Human Umbilical Cord Mesenchymal Stem Cells Promote Anti-Inflammation and Angiogenesis by Targeting Macrophages in a Rat Uterine Scar Model.

BACKGROUND: Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have demonstrated efficacy in repairing uterine scars, although the underlying mechanisms remain unclear. METHODS: Uterine injury was surgically induced in a rat model, followed by immediate transplantation of 5 × 10 ^ 5 hUC-MSCs to each side of the uterus. Uterine morphology was evaluated at days 14 and 30 using HE and Masson staining. Immunohistochemistry assessed macrophage polarization, angiogenesis and endometrial receptivity in the endometrium. Additionally, the regulatory effects of hUC-MSCs on macrophage polarization were explored through coculture. qRT-PCR quantified the expression of anti-inflammatory (IL10 and Arg1) and pro-inflammatory (iNOS and TNF-α) factors. Western blotting evaluated CD163 expression. RESULTS: Transplantation of hUC-MSCs promoted the healing of uterine injuries and tissue regeneration while inhibiting tissue fibrosis. Immunohistochemistry at days 14 and 30 post-transplantation demonstrated the polarization of macrophages toward the M2 phenotype in the uterine injury area in the presence of hUC-MSCs. Furthermore, hUC-MSC transplantation improved angiogenesis and endometrial receptivity in the uterine injury rat model, associated with increased IL10 expression. hUC-MSC-induced angiogenesis can be resisted by depleted macrophages. In vitro coculture experiments further demonstrated that hUC-MSCs promoted IL10 expression in macrophages while suppressing TNF-α and iNOS expression. Western blotting showed enhanced CD163 expression in macrophages following hUC-MSC treatment. CONCLUSIONS: hUC-MSCs contribute to the healing of uterine injuries by targeting macrophages to promote angiogenesis and the expression of anti-inflammatory factors.

Characteristics and utility of high-resolution optical coherence microscopy images of endocervical canal lesions.

OBJECTIVES: To investigate optical coherence microscopy (OCM) imaging features and the application value of these high-resolution images for identifying endocervical canal lesions (ECLs), which is a clinical dilemma in cervical cancer screening programs. METHODS: In total, 520 OCM images were obtained by scanning the cervical canal lesions with an ultra-high-resolution OCM system (204 specimens from 73 patients). The OCM morphologic characteristics of ECLs were observed and summarized, and then 3 researchers performed a diagnostic test of OCM images of cervical canal lesions. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value, 95% confidence interval of each parameter, and interinvestigator agreement (κ) were calculated. RESULTS: Normal endocervix, cysts, squamous metaplasia, high-grade squamous intraepithelial lesions involving glands, and invasive carcinoma had distinct OCM characteristics, which correlated well with corresponding H&E histologic sections. The accuracy, sensitivity, and specificity of the 3 researchers were 90.6%, 89.3% (95% CI, 86.5%-91.7%) and 91.6% (95% CI, 89.2%-93.5%), respectively. The positive predictive value was 90.1% (95% CI, 87.3%-92.4%), and the negative predictive value was 90.9% (95% CI, 88.5%-92.9%), with almost perfect agreement (κ = 0.874). CONCLUSIONS: The application of the OCM system in cervical canal lesions is feasible and could help improve detection of occult ECLs in cervical cancer screening programs. This study lays the foundation for further research on OCM in cervical canal lesions in vivo, which also has a potential impact on projecting pathologic evaluation beyond what is currently possible, perhaps globally.

Assessment of Efficacy and Accuracy of Cervical Cytology Screening With Artificial Intelligence Assistive System.

