knowledge of the mechanisms of IFITM3 in Porcine deltacoronavirus (PDCoV) infection has been lacking. In this study, we demonstrate that IFN-α treatment induces the upregulation of IFITM3 activity and thus attenuates PDCoV infection. PDCoV replication is inhibited in a dose-dependent manner by IFITM3 overexpression. To clarify the novel roles of IFITM3 during PDCoV infection, proteins that interact with IFITM3 were screened by TAP/MS in an ST cell line stably expressing IFITM3 via a lentivirus. We identified known and novel candidate IFITM3-binding proteins and analyzed the protein complexes using GO annotation, KEGG pathway analysis, and protein interaction network analysis. A total of 362 cellular proteins associate with IFITM3 during the first 24â¯h post-infection. Of these proteins, the relationship between IFITM3 and Rab9a was evaluated by immunofluorescence colocalization analysis using confocal microscopy. IFITM3 partially colocalized with Rab9a and Rab9a exhibited enhanced colocalization following PDCoV infection. We also demonstrated that IFITM3 interacts specifically with Rab9a. Our results considerably expand the protein networks of IFITM3, suggesting that IFITM3 participates in multiple cellular processes during PDCoV infection.
Subject(s)
Membrane Proteins , Protein Binding , Membrane Proteins/metabolism , Animals , Swine , Coronavirus/metabolism , Protein Interaction Maps , Chromatography, Affinity/methods , Humans , Virus Replication , RNA-Binding Proteins/metabolism , Cell Line , Tandem Mass Spectrometry , Interferon-alpha/metabolism , Interferon-alpha/pharmacologyABSTRACT
The interactions between ether naphthotube and a series of dication guests in organic solution were investigated. It was found that ether naphthotube formed stable host-guest complexes selectively with these guests in a 1 : 1 stoichiometric ratio with association constants ranging from 102 to 106â M-1, which were confirmed by 1H-NMR spectra and ITC experiments. The host-guest interactions are driven by enthalpy change as the entropic factors are unfavorable. Positive correlations between ΔH and ΔS have been observed in the host-guest complexes. Furthermore, the para-substitution of the guests can significantly affect the binding affinities through a combination of field/inductive and resonance effects by following a linear free energy relationship. Based on the host-guest complexes composed of ether naphthotube and organic cations, two interlocked [2]rotaxanes were prepared by cationization reaction and Huisgen cycloaddition between the cations and the stopper components. The ether naphthotube-based host-guest complexes are useful for creating sophisticated interlocked molecules.
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Objective: The study established a nomogram based on quantitative parameters of spectral computed tomography (CT) and clinical characteristics, aiming to evaluate its predictive value for preoperative lymphovascular invasion (LVI) in gastric cancer (GC). Methods: From December 2019 to December 2021, 171 patients with pathologically confirmed GC were retrospectively collected with corresponding clinical data and spectral CT quantitative data. Patients were divided into LVI-positive and LVI-negative groups based on their pathological results. The univariate and multivariate logistic regression analyses were used to identify the risk factors and construct a nomogram. The calibration curve and receiver operating characteristic (ROC) curve were adopted to evaluate the predictive accuracy of nomogram. Results: Four clinical characteristics or spectral CT quantitative parameters, including Borrmann classification (P = 0.039), CA724 (P = 0.007), tumor thickness (P = 0.031), and iodine concentration in the venous phase (VIC) (P = 0.004) were identified as independent factors for LVI in GC patients. The nomogram was established based on the four factors, which had a potent predictive accuracy in the training, internal validation and external validation cohorts, with the area under the ROC curve (AUC) of 0.864 (95% CI, 0.798-0.930), 0.964 (95% CI, 0.903-1.000) and 0.877 (95% CI, 0.759-0.996), respectively. Conclusion: This study constructed a comprehensive nomogram consisting spectral CT quantitative parameters and clinical characteristics of GC, which exhibited a robust efficiency in predicting LVI in GC patients.
