Identification and Validation of Basement Membrane Related LncRNA Signatures as a Novel Prognostic Model for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a significant cancer with limited treatments and a poor prognosis, with the basement membrane (BM) playing a crucial role in its initiation and growth. This study utilized data from The Cancer Genome Atlas and the Gene Expression Omnibus (GEO) databases to identify basement membrane-related genes differentially expressed in HCC. Through gene co-expression analysis, BM-associated long non-coding RNAs (lncRNAs) were discovered. LncRNAs related to HCC survival were selected via univariate analysis, and a prognostic model was constructed using LASSO regression and multivariate analysis. This model effectively classified HCC patients into high and low-risk groups, uncovering significant differences in prognosis, immune response, mutation, and drug sensitivity. Six BM-related lncRNAs (GSEC, MIR4435-2HG, AC092614.1, AC127521.1, LINC02580, and AC008050.1) were validated in normal and HCC cell lines, and the key role of AC092614.1 in regulating proliferation, migration, and invasion of HCC cells in vitro was explored. This research emphasizes the prognostic and therapeutic relevance of BM-related lncRNAs in HCC, highlighting AC092614.1's role in disease progression and as a potential target for targeted therapy.

Neoadjuvant Chemotherapy of Taxanes With or Without Anthracyclines in Different Molecular Subtypes of Breast Cancer: A Propensity Score Matching Study.

PURPOSE: To compare the efficacy of taxane (T) based neoadjuvant chemotherapy (NAC) with T and anthracycline (A) based NAC in different molecular types of breast cancer (BC). METHODS: We retrospectively analyzed the date of NAC for BC from 20 hospitals in China from January 2010 to December 2020, 7870 cases were enrolled. The propensity score matching was used to equalize the baseline characteristics. Pathological complete response (pCR) rate, clinical response rate and breast-conserving rate were analyzed. RESULTS: The efficacy of 2 regimens were similar in luminal A subtype. The breast-conserving rate was higher in T-based NAC in luminal B subtype (17.9% vs. 10.2%, P = .043).The pCR (T0/isN0M0) and tpCR (T0N0M0) rates in T-based NAC were higher than those in TA-based NAC for triple-negative subtype (pCR: 34.5% vs. 25.8%, P = .041, tpCR: 26.9% vs. 17.1%, P = .008). For HER2+(HR-) subtype, the pCR, and tpCR rates were higher in T-based NAC in insufficient anti-HER2 therapy (P < .05), and those were higher in TA-based NAC in dual-target anti-HER2 therapy (pCR: 69.2% vs. 53.8%, P = .254, tpCR: 61.5% vs. 42.3%, P = .165). For HER2+(HR+) breast cancer, both pCR and tpCR rates were higher in TA group, regardless of the adequacy of anti-HER2 treatment. CONCLUSIONS: T-based NAC could replace TA-based NAC for luminal A, luminal B, and triple-negative early-stage BC, but anthracyclines cannot be abandoned in HER2+ breast cancer. The development of anthracyclines with lower adverse reactions is one of the directions for the treatment of HER2+ breast cancer.

Assessment of key parameters of normal uterus in women of reproductive age.

Currently, the precise and detailed anatomical data of the normal uterus, especially the myometrium thickness in various parts of the uterus, are lacking. This study aims to provide normal references for uterine size in healthy reproductive-aged Chinese women to facilitate the application of hysteroscopic surgery. A total of 298 women of reproductive age with normal uterine were included. Parity was significantly correlated with uterine measurements (P < 0.05), and age impacted several measurements (P < 0.05). At each uterine site examined, the myometrium was thinner in nulliparous women than in parous or primiparous women (P < 0.001). Similarly, the extrauterine measurements for parous or primiparous women were larger than those for nulliparous women. Weight affected some external measurements but not myometrial thicknesses, while height did not affect uterine measurements (P > 0.05). There was a positive correlation between body mass index (BMI) and extrauterine measurements as well as myometrial thickness (P < 0.05). The mathematical model of the uterine size for women of reproductive age was constructed stratified by parity. The study is the first to provide a detailed statistical description of the accurate anatomical parameters of the uterus in Chinese reproductive-aged women and has great significance for improving the safety and effectiveness of hysteroscopic surgery for patients.