The role of artificial intelligence (AI) in pathology offers many exciting new possibilities for improving patient care. This study contributes to this development by identifying the viability of the AICyte assistive system for cervical screening, and investigating the utility of the system in assisting with workflow and diagnostic capability. In this study, a novel scanner was developed using a Ruiqian WSI-2400, trademarked AICyte assistive system, to create an AI-generated gallery of the most diagnostically relevant images, objects of interest (OOI), and provide categorical assessment, according to Bethesda category, for cervical ThinPrep Pap slides. For validation purposes, 2 pathologists reviewed OOIs from 32,451 cases of ThinPrep Paps independently, and their interpretations were correlated with the original ThinPrep interpretations (OTPI). The analysis was focused on the comparison of reporting rates, correlation between cytological results and histologic follow-up findings, and the assessment of independent AICyte screening utility. Pathologists using the AICyte system had a mean reading time of 55.14 seconds for the first 3000 cases trending down to 12.90 seconds in the last 6000 cases. Overall average reading time was 22.23 seconds per case compared with a manual reading time approximation of 180 seconds. Usage of AICyte compared with OTPI had similar sensitivity (97.89% vs 97.89%) and a statistically significant increase in specificity (16.19% vs 6.77%) for the detection of cervical intraepithelial neoplsia 2 and above lesions. When AICyte was run alone at a 50% negative cutoff value, it was able to read slides with a sensitivity of 99.30% and a specificity of 9.87%. When AICyte was run independently at this cutoff value, no sole case of high-grade squamous intraepithelial lesions/squamous cell carcinoma squamous lesion was missed. AICyte can provide a potential tool to help pathologists in both diagnostic capability and efficiency, which remained reliable compared with the baseline standard. Also unique for AICyte is the development of a negative cutoff value for which AICyte can categorize cases as "not needed for review" to triage cases and lower pathologist workload. This is the largest case number study that pathologists reviewed OOI with an AI-assistive system. The study demonstrates that AI-assistive system can be broadly applied for cervical cancer screening.

Erdheim­Chester disease of multisystem involvement with delayed diagnosis: A case report and literature review.

Erdheim-Chester disease (ECD) is a rare tumor of histiocytic origin, characterized by foamy or lipid-laden histiocytes mixed or surrounded by fibrosis that infiltrate multiple organs. Misdiagnosis is common due to the diversity of clinical presentations. The present study reported a case of ECD with the involvements of bone, cardiac, aorta and retroperitoneum. The patient had no obvious clinical symptoms and no noteworthy foamy histiocytes or Touton giant cells were found on pathological examination, delaying the diagnosis. The patient was a young male found to have pericardial effusion on physical examination, and computed tomography (CT) revealed soft tissue infiltrates in the retroperitoneum and around the aorta. A mediastinal biopsy revealed fibrous connective tissue with small-vessel hyperplasia and acute-chronic inflammatory cell infiltration. The initial diagnosis was retroperitoneal fibrosis (RPF), and hormonal and tamoxifen treatments were administered. The patient presented with oliguria, eyelid edema and fever four years later. A repeat CT revealed an increase in the extent of tissue infiltration and pericardial effusion compared with the previous CT. Subsequent cardiac magnetic resonance imaging revealed massive thickening in the form of fibrotic tissue infiltrating the heart and surrounding thoracic and abdominal aorta. Single photon emission CT revealed multiple areas of increased bone metabolism, particularly symmetrical involvement of the long bones of both lower extremities. A biopsy of the perirenal tissue revealed fibrous tissue and a small number of lymphocytes and macrophages [typical foamy histiocytes observed via x200 magnification and hematoxylin-eosin (HE) staining, no presence of xanthogranuloma or Touton giant cells]. After a comprehensive evaluation and ruling out other diseases, the diagnosis of ECD was determined. The prognosis of this disease is poor; early diagnosis is critical and requires accurate judgment by clinicians. Biopsies of all involved sites and refinement of genetic tests to guide treatment, if possible, are both necessary.

SPARC stabilizes ApoE to induce cholesterol-dependent invasion and sorafenib resistance in hepatocellular carcinoma.