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OBJECTIVE: To confirm the direct regulatory effect of WTAP-mediated RNA m6A modification on the KDM4B gene in t (8;21) acute myeloid leukemia (AML) cells through MeRIP combined with reverse transcription real-time quantitative PCR (RT-qPCR) technology. METHODS: The lentivirus-mediated shRNA target WTAP or KDM4B gene was used to transfect the t (8;21) AML cell lines: Kasumi-1 and SKNO-1, and cells transfected with randomly shuffled shRNA as the control. Using the Ultrapure RNA Extraction Kit (DNase I) to extract RNA. The Magna MeRIPTM m6A Kit was used to enrich methylated modified fragments, and detect the m6A methylated RNA regions by RT-qPCR, and the protein and mRNA expression levels of WTAP and KDM4B in cells were detected by Western blot and reverse transcription real-time quantitative PCR (RT-qPCR). Colony formation assays were used to detect the colony ability of cells in vitro. RESULTS: Silencing the expression of WTAP in Kasumi-1 cells, the enrichment of m6A methylation modification was significantly decreased in the 3'UTR of KDM4B mRNA(P < 0.01), and the protein(P < 0.001) and mRNA (Kasumi-1:P < 0.001; SKNO-1: P < 0.01) expression levels of KDM4B were also significantly inhibited in Kasumi-1 and SKNO-1 cells upon WTAP knockdown (all P < 0.01), accompanied by a significant decrease in the colony-forming ability of both cell lines (both P < 0.01). CONCLUSION: In t(8;21) AML cell lines, WTAP could regulate the expression of KDM4B by regulating the m6A modification of the 3'UTR of KDM4B mRNA, and silencing the expression of KDM4B could inhibit the cellular proliferation in vitro.
Subject(s)
Jumonji Domain-Containing Histone Demethylases , Leukemia, Myeloid, Acute , Humans , Jumonji Domain-Containing Histone Demethylases/genetics , Leukemia, Myeloid, Acute/genetics , Cell Line, Tumor , Methylation , RNA, Messenger/genetics , RNA, Small Interfering/geneticsABSTRACT
OBJECTIVE: To investigate the relationship between IGF2BP3 gene expression and prognosis in patients with acute myeloid leukemia (AML). METHODS: High throughput transcriptome sequencing was performed on bone marrow primary leukemia cells from 27 patients with AML in our center, the relationship between IGF2BP3 expression levels and clinical characteristics were analyzed and verify the samples from patients with newly treated AML and refractory AML. The expression level of IGF2BP3 gene were analyzed in 20 healthy subjects and 26 patients with AML. The expression of IGF2BP3 in two anthracycline-resistant cell lines (HL60/ADR, K562/ADR) was detected by RT-qPCR and Western blot, and the expression difference of IGF2BP3 was compared with that in sensitive cells (HL60, K562). The relationship between the expression level of IGF2BP3 in patients with AML and prognostic were analyzed through data analysis of 746 patients with AML, and the prognostic value of IGF2BP3 in AML was analyzed by multivariate Cox regression analysis. RESULTS: In the bone marrow primary leukemia cells of 27 AML patients in our center, the expression level of IGF2BP3 in patients with refractory AML was significantly higher than that in chemotherapy sensitive patients (P =0.0343). The expression of IGF2BP3 in leukemia patients with extramedullary infiltration (EMI) was significantly higher than that in AML patients without extramedullary infiltration (P =0.0049). Compared with healthy subjects (n=20), IGF2BP3 expression in AML patients (n=26) was higher (P =0.0009). The expression of IGF2BP3 mRNA in the anthracycline resistant cell lines (HL60/ADR, K562/ADR) was significantly higher than that in the sensitive cell lines (K562/ADR vs K562,P =0.0430; HL60/ADR vs HL60, P =0.7369). Western blot results showed that the expression of IGF2BP3 protein in mycin resistant cells was significantly higher than that in sensitive cells (P < 0.001). qPCR results showed that the expression level of IGF2BP3 mRNA in refractory AML patients was significantly higher than that in patients with chemotherapy sensitive (P =0.002). High expression of IGF2BP3 was associated with poor prognosis in AML (P < 0.05) in 3 large sample cohorts of AML patients. Univariate and multivariate prognostic analyses demonstrated that high expression of IGF2BP3 was significantly associated with shorter event-free survival (EFS, HR=1.887, P =0.024) and overall survival (OS, HR=1.619, P =0.016). CONCLUSION: The high expression of IGF2BP3 gene may be an important factor in the poor prognosis of AML, suggesting that IGF2BP3 gene may be a new molecular marker for the clinical prognosis evaluation and treatment strategy of AML.
