Retinol-binding protein 4 as a promising serum biomarker for the diagnosis and prognosis of hepatocellular Carcinoma.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) is universally poor. Early diagnosis plays a pivotal role in determining the outcome of HCC. METHODS: We employed a comparative proteomics approach to identify potential biomarkers and validated the application of retinol-binding protein 4 (RBP4) as a biomarker for HCC. RBP4 protein expression was examined in liver tissues from 80 HCC patients through immunohistochemical analysis. Serum RBP4 concentrations were measured by ELISA in a cohort comprising 290 HCC patients, matched 202 chronic hepatitis B patients and 269 healthy controls. Survival data were collected from HCC patients. The diagnostic and prognostic values of RBP4 were evaluated using receiver operating curve (ROC) analysis. RESULTS: The validation results demonstrated a significant reduction in RBP4 levels in both liver tissues and serum samples from HCC patients. ROC analysis of the diagnostic value of RBP4 revealed an AUC of 0.879 (95 % CI: 0.854∼0.903) for HCC. When combined with AFP, the AUC increased to 0.919, with a sensitivity of 87.9 % and specificity of 80 %. Survival analysis revealed significantly reduced overall survival time in individuals with low-expression of RBP4 compared to those with high-expression. The joint prognostic model exhibited an AUC of 0.926 (95 % CI: 0.888∼0.964), which was significantly higher than that of AFP alone (AUC=0.809; P <0.0001). CONCLUSIONS: RBP4 shows a great potential as a biomarker with appreciable diagnostic value, complementing the AFP in HCC diagnosis. Additionally, it holds promise as a prognostic biomarker that, when integrated into a combined prognostic model, could greatly improve HCC prognosis efficiency.

Differentiation of bone marrow mesenchymal stem cells into Leydig-like cells with testicular extract liquid in vitro.

Differentiation of Leydig cells plays a key role in male reproductive function. Bone marrow mesenchymal stem cells (BMSCs) have emerged as a potential cell source for generating Leydig-like cells due to their multipotent differentiation capacity and accessibility. This study aimed to investigate the morphological and genetic expression changes of BMSCs during differentiation into Leydig-like cells. Testicular extract liquid, which simulates the microenvironment in vivo, induced the third passage BMSCs differentiated into Leydig-like cells. Changes in cell morphology were observed by microscopy, the formation of lipid droplets of androgen precursor was identified by Oil Red Staining, and the expression of testicular specific genes 3ß-HSD and SF-1 in testicular stromal cells was detected by RT-qPCR. BMSCs isolated from the bone marrow of Sprague-Dawley (SD) rats were cultured for 3 generations and identified as qualified BMSCs in terms of morphology and cell surface markers. After 14 days of induction with testicular tissue lysate, lipid droplets appeared in the cytoplasm of P3 BMSCs by Oil Red O staining. RT-qPCR detection was performed on BMSCs on the 3rd, 7th, 14th, and 21st day after induction. Relative expression levels of 3ß-HSD mRNA significantly increased after 14 days of induction, while the relative expression of SF-1 mRNA increased after 14 days of induction but was not significant. BMSCs can differentiate into testicular interstitial cells with reserve androgen precursor lipid droplets after induction by testicular tissue lysate. The differentiation ability of BMSCs provides the potential to reconstruct the testicular microenvironment and is expected to fundamentally improve testicular function and provide new treatment options for abnormal spermatogenesis diseases.

Evaluation of tubal patency based on peak injection pressure in four-dimensional hysterosalpingo-contrast sonography among infertile females: a preliminary study.

