Exploration of a hypoxia-immune-related microenvironment gene signature and prediction model for hepatitis C-induced early-stage fibrosis.

BACKGROUND: Liver fibrosis contributes to significant morbidity and mortality in Western nations, primarily attributed to chronic hepatitis C virus (HCV) infection. Hypoxia and immune status have been reported to be significantly correlated with the progression of liver fibrosis. The current research aimed to investigate the gene signature related to the hypoxia-immune-related microenvironment and identify potential targets for liver fibrosis. METHOD: Sequencing data obtained from GEO were employed to assess the hypoxia and immune status of the discovery set utilizing UMAP and ESTIMATE methods. The prognostic genes were screened utilizing the LASSO model. The infiltration level of 22 types of immune cells was quantified utilizing CIBERSORT, and a prognosis-predictive model was established based on the selected genes. The model was also verified using qRT-PCR with surgical resection samples and liver failure samples RNA-sequencing data. RESULTS: Elevated hypoxia and immune status were linked to an unfavorable prognosis in HCV-induced early-stage liver fibrosis. Increased plasma and resting NK cell infiltration were identified as a risk factor for liver fibrosis progression. Additionally, CYP1A2, CBS, GSTZ1, FOXA1, WDR72 and UHMK1 were determined as hypoxia-immune-related protective genes. The combined model effectively predicted patient prognosis. Furthermore, the preliminary validation of clinical samples supported most of the conclusions drawn from this study. CONCLUSION: The prognosis-predictive model developed using six hypoxia-immune-related genes effectively predicts the prognosis and progression of liver fibrosis. The current study opens new avenues for the future prediction and treatment of liver fibrosis.

Correlation between second and first primary cancer: systematic review and meta-analysis of 9 million cancer patients.

BACKGROUND: Many survivors of a first primary cancer (FPCs) are at risk of developing a second primary cancer (SPC), with effects on patient prognosis. Primary cancers have different frequencies of specific SPC development and the development of SPCs may be closely related to the FPC. The aim of this study was to explore possible correlations between SPCs and FPCs. METHODS: Relevant literature on SPCs was retrospectively searched and screened from four databases, namely, PubMed, EMBASE, Web of Science, and PMC. Data on the number of patients with SPC in 28 different organ sites were also collected from The Surveillance, Epidemiology, and End Results (SEER) 8 Registry and NHANES database. RESULTS: A total of 9 617 643 patients with an FPC and 677 430 patients with an SPC were included in the meta-analysis. Patients with a first primary gynaecological cancer and thyroid cancer frequently developed a second primary breast cancer and colorectal cancer. Moreover, those with a first primary head and neck cancer, anal cancer and oesophageal cancer developed a second primary lung cancer more frequently. A second primary lung cancer and prostate cancer was also common among patients with first primary bladder cancer and penile cancer. Patients with second primary bladder cancer accounted for 56% of first primary ureteral cancer patients with SPCs. CONCLUSIONS: This study recommends close clinical follow-up, monitoring and appropriate interventions in patients with relevant FPCs for better screening and early diagnosis of SPCs.

Development of a screening system of gene sets for estimating the time of early skeletal muscle injury based on second-generation sequencing technology.

The present study is aimed to address the challenge of wound age estimation in forensic science by identifying reliable genetic markers using low-cost and high-precision second-generation sequencing technology. A total of 54 Sprague-Dawley rats were randomly assigned to a control group or injury groups, with injury groups being further divided into time points (4 h, 8 h, 12 h, 16 h, 20 h, 24 h, 28 h, and 32 h after injury, n = 6) to establish rat skeletal muscle contusion models. Gene expression data were obtained using second-generation sequencing technology, and differential gene expression analysis, weighted gene co-expression network analysis (WGCNA) and time-dependent expression trend analysis were performed. A total of six sets of biomarkers were obtained: differentially expressed genes at adjacent time points (127 genes), co-expressed genes most associated with wound age (213 genes), hub genes exhibiting time-dependent expression (264 genes), and sets of transcription factors (TF) corresponding to the above sets of genes (74, 87, and 99 genes, respectively). Then, random forest (RF), support vector machine (SVM) and multilayer perceptron (MLP), were constructed for wound age estimation from the above gene sets. The results estimated by transcription factors were all superior to the corresponding hub genes, with the transcription factor group of WGCNA performed the best, with average accuracy rates of 96% for three models' internal testing, and 91.7% for the highest external validation. This study demonstrates the advantages of the indicator screening system based on second-generation sequencing technology and transcription factor level for wound age estimation.