Subject(s)
Leukemia, Myeloid, Acute , RNA-Binding Proteins , Humans , Leukemia, Myeloid, Acute/genetics , Prognosis , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Gene Expression , HL-60 Cells , K562 Cells , Drug Resistance, Neoplasm , Cell Line, TumorABSTRACT
Phthorimaea operculella is a major potato pest of global importance, early warning and detection of which are of significance. In this study, we analyzed the climate niche conservation of P. operculella during its invasion by comparing the overall climate niche from three dimensions, including the differences between native range (South America) and entire invaded region (excluding South America), the differences bwtween native range (South America) and five invaded continents (North America, Oceania, Asia, Africa, and Europe), as well as the differences between native region (South America) and an invaded region (China). We constructed ecological niche models for its native range (South America) and invaded region (China). The results showed that the climatic niche of the pest has expanded to varying degrees in different regions, indicating that the pest could well adapt to new environments during the invasion. Almost all areas of South America are suitable for P. operculella. In China, its suitable area is mainly concentrated in Shandong, Hebei, Tianjin, Beijing, Henan, Hubei, Yunnan, Guizhou, Sichuan, Hainan, northern Guangxi, southern Hunan, Anhui, Guangdong, Jiangsu, southern Shanxi, and southern Shaanxi. With increasing greenhouse gas emissions and global temperature, its suitable area will decrease at low latitude and increase gradually at high latitude. Specifically, the northern boundary will extend to Liaoning, Jilin, and the southeastern region of Inner Mongolia, while the western boundary extends to Sichuan and the southeast Qinghai-Tibet Plateau. The suitable area in the southeast Yunnan-Guizhou Plateau, Hainan Island, and the south of Yangtze River, will gradually decrease. The total suitable habitat area for P. operculella in China is projected to increase under future climate condition. From 2081 to 2100, under the three greenhouse gas emissions scenarios of ssp126, ssp370, and ssp585, the suitable area is expected to increase by 27.78, 165.54, and 140.41 hm2, respectively. Therefore, it is crucial to strengtehen vigilance and implement strict measures to prevent the further expansion of P. operculella.
Subject(s)
Ecosystem , Introduced Species , China , Animals , South America , ClimateABSTRACT
A research strategy combining transcriptome data mining and experimental verification was adopted to identify the marker genes characterizing the syndrome elements of phlegm, stasis, and deficiency in steroid-induced osteonecrosis of the femoral head(SONFH). Firstly, the common differentially expressed gene sets of SONFH with the syndromes of phlegm-stasis obstructing collaterals, vessel obstruction, and liver-kidney deficiency were obtained from the clinical transcriptomic analysis of a previous study. The differential expression trend analysis and functional gene mining were then employed to predict the candidate marker gene sets representing phlegm, stasis, and deficiency. The whole blood samples from SONFH patients, whole blood samples from SONFH rats, and affected femoral head tissue samples were collected for qPCR, which aimed to determine the expression levels of the candidate marker genes mentioned above. Furthermore, the receiver operating characteristic curve(ROC) was established to objectively evaluate the syndrome differentiation effectiveness of the candidate marker genes mentioned above. The transcriptome data analysis results showed that the candidate marker genes for phlegm was ELOVL fatty acid elongase 6(ELOVL6), and those for stasis were ankyrin 1(ANK1), glycophorin A/B(GYPA/B), and Rh-associated glycoprotein(RHAG). The candidate marker genes for deficiency were solute carrier family 2 member 1(SLC2A1) and stomatin(STOM). The qPCR results showed that compared with that in the non-SONFH group, ELOVL6 had the lowest expression level in the peripheral blood of the SONFH patients with the syndrome of phlegm-stasis obstructing collaterals(P<0.05). Compared with that in the normal control group, ELOVL6 had the lowest expression level in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 4 weeks(P<0.01), and it showed better syndrome differentiation effectiveness of rats modeled for 4 weeks(AUC=0.850, P=0.006) than at other modeling time points(8, 12, 16, and 21 weeks, AUC of 0.689, 0.766, 0.588, and 0.662, respectively). Compared with that in the non-SONFH group, the expression levels of ANK1, GYPA, and RHAG were the lowest in the peripheral blood of SONFH patients with the vessel obstruction syndrome(P<0.05). The expression levels of the three genes were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 12 weeks(P<0.05, P<0.01), and their syndrome differentiation effectiveness in the rats modeled for 12 weeks(GYPA: AUC=0.861, P=0.012; ANK1: AUC=0.855, P=0.006; RHAG: AUC=0.854, P=0.009) was superior to that for 4, 8, 16, and 21 weeks(GYPA: AUC=0.646, 0.573, 0.691, and 0.617, respectively; ANK: AUC1=0.630, 0.658, 0.657, and 0.585, respectively; RHAG: AUC=0.592, 0.511, 0.515, and 0.536, respectively). Compared with the non-SONFH group, both SLC2A1 and STOM had the lowest expression levels in the peripheral blood of patients with the syndrome of liver and kidney deficiency(P<0.05). Compared with the normal control group, their expression levels were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 21 weeks(P<0.05, except STOM in the peripheral blood of rats). Moreover, the syndrome differentiation effectiveness of SLC2A1 in the rats modeled for 21 weeks(AUC=0.806, P=0.009) was superior to that for 4, 8, 12, and 16 weeks(AUC=0.520, 0.580, 0.741, 0.774, respectively), and STOM was meaningless in syndrome differentiation. In summary, the candidate marker gene for phlegm in SONFH is ELOVL6; the candidate marker genes for stasis are GYPA, RHAG, and ANK1; the candidate marker gene for deficiency is SLC2A1. The results help to reveal the biological connotations of phlegm, stasis, and deficiency in SONFH at the genetic level.
Subject(s)
Animal Experimentation , Osteonecrosis , Vascular Diseases , Humans , Rats , Animals , Transcriptome , Femur Head , Syndrome , Steroids/adverse effectsABSTRACT
Glutathione (GSH) depletion, mitochondrial damage, and oxidative stress have been implicated in the pathogenesis of acetaminophen (APAP) hepatotoxicity. Here, we demonstrated that the expression of histone deacetylase 6 (HDAC6) is highly elevated, whereas malate dehydrogenase 1 (MDH1) is downregulated in liver tissues and AML-12 cells induced by APAP. The therapeutic benefits of LT-630, a novel HDAC6 inhibitor on APAP-induced liver injury, were also substantiated. On this basis, we demonstrated that LT-630 improved the protein expression and acetylation level of MDH1. Furthermore, after overexpression of MDH1, an upregulated NADPH/NADP+ ratio and GSH level and decreased cell apoptosis were observed in APAP-stimulated AML-12 cells. Importantly, MDH1 siRNA clearly reversed the protection of LT-630 on APAP-stimulated AML-12 cells. In conclusion, LT-630 could ameliorate liver injury by modulating MDH1-mediated oxidative stress induced by APAP.
Subject(s)
Chemical and Drug Induced Liver Injury, Chronic , Chemical and Drug Induced Liver Injury , Histone Deacetylase 6 , Leukemia, Myeloid, Acute , Animals , Humans , Mice , Acetaminophen , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury, Chronic/metabolism , Glutathione/metabolism , Histone Deacetylase 6/antagonists & inhibitors , Leukemia, Myeloid, Acute/metabolism , Liver/pathology , Mice, Inbred C57BL , Oxidative Stress/drug effectsABSTRACT
BACKGROUND: Lymphovascular invasion (LVI) and perineural invasion (PNI) are important prognostic factors for gastric cancer (GC) that indicate an increased risk of metastasis and poor outcomes. Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment decisions. However, prior models using conventional computed tomography (CT) images to predict LVI or PNI separately have had limited accuracy. Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion. We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients. AIM: To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately. METHODS: This study used a retrospective dataset involving 257 GC patients (training cohort, n = 172; validation cohort, n = 85). First, several clinical indicators, including serum tumor markers, CT-TN stages and CT-detected extramural vein invasion (CT-EMVI), were extracted, as were quantitative spectral CT parameters from the delineated tumor regions. Next, a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters. A logistic regression (LR)-based nomogram model was subsequently constructed to predict LVI/PNI status, and its performance was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: In both the training and validation cohorts, CT T3-4 stage, CT-N positive status, and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant (P < 0.05). LR analysis of the training group showed preoperative CT-T stage, CT-EMVI, single-energy CT values of 70 keV of venous phase (VP-70 keV), and the ratio of standardized iodine concentration of equilibrium phase (EP-NIC) were independent influencing factors. The AUCs of VP-70 keV and EP-NIC were 0.888 and 0.824, respectively, which were slightly greater than those of CT-T and CT-EMVI (AUC = 0.793, 0.762). The nomogram combining CT-T stage, CT-EMVI, VP-70 keV and EP-NIC yielded AUCs of 0.918 (0.866-0.954) and 0.874 (0.784-0.936) in the training and validation cohorts, which are significantly higher than using each of single independent factors (P < 0.05). CONCLUSION: The study found that using portal venous and EP spectral CT parameters allows effective preoperative detection of LVI/PNI in GC, with accuracy boosted by integrating clinical markers.
