Comprehensive Analysis of the Expression and Prognosis for Lipid Metabolism-Related Genes in Hepatocellular Carcinoma.

Hao DingBackground This study aimed to screen potential key genes associated with lipid metabolism and to evaluate their expressions and prognosis values in hepatocellular carcinoma (HCC). Methods Data sets GSE6764, GSE14520, and GSE112790 were used to identify the common differentially expressed genes (DEGs). Protein-protein interaction (PPI) network was constructed by STRING database. Hub genes in PPI network were identified and subjected to functional enrichment analysis to screen lipid metabolism-related genes. The expressions of selected genes and their associations with prognosis were analyzed using UALCAN, The Human Protein Atlas, and Kaplan-Meier plotter databases. The transcriptional factor (TF)-gene regulatory network was constructed using NetworkAnalyst. Results A total of 331 common DEGs including 106 upregulated and 225 downregulated genes were identified. PPI network analysis showed that 76 genes with high degrees were identified as hub genes, among which 14 genes were lipid metabolism-related genes. PON1, CYP2C9, and SPP1 were found to be the independent prognostic markers. Key TFs with close interactions with these prognostic genes, including HINFP, SRF, YY1, and NR3C1, were identified from the TF-gene regulatory network. Conclusion This study presented evidence for the prognostic capabilities of lipid metabolism-related genes in HCC, and newly identified HINFP and NR3C1 as potential biomarkers for HCC.

Camrelizumab combined with apatinib in the treatment of patients with hepatocellular carcinoma: a real-world assessment.

Although a phase II clinical trial confirmed that camrelizumab combined with apatinib is effective in patients with hepatocellular carcinoma (HCC), we generally lack data on the results of this regimen in real-world clinical practice. In this study, the efficacy and safety of camrelizumab combined with apatinib in the treatment of patients with HCC were re-evaluated. Data from 86 patients with HCC were collected and combinatorically treated with camrelizumab and apatinib at the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China. The objective remission rate and disease control rate were 25.6% and 72.1%, respectively. The median progression-free survival was 5 months (95% CI 3.7-6.3 months), and the median overall survival time was 19.0 months (95% CI 16.9-21.1 months). The 12- and 18-month survival rates were 70.9% and 54.2%, respectively. The most common grade 3-4 adverse events were hypertension (24.4%), thrombocytopenia (16.3%), and hyperbilirubinemia (9.3%). Multivariate regression analysis showed that operation history was an independent risk factor for overall survival.

Preparation of protein-loaded nanoparticles based on poly(succinimide)-oleylamine for sustained protein release: a two-step nanoprecipitation method.

Currently, the treatment for acute disease encompasses the use of various biological drugs (BDs). However, the utilisation of BDs is limited due to their rapid clearance and non-specific accumulation in unwanted sites, resulting in a lack of therapeutic efficacy together with adverse effects. While nanoparticles are considered good candidates to resolve this problem, some available polymeric carriers for BDs were mainly designed for long-term sustained release. Thus, there is a need to explore new polymeric carriers for the acute disease phase that requires sustained release of BDs over a short period, for example for thrombolysis and infection. Poly(succinimide)-oleylamine (PSI-OA), a biocompatible polymer with a tuneable dissolution profile, represents a promising strategy for loading BDs for sustained release within a 48-h period. In this work, we developed a two-step nanoprecipitation method to load the model protein (e.g. bovine serum albumin and lipase) on PSI-OA. The characteristics of the nanoparticles were assessed based on various loading parameters, such as concentration, stirring rate, flow rate, volume ratio, dissolution and release of the protein. The optimised NPs displayed a size within 200 nm that is suitable for vasculature delivery to the target sites. These findings suggest that PSI-OA can be employed as a carrier for BDs for applications that require sustained release over a short period.

Altered interhemispheric functional connectivity in patients with comitant exotropia before and after surgery: a resting-state fMRI study.