[Spatial Constraints of Rectangular Hydrogel Microgrooves Regulate the Morphology and Arrangement of Human Umbilical Vein Endothelial Cells]. / çŸ©å½¢æ°´å‡èƒ¶å¾®å‡¹æ§½çš„ç©ºé—´çº¦æŸè°ƒæŽ§äººè„é™è„‰å† çš®ç»†èƒžçš„å½¢æ€å’ŒæŽ’åˆ—.

Objective: To construct microscale rectangular hydrogel grooves and to investigate the morphology and alignment of human umbilical vein endothelial cells (HUVECs) under spatial constraints. Vascular endothelial cell morphology and alignment are important factors in vascular development and the maintenance of homeostasis. Methods: A 4-arm polyethylene glycol-acrylate (PEG-acrylate) hydrogel was used to fabricate rectangular microgrooves of the widths of 60 µm, 100 µm, and 140 µm. The sizes and the fibronectin (FN) adhesion of these hydrogel microgrooves were measured. HUVECs were seeded onto the FN-coated microgrooves, while the flat surface without micropatterns was used as the control. After 48 hours of incubation, the morphology and orientation of the cells were examined. The cytoskeleton was labelled with phalloidine and the orientation of the cytoskeleton in the hydrogel microgrooves was observed by laser confocal microscopy. Results: The hydrogel microgrooves constructed exhibited uniform and well-defined morphology, a complete structure, and clear edges, with the width deviation being less than 3.5%. The depth differences between the hydrogel microgrooves of different widths were small and the FN adhesion is uniform, providing a micro-patterned growth interface for cells. In the control group, the cells were arranged haphazardly in random orientations and the cell orientation angle was (46.9±1.8)°. In contrast, the cell orientation angle in the hydrogel microgrooves was significantly reduced (P<0.001). However, the cell orientation angles increased with the increase in hydrogel microgroove width. For the 60 µm, 100 µm, and 140 µm hydrogel microgrooves, the cell orientation angles were (16.4±2.8)°, (24.5±3.2)°, and (30.3±3.5)°, respectively. Compared to that of the control group (35.7%), the number of cells with orientation angles <30° increased significantly in the hydrogel microgrooves of different widths (P<0.001). However, as the width of the hydrogel microgrooves increased, the number of cells with orientation angles <30° gradually decreased (79.9%, 62.3%, 54.7%, respectively), while the number of cells with orientation angles between 60°-90° increased (P<0.001). The cell bodies in the microgrooves were smaller and more rounded in shape. The cells were aligned along the direction of the microgrooves and corresponding changes occurred in the arrangement of the cell cytoskeleton. In the control group, cytoskeletal filaments were aligned in random directions, presenting an orientation angle of (45.5±3.7)°. Cytoskeletal filaments were distributed evenly within various orientation angles. However, in the 60 µm, 100 µm, and 140 µm hydrogel microgrooves, the orientation angles of the cytoskeletal filaments were significantly decreased, measuring (14.4±3.1)°, (24.7±3.5)°, and (31.9±3.3)°, respectively. The number of cytoskeletal filaments with orientation angles <30° significantly increased in hydrogel microgrooves of different widths (P<0.001). However, as the width of the hydrogel microgrooves increased, the number of cytoskeletal filaments with orientation angles <30° gradually decreased, while the number of cytoskeletal filaments with orientation angles between 60°-90° gradually increased (P<0.001). Conclusion: Hydrogel microgrooves can regulate the morphology and orientation of HUVECs and mimic to a certain extent the in vivo microenvironment of vascular endothelial cells, providing an experimental model that bears better resemblance to human physiology for the study of the unique physiological functions of vascular endothelial cells. Nonetheless, the molecular mechanism of spatial constraints on the morphology and the assembly of vascular endothelial cell needs to be further investigated.

Prognostic nomograms for HBV-related BCLC 0-a stage hepatocellular carcinoma incorporating aspartate aminotransferase to albumin ratio.