Dysregulation of cholesterol homeostasis is implicated in the development and progression of hepatocellular carcinoma (HCC) that is characterized by intrahepatic and early extrahepatic metastasis. A better understanding of the underlying mechanisms regulating cholesterol metabolism in HCC could help identify strategies to circumvent the aggressive phenotype. Here, we found that high expression of intracellular SPARC was significantly associated with elevated cholesterol levels and an enhanced invasive phenotype in HCC. SPARC potentiated cholesterol accumulation in HCC cells during tumor progression by stabilizing the ApoE protein. Mechanistically, SPARC competitively bound to ApoE, impairing its interaction with the E3 ligase tripartite motif containing 21 (TRIM21) and preventing its ubiquitylation and subsequent degradation. ApoE accumulation led to cholesterol enrichment in HCC cells, stimulating PI3K-AKT signaling and inducing epithelial-mesenchymal transition (EMT). Importantly, sorafenib-resistant HCC cells were characterized by increased expression of intracellular SPARC, elevated cholesterol levels, and enhanced invasive capacity. Inhibiting SPARC expression or reducing cholesterol levels enhanced the sensitivity of HCC cells to sorafenib treatment. Together, these findings unveil interplay between SPARC and cholesterol homeostasis. Targeting SPARC-triggered cholesterol-dependent oncogenic signaling is a potential therapeutic strategy for advanced HCC.

Development of a prognostic model for long-term survival of young patients with bladder cancer: a retrospective analysis of the SEER Database.

OBJECTIVES: This study aims to present the clinical characteristics of young patients with bladder cancer (YBCa), evaluate related risk factors and construct a nomogram based on data acquired from the Surveillance, Epidemiology, and End Results (SEER) Database. DESIGN: Retrospective analysis of the SEER Database (2004-2015) for primary YBCa. SETTING AND PARTICIPANTS: Data for YBCa (defined as those aged 40 years or younger) were extracted from the SEER Database, which covers approximately 28% of the US population, using the SEER*Stat software (V.8.4.0.1). A total of 1233 YBCa were identified. Patients were randomly assigned to the training and validation sets. The database included clinicopathological features, demographic information and survival outcomes, such as age, gender, race, year of diagnosis, marital status at diagnosis, primary tumour site, histological type, tumour grade, tumour, node, metastases (TNM) staging, treatment regimen for the primary tumour, cause of death and survival time. A nomogram model was developed using univariate and multivariate analyses. The prediction model was validated using the consistency index (C-index), calibration curve and receiver operating characteristic curve. PRIMARY OUTCOME MEASURES: 3-year, 5-year and 10-year overall survival (OS). RESULTS: 1233 YBCa from 2004 to 2015 were randomly assigned to the training set (n=865) and validation set (n=368). Age, marital status, tumour grade, histological type and TNM staging were included in the nomogram. The C-index of the model was 0.876. The 3-year, 5-year and 10-year OS area under the curve values for the training and validation sets were 0.949, 0.923 and 0.856, and 0.919, 0.890 and 0.904, respectively. Calibration plots showed that the nomogram had a robust predictive accuracy. CONCLUSIONS: To our knowledge, this is the first study to establish a precise nomogram predicting the 3-year, 5-year and 10-year OS in YBCa based on multivariate analyses. Our nomogram may serve as a valuable reference for future diagnostics and individualised treatments for YBCa. However, external validation is warranted to assess the accuracy and generalisability of our prognostic model.

In Situ Reaction-Generated Aldehyde-Scavenging Polypeptides-Curcumin Conjugate Nanoassemblies for Combined Treatment of Spinal Cord Injury.

The microenvironment after traumatic spinal cord injury (SCI) involves complex pathological processes, including elevated oxidative stress, accumulated reactive aldehydes from lipid peroxidation, excessive immune cell infiltration, etc. Unfortunately, most of current neuroprotection therapies cannot cope with the intricate pathophysiology of SCI, leading to scant treatment efficacies. Here, we developed a facile in situ reaction-induced self-assembly method to prepare aldehyde-scavenging polypeptides (PAH)-curcumin conjugate nanoassemblies (named as PFCN) for combined neuroprotection in SCI. The prepared PFCN could release PAH and curcumin in response to oxidative and acidic SCI microenvironment. Subsequently, PFCN exhibited an effectively neuroprotective effect through scavenging toxic aldehydes as well as reactive nitrogen and oxygen species in neurons, modulating microglial M1/M2 polarization, and down-regulating the expression of inflammation-related cytokines to inhibit neuroinflammation. The intravenous administration of PFCN could significantly ameliorate the malignant microenvironment of injured spinal cord, protect the neurons, and promote the motor function recovery in the contusive SCI rat model.