Purpose: To assess the interhemispheric homotopic connectivity alterations in patients with comitant exotropia (CE) before and after surgery, using resting-state functional magnetic resonance imaging (rs-fMRI) with voxel-mirrored homotopic connectivity (VMHC). Methods: Thirty-four patients with CE and twenty-four well-matched healthy controls (HCs) were enrolled to undergo a preoperative rs-fMRI scan. The rs-fMRI scan was performed again in twenty-four patients 1 month after surgery. The VMHC method was applied to evaluate the group differences of interhemispheric functional connectivity. The correlations between VMHC values and clinical variables were analyzed in the patient group. Results: Compared with HCs, 34 patients with CE showed significantly increased VMHC values in occipital lobe (cuneus/superior occipital gyrus/middle occipital gyrus/calcarine), cerebellar area 8/cerebellar Crus1 area, and cerebellar Crus1 area. In CE group, VMHC in the cuneus was positively correlated with stereoacuity (r = 0.417, P = 0.014), meanwhile VMHC in the cerebellar Crus1 area was positively correlated with stereoacuity (r = 0.395, P = 0.021). One month after surgery, the 24 CE patients with follow-up showed decreased VMHC values in the cuneus and superior occipital gyrus compared with preoperative collection, meanwhile, non-significant difference compared with HCs. Conclusion: Our study revealed the interhemispheric homotopic connectivity changes of patients with CE in the occipital lobe and cerebellum before and after surgery. The findings may provide a new perspective for the neurological alterations of CE.

Assessing the effectiveness of camrelizumab plus apatinib versus sorafenib for the treatment of primary liver cancer: a single-center retrospective study.

Although the effectiveness of camrelizumab plus apatinib has been confirmed in a phase II clinical study, the efficacy of camrelizumab plus apatinib versus sorafenib for primary liver cancer (PLC) remains unverified. We retrospectively collected the data of 143 patients with PLC who received camrelizumab plus apatinib or sorafenib as the first-line treatment at The First Affiliated Hospital of Anhui Medical University from April 2018 to November 2021. Of these, 71 patients received an intravenous injection of camrelizumab 200 mg (body weight ≥ 50 kg) or 3 mg/kg (body weight < 50 kg) followed by an oral dosage of apatinib 250 mg/day every 3 weeks and 72 patients received sorafenib 400 mg orally, twice a day in 28-day cycles. The primary outcomes were overall survival and progression-free survival. The secondary outcomes were objective response rate, disease control rate, and safety. The median median progression-free survival and median overall survival with camrelizumab plus apatinib and sorafenib were 6.0 (95% confidence interval (CI) 4.2-7.8) and 3.0 months (95% CI 2.3-3.7) and 19.0 (95% CI 16.4-21.6) and 12.0 months (95% CI 8.9-15.1), respectively (death hazard ratio: 0.61, P = 0.023). Grade 3/4 treatment-related adverse events were noted in 50 (70.4%) patients in the camrelizumab plus apatinib group and 19 (26.4%) patients in the sorafenib group. Two treatment-related deaths were recorded. Clinically significant improvements were observed in overall survival and progression-free survival with camrelizumab plus apatinib versus sorafenib. Although the side effects of camrelizumab plus apatinib are relatively high, they can be controlled.

Asymmetrical Obstacles Enable Unilateral Inertial Focusing and Separation in Sinusoidal Microchannel.

Inertial microfluidics uses the intrinsic fluid inertia in confined channels to manipulate the particles and cells in a simple, high-throughput, and precise manner. Inertial focusing in a straight channel results in several equilibrium positions within the cross sections. Introducing channel curvature and adjusting the cross-sectional aspect ratio and shape can modify inertial focusing positions and can reduce the number of equilibrium positions. In this work, we introduce an innovative way to adjust the inertial focusing and reduce equilibrium positions by embedding asymmetrical obstacle microstructures. We demonstrated that asymmetrical concave obstacles could break the symmetry of original inertial focusing positions, resulting in unilateral focusing. In addition, we characterized the influence of obstacle size and 3 asymmetrical obstacle patterns on unilateral inertial focusing. Finally, we applied differential unilateral focusing on the separation of 10- and 15-µm particles and isolation of brain cancer cells (U87MG) from white blood cells (WBCs), respectively. The results indicated an excellent cancer cell recovery of 96.4% and WBC rejection ratio of 98.81%. After single processing, the purity of the cancer cells was dramatically enhanced from 1.01% to 90.13%, with an 89.24-fold enrichment. We believe that embedding asymmetric concave micro-obstacles is a new strategy to achieve unilateral inertial focusing and separation in curved channels.