BACKGROUND: Curative hepatectomy is currently the first-line treatment for hepatocellular carcinoma (HCC), but the prognosis is still not optimistic. The prediction model for prognosis of hepatitis B virus (HBV)-related BCLC 0-A stage HCC has not been well established. Therefore, we aimed to develop new nomograms to predict recurrence and survival in these patients. METHODS: A total of 982 patients with HBV-related BCLC 0-A stage HCC who underwent curative hepatectomy at West China Hospital from February 2007 to February 2016 were retrospectively collected and randomly allocated to a training set and a validation set in a ratio of 4:1. Prognostic nomograms using data from the training set were developed using a Cox regression model and validated on the validation set. RESULTS: We constructed nomograms based on independent factors for recurrence-free survival (RFS) (tumor size, satellite, microvascular invasion, capsular invasion, differentiation and aspartate aminotransferase to albumin ratio (ASAR)) and overall survival (OS) (gender, tumor size, satellite, microvascular invasion, differentiation, lymphocyte count, and ASAR). Compared with conventional HCC staging systems and other nomograms reported by previous literature, our ASAR integrated nomograms predicted RFS and OS with the highest C-indexes (0.682 (95%CI: 0.646-0.709), 0.729 (95%CI: 0.691-0.766), respectively) and had well-fitted calibration curves in the training set. Concurrently, the nomograms also obtained consistent results in the validation set. DCA revealed that our nomograms provided the largest clinical net benefits. CONCLUSION: We first constructed ASAR integrated nomograms to predict the prognosis of HBV-related BCLC 0-A stage HCC patients after curative hepatectomy with good performance.

How seasonality affects the environmental performance of fresh appetite: Insights from cherry consumption in China.

Urbanization and globalization are changing the conventional constraints of seasonality and geography on food consumption, such as that of fresh cherries. The rising demand for year-round cherry consumption in China is currently satisfied by open-field, greenhouse-produced, and imported products. This study conducted a spatial-temporal life cycle evaluation of the environmental performance of cherry consumption behaviors during different seasons of the year. Moreover, based on the definitions of global and local seasonality, the additional environmental costs of out-of-season cherry consumption were estimated. Results show that seasonality was an important factor affecting the environmental burdens of cherry consumption. Eating cherries imported from Chile by air in October resulted in the highest greenhouse gas (GHG) emissions of 6.38 kg CO2-eq/kg, while eating domestic open-field cherries during May to July (the natural harvest season) was a relatively environmentally beneficial option. The total cherry consumption in China in 2019 generated GHG emissions of 126.99 × 104 t CO2-eq. Under the definitions of global and local seasonality, the out-of-season consumption led to additional environmental costs of 57.59 × 104 and 85.67 × 104 t CO2-eq, accounting for 45.35% and 67.46% of total emissions, respectively. Furthermore, the time-environment trade-off effect of cherry consumption illustrates the higher environmental costs are exchanged for satisfying the appetite for out-of-season fresh foods. Our findings emphasize the meaningful implications for developing a sustainable consumption pattern for all stakeholders involved in the entire food chain.

[Research progress on vascularization of organoids].

Organoids are three-dimensional structures formed by self-organizing growth of cells in vitro, which own many structures and functions similar with those of corresponding in vivo organs. Although the organoid culture technologies are rapidly developed and the original cells are abundant, the organoid cultured by current technologies are rather different with the real organs, which limits their application. The major challenges of organoid cultures are the immature tissue structure and restricted growth, both of which are caused by poor functional vasculature. Therefore, how to develop the vascularization of organoids has become an urgent problem. We presently reviewed the progresses on the original cells of organoids and the current methods to develop organoids vascularization, which provide clues to solve the above-mentioned problems.

Anisodamine hydrobromide attenuates oxidative stress and proinflammatory cytokines in septic rats induced by cecal ligation and puncture.