Association between blood ethylene oxide levels and periodontitis risk: a population-based study.

Background: The etiopathogenesis of periodontitis is closely associated with environmental conditions. However, the relationship between ethylene oxide exposure and periodontitis risk remains unclear. Methods: We selected qualified participants from National Health and Nutrition Examination Survey (NHANES) 2013-2014. Periodontitis was identified according to the criteria of the Community Periodontal Index (CPI), Centers for Disease Control and Prevention (CDC)/American Academy of Periodontology (AAP) definition. Ethylene oxide exposure was quantified by hemoglobin adducts of ethylene oxide (HbEO) levels. Log2-transformation was used to normalize HbEO levels. We designed three logistic regression models to explore potential relationship between HbEO and periodontitis. Restricted cubic spline (RCS) and subgroup analysis were also conducted with all covariates adjusted. We performed multivariable linear regression to appraise the association between the risk of periodontitis and different indicators of inflammation, including white blood cells, neutrophils, lymphocytes, and monocytes. Mediation analysis was subsequently performed to examine whether ethylene oxide exposure contributed to periodontitis development through systemic body inflammation. Results: A total of 1,065 participants aged more than 30 were incorporated in this study. We identified that participants with higher HbEO levels showed increased risk of periodontitis after adjusting for all covariates (OR = 1.49, 95% CI: 1.14, 1.95, p = 0.0014). The results of subgroup analysis remained stable. The restricted cubic spline (RCS) curve also revealed a non-linear correlation between log2-transformed HbEO levels with the risk of periodontitis (p for nonlinear < 0.001). Mediation analysis indicated that HbEO level was significantly associated with four inflammatory mediators, with the mediated proportions of 14.44% (p < 0.001) for white blood cell, 9.62% (p < 0.001) for neutrophil, 6.17% (p = 0.006) for lymphocyte, and 6.72% (p < 0.001) for monocyte. Conclusion: Participants with higher ethylene oxide exposure showed higher risk of periodontitis, which was partially mediated by systemic body inflammation. More well-designed longitudinal studies should be carried out to validate this relationship.

PLOD3 facilitated T cell activation in the colorectal tumor microenvironment and liver metastasis by the TNF-α/ NF-κB pathway.

BACKGROUND: Colorectal cancer (CRC) has been the third most prevalent cancer worldwide. Liver metastasis is the critical factor for the poor prognosis of CRC. Here, we investigated the expression and role of PLOD3 in CRC. METHODS: Different liver metastasis models were established by injecting PLOD3 stable knockdown or overexpression CT26 or MC38 mouse CRC cells into the spleen of mice to verify the tumorigenicity and metastasis ability in vivo. RESULTS: We identified PLOD3 is significantly overexpressed in liver metastasis samples of CRC. High expression of PLOD3 was significantly associated with poor survival of CRC patients. The knockdown of PLOD3 exhibited remarkable inhibition of proliferation, migration, and invasion in CRC cells, while the opposite results could be found in different PLOD3-overexpressed CRC cells. Stable knockdown of PLOD3 also significantly inhibited liver metastasis of CRC cells in different xenografts models, while stable overexpression of PLOD3 promotes liver metastasis and tumor progression. Further studies showed that PLOD3 facilitated the T cell activation in the tumor microenvironment and affected the TNF-α/ NF-κB pathway. CONCLUSIONS: This study revealed the essential biological functions of PLOD3 in colon cancer progression and metastasis, suggesting that PLOD3 is a promising translational medicine target and bioengineering targeting PLOD3 overcomes CRC liver metastasis.

NK cells as powerful therapeutic tool in cancer immunotherapy.