Subject(s)
Stomach Neoplasms , Humans , Retrospective Studies , Prognosis , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Tomography, X-Ray Computed/methods , Machine LearningABSTRACT
BACKGROUND: Portal vein thrombosis (PVT) is a commonthsn complication after splenectomy in patients with cirrhosis. However, the predictors of postoperative PVT are not known. AIM: To investigate the predictors of PVT after splenectomy in patient with cirrhosis. METHODS: A total of 45 patients with cirrhosis who underwent splenectomy were consecutively enrolled from January 2017 to December 2018. The incidence of PVT at 1 months, 3 months, and 12 months after splenectomy in patients with cirrhosis was observed. The hematological indicators, biochemical and coagulation parameters, and imaging features were recorded at baseline and at each observation point. The univariable, multivariable, receiver operating characteristic curve and time-dependent curve analyses were performed. RESULTS: The cumulative incidence of PVT was 40.0%, 46.6%, and 48.9% at 1 months, 3 months, and 12 months after splenectomy. Multivariable analysis showed that portal vein diameter (PVD) ≥ 14.5 mm and monthsdel end-stage liver disease (MELD) score > 10 were independent predictors of PVT at 1 months, 3 months, and 12 months after splenectomy (P < 0.05). Time-dependent curve showed that the cumulative incidence of PVT was significantly different between patients with MELD score ≤ 10 and > 10 (P < 0.05). In addition, the cumulative incidence of PVT in the PVD ≥ 14.5 mm group was significantly higher than that in the PVD < 14.5 mm group (P < 0.05). CONCLUSION: Wider PVD and MELD score > 10 were independent predictors of PVT at 1 months, 3 months, and 12 months after splenectomy in patient with cirrhosis.
ABSTRACT
OBJECTIVE: A study was conducted to quantify the performance differences of the nearinfrared spectroscopy (NIRS) calibration models developed with different degrees of hay sample preparations. METHODS: A total of 227 imported alfalfa (Medicago sativa L.) and another 360 imported timothy (Phleum pratense L.) hay samples were used to develop calibration models for nutrient value parameters such as moisture, neutral detergent fiber, acid detergent fiber, crude protein, and in vitro dry matter digestibility. Spectral data of hay samples prepared by milling into 1-mm particle size or unground were separately regressed against the wet chemistry results of the abovementioned parameters. RESULTS: The performance of the developed NIRS calibration models was evaluated based on R2, standard error, and ratio percentage deviation (RPD). The models developed with ground hay were more robust and accurate than those with unground hay based on calibration model performance indexes such as R2 (coefficient of determination), standard error, and RPD. Although the R2 of calibration models was mainly greater than 0.90 across the feed value indexes, the R2 of cross-validations was much lower. The R2 of cross-validation varies depending on feed value indexes, which ranged from 0.61 to 0.81 in alfalfa, and from 0.62 to 0.95 in timothy. Estimation of feed values in imported hay can be achievable by the calibrated NIRS. However, the NIRS calibration models must be improved by including a broader range of imported hay samples in the modeling. CONCLUSION: Although the analysis accuracy of NIRS was substantially higher when calibration models were developed with ground samples, less sample preparation will be more advantageous for achieving rapid delivery of hay sample analysis results. Therefore, further research warrants investigating the level of sample preparations compromising analysis accuracy by NIRS.