Vulvar squamous intraepithelial neoplasia epithelial thickness in hairy and non-hairy sites: a single center experience from China.

Introduction: A large-sample study focusing on VIN lesions of a more precise thickness is needed to help guide clinical treatment. This study aimed to investigate the depth of vulvar intraepithelial neoplasia (VIN) and involved skin appendages to provide evidence for laser surgery. Methods: The study retrospectively enrolled and analyzed the clinical characteristics of VIN patients in the obstetrics and gynecology department of a university hospital between January 1, 2019 and December 30, 2021. The study further explored the thickness of epithelium and skin appendages of 285 women with low-grade VIN (VIN1) and 285 women with high-grade VIN (VIN2/3). Results: The study included 1,139 (80%) VIN1 and 335 (20%) VIN2/3 cases. The VIN1 and VIN2/3 groups showed a significant difference in human papillomavirus infection (P<0.01) but not in cytology (P = 0.499). Most (89.90%, 1,325) cases occurred in one area of the vulva, whereas 10.11% were multifocal. VIN commonly occurred on the posterior fourchette (76.85%), labia majora (11.61%), and labia minora (9.92%). The VIN2/3 group reported a significantly higher positive rate for concurrent cervical and vaginal intraepithelial neoplasia (160 of 285) than the VIN1 group (321 of 953) (P=0.000). The involved epithelial thicknesses in VIN2/3 and VIN1 were 0.69 ± 0.44 and 0.49 ± 0.23 mm, respectively, both of which were greater than the corresponding noninvolved epithelial thickness (0.31 ± 0.19 and 0.32 ± 0.10 mm, P<0.001 and P<0.001, respectively). In cases of appendage involvement, the VIN thickness was 1.98 ± 0.64 mm. Conclusions: VIN thickness was generally ≤1 mm for the superficial lesions in non-hairy areas. However, for lesions extending onto hairy areas, the thickness was approximately 3 mm, leading to the destruction of involved skin appendages.

Design, strategies, and therapeutics in nanoparticle-based siRNA delivery systems for breast cancer.

Utilizing small interfering RNA (siRNA) as a treatment for cancer, a disease largely driven by genetic aberrations, shows great promise. However, implementing siRNA therapy in clinical practice is challenging due to its limited bioavailability following systemic administration. An attractive approach to address this issue is the use of a nanoparticle (NP) delivery platform, which protects siRNA and delivers it to the cytoplasm of target cells. We provide an overview of design considerations for using lipid-based NPs, polymer-based NPs, and inorganic NPs to improve the efficacy and safety of siRNA delivery. We focus on the chemical structure modification of carriers and NP formulation optimization, NP surface modifications to target breast cancer cells, and the linking strategy and intracellular release of siRNA. As a practical example, recent advances in the development of siRNA therapeutics for treating breast cancer are discussed, with a focus on inhibiting cancer growth, overcoming drug resistance, inhibiting metastasis, and enhancing immunotherapy.

What Matters in Radiological Image Segmentation? Effect of Segmentation Errors on the Diagnostic Related Features.