We previously demonstrated that anisodamine hydrobromide (Ani HBr) ameliorates septic organ injury induced by lipopolysaccharide. The present study is aimed to explore the role of Ani HBr in protecting of organs against inflammation and oxidative stress in septic rats induced by cecal ligation and puncture (CLP). A total of forty-two rats were randomly divided into sham (sham operation), septic shock (CLP), Ani HBr, atropine and racemic anisodamine (Rac Ani) groups. Ani HBr (1.8, 3.6, and 5.4 mg/kg), atropine (5.4 mg/kg), and Rac Ani (5.4 mg/kg) were administrated to septic rats. After 24 h, the plasma and organs including brain, heart, liver, lung, kidney, and intestine were obtained. Then, the H&E staining and TUNEL staining were performed. The proinflammatory factors TNF-α and IL-6 and oxidative stress markers SOD and MDA in plasma were detected by ELISA. H&E staining showed that the tissues in the brain, heart, liver, lung, kidney and intestine in the septic shock group were seriously damaged. Consistently, TUNEL staining showed an increase of apoptotic cells in those tissues. Ani HBr treatment alleviated the injury and apoptotic cells in all those organs in septic rats. Ani HBr, atropine, and Rac Ani reduced the plasma TNF-α and IL-6 levels in septic rats, whereas 5.4 mg/kg Ani HBr reduced the cytokines more than Rac Ani. Ani HBr raised SOD activity and reduced plasma MDA levels in a concentration-dependent manner, which at 5.4 mg/kg were greater than atropine and Rac Ani. Therefore, anisodamine hydrobromide suppressed the proinflammatory cytokines and oxidative stress, thereby alleviating organ injury in rats with septic shock. Moreover, the therapeutic effect of Ani HBr is more powerful than that of atropine or Rac Ani, which suggests that Ani HBr is a preferred treatment for septic shock.

The impact of tumor burden at the initial hepatectomy on the recurrence-to-death survival after repeat surgical resection/radiofrequency ablation: a retrospective study.

BACKGROUND: Previous studies have reported the surgical resection (SR) and radiofrequency ablation (RFA) could achieve comparable recurrence-to-death survival (RTDS). However, the impact of primary tumor burden on RTDS of patients with recurrent hepatocellular carcinoma (HCC) following SR or RFA has not been clarified. METHODS: From January 2009 to March 2015, 171 patients who underwent initial hepatectomy and second curative treatments in West China Hospital were retrospectively analyzed. Survival analysis was performed by the Kaplan-Meier method. Risk factors were identified using the Cox proportional hazard model. RESULTS: At initial hepatectomy, 96 patients (56.1%) were diagnosed with HCC within the Milan criteria (MC), and 75 patients (43.9%) were HCC beyond the MC. The clinicopathological features and re-treatment methods of recurrent HCC were similar between patients with primary HCC within or beyond the MC. Patients with primary HCC within the MC had longer recurrence time (31.4 ± 24.2 months vs. 20.2 ± 16 months, P < 0.001). The 1- and 3- year RTDS within and beyond the MC group were 88.8%, 57.6% and 79.0%, 46.3%, respectively (P = 0.093). In multivariate analysis, the recurrence time, tumor size and AFP > 400 ng/mL at the time of recurrence were associated with RTDS. CONCLUSIONS: The primary tumor burden had no impact on RTDS, but had an impact on recurrence time. The recurrence time had an impact on RTDS and might be a good index to reflect the biology of recurrent HCC.

Preoperative aspartate aminotransferase to albumin ratio correlates with tumor characteristics and predicts outcome of hepatocellular carcinoma patients after curative hepatectomy: a multicenter study.

AIMS: This study aimed to evaluate the clinical significance of the preoperative aminotransferase to albumin ratio (AAR) in patients with hepatocellular carcinoma (HCC) after hepatectomy. METHODS: From five hospitals, a total of 991 patients with HCC admitted between December 2014 and December 2019 were included as the primary cohort and 883 patients with HCC admitted between December 2010 and December 2014 were included as the validation cohort. The X-tile software was conducted to identify the optimal cut-off value of AAR. RESULTS: In the primary cohort, the optimal cut-off value of the AAR was defined as 0.7 and 1.6, respectively. Compared to patients with AAR 0.7-1.6, those with AAR > 1.6 showed significantly worse overall survival (OS) and RFS, whereas those with AAR < 0.7 showed significantly better OS and RFS (all p < 0.001). Pathologically, patients with AAR > 1.6 had more aggressive tumour characteristics, such as larger tumour size, higher incidence of microvascular invasion, and severe histologic activity, and higher AFP level than patients with AAR < 0.7. Consistently, the abovementioned clinical significance of AAR was confirmed in the validation cohort. CONCLUSIONS: A high AAR was significantly correlated with advanced tumours and severe hepatic inflammation, and a worse prognosis of HCC.

Baseline HBV-DNA load plus AST/ALT ratio predicts prognosis of HBV-related hepatocellular carcinoma after hepatectomy: A multicentre study.