Background: Although the application of four-dimensional hysterosalpingo-contrast sonography (4D-HyCoSy) has relatively good diagnostic accuracy for assessing the patency of the fallopian tubes, the evaluation process mainly relies on morphological findings of the fallopian tubes and pelvic cavity. The purpose of this study was to explore the relationship of peak injection pressure during 4D-HyCoSy and tubal patency to provide a quantitative indicator for the evaluation of fallopian tube patency. Methods: This study included infertile patients who underwent 4D-HyCoSy and laparoscopic chromopertubation (LC) between 2020 and 2022, with LC serving as the reference test for assessing tubal patency. For the HyCoSy procedure, the ultrasound contrast agent was injected automatically using a liquid injection machine, and real-time pressure values were recorded. Patients were classified based on tubal patency status in LC as bilaterally patent, unilaterally patent, or bilaterally nonpatent. The average peak injection pressure and contrast agent volume of different groups were compared. Receiver operating characteristic (ROC) curve analysis was employed to determine the cutoff value. Results: A total of 268 infertile patients were enrolled in the study. With LC as the standard examination, the sensitivity and specificity of 4D-HyCoSy in diagnosing nonpatent fallopian tubes were 91.1% and 95.1%, respectively. In general, peak injection pressure was observed to gradually increase as tubal patency decreased (P<0.001), with average peak injection pressures of 233.5±66.3, 338.8±99.8, and 469.6±63.1 mmHg in the bilaterally patent, unilaterally patent, and bilaterally nonpatent groups, respectively. The volume of contrast agent used in patients in the bilaterally nonpatent group was significantly lower than that in the other two groups (P<0.01), with average volumes of 22.7±6.3, 24.3±9.3, and 18.9±9.2 mL, respectively. When one fallopian tube was patent, the area under the curve (AUC) for distinguishing obstruction from patency of the other fallopian tube was 0.827, with a sensitivity of 79.8% and a specificity of 74.3% (cutoff value: 254.3 mmHg). Similarly, when one fallopian tube was nonpatent, the AUC was 0.866, with a sensitivity of 90.6% and a specificity of 78.3% (cutoff value: 401.3 mmHg). Conclusions: Peak injection pressure during 4D-HyCoSy demonstrates promising diagnostic performance in evaluating fallopian tube patency in infertile patients.

Ethanol responsive lnc171 promotes migration and invasion of HCC cells via mir-873-5p/ZEB1 axis.

BACKGROUNDS: Long nonconding RNAs (lncRNAs) have been found to be a vital regulatory factor in the development process of human cancer, and could regarded as diagnostic or prognostic biomarkers for human cancers. Here, we aim to confirm the expression and molecular mechanism of RP11-171K16.5 (lnc171) in hepatocellular carcinoma (HCC). METHODS: Screening of differentially expressed lncRNAs by RNA sequencing. Expression level of gene was studied by quantitative real-time PCR (qRT-PCR). The effects of lnc171, mir-873-5p, and ethanol on migration and invasion activity of cells were studied used transwell assay, and luciferase reporter assay was used to confirm the binding site. RESULTS: RNA sequencing showed that lnc171 was markedly up-regulated in HCC. siRNA-mediated knockdown of lnc171 repressed the migration and invasion ability of HCC cells. Bioinformatic analysis, dual luciferase reporter assay, and qRT-PCR indicated that lnc171 interacted with mir-873-5p in HCC cells, and Zin-finger E-box binding homeobox (ZEB1) was a downstream target gene of mir-873-5p. In addition, lnc171 could enhance migration and invasion ability of HCC cells by up-regulating ZEB1 via sponging mir-873-5p. More interestingly, ethanol stimulation could up-regulate the increase of lnc171, thereby regulating the expression of competing endogenous RNA (ceRNA) network factors which lnc171 participated in HCC cells. CONCLUSIONS: Our date demonstrates that lnc171 was a responsive factor of ethanol, and plays a vital role in development of HCC via binding of mir-873-5p.

Nomogram for predicting difficult total laparoscopic hysterectomy: A multi-institutional, retrospective model development and validation study.

BACKGROUND: Total laparoscopic hysterectomy (TLH) is the most commonly performed gynecological surgery. However, the difficulty of the operation varies depending on the patient and surgeon. Subsequently, patient's outcomes and surgical efficiency are affected. We aimed to develop and validate a pre-operative nomogram to predict the operative difficulty in patients undergoing TLH. METHODS: This retrospective study included 663 patients with TLH from XXX Hospital and 102 patients from YYY Hospital in Chongqing, China. A multivariate logistic regression analysis was used to identify the independent predictors of operative difficulty, and a nomogram was constructed. The performance of the nomogram was validated internally and externally. RESULTS: The uterine weight, history of pelvic surgery, presence of adenomyosis, surgeon's years of practice, and annual hysterectomy volume were identified as significant independent predictors of operative difficulty. The nomogram demonstrated good discrimination in the training dataset (area under the receiver operating characteristic curve [AUC], 0.827 (95% confidence interval [CI], 0.783-0.872), internal validation dataset (AUC, 0.793 [95% CI, 0.714-0.872]), and external validation dataset (AUC, 0.756 [95% CI, 0.658-0.854]). The calibration curves showed good agreement between the predictions and observations for both internal and external validations. CONCLUSION: The developed nomogram accurately predicted the operative difficulty of TLH, facilitated pre-operative planning and patient counseling, and optimized surgical training. Further prospective multicenter clinical studies are required to optimize and validate this model.