Segmentation is a crucial step in extracting the medical image features for clinical diagnosis. Though multiple metrics have been proposed to evaluate the segmentation performance, there is no clear study on how or to what extent the segmentation errors will affect the diagnostic related features used in clinical practice. Therefore, we proposed a segmentation robustness plot (SRP) to build the link between segmentation errors and clinical acceptance, where relative area under the curve (R-AUC) was designed to help clinicians to identify the robust diagnostic related image features. In experiments, we first selected representative radiological series from time series (cardiac first-pass perfusion) and spatial series (T2 weighted images on brain tumors) of magnetic resonance images, respectively. Then, dice similarity coefficient (DSC) and Hausdorff distance (HD), as the widely used evaluation metrics, were used to systematically control the degree of the segmentation errors. Finally, the differences between diagnostic related image features extracted from the ground truth and the derived segmentation were analyzed, using the statistical method large sample size T-test to calculate the corresponding p values. The results are denoted in the SRP, where the x-axis indicates the segmentation performance using the aforementioned evaluation metric, and the y-axis shows the severity of the corresponding feature changes, which are expressed in either the p values for a single case or the proportion of patients without significant change. The experimental results in SRP show that when DSC is above 0.95 and HD is below 3 mm, the segmentation errors will not change the features significantly in most cases. However, when segmentation gets worse, additional metrics are required for further analysis. In this way, the proposed SRP indicates the impact of the segmentation errors on the severity of the corresponding feature changes. By using SRP, one could easily define the acceptable segmentation errors in a challenge. Additionally, the R-AUC calculated from SRP provides an objective reference to help the selection of reliable features in image analysis.

miR-9 targeting RUNX1 improves LPS-induced alveolar hypercoagulation and fibrinolysis inhibition through NF-κB inactivation in ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a clinical and pathophysiological complex syndrome with high mortality. Alveolar hypercoagulation and fibrinolytic inhibition constitute the core part of the pathophysiology of ARDS. miR-9 (microRNA-9a-5p) plays an important role in the pathogenesis of ARDS, but whether it regulates alveolar pro-coagulation and fibrinolysis inhibition in ARDS remains to be elucidated. We aimed to determine the contributing role of miR-9 on alveolar hypercoagulation and fibrinolysis inhibition in ARDS. METHODS: In the ARDS animal model, we first observed the miR-9 and runt-related transcription factor 1 (RUNX1) expression in lung tissue, the effects of miR-9 on alveolar hypercoagulation and fibrinolytic inhibition in ARDS rats, and the efficacy of miR-9 on acute lung injury. In the cell, alveolar epithelial cells type II (AECII) were treated with LPS, and the levels of miR-9 and RUNX1 were detected. Then we observed the effects of miR-9 on procoagulant and fibrinolysis inhibitor factors in cells. Finally, we explored whether the efficacies of miR-9 were associated with RUNX1; we also preliminarily examined the miR-9 and RUNX1 levels in plasma in patients with ARDS. RESULTS: In ARDS rats, miR-9 expression decreased, but RUNX1 expression increased in the pulmonary tissue of ARDS rats. miR-9 displayed to attenuate lung injury and pulmonary wet/dry ratio. Study results in vivo demonstrated that miR-9 ameliorated alveolar hypercoagulation and fibrinolysis inhibition and attenuated the collagen III expressions in tissue. miR-9 also inhibited NF-κB signaling pathway activation in ARDS. In LPS-induced AECII, the expression changes of both miR-9 and RUNX1 were similar to those in pulmonary tissue in the animal ARDS model. miR-9 effectively inhabited tissue factor (TF), plasma activator inhibitor (PAI-1) expressions, and NF-κB activation in LPS-treated ACEII cells. Besides, miR-9 directly targeted RUNX1, inhibiting TF and PAI-1 expression and attenuating NF-κB activation in LPS-treated AECII cells. Clinically, we preliminarily found that the expression of miR-9 was significantly reduced in ARDS patients compared to non-ARDS patients. CONCLUSION: Our experimental data indicate that by directly targeting RUNX1, miR-9 improves alveolar hypercoagulation and fibrinolysis inhibition via suppressing NF-κB pathway activation in LPS-induced rat ARDS, implying that miR-9/RUNX1 is expected to be a new therapeutic target for ARDS treatment.

Construction and evaluation of intrauterine adhesion model in rats by different methods of mechanical injury.