Hepatitis B viral (HBV) load and hepatic enzymes play a critical role in hepatocellular carcinoma (HCC) development. However, the clinical significance of these in HBV-related HCC patients after hepatectomy remains unclear. In this study, we analysed 1,940 HBV-related HCC patients who underwent hepatectomy from four hospitals in west China. Risk classification was constructed based on baseline HBV-DNA load and AST/ALT ratio. Based on the HBV-DNA load and AST/ALT ratio classification, four types with distinguishable prognoses were established. Type 1 patients had the best prognosis with 5-year overall survival (OS) of 69.8%, followed by type 2 and type 3 patients, whereas type 4 patients had the worst prognosis with 5-year OS of 42.7%. Similarly, the four types had statistically different recurrence-free survival. This classification was significantly associated with HCC recurrence (hazard ratio [HR]:1.492, p < .001) and long-term survival (HR: 1.574, p = .001). Pathologically, type 4 correlated with more advanced tumours considering tumour size and microvascular invasion than those in type 1, 2, or 3. Moreover, type 4 patients had more severe hepatic inflammation in underlying liver. Conversely, type 1 patients had an active tumour immune microenvironment as indicated by more CD8+ T cell infiltration and less PD-L1 expression. In conclusion, the classfication based on baseline HBV-DNA load and AST/ALT ratio could effectively stratify HBV-related HCC patients with distinguishable prognoses after hepatectomy.

Association between postpartum depression and social support satisfaction levels at four months after childbirth.

This study clarifies the association between postpartum depression (PPD) and satisfaction with social support after childbirth through an anonymous survey of 427 postpartum mothers. Mothers' PPD was found to be significantly associated with satisfaction levels regarding formal-instrumental support (OR: 0.32, 95% CI: 0.162-0.632), informal-instrumental support (OR: 0.547, 95% CI: 0.313-0.955), and informal-psychological support (OR: 0.591, 95% CI: 0.384-0.912) in a multivariate logistic regression analysis. To prevent PPD, specialists as formal support providers must provide qualified care based on comprehensive judgments, and families as informal support providers should help with childcare, housework, and mental support.

Functional oral nanoparticles for delivering silibinin and cryptotanshinone against breast cancer lung metastasis.

BACKGROUND: Breast cancer lung metastasis occurs in more than 60% of all patients with breast cancer, and most of those afflicted by it eventually die of recurrence. The tumor microenvironment plays vital roles in metastasis. Modulating the tumor microenvironment via multiple pathways could efficiently prevent or inhibit lung metastasis. Silibinin and cryptotanshinone are natural plant products that demonstrate anti-metastasis effects and modulate the tumor microenvironment via different pathways. However, they have poor aqueous solubility, membrane permeability, and oral bioavailability. Oral drug administration may help improve the quality of life and compliance of patients with breast cancer, primarily under long-term and/or follow-up therapy. Herein, we developed poly-N-(2-hydroxypropyl) methacrylamide (pHPMA)-coated wheat germ agglutinin-modified lipid-polymer hybrid nanoparticles, co-loaded with silibinin and cryptotanshinone (S/C-pW-LPNs). We assessed their oral bioavailability, and evaluated their anti-metastasis efficacy in a 4T1 breast cancer tumor-bearing nude mouse model. RESULTS: An in vitro mucus diffusion study revealed that pHPMA enhanced W-LPN mucus penetration. After oral administration, pHPMA enhanced nanoparticle distribution in rat jejunum and substantially augmented oral bioavailability. S/C-W-LPNs markedly increased 4T1 cell toxicity and inhibited cell invasion and migration. Compared to LPNs loaded with either silibinin or cryptotanshinone alone, S/C-pW-LPNs dramatically slowed tumor progression in 4T1 tumor-bearing nude mice. S/C-pW-LPNs presented with the most robust anti-metastasis activity on smooth lung surfaces and mitigated lung metastasis foci. They also downregulated tumor microenvironment biomarkers such as CD31, TGF-ß1, and MMP-9 that promote metastasis. CONCLUSIONS: Silibinin- and cryptotanshinone-co-loaded pW-LPNs efficiently penetrate intestinal barriers, thereby enhancing the oral bioavailability of the drug loads. These nanoparticles exhibit favorable anti-metastasis effects in breast cancer-bearing nude mice. Hence, S/C-pW-LPNs are promising oral drug nanocarriers that inhibit breast cancer lung metastasis.