Puerarin Induces Macrophage M2 Polarization to Exert Antinonalcoholic Steatohepatitis Pharmacological Activity via the Activation of Autophagy.

To determine the protective mechanism of puerarin against nonalcoholic steatohepatitis (NASH), the pharmacodynamic effects of puerarin on NASH were evaluated by using zebrafish, cells, and mice. Western blotting, flow cytometry, immunofluorescence, and qRT-PCR were used to detect the effects of puerarin on RAW264.7 autophagy and polarization. Key target interactions between autophagy and polarization were detected using immunoprecipitation. Puerarin regulated the M1/M2 ratio of RAW 264.7 cells induced by LPS + INF-γ. Transcriptomics revealed that PAI-1 is a key target of puerarin in regulating macrophage polarization. PAI-1 knockout reduced the number of M1-type macrophages and increased the number of M2-type macrophages. Puerarin regulated PAI-1 and was associated with macrophage autophagy. It increased p-ULK1 expression in macrophages and activated autophagic flux, reducing the level of PAI-1 expression. Stat3/Hif-1α and PI3K/AKT signaling pathways regulated the number of macrophage polarization phenotypes, reducing liver lipid droplet formation, alleviating liver structural abnormalities, decreasing the number of cytoplasmic vacuoles, and decreasing the area of blue collagen in NASH mice. Puerarin is a promising dietary component for NASH alleviation.

Radiofrequency radiation reshapes tumor immune microenvironment into antitumor phenotype in pulmonary metastatic melanoma by inducing active transformation of tumor-infiltrating CD8+ T and NK cells.

Immunosuppression by the tumor microenvironment is a pivotal factor contributing to tumor progression and immunotherapy resistance. Priming the tumor immune microenvironment (TIME) has emerged as a promising strategy for improving the efficacy of cancer immunotherapy. In this study we investigated the effects of noninvasive radiofrequency radiation (RFR) exposure on tumor progression and TIME phenotype, as well as the antitumor potential of PD-1 blockage in a model of pulmonary metastatic melanoma (PMM). Mouse model of PMM was established by tail vein injection of B16F10 cells. From day 3 after injection, the mice were exposed to RFR at an average specific absorption rate of 9.7 W/kg for 1 h per day for 14 days. After RFR exposure, lung tissues were harvested and RNAs were extracted for transcriptome sequencing; PMM-infiltrating immune cells were isolated for single-cell RNA-seq analysis. We showed that RFR exposure significantly impeded PMM progression accompanied by remodeled TIME of PMM via altering the proportion and transcription profile of tumor-infiltrating immune cells. RFR exposure increased the activation and cytotoxicity signatures of tumor-infiltrating CD8+ T cells, particularly in the early activation subset with upregulated genes associated with T cell cytotoxicity. The PD-1 checkpoint pathway was upregulated by RFR exposure in CD8+ T cells. RFR exposure also augmented NK cell subsets with increased cytotoxic characteristics in PMM. RFR exposure enhanced the effector function of tumor-infiltrating CD8+ T cells and NK cells, evidenced by increased expression of cytotoxic molecules. RFR-induced inhibition of PMM growth was mediated by RFR-activated CD8+ T cells and NK cells. We conclude that noninvasive RFR exposure induces antitumor remodeling of the TIME, leading to inhibition of tumor progression, which provides a promising novel strategy for TIME priming and potential combination with cancer immunotherapy.

Recent advances in the treatment of renal stones using flexible ureteroscopys.