PURPOSE: The study aimed to establish a stable and effective animal model for the experimental study of intrauterine adhesion (IUA) by evaluating various mechanical injury methods. METHODS: A total of 140 female rats were divided into four groups according to the extent and area of endometrial injury: group A (excision area: 2.0 × 0.5 cm2), group B (excision area: 2.0 × 0.25 cm2), group C (endometrial curettage) and group D (sham operation). On the 3rd, 7th, 15th and 30th day after the operation, the tissue samples of each group were collected, and the uterine cavity stenosis and histological changes were recorded by HE and Masson staining. Immunohistochemistry of CD31 was applied to visualize microvessel density (MVD). The pregnancy rate and the number of gestational sacs were used to evaluate the reproductive outcome. RESULTS: The results showed that endometrium injured by small-area endometrial excision or simple curettage could be repaired. The ratio of fibrosis in groups A and B was higher than that in groups C and group D 30 days after modeling (P < 0.001). The number of endometrial glands and MVD in group A was significantly lower than those in groups B, C and D (P < 0.05). The pregnancy rate in group A was 20%, which was lower than that in groups B (33.3%), C (89%) and D (100%) (P < 0.05). CONCLUSION: Full-thickness endometrial excision has a high rate of success in constructing stable and effective IUA models in rats.

Clinical Diagnostic Value of Atypical Glandular Cells in Cervical Cytology: A Single Center Experience From China.

OBJECTIVE: This study aimed to investigate the diagnostic value of atypical glandular cells (AGCs) by analyzing the prevalence and histopathology of AGCs according to cervical cytology. METHODS: The authors retrospectively reviewed and analyzed the demographic characteristics and histopathological outcomes including pathological diagnosis, pathological site, and epithelial distribution of the AGC cases that were diagnosed by cervical cytology. RESULTS: A total of 387 AGC patients with follow-up records were included. Among them, the prevalence of AGC-not otherwise specified (NOS) and AGC-favor neoplastic (FN) was 73.39% (284/387) and 26.62% (103/387), respectively. The high-risk human papillomavirus (hr-HPV)-positive rate was higher in AGC-FN than in AGC-NOS ( p = .002). The difference in pathological severity was statistically significant between hr-HPV-positive and negative AGC patients ( p = .010). Hr-HPV-positive AGC mainly occurs in cervical diseases, whereas hr-HPV-negative AGC is mainly related to endometrial lesions. Precancerous or malignant lesions were found in 36.43% (141/387) of AGC cases and were more commonly seen in AGC-FN than AGC-NOS ( p < .001). The histopathological severity and the incidence of uterine disease were higher among AGC women aged 40 years and older than those younger than 40 years ( p < .05). The possibility of the abnormal origin of glandular epithelial was higher than that of squamous epithelial in AGC patients aged 40 years and older ( p = .0003). CONCLUSIONS: The management of AGC women by age triage is reasonable because the incidence of the glandular epithelial lesion and uterine disease increases in AGC patients 40 years or older. Standardized clinical diagnosis and regular follow-up are recommended for all AGC patients.

Analysis of prognostic factors and construction of prognostic models for triple-positive breast cancer.

Objective: By identifying the clinicopathological characteristics and prognostic influences of patients with triple-positive breast cancer (TPBC) at Xijing Hospital in China compared with those in the United States, this study aims to construct a nomogram model to forecast the overall survival rate (OS) of TPBC patients. Method: The Surveillance, Epidemiology, and End Results (SEER) database was used to screen 5769 patients as the training cohort, and 191 patients from Xijing Hospital were used as the validation cohort. Cox risk-proportional model was applied to select variables and the nomogram model was constructed based on the training cohort. The performance of the model was evaluated by calculating the C-index and generating calibration plots in the training and validation cohorts. Results: Cox multifactorial analysis showed that age, chemotherapy, radiotherapy, M-stage, T-stage, N-stage, and the mode of surgery were all independent risk factors for the prognosis of TPBC patients (all P<0.05). With this premise, the nomogram model was constructed and evaluated. The C-index value of the nomogram model was 0.830 in the training group and 0.914 in the validation group. Moreover, both the calibration and ROC curves for the proposed model exhibited reliable performance, and the clinical decision curve analysis showed that the proposed model can bring clinical benefits. Conclusions: The constructed nomogram can accurately predict individual survival probabilities and may serve as a clinical decision support tool for clinicians to optimize treatment in individuals.