BACKGROUND: Natural killer (NK) cells have gained considerable attention and hold great potential for their application in tumor immunotherapy. This is mainly due to their MHC-unrestricted and pan-specific recognition capabilities, as well as their ability to rapidly respond to and eliminate target cells. To artificially generate therapeutic NK cells, various materials can be utilized, such as peripheral blood mononuclear cells (PBMCs), umbilical cord blood (UCB), induced pluripotent stem cells (iPSCs), and NK cell lines. Exploiting the therapeutic potential of NK cells to treat tumors through in vivo and in vitro therapeutic modalities has yielded positive therapeutic results. CONCLUSION: This review provides a comprehensive description of NK cell therapeutic approaches for tumors and discusses the current problems associated with these therapeutic approaches and the prospects of NK cell therapy for tumors.

Advances and prospects of mRNA vaccines in cancer immunotherapy.

Cancer vaccines, designed to activate the body's own immune system to fight against tumors, are a current trend in cancer treatment and receiving increasing attention. Cancer vaccines mainly include oncolytic virus vaccine, cell vaccine, peptide vaccine and nucleic acid vaccine. Over the course of decades of research, oncolytic virus vaccine T-VEC, cellular vaccine sipuleucel-T, various peptide vaccines, and DNA vaccine against HPV positive cervical cancer have brought encouraging results for cancer therapy, but are losing momentum in development due to their respective shortcomings. In contrast, the advantages of mRNA vaccines such as high safety, ease of production, and unmatched efficacy are on full display. In addition, advances in technology such as pseudouridine modification have cracked down the bottleneck for developing mRNA vaccines including instability, innate immunogenicity, and low efficiency of in vivo delivery. Several cancer mRNA vaccines have achieved promising results in clinical trials, and their usage in conjunction with other immune checkpoint inhibitors (ICIs) has further boosted the efficiency of anti-tumor immune response. We expect a rapid development of mRNA vaccines for cancer immunotherapy in the near future. This review provides a brief overview of the current status of mRNA vaccines, highlights the action mechanism of cancer mRNA vaccines, their recent advances in clinical trials, and prospects for their clinical applications.

Gene engineered exosome reverses T cell exhaustion in cancer immunotherapy.

Cancer patients by immune checkpoint therapy have achieved long-term remission, with no recurrence of clinical symptoms of cancer for many years. Nevertheless, more than half of cancer patients are not responsive to this therapy due to immune exhaustion. Here, we report a novel gene engineered exosome which is rationally designed by engineering PD1 gene and simultaneously enveloping an immune adjuvant imiquimod (PD1-Imi Exo) for boosting response of cancer immune checkpoint blockage therapy. The results showed that PD1-Imi Exo had a vesicular round shape (approximately 139 nm), revealed a significant targeting and a strong binding effect with both cancer cell and dendritic cell, and demonstrated a remarkable therapeutic efficacy in the melanoma-bearing mice and in the breast cancer-bearing mice. The mechanism was associated with two facts that PD1-Imi Exo blocked the binding of CD8+ T cell with cancer cell, displaying a PD1/PDL1 immune checkpoint blockage effect, and that imiquimod released from PD1-Imi Exo promoted the maturation of immature dendritic cell, exhibiting a reversing effect on the immune exhaustion through activating and restoring function of CD8+ T cell. In conclusion, the gene engineered exosome could be used for reversing T cell exhaustion in cancer immunotherapy. This study also offers a promising new strategy for enhancing PD1/PDL1 therapeutic efficacy, preventing tumor recurrence or metastasis after surgery by rebuilding the patients' immunity, thus consolidating the overall prognosis.

Covalent drugs based on small molecules and peptides for disease theranostics.

Biomacromolecules, such as proteins, nucleic acids and polysaccharides, are widely distributed in the human body, and some of them have been recognized as the targets of drugs for disease theranostics. Drugs typically act on targets in two ways: non-covalent bond and covalent bond. Non-covalent bond-based drugs have some disadvantages, such as structural instability and environmental sensitivity. Covalent interactions between drugs and targets have a longer action time, higher affinity and controllability than non-covalent interactions of conventional drugs. With the development of artificial intelligence, covalent drugs have received more attention and have been developed rapidly in pharmaceutical research in recent years. From the perspective of covalent drugs, this review summarizes the design methods and the effects of covalent drugs. Finally, we discuss the application of covalent peptide drugs and expect to provide a new reference for cancer treatment.

