Background:
Gastric cancer (GC) is a malignant tumor originated from gastric mucosa epithelium. It is the third leading cause of cancer mortality in China. The early symptoms are not obvious. When it ...is discovered, it has developed to the advanced stage, and the prognosis is poor. In order to screen for potential genes for GC development, this study obtained GSE118916 and GSE109476 from the gene expression omnibus (GEO) database for bioinformatics analysis.
Methods:
First, GEO2R was used to identify differentially expressed genes (DEG) and the functional annotation of DEGs was performed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The Search Tool for the Retrieval of Interacting Genes (STRING) tool was used to construct protein-protein interaction (PPI) network and the most important modules and hub genes were mined. Real time quantitative polymerase chain reaction assay was performed to verify the expression level of hub genes.
Results:
A total of 139 DEGs were identified. The functional changes of DEGs are mainly concentrated in the cytoskeleton, extracellular matrix and collagen synthesis. Eleven genes were identified as core genes. Bioinformatics analysis shows that the core genes are mainly enriched in many processes related to cell adhesion and collagen.
Conclusion:
In summary, the DEGs and hub genes found in this study may be potential diagnostic and therapeutic targets.
Prediction and early diagnosis of Parkinson's disease (PD) and Parkinson's disease with depression (PDD) are essential for the clinical management of PD.
The present study aimed to develop a plasma ...Family with sequence similarity 19, member A5 (FAM19A5) and MRI-based radiomics nomogram to predict PD and PDD.
The study involved 176 PD patients and 181 healthy controls (HC). Sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure FAM19A5 concentration in the plasma samples collected from all participants. For enrolled subjects, MRI data were collected from 164 individuals (82 in the PD group and 82 in the HC group). The bilateral amygdala, head of the caudate nucleus, putamen, and substantia nigra, and red nucleus were manually labeled on the MR images. Radiomics features of the labeled regions were extracted. Further, machine learning methods were applied to shrink the feature size and build a predictive radiomics signature. The resulting radiomics signature was combined with plasma FAM19A5 concentration and other risk factors to establish logistic regression models for the prediction of PD and PDD.
The plasma FAM19A5 levels (2.456 ± 0.517) were recorded to be significantly higher in the PD group as compared to the HC group (2.23 ± 0.457) (
< 0.001). Importantly, the plasma FAM19A5 levels were also significantly higher in the PDD subgroup (2.577 ± 0.408) as compared to the non-depressive subgroup (2.406 ± 0.549) (
= 0.045 < 0.05). The model based on the combination of plasma FAM19A5 and radiomics signature showed excellent predictive validity for PD and PDD, with AUCs of 0.913 (95% CI: 0.861-0.955) and 0.937 (95% CI: 0.845-0.970), respectively.
Altogether, the present study reported the development of nomograms incorporating radiomics signature, plasma FAM19A5, and clinical risk factors, which might serve as potential tools for early prediction of PD and PDD in clinical settings.
Phosphatidylethanolamine (PE) is considered to be one of the pivotal lipids for normal cellular function as well as disease initiation and progression. In this study, a simple, efficient, reliable, ...and inexpensive method for the qualitative analysis and relative quantification of PE, based on acetone stable isotope derivatization combined with double neutral loss scan-shotgun electrospray ionization tandem-quadrupole mass spectrometry analysis (ASID-DNLS-Shotgun ESI-MS/MS), was developed. The ASID method led to alkylation of the primary amino groups of PE with an isopropyl moiety. The use of acetone (d0-acetone) and deuterium-labeled acetone (d6-acetone) introduced a 6 Da mass shift that was ideally suited for relative quantitative analysis, and enhanced sensitivity for mass analysis. The DNLS model was introduced to simultaneously analyze the differential derivatized PEs by shotgun ESI-MS/MS with high selectivity and accuracy. The reaction specificity, labeling efficiency, and linearity of the ASID method were thoroughly evaluated in this study. Its excellent applicability was validated by qualitative and relative quantitative analysis of PE species presented in liver samples from rats fed different diets. Using the ASID-DNLS-Shotgun ESI-MS/MS method, 45 PE species from rat livers have been identified and quantified in an efficient manner. The level of total PEs tended to decrease in the livers of rats on high fat diets compared with controls. The levels of PE 32:1, 34:3, 34:2, 36:3, 36:2, 42:10, plasmalogen PE 36:1 and lyso PE 22:6 were significantly reduced, while levels of PE 36:1 and lyso PE 16:0 increased.
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•A novel isotope reagent acetone was explored for the derivatization of PEs.•The labeling reaction was carried out under mild conditions with high specificity.•Enhanced detection sensitivity of PEs was achieved after derivatization.•The ASID-DNLS-Shotgun MS/MS method was used to relative quantification of PEs.