Preparation of Aliphatic Hydroxamic Acid from Litsea cubeba Kernel Oil and Its Application to Flotation of Fe(III)-Activated Wolframite.

Litsea cubeba is a characteristic woody oil resource in Hunan. As a solid waste of woody oil resources, Litsea cubeba kernels are rich in Litsea cubeba kernel oil with a carbon chain length of C10-12 fatty acid. In this work, aliphatic hydroxamic acids (AHAs) with carbon chain lengths of C10-12 were prepared from Litsea cubeba kernel oil via methylation and hydroximation reactions. The adsorption and hydrophobicity mechanism of AHA towards wolframite was explored by contact angle, zeta potential, Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The flotation results demonstrated that AHA was a superior collector than the traditional collector such as benzoyl hydroxamic acid (BHA). Zeta potential and contact angle results have shown that AHA was adsorbed on the surface of the Fe(III)-activated wolframite in its anionic form, which significantly improved the surface hydrophobicity of wolframite. FTIR and XPS revealed that AHA was chemically adsorbed on the surface of Fe(III)-activated wolframite in the form of a five-member ring, which made the hydrophobic chain reach into the solution, come in contact with bubbles, and achieve flotation separation.

Transplantation of bFGF-transfected bone mesenchymal stem cells on collagen scaffolds promotes the regeneration of injured rat endometrium.

OBJECTIVE: This study aimed to verify the role of basic fibroblast growth factor (bFGF)-bone mesenchymal stem cells (BMSCs) loaded on collagen scaffolds for the repair of injured endometrium. METHODS: We established an intrauterine adhesion (IUA) model in rats by endometrial resection and implanted BMSCs and bFGF-BMSCs loaded on collagen scaffolds into uteri. A total of 100 IUA model rats were divided into five groups: the control group, scaffold group, BMSC+scaffold group, vector-BMSC group, and bFGF-BMSC+scaffold group. The rats were sacrificed on the 3rd, 7th, 15th, and 45th days. The endometrium thickness, number of glands, and microvascular density were measured by hematoxylin and eosin staining, Masson staining, and immunohistochemistry staining of CD31. The expression of bFGF, vascular endothelial growth factor (VEGF), vimentin, and Ki67 was assayed by immunohistochemistry staining. RESULTS: The bFGF-BMSCs loaded on the collagen scaffold significantly increased the endometrial thickness, gland number, and microvascular density, which greatly promoted the regeneration of the injured endometrium (P<0.0001). In addition, the expression levels of bFGF, VEGF, vimentin, and Ki67 were significantly higher in the bFGF-BMSC+scaffold group than in the BMSC+scaffold group (P<0.05). CONCLUSIONS: Our findings indicated that bFGF-BMSCs loaded on collagen scaffolds have the ability to prompt the regeneration of the endometrium after injury, contributing to a better understanding of stem cell treatment for intrauterine adhesion.

Identification of cuprotosis-mediated subtypes, the development of a prognosis model, and influence immune microenvironment in hepatocellular carcinoma.