Trimethylamine-N-oxide (TMAO) and predicted risk of cardiovascular events after partial nephrectomy.

INTRODUCTION: Emerging evidence suggests that uremic toxins, in particular trimethylamine-N-oxide(TMAO), indoxyl-sulfate(IS), and p-cresyl-sulfate(PCS), may associate with increased risk of cardiovascular events(CVe). However, whether uremic toxins increase after partial nephrectomy(PN) and their correlation with risk for CVe remains unknown. METHODS: 100 patients managed with PN were retrospectively reviewed. TMAO/IS/PCS levels were examined by liquid chromatography-mass-spectrometry. Renal-parenchymal-volume-preservation(RPVP) was estimated from CT scans. Predicted risks for CVe were obtained using the Framingham score. Linear regression assessed association between uremic toxins, GFR and risk of CVe. Logistic regression evaluated factors associated with post-PN TMAO. RESULTS: TMAO, IS and PCS increased from 1.7, 3.7 and 3.5 µmol/L before PN to 3.6, 5.4 and 7.4 µmol/L at latest follow-up, respectively, while GFR declined from 102 to 93 ml/min/1.73 m2 (all p<0.001). TMAO, IS and PCS levels all negatively correlated with GFR(all p<0.001). Predicted 10-year risk of CVe increased from 1.1% pre-PN to 1.7% post-PN(p<0.001), primarily due to increased age(p<0.001), blood pressure(p = 0.002) and total cholesterol(p = 0.003). TMAO(ß = 0.038) and GFR (ß = -0.02) were independent predictors for predicted 10-year CVe risk on multivariable-analysis. Increased TMAO was an early and sustained finding maintained through 5 years, unlike IS, PCS and eGFR. On multivariable analysis, increased pre-PN TMAO(OR = 2.79) and decreased RPVP(OR = 3.23) were identified as independent risk factors for higher post-PN TMAO, while ischemia type/duration failed to correlate. CONCLUSION: Uremic toxin levels increased after PN correlating with reduced GFR. Higher TMAO independently associated with greater predicted 10-year CVe risk. Parenchymal mass preserved rather than ischemia time or type associated with increased TMAO.

CAV1 and KRT5 are potential targets for prostate cancer.

Prostate cancer is the most common malignant tumor of male urogenital system that occurs in prostate epithelium. However, relationship between CAV1 and KRT5 and prostate cancer remains unclear. The prostate cancer datasets GSE114740 and GSE200879 were downloaded from Gene Expression Omnibus generated by GPL11154 and GPL32170. De-batch processing was performed, differentially expressed genes (DEGs) were screened, and weighted gene co-expression network analysis. The construction and analysis of protein-protein interaction network, functional enrichment analysis, gene set enrichment analysis. Gene expression heat map was drawn and immune infiltration analysis was performed. Comparative toxicogenomics database analysis were performed to find the disease most related to core gene. In addition, the cell experiment was performed to verify the role of CAV1 and KRT5 by western blot. Divided into 4 groups: control, prostate cancer, prostate cancer-over expression, and prostate cancer- knock out. TargetScan screened miRNAs that regulated central DEGs; 770 DEGs were identified. According to Gene Ontology analysis, they were mainly concentrated in actin binding and G protein coupled receptor binding. In Kyoto Encyclopedia of Gene and Genome analysis, they were mainly concentrated in PI3K-Akt signal pathway, MAPK signal pathway, and ErbB signal pathway. The intersection of enrichment terms of differentially expressed genes and GOKEGG enrichment terms was mainly concentrated in ErbB signaling pathway and MAPK signaling pathway. Three important modules were generated. The protein-protein interaction network obtained 8 core genes (CAV1, BDNF, TGFB3, FGFR1, PRKCA, DLG4, SNAI2, KRT5). Heat map of gene expression showed that core genes (CAV1, TGFB3, FGFR1, SNAI2, KRT5) are highly expressed in prostate cancer tissues and low in normal tissues. Comparative toxicogenomics database analysis showed that core genes (CAV1, TGFB3, FGFR1, SNAI2, KRT5) were associated with prostate tumor, cancer, tumor metastasis, necrosis, and inflammation. CAV1 and KRT5 are up-regulated in prostate cancer. CAV1 and KRT5 are highly expressed in prostate cancer. The higher expression of CAV1 and KRT5, the worse prognosis.