Upper urinary tract stones are a common urological disease that can be treated by flexible ureteroscopy (FURS) through the natural urinary tract, in addition to extracorporeal shock wave lithotripsy (ESWL) and percutaneous nephrolithotomy (PCNL). The advantages of FURS are less trauma, faster recovery, and fewer complications, while its disadvantages include poor results of lithotripsy and stone extraction when dealing with larger stones, and prolonged operation time. Over the last two decades, the emergence of new technologies such as FURS combined with negative pressure suction, robot-assisted FURS, and artificially intelligent FURS, coupled with improvements in laser technology (the use of thulium fiber lasers (TFL) and the invention of single-use flexible ureteroscopes (su-fURS) suitable for primary level application, have significantly increased the global adoption of FURS. This surge in usage holds a promising future in clinical application, benefiting a growing number of patients with renal calculi. Accompanied by changes in technical concepts and therapeutic modalities, the scope of indications for FURS is broadening, positioning it as a potential primary choice for urolithiasis treatment in the future. This review outlines the progress in employing flexible ureteroscopy for the treatment of renal calculi in order to generate insights for further research.

Mage transposon: a novel gene delivery system for mammalian cells.

Transposons, as non-viral integration vectors, provide a secure and efficient method for stable gene delivery. In this study, we have discovered Mage (MG), a novel member of the piggyBac(PB) family, which exhibits strong transposability in a variety of mammalian cells and primary T cells. The wild-type MG showed a weaker insertion preference for near genes, transcription start sites (TSS), CpG islands, and DNaseI hypersensitive sites in comparison to PB, approaching the random insertion pattern. Utilizing in silico virtual screening and feasible combinatorial mutagenesis in vitro, we effectively produced the hyperactive MG transposase (hyMagease). This variant boasts a transposition rate 60% greater than its native counterpart without significantly altering its insertion pattern. Furthermore, we applied the hyMagease to efficiently deliver chimeric antigen receptor (CAR) into T cells, leading to stable high-level expression and inducing significant anti-tumor effects both in vitro and in xenograft mice models. These findings provide a compelling tool for gene transfer research, emphasizing its potential and prospects in the domains of genetic engineering and gene therapy.

Peripheral blood lymphocyte subsets predict the efficacy of TACE with or without PD-1 inhibitors in patients with hepatocellular carcinoma: a prospective clinical study.

Background: Although peripheral blood lymphocyte subsets, particularly PD-1+ T cells, are promising prognostic indicators for patients with cancer. However, their clinical significance remains unclear. Methods: We prospectively enrolled 157 patients with hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization combined with or without PD-1 inhibitors. Twenty peripheral lymphocyte subsets and cytokines were analyzed. We analyzed the differences in PD-1+ T cells between patients treated with and without PD-1 inhibitors and their associations with tumor response, survival prognosis, and clinical features. Results: We found that the baseline CD8+PD-1+ and CD4+PD-1+ T-cell frequencies in patients who had received PD-1 inhibitors were lower than those in patients who had not received PD-1 inhibitors (p < 0.001). In the former patients, there were no differences in PD-1+ T-cell frequencies between the responder and non-responder subgroups (p > 0.05), whereas in the latter patients, the levels of CD8+PD-1+ T cells, CD4+PD-1+ T cells, and CD8+PD-1+/CD4+PD-1+ ratio did not predict tumor response, progression-free survival (PFS), or overall survival (OS) (p>0.05). Furthermore, in multivariate analysis of patients treated with or without PD-1 inhibitors revealed that the levels of CD8+CD38+ T cells (OR = 2.806, p = 0.006) were associated with tumor response, whereas those of CD8+CD28+ T cells (p = 0.038, p = 0.001) and natural killer (NK) cells (p = 0.001, p = 0.027) were associated with PFS and OS. Although, these independent prognostic factors were associated with progressive tumor characteristics (p<0.05), with the exception of CD8+CD28+ T cells, changes in these factors before and after treatment were unassociated with tumor response (p > 0.05). Conclusion: Circulating CD8+CD38+ T cells, CD8+CD28+ T cells, and NK cells were identified as potential prognostic factors for tumor response and survival in patients with HCC. Contrastingly, although PD-1 inhibitors can effectively block the T cell PD-1 receptor, the baseline PD-1+ T-cell frequencies and changes in the frequency of these cells have limited prognostic value.