Purpose: Cuprotosis is a newly discovered form of non-apoptotic regulated cell death and is characterized by copper-dependent and associated with mitochondrial respiration. However, the prognostic significance and function of cuprotosis-related genes (CRGs) in hepatocellular carcinoma (HCC) are unknown. This study aims to develop cuprotosis-mediated patterns-related gene (CMPRG) prediction models for the prognosis of patients with HCC, exploring the functional underlying the CRGs on the influence of tumor microenvironment (TME) features. Experimental design: This study obtained transcriptome profiling and the corresponding clinical information from the TCGA and GEO databases. Besides, the Cox regression model with LASSO was implemented to build a multi-gene signature, which was then validated in an internal validation set and two external validation sets through Kaplan-Meier, DCA, and ROC analyses. Results: According to the LASSO analysis, we screened out a cuprotosis-mediated pattern 5-gene combination (including PBK; MMP1; GNAZ; GPC1 and AKR1D1). A nomogram was constructed for the presentation of the final model. The ROC curve assessed the model's predictive ability, which resulted in an area under the curve (AUC) values ranging from 0.604 to 0.787 underwent internal and two external validation sets. Meanwhile, the risk score divided the patients into two groups of high and low risk, and the survival rate of high-risk patients was significantly lower than that of low-risk patients (P<0.01). The risk score could be an independent prognostic factor in the multifactorial Cox regression analysis (P<0.01). Functional analysis revealed that immune status, mutational loads, and drug sensitivity differed between the two risk groups. Conclusions: In summary, we identified three cuprotosis-mediated patterns in HCC. And CMPRGs are a promising candidate biomarker for HCC early detection, owing to their strong performance in predicting HCC prognosis and therapy. Quantifying cuprotosis-mediated patterns in individual samples may help improve the understanding of multiomic characteristics and guide the development of targeted therapy for HCC.

LSD1 regulates the FOXF2-mediated Wnt/ß-catenin signaling pathway by interacting with Ku80 to promote colon cancer progression.

Lysine-specific demethylase 1 (LSD1) is widely involved in the proliferation, invasion, and metastasis of cancers. However, it is uncertain whether LSD1 plays a role in facilitating colon cancer progression. Here, we have clarified the molecular mechanism by which LSD1 interacts with X-ray repair cross complementing protein 5 (Ku80) to promote colon cancer progression by directly targeting forehead protein transcription factor 2 (FOXF2). First, the interacting proteins of LSD1 were identified by immunoprecipitation and mass spectrometry. The expression of Ku80 and FOXF2 in colon cancer was detected using immunohistochemistry, real-time quantitative transcription polymerase chain reaction, and western blot. Next, the proliferation, invasion, and metastasis of colon cancer in vitro and in vivo were detected by methyl thiazolyl tetrazolium, 5-ethynyl-20-deoxyuridine, colony formation, wound healing, and nude mice xenograft model assays, respectively. Chromatin immunoprecipitation (ChIP) and ChIP-PCR were performed to investigate the molecular mechanism of LSD1 and Ku80 in colon cancer. Our results indicated that Ku80 expression was positively correlated with the invasion and migration of colon cancer cells, and negatively correlated with FOXF2 expression. More importantly, the high expression of Ku80 and the low expression of FOXF2 were particularly associated with driving the progression of colon cancer. Ku80 knockdown and LSD1 silencing inhibited the proliferation, migration, and invasion of colon cancer in vitro and in vivo. Mechanically, LSD1 interacts with Ku80 and also binds directly to the 687-887-bp portion of the FOXF2 promoter region. The upregulated methylation level of H3K4me2 in the FOXF2 promoter region facilitated the transcriptional activation of FOXF2, and downregulated protein expression associated with the Wnt/ß-catenin signaling pathway. In conclusion, our study suggests that LSD1 regulates the FOXF2-mediated Wnt/ß-catenin signaling pathway by interacting with Ku80, promoting the malignant biological properties of colon cancer, highlighting the binding of LSD1 and Ku80 as a useful anti-cancer target for colon cancer.

LncRNA OSTM1-AS1 acts as an oncogenic factor in Wilms' tumor by regulating the miR-514a-3p/MELK axis.

