Head and neck squamous cell carcinomas of unknown primary: Can ancillary studies help identify more primary tumor sites?

A subset of head and neck squamous cell carcinomas present solely as metastatic disease in the neck and are of unknown primary origin (SCCUP). Most primary tumors will ultimately be identified, usually in the oropharynx. In a minority of cases, the primary site remains elusive. Here, we examine the role of ancillary testing, including mutational signature analysis (MSA), to help identify likely primary sites in such cases. Twenty-two cases of SCCUP in the neck, collected over a 10-year period, were classified by morphology and viral status; including human papillomavirus (HPV) testing by p16 immunohistochemistry (IHC) and RT-qPCR, as well as Epstein-Barr virus (EBV) testing by EBER-ISH. CD5 and c-KIT (CD117) IHC was done to evaluate for possible thymic origin in all virus-negative cases. Whole exome sequencing, followed by MSA, was used to identify UV signature mutations indicative of cutaneous origin. HPV was identified in 12 of 22 tumors (54.5%), favoring an oropharyngeal origin, and closely associated with nonkeratinizing tumor morphology (Fisher's exact test; p = 0.0002). One tumor with indeterminant morphology had discordant HPV and p16 status (p16+/HPV-). All tumors were EBV-negative. Diffuse expression of CD5 and c-KIT was identified in 1 of 10 virus-negative SCCUPs (10%), suggesting a possible ectopic thymic origin rather than a metastasis. A UV mutational signature, indicating cutaneous origin, was identified in 1 of 10 (10%) virus-negative SCCUPs. A cutaneous auricular primary emerged 3 months after treatment in this patient. Primary tumors became clinically apparent in 2 others (1 hypopharynx, 1 hypopharynx/larynx). Thus, after follow-up, 6 tumors remained unclassifiable as to the possible site of origin (27%). Most SCCUPs of the neck in our series were HPV-associated and thus likely of oropharyngeal origin. UV signature mutation analysis and additional IHC for CD5 and c-KIT for possible thymic origin may aid in further classifying virus-negative unknown primaries. Close clinical inspection of hypopharyngeal mucosa may also be helpful, as a subset of primary tumors later emerged at this site.

Kruppel-like factor 14 ameliorated obesity and related metabolic disorders by promoting adipose tissue browning.

Obesity has been identified as a serious and debilitating disease that threatens human health, but the current treatment strategies still have some shortcomings. Exercise and dieting are difficult for many people to adhere to, and a series of surgical risks and pain brought about by volume reduction have made it difficult for the current weight loss effect to meet human expectations. In this study, we first found that mice with overexpression of the transcription factor Kruppel-like factor 14 (KLF14) in subcutaneous adipose tissue gained weight more slowly while consuming a high-fat diet than did control mice, and these mice also showed reduced insulin resistance and liver lipid deposition abnormalities. Mechanistically, the browning of white adipose tissue was promoted in adipose tissue with KLF14 overexpression; therefore, we preliminarily concluded that KLF14 can improve obesity by promoting the browning of white adipose tissue and energy consumption, thus ameliorating obesity and related metabolic disturbances. In summary, our results revealed that KLF14 may promote white adipose tissue browning, thus ameliorating high-fat diet-induced obesity and hepatic steatosis, as well as serum lipid levels and insulin resistance, thereby achieving a positive effect on metabolism.NEW & NOTEWORTHY Our study first explored the role of KLF14 in the development and progression of HFD-induced obesity in male mice. Its beneficial effect on adipose browning and metabolic disorders suggests that KLF14 may provide us a new therapeutic strategy for obesity and related metabolic complications. This health problem is of global concern and needs to be addressed.

Development of Small-Molecule Fluorescent Probes Targeting Enzymes.

As biological catalysts, enzymes are vital in controlling numerous metabolic reactions. The regulation of enzymes in living cells and the amount present are indicators of the metabolic status of cell, whether in normal condition or disease. The small-molecule fluorescent probes are of interest because of their high sensitivity and selectivity, as well as their potential for automated detection. Fluorescent probes have been useful in targeting particular enzymes of interest such as proteases and caspases. However, it is difficult to develop an ideal fluorescent probe for versatile purposes. In the future, the design and synthesis of enzyme-targeting fluorescent probes will focus more on improving the selectivity, sensitivity, penetration ability and to couple the fluorescent probes with other available imaging molecules/technologies.

Quality assessment of Succus Bambusae oral liquids based on gas chromatography/mass spectrometry fingerprints and chemometrics.

RATIONALE: Succus Bambusae is consumed as a kind of herbal medicine and natural beverage in China. However, the current quality standards for Succus Bambusae are low and lack safety indicators, which makes it difficult to effectively guarantee its quality. Therefore, it is of great significance to study the identification and quality control technology for the product. METHODS: We have developed a set of qualitative and quantitative methods based on gas chromatography/mass spectrometry (GC/MS) for the analysis of volatile components in Succus Bambusae oral liquid (SBOL). Combining GC/MS fingerprint analysis and related chemometrics algorithms, with similarity evaluation, Hotelling T2 and distance to Model X (DModX) as criteria, the quality consistency of different batches was evaluated, and SBOL samples from different manufacturers were differentiated. RESULTS: Twenty-nine volatile components were preliminarily identified from 40 batches of SBOL samples from six manufacturers, and six Q-markers (Quality Markers) for the SBOLs were discussed and determined using GC/MS. The products from different manufacturers were distinguished using chemometrics. CONCLUSIONS: The results showed that the quality of the SBOL samples from different batches and different manufacturers fluctuated greatly, which suggested that research into the raw materials and manufacturing techniques should be strengthened to improve the quality of SBOL and ensure its quality consistency.