Imaging-based adipose biomarkers for predicting clinical outcomes of cancer patients treated with immune checkpoint inhibitors: a systematic review.

Background: Since the application of Immune checkpoint inhibitors (ICI), the clinical outcome for metastatic cancer has been greatly improved. Nevertheless, treatment response varies in patients, making it urgent to identify patients who will receive clinical benefits after ICI therapy. Adipose body composition has proved to be associated with tumor response. In this systematic review, we aimed to summarize the current evidence on imaging adipose biomarkers that predict clinical outcomes in patients treated with ICI in various cancer types. Methods: Embase and PubMed were searched from database inception to 1st February 2023. Articles included investigated the association between imaging-based adipose biomarkers and the clinical outcomes of patients treated with ICI. The methodological quality of included studies was evaluated through Newcastle- Ottawa Quality Assessment Scale and Radiomics Quality Score tools. Results: Totally, 22 studies including 2256 patients were selected. Non-small cell lung cancer (NSCLC) had the most articles (6 studies), followed by melanoma (5 studies), renal cell carcinoma (RCC) (3 studies), urothelial carcinoma (UC) (2 studies), head and neck squamous cell carcinoma (HNSCC) (1 study), gastric cancer (1 study) and liver cancer (1 study). The remaining 3 studies investigated metastatic solid tumors including various types of cancers. Adipose biomarkers can be summarized into 5 categories, including total fat, visceral fat, subcutaneous fat, intramuscular fat and others, which exerted diverse correlations with patients' prognosis after being treated with ICI in different cancers. Most biomarkers of body fat were positively associated with survival benefits. Nevertheless, more total fat was predictable of worse outcomes in NSCLC, while inter-muscular fat was associated with poor clinical benefits in UC. Conclusion: There is relatively well-supported evidence for imaging-based adipose biomarkers to predict the clinical outcome of ICI. In general, most of the studies show that adipose tissue is positively correlated with clinical outcomes. This review summarizes the significant biomarkers proven by researches for each cancer type. Further validation and large independent prospective cohorts are needed in the future. The protocol of this systematic review has been registered at the International Prospective Register of Systematic Reviews (http://www.crd.york.ac.uk/PROSPERO, registration no: CRD42023401986).

RHOJ Induces Epithelial-to-Mesenchymal Transition by IL-6/STAT3 to Promote Invasion and Metastasis in Gastric Cancer.

Background: Recently, the molecular classification of gastric cancer (GC) promotes the advances of GC patients' precision therapy and prognosis prediction. According to the Asian Cancer Research Group (ACRG), GC is classified as microsatellite instable (MSI) subtype GC, microsatellite stable/epithelial-to-mesenchymal transition (MSS/EMT) subtype GC, MSS/TP53- subtype GC, and MSS/TP53+ subtype GC. Due to the easy metastasis of EMT-subtype GC, it has the worst prognosis, the highest recurrence rate, and the tendency to occur at a younger age. Therefore, it is curious and crucial for us to understand the molecular basis of EMT-subtype GC. Methods: The expression of RHOJ was detected by quantitative real-time PCR (qPCR) and immunohistochemistry (IHC) in GC cells and tissues. Western blotting and immunofluorescence (IF) were conducted to examine the effects of RHOJ on the EMT markers' expression of GC cells. The GC cells' migration and invasion were investigated by transwell assay. The tumor growth and metastasis were demonstrated correspondingly in different xenograft models. Results: Firstly, it was noticed that RHOJ was significantly upregulated in EMT-subtype GC and RHOJ has close relationships with the EMT process of GC, based on the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases. Next, transwell assay and tail vein metastasis models were conducted to verify that RHOJ mediates the EMT to regulate the invasion and metastasis of GC in vitro and in vivo. In addition, weakened tumor angiogenesis was observed after RHOJ knockdown by the angiogenesis assay of HUVEC. RNA-seq and further study unveiled that RHOJ aggravates the malignant progression of GC by inducing EMT through IL-6/STAT3 to promote invasion and metastasis. Finally, blocking the IL-6/STAT3 signaling overcame RHOJ-mediated GC cells' growth and migration. Conclusions: These results indicate that the upregulation of RHOJ contributes to EMT-subtype GC invasion and metastasis via IL-6/STAT3 signaling, and RHOJ is expected to become a promising biomarker and therapeutic target for EMT-subtype GC patients.