Wilms' tumor (WT) is the most typical basic renal tumor in children and is associated with a high recurrence rate and improper diagnosis. Long noncoding RNAs (lncRNAs) play important roles in WT development. However, the impact of the OSTM1 antisense RNA 1 (OSTM1-AS1) lncRNA on WT remains largely unexplored. Differential expression of OSTM1-AS1, miR-514a-3p and maternal embryonic leucine zipper kinase (MELK) in mice with WT cells was assessed via quantitative reverse transcription-PCR and western blotting. Changes in the proliferation, migration and apoptosis of WT cells after OSTM1-AS1, miR-514a-3p or MELK knockdown were assessed using the cell counting kit-8, Transwell and caspase-3 activity assays, respectively. Additionally, the tumorigenicity of WT cells after OSTM1-AS1 knockdown in vivo was analyzed using a xenograft tumor assay. The association among OSTM1-AS1, MELK and miR-514a-3p was confirmed using the RNA binding protein immunoprecipitation and luciferase reporter assays. OSTM1-AS1 and MELK were upregulated in WT cells, whereas miR-514a-3p was downregulated. OSTM1-AS1 was mostly observed in the cytoplasm, and its knockout suppressed WT cell migration and proliferation in vitro , triggered apoptosis and attenuated tumor development in vivo . MiR-514a-3p was sponged by OSTM1-AS1, and miR-514a-3p interference counteracted the tumoricidal effect of OSTM1-AS1 knockdown. MiR-514a-3p reduced WT progression by downregulating the expression of MELK, which is the target gene of miR-514a-3p. lncRNA OSTM1-AS1 acts as an oncogenic factor in WT by releasing MELK through sponging miR-514a-3p and could be a useful target for WT diagnosis and therapy.

A Differentiation-Related Gene Prognostic Index Contributes to Prognosis and Immunotherapy Evaluation in Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common gastrointestinal tumor with a poor prognosis, which is associated with poor differentiation of tumor cells. However, the potential value of cell differentiation-related molecules in predicting the benefit and prognosis of immune checkpoint inhibitors (ICI) therapy remains unknown. Herein, to investigate the differentiation trajectory of HCC cells and their clinical significance, a differentiation-related gene prognostic index (DRGPI) based on HCC differentiation-related genes (HDRGs) was constructed to elucidate the immune characteristics and therapeutic benefits of ICI in the HCC subgroup defined by DRGPI. Single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from four HCC samples were integrated for bioinformatics analysis. Then, PON1, ADH4, SQSTM1, HSP90AA1, and STMN1 were screened out to construct a DRGPI. More intriguingly, RT-qPCR validation of the expression of these genes yielded consistent results with the TCGA database. Next, the risk scoring (RS) constructed based on DRGPI suggested that the overall survival (OS) of the DRGPI-high patients was significantly worse than that of the DRGPI-low patients. A nomogram was constructed based on DRGPI-RS and clinical characteristics, which showed strong predictive performance and high accuracy. The comprehensive results indicated that a low DRGPI score was associated with low TP53 mutation rates, high CD8 T cell infiltration, and more benefit from ICI therapy. Homoplastically, the high DRGPI score reflected the opposite results. Taken together, our study highlights the significance of HCC cell differentiation in predicting prognosis, indicating immune characteristics, and understanding the therapeutic benefits of ICI, and suggests that DRGPI is a valuable prognostic biomarker for HCC.