Advances in next-generation lipid-polymer hybrid nanocarriers with emphasis on polymer-modified functional liposomes and cell-based-biomimetic nanocarriers for active ingredients and fractions from Chinese medicine delivery.

Recently, functional liposomes modified with versatile polymer and cell-based- biomimetic nanoparticles have emerged as the most advanced lipid-polymer hybrid nanocarriers (LPNs) for drug delivery. This review highlights the advances of these two LPNs in the delivery of active ingredients and fractions from Chinese medicine with promising therapeutic, chemopreventive, or chemosensitive effects. To understand their complete potency, the relationship between the nanoparticle characteristics and their in vitro and in vivo performance characteristics has been discussed. Polymer-modified liposomes and cell-based biomimetic nanoparticles are beneficial for improving absorption, modulating release, targeting and overcoming multidrug resistance, and reducing side effects. The associated challenges, current limitations, and opportunities in this field are also discussed.

IL1B polymorphism is associated with essential tremor in Chinese population.

BACKGROUND: The aim of the study was to investigate the genetic risk factors of essential tremor (ET) in Chinese Population. METHODS: A total of 225 ET patients (25 ET patients also had restless legs syndrome (RLS) and were excluded from final analysis) and 229 controls were recruited. The diagnosis of ET was based on the Consensus Statement of the Movement Disorders Society on tremor. Polymerase chain reaction (PCR) and sequencing were used to detect 12 single nucleotide polymorphisms (SNPs) in seven candidate genes for RLS (HMOX1, HMOX2, VDR, IL17A, IL1B, NOS1 and ADH1B). RESULTS: We found that one SNP was associated with the risk of ET in Chinese population after adjusting for age and gender: rs1143633 of IL1B (odds ratio [OR] =2.57, p = 0.003, recessive model), and the statistical result remained significant after Bonferroni correction. Then, we performed a query in Genotype-tissue Expression (GTEx), Brain eQTL Almanac (Braineac) databases and Blood expression quantitative trait loci (eQTL) browser. The significant association was only found between genotype at rs1143633 and IL1B expression level of putamen and white matter in Braineac database, which was more prominent with homozygous (GG) carriers. CONCLUSIONS: Our study firstly reported the association of IL1B polymorphism with the risk of ET in Chinese population. However, the association might only suggest a marker of IL1B SNP associated with ET instead of the casual variant. Further studies are needed to confirm our finding.

Functional lipid polymeric nanoparticles for oral drug delivery: Rapid mucus penetration and improved cell entry and cellular transport.

To improve Biopharmaceutics Classification System class IV drug bioavailability, mucus and underlying intestinal epithelial barriers must be overcome. Hydrophilic nanoparticle coatings may hinder cellular uptake and transport. We integrated hydrophilic, detachable poly(N-(2-hydroxypropyl) methacrylamide) with vitamin B12-modified chitosan into lipid polymeric nanoparticles (H/VC-LPNs) to enhance mucus penetration, intracellular uptake, and transepithelial absorption. Multiple particle tracking revealed accelerated mucus diffusion into porcine mucus in vitro. The nanoparticles increased uptake and intracellular distribution in Caco-2 cells, which may involve intrinsic factor receptor-mediated endocytosis and intercellular tight junctions. Integration of improved mucus penetration and intracellular absorption was confirmed by in vitro internalization kinetics in HT29-MTX/Caco-2 co-cultures and in vivo distribution, transport, and mouse Peyer's patch absorption. H/VC-LPNs substantially increased curcumin bioavailability in rats. A nanocarrier with a dissociable shell, receptor-mediated intracellular penetration, and paracellular transport may be promising for oral curcumin delivery. This study identified the key factors involved in oral bioavailability enhancement.

Solasodine reverses stemness and epithelial-mesenchymal transition in human colorectal cancer.

Adverse side effects of conventional chemotherapy, acquired resistance and fatal tumor metastasis of human colorectal cancer (CRC) are propelling the exploration for novel selective anticarcinogens. Solasodine is a main active component isolated from Solanum incanum L that exhibited a potent stemness and invasion inhibitory effect on human colorectal cancer HCT116 cells. Colony Spheroid formation assay showed that solasodine dose-dependently prohibited HCT116 cell stemness. CD133, CD44, Nanog, Oct-4 and Sox-2 were inhibited by solasodine to reverse stemness and similar mechanism was stimulated in vivo. Transwell and scratch wound assays revealed that solasodine impeded HCT116 cell invasion and migration potential strengthened by TGF-ß1. Moreover, solasodine attenuated TGF-ß1-induced EMT and decreased MMPs while in vivo study showed the same trend. The results of this study implied that solasodine may be a novel therapeutic drug for CRC treatment.