Tobacco smoke is a common global environmental pollutant. Maternal tobacco smoke/nicotine exposure has long-term toxic effects on immune organs. We previously found that prenatal nicotine exposure ...(PNE)-induced programmed immune diseases caused by fetal thymic hypoplasia, but the mechanism still unknown. Autophagy has important functions in maintaining thymopoiesis, whether autophagy was involved in PNE-inhibited fetal thymocytes development is also obscure. Therefore, this study aimed to investigate how nicotine changed the development of fetal thymocytes from the perspective of autophagy in vivo and in vitro. PNE model was established by 3 mg/kg nicotine administration in Balb/c mice from gestational day 9 to 18. The results showed that PNE reduced the percentage and absolute number of CD69−CD4+SP cells, suggesting a block of fetal thymocytes mature. PNE promoted autophagosome formation, autophagy related proteins (Beclin1, LC3I/II) expression, and upregulated α7 nAChR as well as AMPK phosphorylation in fetal thymus. Moreover, PNE promoted Bcl10 degradation via autophagy-mediated proteolysis and inhibited p65 activation, blocking the transition of thymocytes between the DP to SP stage. Further, primary thymocytes were treated with nicotine in vitro and showed induced autophagy in a dose- and time-dependent manner. In addition, nicotine-inhibited CD69−CD4+SP cells and the Bcl10/p-p65 pathway have been reversed by an autophagy inhibitor. The α7 nAChR specific antagonist abrogated nicotine-induced AMPK phosphorylation and autophagy initiation. In conclusion, our findings showed that PNE repressed the Bcl10/p-p65 development pathway of CD4+SP cells by triggering autophagy, and illuminated the developmental origin mechanism of programmed immune diseases in PNE offspring.
•PNE blocked the development and emigration of CD4+SP cells in fetal thymus.•Autophagy mediated the inhibition of thymocytes development in PNE fetus.•PNE triggered autophagy via α7 nAChR/AMPK pathway in fetal thymocytes.•PNE promoted Bcl10 degradation mediated by p62 and inhibited p65 activation.
Hand‐in‐hand or head‐to‐head: A novel naphthalimide derivative is successfully designed and synthesized, which can self‐assemble to produce hydrogels. When injecting this compound into CB8 solution, ...the nanovesicles are obtained with a narrow size distribution. The cytotoxicity assay confirms that doxorubicin‐loaded nanocarriers show therapeutic effects to cancer cells.
Abstract
Background
Intrahepatic cholestasis of pregnancy (ICP) is a common gestational complication characterized by pruritus and elevated bile acids, usually occurring in the third trimester when ...the serum estrogen and progesterone levels are highest. Hyperandrogenism during pregnancy is a pathological state that is mostly induced by polycystic ovary syndrome (PCOS) but rarely by concomitant androgen-secreting ovarian tumours. To date, no correlation has been drawn between ICP and hyperandrogenism.
Case presentation
Here, we present a rare case of early-onset severe ICP in a PCOS patient conceived via in vitro fertilization-embryo transfer, with worsening hirsutism and acne due to high levels of testosterone and dehydroepiandrosterone sulphate, both of which were produced by a fast-growing ovarian Sertoli–Leydig cell tumour. Her serum estradiol was also very high, which was speculated to be converted from the circulating androgens by the placenta. She had preterm premature rupture of membranes and delivered at 30 weeks, followed by a rapid remission of ICP as her serum estradiol dropped. However, the excessive androgens did not retreat until the large ovarian tumour was surgically removed.
Conclusion
This unusual case highlights the concurrence of original hyperandrogenism and subsequent hyperestrogenism during pregnancy and the resultant confounding manifestations. Obstetricians should be aware of the potential association between androgen excess and ICP via placental aromatization.
To evaluate the safety and efficacy of interventional therapy (iodine-125
I seed strand and portal vein stent PVS implantation plus transarterial chemoembolization TACE) combined with systemic ...therapy (lenvatinib plus anti-PD-1 antibody) as first-line treatment for hepatocellular carcinoma (HCC) patients with Vp4 portal vein tumor thrombus (PVTT).
From December 2018 to October 2021, 87 HCC patients with Vp4 PVTT were included in this single-center retrospective study. Forty-seven patients underwent interventional therapy combined with lenvatinib and anti-PD-1 antibody (group A), while 40 cases underwent interventional therapy combined with lenvatinib only (group B). Overall response rate (ORR), stent occlusion rates (SOR), median overall survival (OS), median progression-free survival (PFS) and median stent patency time (SPT) were compared between the 2 groups.
The mean intended dose (r = 10 mm; z = 0; 240 days) was 64.9 ± 1.0 Gy and 64.5 ± 1.1 Gy in group A and B, respectively (
= 0.133). ORR and SOR were significantly different between group A and B (ORR, 55.3% vs 17.5%,
< 0.001; SOR, 12.8% vs 35.0%,
= 0.014). In the propensity-score matching (PSM) cohort, the median OS, median PFS and median SPT were significantly longer in group A compared with group B (32 PSM pairs; OS, 17.7 ± 1.7 vs 12.0 ± 0.8 months,
= 0.010; PFS, 17.0 ± 4.3 vs 8.0 ± 0.7 months,
< 0.001; SPT, not-reached vs 12.5 ± 1.1 months,
= 0.028).