Construction of a ceRNA Network and Analysis of Tumor Immune Infiltration in Pancreatic Adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is characterized by high malignancy, frequent metastasis, and recurrence with an unfavorable prognosis. This study is aimed at constructing a prognostic model for tumor-infiltrating immune cells and a competing endogenous RNA (ceRNA) network in PAAD and analyzing susceptibilities of chemotherapy and immunotherapy of PAAD. Gene expression profiles and clinical information of PAAD were downloaded from The Cancer Genome Atlas (TCGA) database and divided into the tumor group and the normal group. A total of five PAAD survival-related key genes in the ceRNA network and three survival-related immune infiltrating cells were uncovered, and two survival risk models and nomograms were constructed. The efficiency and performance of the two models were verified using multi-index area under the curve analysis at different time points, decision curve analysis, and calibration curves. Co-expression analysis showed that LRRC1, MIR600HG, and RNF166 in the ceRNA network and tumor-infiltrating immune cells including CD8 T cells and M1 macrophages were likely related to the PAAD prognosis, and the expression of key ceRNA-related genes was experimently validated in tissues and cell lines by RT-qPCR. Patients with low risk scores for key genes in the ceRNA network displayed a positive response to anti-programmed death-1 (PD-1) treatment and greater sensitivity to chemotherapeutic drugs such as docetaxel, lapatinib, and paclitaxel. More importantly, our results suggested that the IC50 values of gemcitabine in PAAD were not significantly different between the high and low risk groups. The expression levels of immune checkpoints were significantly different in the high-risk and low-risk groups. The prognostic model, nomogram, and drug analysis may provide an essential reference for PAAD patient management in the clinic.

USP41 promotes breast cancer via regulating RACK1.

BACKGROUND: Breast cancer (BC) is the most common cancer diagnosed among women and is the second leading cause of cancer death. It is of great significance to explore potential candidate targets for BC. METHODS: The expression of ubiquitin-specific protease 41 (USP41) and its prognosis prediction function was firstly evaluated by TCGA database analysis. Using BC cell lines and specimens from 10 patients with primary BC, the upregulation of USP41 in BC was ensured. By USP41 overexpression or knockdown, its function was studied by cell function assays, small interfering RNA (siRNA), western blot, mass spectrometry, and flow cytometry. The potential mechanism of USP41 was explored via Co-Immunoprecipitation mass spectrometry, and western blot. RESULTS: TCGA database analysis revealed that in metastatic BC, USP41 expression was upregulated and negatively correlated with BC prognosis. In BC cancer cells and cancer specimens, USP41 was also upregulated. Overexpression of USP41 greatly enhanced BC colony-forming ability, proliferation, and migration. In contrast, USP41 knockdown significantly inhibited BC colony-forming ability, proliferation, and migration. Moreover, Co-Immunoprecipitation mass spectrometry results indicated that USP41 could interact with RACK1. USP41 promoted the protein expression of RACK1. The expression of RACK1 in BC tissues was upregulated. Knockdown of RACK1 inhibited cell growth and migration, and reversed the oncogenic function of USP41 in BC cells. CONCLUSIONS: USP41 can be a potential therapeutic target against BC via RACK1.

Fluorescence in situ hybridization-based confirmation of acute graft-vs-host disease diagnosis following liver transplantation: A case report.

BACKGROUND: Although acute graft-vs-host disease (aGvHD) is a rare complication of liver transplantation, it is poorly understood and has an extremely high mortality rate. No standardized diagnostic criteria or treatment regimens currently exist. CASE SUMMARY: The present study investigated the etiology, diagnosis, and treatment of aGvHD following liver transplantation. Presentation, diagnosis, disease course, histology, and treatment of an aGvHD case are reported, and associated literature is reviewed. A 64-year-old female required LTx due to primary biliary cirrhosis. The donor was a 12-year-old male. Three weeks following liver transplantation, the recipient developed pyrexia, diarrhea, rashes, and antibiotic-unresponsive pancytopenia. Clinical symptoms together with laboratory investigations suggested a diagnosis of aGvHD, which was confirmed via peripheral blood fluorescent in situ hybridization. Donor XY chromosome fluorescent in situ hybridization indicating early chimerism achieved 93% sensitivity in the detection of GvHD. Existing immunosuppressants were discontinued, and high-dose intravenous methylprednisolone was initiated along with antibiotics. While diarrhea resolved, the patient's general condition continued to deteriorate until demise due to multi-system organ failure at 37 d post-liver transplantation. This case illustrates the life-threatening nature of aGvHD. CONCLUSION: Herein, we have summarized a post-LTx aGvHD case and reviewed associated literature in order to increase awareness and provide potentially risk-mitigating recommendations.