STING-IRG1 inhibits liver metastasis of colorectal cancer by regulating the polarization of tumor-associated macrophages.

The liver is the main site of colorectal cancer (CRC) metastasis. Tumor-associated macrophages (TAMs) play a key role in tumor metastasis. Therefore, modulating the function of tumor-associated macrophages is a potential therapeutic strategy to control tumor metastasis. We found in vivo experiments that the activation of STING inhibited CRC liver metastasis in model mice and affected the macrophage phenotype in the tumor microenvironment. Mechanistically, STING affects TAM polarization and regulates macrophage function through IRG1. And STING activates IRG1 to promote the nuclear translocation of TFEB, affecting the ability of macrophages to suppress tumor metastasis.Therefore, this study highlights the critical role of the STING-IRG1 axis on TAM reprogramming and its role in the process of tumor liver metastasis, which may provide a promising therapeutic strategy for CRC liver metastasis.

Benign Metastasizing Leiomyoma: Is "Wait and Watch" Strategy Feasible?

Benign metastasizing leiomyoma (BML) is a rare disease that affects women with a history of uterine leiomyoma. The aim of this study is to investigate the clinical characteristics and outcome patterns. We collected 385 cases from previous reports indexed in PubMed and Google Scholar and made a thorough review. All relevant clinical parameters were carefully reviewed, including age at diagnosis, clinical presentations, course of disease, medical history, imaging, molecular tests, treatment, and outcomes. Univariate survival analysis was performed to investigate the effects of treatment strategies on outcomes. The mean age at diagnosis was 46.2 years. The most common site for the metastasis was lung, and followed by abdomen/pelvis/retroperitoneum, bone, lymph nodes, and heart. The medical histories and molecular alterations were non-specific, and the pathogenesis was still unclear. Due to its unresectable nature, hormone deprivation treatment, including oophorectomy and hormone drugs, is the most effective strategy to reduce or delay tumor progression. The present study may provide a useful consultation for diagnosing and managing BMLs.

Bioorthogonal Engineered Virus-Like Nanoparticles for Efficient Gene Therapy.

Gene therapy offers potentially transformative strategies for major human diseases. However, one of the key challenges in gene therapy is developing an effective strategy that could deliver genes into the specific tissue. Here, we report a novel virus-like nanoparticle, the bioorthgonal engineered virus-like recombinant biosome (reBiosome), for efficient gene therapies of cancer and inflammatory diseases. The mutant virus-like biosome (mBiosome) is first prepared by site-specific codon mutation for displaying 4-azido-L-phenylalanine on vesicular stomatitis virus glycoprotein of eBiosome at a rational site, and the reBiosome is then prepared by clicking weak acid-responsive hydrophilic polymer onto the mBiosome via bioorthogonal chemistry. The results show that the reBiosome exhibits reduced virus-like immunogenicity, prolonged blood circulation time and enhanced gene delivery efficiency to weakly acidic foci (like tumor and arthritic tissue). Furthermore, reBiosome demonstrates robust therapeutic efficacy in breast cancer and arthritis by delivering gene editing and silencing systems, respectively. In conclusion, this study develops a universal, safe and efficient platform for gene therapies for cancer and inflammatory diseases.