Polymeric nanomaterial strategies to encapsulate and deliver biological drugs: points to consider between methods.

Biological drugs (BDs) play an increasingly irreplaceable role in treating various diseases such as cancer, and cardiovascular and neurodegenerative diseases. The market share of BDs is increasingly promising. However, the effectiveness of BDs is currently limited due to challenges in efficient administration and delivery, and issues with stability and degradation. Thus, the field is using nanotechnology to overcome these limitations. Specifically, polymeric nanomaterials are common BD carriers due to their biocompatibility and ease of synthesis. Different strategies are available for BD transportation, but the use of core-shell encapsulation is preferable for BDs. This review discusses recent articles on manufacturing methods for encapsulating BDs in polymeric materials, including emulsification, nanoprecipitation, self-encapsulation and coaxial electrospraying. The advantages and disadvantages of each method are analysed and discussed. We also explore the impact of critical synthesis parameters on BD activity, such as sonication in emulsifications. Lastly, we provide a vision of future challenges and perspectives for scale-up production and clinical translation.

Altered spontaneous brain activity in patients with comitant exotropia before and after surgery: A resting-state fMRI study.

Patients with comitant exotropia (CE) would usually develop compromised binocular vision and impaired stereoscopic depth perception, which could result in a profound decrease in quality of life. Although the deviated optic axis could be corrected surgically, the impaired stereovision and sensory eye balance may sometimes remain remnant. This study was to investigate the brain functional alterations in patients with CE before and after surgery, using resting-state functional magnetic resonance imaging (fMRI) with amplitude of low-frequency fluctuation (ALFF). Thirty-five patients with CE were recruited to undergo a preoperative fMRI scan, as well as 24 healthy controls (HCs). Twenty-four of the patients were available for rescanned fMRI one month after surgery. The ALFF method was used to evaluate the group differences of spontaneous brain activity. The correlations between ALFF values and clinical variables were analyzed in the patient group. Preoperatively, compared with HCs, 35 patients with CE showed significantly decreased ALFF values in one cluster involving bilateral calcarine sulcus, lingual gyrus and cuneus. The ALFF values in the above cluster were negatively correlated with disease duration (r = -0.379, P = 0.033). One month after surgery, 24 patients with available rescanned fMRI demonstrated increased ALFF values in one cluster located in bilateral cuneus, calcarine sulcus and lingual gyrus relative to the preoperative collection, while still reduced ALFF values in the cluster involving left calcarine sulcus and lingual gyrus compared with HCs. Our study revealed the functional changes of patients with CE in visual-associated brain areas before and after surgery. The findings may provide a new perspective for understanding the underlying pathological mechanisms of CE.

All-Trans Retinoic Acid Potentiates Antitumor Efficacy of Cisplatin by Increasing Differentiation of Cancer Stem-Like Cells in Cervical Cancer.

OBJECTIVE: All-trans retinoic acid (ATRA), a derivative of vitamin A, has been reported to exert its synergistic antitumor effect with chemotherapy in various cancer types; however, its effect in cervical cancer remains unclear. The objective of this study was to investigate the antitumor effect of ATRA with or without cisplatin and elucidate its potential mechanisms in cervical cancer cells. METHODS: Cell viability was determined by CCK-8 assay. Cell cycle and cell apoptosis were analyzed by flow cytometry. Caspase-3, cleaved caspase-3 and cell cycle-related proteins were detected by western blotting. Scratch wound-healing assay was performed to evaluate cell migration ability. The expression of CD44, a biomarker of cervical cancer stem-like cells, was determined by flow cytometry and western blotting. In addition, the activity of the Wnt signaling pathway was monitored by luciferase reporter assay and western blotting. RESULTS: Compared with cisplatin treatment alone, combined use of ATRA and cisplatin significantly inhibited cell proliferation (p<0.01) and migration (p<0.01), and induced G0/G1 phase arrest (p<0.01) and apoptosis (p<0.05) in cervical cancer Hela cells. Furthermore, ATRA treatment also effectively induced differentiation of cancer stem-like cells as represented by reduced expression of CD44 and inhibited Wnt signaling pathway activity. CONCLUSIONS: ATRA significantly enhanced the antitumor effect of cisplatin in cervical cancer cells, the mechanism of which might be attributed to its effect of inducing the differentiation of cancer stem-like cells.