This interventional therapy combined with lenvatinib and anti-PD-1 antibody is safe and effective for HCC patients with Vp4 PVTT.
Purpose
Persistent acute kidney injury (AKI) has been shown to be closely associated with poor prognosis in critical patients. Recent studies have shown that procalcitonin (PCT) is valuable for the ...early prediction of AKI in critically patients. Our aim was to determine whether PCT and its kinetic changes could predict the occurrence of persistent AKI in critical patients.
Methods
This is a prospective observational study. The definition of AKI was based on the Kidney Disease: Improving Global Outcomes criteria. Persistent AKI was defined as renal function that does not return to baseline serum creatinine levels within 48 h. Blood samples were obtained at the onset of AKI and two subsequent days of hospital stay. 24‐h PCT change (ΔPCT‐24 h) was defined as 24 h PCT minus baseline PCT (day 0).
Results
A total of 91 critical patients with AKI were included in this study. The persistent AKI group had a stepwise increase in PCT concentration. ΔPCT‐24 h was higher in the persistent AKI group (p < .01). Logistic regression analysis showed that ΔPCT‐24 h (p = .04) was independent predictors of persistent AKI. The receiver operating characteristic curves showed that area under the curve of ΔPCT‐24 h was 0.84 (p < .01), and the cut‐off value for PCT to predict persistent AKI was 0.56 ng/ml.
Conclusion
Our study showed that the observation of kinetic changes in PCT is more significant for the early prediction of persistent AKI than the index of PCT at a single time point. ΔPCT‐24 h is a good predictor of persistent AKI in critical patients.
SUMMARY AT A GLANCE
Kinetic changes of serum procalcitonin within the first 24 h of AKI could predict persistent AKI more than spot serum procalcitonin taken at a single time point in critically ill patients.
Intratumoral immune status influences tumor therapeutic response, but it remains largely unclear how the status determines therapies for patients with intrahepatic cholangiocarcinoma. Here, we ...examine the single-cell transcriptional and TCR profiles of 18 tumor tissues pre- and post- therapy of gemcitabine plus oxaliplatin, in combination with lenvatinib and anti-PD1 antibody for intrahepatic cholangiocarcinoma. We find that high CD8 GZMB
and CD8 proliferating proportions and a low Macro CD5L
proportion predict good response to the therapy. In patients with a poor response, the CD8 GZMB
and CD8 proliferating proportions are increased, but the CD8 GZMK
proportion is decreased after the therapy. Transition of CD8 proliferating and CD8 GZMB
to CD8 GZMK
facilitates good response to the therapy, while Macro CD5L
-CD8 GZMB
crosstalk impairs the response by increasing CTLA4 in CD8 GZMB
. Anti-CTLA4 antibody reverses resistance of the therapy in intrahepatic cholangiocarcinoma. Our data provide a resource for predicting response of the combination therapy and highlight the importance of CD8
T-cell status conversion and exhaustion induced by Macro CD5L
in influencing the response, suggesting future avenues for cancer treatment optimization.
To evaluate the safety and efficacy of microwave (MW) ablation combined with transarterial chemoembolization in a single stage for the treatment of large (≥ 5 cm) hepatocellular carcinoma (HCC).
From ...March 2013 to January 2015, 66 patients (54 men and 12 women; mean age, 54 y; range, 29-83 y) with 72 large HCC lesions were included in this study. Eighteen (27.3%) had Barcelona Clinic Liver Cancer class B disease, and 48 (72.7%) had class C disease. Seventy-nine percent of patients (n = 52) had hepatitis B virus infection. The average tumor size was 9.0 cm ± 3.9, ranging from 5 to 19 cm. MW ablation was performed under ultrasound guidance, immediately followed by chemoembolization. Local tumor response, progression-free survival (PFS), and overall survival (OS) were assessed.
The technique was successfully performed in all patients. Complete response (CR) was achieved in 28 cases (42.4%), and partial response (PR) was achieved in 34 cases (51.5%) at 1 month after the procedure. The objective response rate (ie, CR plus PR) was 93.9%. Median PFS and OS times were 9 months and 21 months, respectively. The 6-, 12-, and 18-month OS rates were 93.9%, 85.3%, and 66.6%, respectively. Hemorrhage was detected in three patients and arteriovenous fistula in two patients after MW ablation; all were promptly treated with embolization. There were no liver abscesses, bile-duct injuries, or other major procedure-related complications.
MW ablation immediately followed by chemoembolization is safe and effective in the treatment of large HCC lesions.
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