Classification and Regression Tree Predictive Model for Acute Kidney Injury in Traumatic Brain Injury Patients.

Background: Acute kidney injury (AKI) is prevalent in hospitalized patients with traumatic brain injury (TBI), and increases the risk of poor outcomes. We designed this study to develop a visual and convenient decision-tree-based model for predicting AKI in TBI patients. Methods: A total of 376 patients admitted to the emergency department of the West China Hospital for TBI between January 2015 and June 2019 were included. Demographic information, vital signs on admission, laboratory test results, radiological signs, surgical options, and medications were recorded as variables. AKI was confirmed since the second day after admission, based on the Kidney Disease Improving Global Outcomes criteria. We constructed two predictive models for AKI using least absolute shrinkage and selection operator (LASSO) regression and classification and regression tree (CART), respectively. Receiver operating characteristic (ROC) curves of these two predictive models were drawn, and the area under the ROC curve (AUC) was calculated to compare their predictive accuracy. Results: The incidence of AKI on the second day after admission was 10.4% among patients with TBI. Lasso regression identified five potent predictive factors for AKI: glucose, serum creatinine, cystatin C, serum uric acid, and fresh frozen plasma transfusions. The CART analysis showed that glucose, serum uric acid, and cystatin C ranked among the top three in terms of the feature importance of the decision tree model. The AUC value of the decision-tree predictive model was 0.892, which was higher than the 0.854 of the LASSO regression model, although the difference was not statistically significant. Conclusion: The decision tree model is valuable for predicting AKI among patients with TBI. This tree-based flowchart is convenient for physicians to identify patients with TBI who are at high risk of AKI and prompts them to develop suitable therapeutic strategies.

Revealing Medicinal Constituents of Bistorta vivipara Based on Non-Targeted Metabolomics and 16S rDNA Gene Sequencing Technology.

Bistorta vivipara is a medicinal plant with a long history, but there are few studies on the effects of its medicinal components and endophytic bacteria on the accumulation of secondary metabolites. Therefore, in this study, non-targeted metabolomics techniques and 16s rDNA techniques were used to study B. vivipara from different regions. A total of 1290 metabolites and 437 differential metabolites were identified from all samples. Among them, flavonoids, isoflavonoids, and benzopyrans are the main medicinal components of B. vivipara; these have potential anticancer, antiviral, and antioxidant properties, as well as potential applications for the treatment of atrial fibrillation. In addition, irigenin, an important medicinal component, was identified for the first time. The endophytic bacterial communities in the root tissues of B. vivipara from different regions were also different in composition and richness. Hierarchical clustering heat map analysis showed that Proteobacteria and Actinobacteriota bacteria significantly affected the accumulation of many medicinal components in the roots of B. vivipara.

CD276 promotes epithelial-mesenchymal transition in esophageal squamous cell carcinoma through the TGF-ß/SMAD signaling.

OBJECTIVE: Aberrant expression of CD276 has been reported in malignant tumors. However, the exact role and mechanisms of CD276 influence the progression of esophageal squamous cell carcinoma (ESCC) still need to be understood. METHODS: Bioinformatics analysis of data from The Cancer Genome Atlas and Gene Expression Omnibus databases, along with immunohistochemistry staining, was used to explore the expression patterns of CD276 in ESCC. Cell counting kit-8 and Transwell assays were employed to evaluate the effects of CD276 expression on tumor cell proliferation and motility. Western blotting and Transwell assays were used to explore the potential pathways through which CD276 mediates the progression of ESCC. Moreover, the in vivo role of CD276 in tumor progression was investigated by establishing a lung metastasis mouse model. RESULTS: A significant upregulation of CD276 was observed in ESCC tissues compared to adjacent tissues. The inhibition of CD276 had no evident impact on ESCC cell proliferation but notably hindered their migratory and invasive properties and the expression of epithelial-mesenchymal transition (EMT) markers. Inversely, overexpressing CD276 led to an upregulation of EMT markers, underscoring the capacity of CD276 to amplify the motility of ESCC cells. Furthermore, CD276 was found to enhance the migratory and invasive abilities of ESCC cells by activating the TGF-ß/SMAD signaling but not the PI3K/AKT pathway. In vivo studies demonstrated that CD276 facilitates pulmonary metastasis. CONCLUSION: CD276 is significant upregulation in ESCC tissues and facilitates the EMT process in ESCC cells via the TGF-ß/SMAD signaling, thus promoting the progression of ESCC.