The prognostic value of microvascular invasion in early-intermediate stage hepatocelluar carcinoma: a propensity score matching analysis.

BACKGROUND: Microvascular invasion (MVI) is well established as a negative prognostic factor for hepatocelluar carcinoma (HCC). However, its prognostic value in different subgroups of Barcelona Clinical Liver Cancer (BCLC) stages remains to be elucidated. METHODS: Four hundred fifty-eight MVI-negative and 204 MVI-positive patients who underwent hepatectomy were retrospectively analyzed. After propensity score matching (PSM) analysis, 187 pairs of matched patients were generated. Long-term survival was compared by the Kaplan-Meier method. RESULTS: Patients with MVI commonly had more advanced tumors. All the patients with MVI had significantly worse survival rate compared to the patients without MVI before and after PSM(p < 0.001). In the subgroup analysis, BCLC stage A HCC patients without MVI had better prognosis than those with MVI before and after PSM (p < 0.001 and p = 0.024). For BCLC stage B HCCs, long-term survival was significantly better for patients without MVI before PSM(p = 0.001). However, the overall survival (OS) rate was comparable between both groups after PSM (p = 0.682), although MVI-positive group had a higher rate of recurrence (p = 0.011).. Surgery type, satellite lesions, tumor size, and serum ALT level were statistically significant factors associated with survival in MVI-positive group. Tumor number, tumor size and neutrophil to lymphocyte ratio (NLR) were predictors of survival in MVI-negative group. CONCLUSIONS: Its prognostic value in different subgroups of BCLC stages differed. MVI is an independent predictor of prognosis in patients with BCLC stage A. For BCLC stage B HCCs, MVI-positive group had poor prognosis through more advanced HCCs.

Proline-rich transmembrane protein 2-negative paroxysmal kinesigenic dyskinesia: Clinical and genetic analyses of 163 patients.

BACKGROUND: Paroxysmal kinesigenic dyskinesia is the most common type of paroxysmal dyskinesia. Approximately half of the cases of paroxysmal kinesigenic dyskinesia worldwide are attributable to proline-rich transmembrane protein 2 mutations. OBJECTIVE: The objective of this study was to investigate potential causative genes and clinical characteristics in proline-rich transmembrane protein 2-negative patients with paroxysmal kinesigenic dyskinesia. METHODS: We analyzed clinical manifestations and performed exome sequencing in a cohort of 163 proline-rich transmembrane protein 2-negative probands, followed by filtering data with a paroxysmal movement disorders gene panel. Sanger sequencing, segregation analysis, and phenotypic reevaluation were used to substantiate the findings. RESULTS: The clinical characteristics of the enrolled 163 probands were summarized. A total of 39 heterozygous variants were identified, of which 33 were classified as benign, likely benign, and uncertain significance. The remaining 6 variants (3 novel, 3 documented) were pathogenic and likely pathogenic. Of these, 3 were de novo (potassium calcium-activated channel subfamily M alpha 1, c.1534A>G; solute carrier family 2 member 1, c.418G>A; sodium voltage-gated channel alpha subunit 8, c.3640G>A) in 3 sporadic individuals, respectively. The other 3 (paroxysmal nonkinesiogenic dyskinesia protein, c.956dupA; potassium voltage-gated channel subfamily A member 1, c.765C>A; Dishevelled, Egl-10, and Pleckstrin domain containing 5, c.3311C>T) cosegregated in 3 families. All 6 cases presented with typical paroxysmal kinesigenic dyskinesia characteristics, except for the Dishevelled, Egl-10, and Pleckstrin domain containing 5 family, where the proband's mother had abnormal discharges in her temporal lobes in addition to paroxysmal kinesigenic dyskinesia episodes. CONCLUSIONS: Our findings extend the genotypic spectrum of paroxysmal kinesigenic dyskinesia and establish the associations between paroxysmal kinesigenic dyskinesia and genes classically related to other paroxysmal movement disorders. De novo variants might be a cause of sporadic paroxysmal kinesigenic dyskinesia. © 2018 International Parkinson and Movement Disorder Society.