Combination of Sodium Cantharidinate with Cisplatin Synergistically Hampers Growth of Cervical Cancer.

BACKGROUND: Sodium cantharidinate (SC) has been broadly applied in lung cancer treatment in China, while its specific function in cervical cancer (CC), a great contributor to death of female reproductive system cancers, remains unclear. Our research evaluated the anti-tumor effects of SC in CC and the mechanism involved. METHODS: First, cisplatin (DDP)-resistant Caski-1 and ME180 cell lines were developed and treated with SC. The effects of SC on CC cell growth were then evaluated. Subsequently, the genes targeted by SC were predicted via the bioinformatics website. The correlations between PTPN1 expression and tumor stage, lymph node metastasis and tumor differentiation were examined. We further conducted rescue experiments by overexpressing PTPN1 in CC cells, followed by SC and cisplatin treatments. The activation of the PI3K/AKT pathway in CC cells, and the effect of SC on the growth and drug resistance of Caski-1 cells in vivo were investigated. RESULTS: The sensitivity of Caski-1 and ME180 cells to DDP was increased after SC treatment, which also enhanced the inhibitory effect of DDP on the cell growth. By prediction, we found that SC could target PTPN1. Patients with high expression of PTPN1 had higher clinical stage, lymph node metastasis and lower tumor differentiation. SC inhibited PTPN1 expression. Overexpression of PTPN1 attenuated the effect of SC. Furthermore, PTPN1 activated the PI3K/AKT pathway. Moreover, SC treatment inhibited the growth and drug resistance of Caski-1 cells in vivo. CONCLUSION: SC promotes drug sensitivity of CC cells to DDP by targeting PTPN1, thereby impairing the PI3K/AKT pathway.

Targeted Molecular Magnetic Resonance Imaging Detects Brown Adipose Tissue with Ultrasmall Superparamagnetic Iron Oxide.

The peptide (CKGGRAKDC-NH2) specifically targets the brown adipose tissue (BAT). Here we applied this peptide coupled with polyethylene glycol (PEG)-coated ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles to detect BAT in vivo by magnetic resonance imaging (MRI). The peptide was conjugated with PEG-coated USPIO nanoparticles to obtain targeted USPIO nanoprobes. Then the nanoprobes for BAT were evaluated in mice. T2⁎-weighted images were performed, precontrast and postcontrast USPIO nanoparticles. Finally, histological analyses proved the specific targeting. The specificity of targeted USPIO nanoprobes was observed in mice. The T2⁎ relaxation time of BAT in the targeted group decreased obviously compared to the controls (P<0.001). Prussian blue staining and transmission electron microscope confirmed the specific presence of iron oxide. This study demonstrated that peptide (CKGGRAKDC-NH2) coupled with PEG-coated USPIO nanoparticles could identify BAT noninvasively in vivo with MRI.

Recurrent myoepithelial carcinoma of the submandibular gland treated by rAd-p53 combined with radiotherapy: A case report.

The aim of the present study was to report the case of a patient with recurrent myoepithelial carcinoma of the submandibular gland without progression for five years following treatment. A 71-year-old male patient presented to hospital with a painless swelling in the region of the right submandibular gland, and received a radical neck dissection on January 29, 2008. A nodule of ~7×4×2 cm was identified at the site of the right submandibular gland, and the pathological results revealed a diagnosis of myoepithelial carcinoma of the right submandibular gland with no lymph node metastasis. However, this case developed local recurrence with wide-spread metastasis in the lungs. Between April and October 2008, the patient underwent several treatment regimens and demonstrated no improvement following 6 cycles of chemotherapy. From then on, the patient was treated with recombinant adenoviral-p53 (rAd-p53) combined with radiotherapy using a 6 millivolt medical linear accelerator. The foci were relieved and the cancer demonstrated no signs of progression during the 5-year follow-up. rAd-p53 combined with radiotherapy was useful for treating myoepithelial carcinoma of the submandibular gland.