Pathogenomics for accurate diagnosis, treatment, prognosis of oncology: a cutting edge overview.

The capability to gather heterogeneous data, alongside the increasing power of artificial intelligence to examine it, leading a revolution in harnessing multimodal data in the life sciences. However, most approaches are limited to unimodal data, leaving integrated approaches across modalities relatively underdeveloped in computational pathology. Pathogenomics, as an invasive method to integrate advanced molecular diagnostics from genomic data, morphological information from histopathological imaging, and codified clinical data enable the discovery of new multimodal cancer biomarkers to propel the field of precision oncology in the coming decade. In this perspective, we offer our opinions on synthesizing complementary modalities of data with emerging multimodal artificial intelligence methods in pathogenomics. It includes correlation between the pathological and genomic profile of cancer, fusion of histology, and genomics profile of cancer. We also present challenges, opportunities, and avenues for future work.

Downregulating DNA methyltransferase 3B by suppressing the PI3K/Akt signaling pathway enhances the chemosensitivity of glioblastoma to temozolomide.

Glioblastoma (GBM) is the most common malignant brain tumor and has the poorest prognosis attributed to its chemoresistance to temozolomide (TMZ), the first-line drug for treating GBM. TMZ resistance represents a significant obstacle to successful GBM treatment, necessitating the development of new strategies to overcome this resistance and augment the chemosensitivity of GBM cells to TMZ. This study established a TMZ-resistant U251 (U251-TMZ) cell line by exposing it to increasing doses of TMZ in vitro. We focused on the DNA methyltransferase 3B (DNMT3B) gene, phosphorylated Akt (p-Akt), total Akt (t-Akt), phosphorylated PI3K (p-PI3K), and total PI3K (t-PI3K) protein expression. Results showed that the DNMT3B gene was significantly upregulated in the U251-TMZ cell line. The p-Akt and p-PI3K protein expression in U251-TMZ cells was also significantly elevated. Moreover, we found that DNMT3B downregulation was correlated with the increased chemosensitivity of GBM cells to TMZ. LY294002 suppressed the PI3K/Akt signaling pathway, leading to a notable inhibition of PI3K phosphorylation and a significant decrease in DNMT3B expression in U251-TMZ cells. Given that DNMT3B expression is mediated by the PI3K/Akt signaling pathway, its downregulation further increased the chemosensitivity of GBM cells to TMZ and therefore is a promising therapeutic for GBM treatment. Our results suggested that DNMT3B downregulation can inhibit the proliferation of GBM cells and induce GBM cell apoptosis in vitro. In addition, the PI3K/Akt signaling pathway plays an important role in the chemosensitivity of GBM cells to TMZ by regulating DNMT3B expression.

Long-term outcome and risk factors of reintervention after high intensity focused ultrasound ablation for uterine fibroids: a systematic review and meta-analysis.

OBJECTIVES: To quantify the reintervention rate and analyze the risk factors for reintervention after high-intensity focused ultrasound (HIFU) ablation of uterine fibroids. METHODS: Eighteen studies were selected from the seven databases. A meta-analysis was applied to synthesize the reintervention rates for fibroids across various follow-up durations. Subgroup-analysis was conducted based on the year of surgery, sample size, guide methods, and non-perfusion volume ratio (NPVR). Signal intensity of T2-weighted imaging (T2WI) was independently evaluated for reintervention risk. RESULTS: The study enrolled 5216 patients with fibroids treated with HIFU. There were 3247, 1239, 1762, and 2535 women reaching reintervention rates of 1% (95% confidence interval (CI): 1-1), 7% (95% CI: 4-11), 19% (95% CI: 11-27), and 29% (95% CI: 14-44) at 12, 24, 36, and 60-month after HIFU. The reintervention rates of patients treated with US-guided HIFU (USgHIFU) were significantly lower than those of patients treated with MR-guided focused ultrasound surgery (MRgFUS). When the NPVR of fibroids was over 50%, the reintervention rates at 12, 36 and 60-month after HIFU were 1% (95% CI: 0.3-2), 5% (95% CI: 3-8), and 15% (95% CI: 9-20). The reintervention risk for hyper-intensity fibroids on T2WI was 3.45 times higher (95% CI: 2.7-4.39) for hypo-/iso-intensity fibroids. CONCLUSION: This meta-analysis showed that the overall reintervention rates after HIFU were acceptable and provided consultative suggestions regarding treatment alternatives for patients with fibroids. Subgroup-analysis revealed that USgHIFU, NPVR ≥ 50%, and hypo-/iso-intensity of fibroids on T2WI were significant factors in reducing reintervention. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023456094.

CDK16 as a potential prognostic biomarker correlated with an immunosuppressive tumor microenvironment and benefits in enhancing the effectiveness of immunotherapy in human cancers.

BACKGROUND: Cyclin-Dependent Kinase 16 (CDK16) plays significant biological roles in various diseases. Nonetheless, its function in different cancer types and its relationship with the Tumor Immune Microenvironment (TIME) are still not well-understood. METHODS: We analyzed the expression profile, genetic alterations, clinical features, and prognostic value of CDK16 in pan-cancer using data from The Cancer Genome Atlas, Genotype-Tissue Expression databases, and in vitro experiments. Additionally, the TIMER2 and ImmuCellAI databases were utilized to assess the correlation between CDK16 expression and immune cell infiltration levels. Finally, we examined the correlation between CDK16 and the response to immunotherapy using collected immunotherapy data. RESULTS: CDK16 is notably overexpressed in pan-cancer and is a risk factor for poor prognosis in various cancers. Our findings reveal that CDK16 regulates not only cell cycle-related functions to promote cell proliferation but also the autoimmunity-related functions of the innate and adaptive immune systems, along with other immune-related signaling pathways. Moreover, CDK16 overexpression contributes to an immunosuppressive tumor microenvironment, extensively suppressing immune-related features such as the expression of immune-related genes and pathways, as well as the count of immune-infiltrating cells. Our analysis indicated that individuals with low CDK16 expression showed higher response rates to immune checkpoint inhibitors and longer overall survival compared to those with high CDK16 expression. CONCLUSIONS: This study establishes CDK16 as a potential biomarker for predicting poor prognosis in a wide range of cancers. Its role in shaping the immunosuppressive tumor microenvironment and influencing the efficacy of immunotherapy highlights the urgent need for developing targeted therapies against CDK16, offering new avenues for cancer treatment and management.

Prediction of immune infiltration and prognosis for patients with cholangiocarcinoma based on a cuproptosis-related lncRNA signature.

Objective: Cholangiocarcinoma (CHOL) is a malignant disease that affects the digestive tract, and it is characterized by a poor prognosis. This research sought to explore the involvement of cuproptosis-related lncRNAs (CRLs) in the prognostic prediction and immune infiltration of cholangiocarcinoma. Methods: The expression profiles and clinical data of CHOL patients were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and CRLs were defined via co-expression analysis. Two molecular clusters distinguished by cuproptosis-related genes (CRGs) were produced. Then a risk signature consisted by four CRLs was formed, and all samples were separated into low- and high-risk groups using a risk score. Kaplan-Meier survival analysis, principal component analysis, differentially expressed analysis, immune cell infiltration analysis, and sensitivities analysis of chemotherapy drugs were conducted between the two groups. Simultaneously, the expression values of four lncRNAs confirmed by real-time PCR in our own 20 CHOL samples were brought into the risk model. Results: The CHOL samples could be differentiated into two molecular clusters, which displayed contrasting survival times. Additionally, patients with higher risk scores had significantly worse prognosis compared to those in the low-risk group. Furthermore, both immune infiltration and enrichment analysis revealed significant discrepancies in the tumor immune microenvironment (TIME) between different risk groups. Moreover, the predictive power and the correlation with CA19-9 and CEA of risk signature were validated in our own samples. Conclusion: We developed a risk signature which could serve as an independent prognostic factor and offer a promising prediction for not only prognosis but also TIME in CHOL patients.