[Research progress on chemical constituents and quality control methods of Succus Bambusae].

Through the investigation of a large number of both domestic and overseas literatures and related quality standards, chemical compositions, quality evaluation system and quality control methods of Succus Bambusae were systematic summarized in this study. There were abundant chemical constituents in Succus Bambusae, mainly including volatile ingredients, amino acids, flavonoids, trace elements and vitamins, with high medicinal and edible value. The quality control methods involved traditional morphological identification, spectroscopy, chromatography and other techniques. However, the current quality standards of Succus Bambusae are relatively low, lacking safety indicators, and cannot effectively ensure its quality, seriously affecting the safety and effectiveness of its clinical use. Therefore, it is particularly important to establish a set of highly sensitive and specific quality evaluation system for Succus Bambusae. In this paper, the current research status of the chemical compositions and quality standards of Succus Bambusae were reviewed, with the purpose of providing a basis for further improvement of its quality evaluation system.

Provision of carbon skeleton for lipid synthesis from the breakdown of intracellular protein and soluble sugar in Phaeodactylum tricornutum under high CO2.

BACKGROUND: Increasing CO2 emissions have resulted in ocean acidification, affecting marine plant photosynthesis and changing the nutrient composition of marine ecosystems. The physiological and biochemical processes of marine phytoplankton in response to ocean acidification have been reported, but have been mainly focused on growth and photosynthetic physiology. To acquire a thorough knowledge of the molecular regulation mechanisms, model species with clear genetic background should be selected for systematic study. Phaeodactylum tricornutum is a pennate diatom with the characteristics of small genome size, short generation cycle, and easy to transform. Furthermore, the genome of P. tricornutum has been completely sequenced. RESULTS AND DISCUSSION: In this study, P. tricornutum was cultured at high and normal CO2 concentrations. Cell composition changes during culture time were investigated. The 13C isotope tracing technique was used to determine fractional labeling enrichments for the main cellular components. The results suggested that when lipid content increased significantly under high CO2 conditions, total protein and soluble sugar contents decreased. The 13C labeling experiment indicated that the C skeleton needed for fatty acid C chain elongation in lipid synthesis under high CO2 conditions is not mainly derived from NaHCO3 (carbon fixed by photosynthesis). CONCLUSION: This study indicated that breakdown of intracellular protein and soluble sugar provide C skeleton for lipid synthesis under high CO2 concentration.

Elevated CO2 improves both lipid accumulation and growth rate in the glucose-6-phosphate dehydrogenase engineered Phaeodactylum tricornutum.

BACKGROUND: Numerous studies have shown that stress induction and genetic engineering can effectively increase lipid accumulation, but lead to a decrease of growth in the majority of microalgae. We previously found that elevated CO2 concentration increased lipid productivity as well as growth in Phaeodactylum tricornutum, along with an enhancement of the oxidative pentose phosphate pathway (OPPP) activity. The purpose of this work directed toward the verification of the critical role of glucose-6-phosphate dehydrogenase (G6PDH), the rate-limiting enzyme in the OPPP, in lipid accumulation in P. tricornutum and its simultaneous rapid growth rate under high-CO2 (0.15%) cultivation. RESULTS: In this study, G6PDH was identified as a target for algal strain improvement, wherein G6PDH gene was successfully overexpressed and antisense knockdown in P. tricornutum, and systematic comparisons of the photosynthesis performance, algal growth, lipid content, fatty acid profiles, NADPH production, G6PDH activity and transcriptional abundance were performed. The results showed that, due to the enhanced G6PDH activity, transcriptional abundance and NAPDH production, overexpression of G6PDH accompanied by high-CO2 cultivation resulted in a much higher of both lipid content and growth in P. tricornutum, while knockdown of G6PDH greatly decreased algal growth as well as lipid accumulation. In addition, the total proportions of saturated and unsaturated fatty acid, especially the polyunsaturated fatty acid eicosapentaenoic acid (EPA; C20:5, n-3), were highly increased in high-CO2 cultivated G6PDH overexpressed strains. CONCLUSIONS: The successful of overexpression and antisense knockdown of G6PDH well demonstrated the positive influence of G6PDH on algal growth and lipid accumulation in P. tricornutum. The improvement of algal growth, lipid content as well as polyunsaturated fatty acids in high-CO2 cultivated G6PDH overexpressed P. tricornutum suggested this G6PDH overexpression-high CO2 cultivation pattern provides an efficient and economical route for algal strain improvement to develop algal-based biodiesel production.

Correlation between circulating endothelial progenitor cells and serum carcinoembryonic antigen level in colorectal cancer.

Circulating endothelial progenitor cells (cEPCs) play an important role in cancer development. Previous studies showed that serum carcinoembryonic antigen (CEA) levels and the number of circulating endothelial progenitor cells (cEPCs) in the peripheral blood are both involved in tumor neoangiogenesis, and can be used for monitoring tumor progression, recurrence, metastasis, and therapeutic responses. However, the clinical relevance of these biomarkers remains unknown. In this study, 40 colorectal cancer (CRC) patients and 17 healthy volunteers were recruited and the amount of cEPCs in the peripheral blood was measured by flow cytometry. The serum CEA level was determined by CEA-RIACT assay. Results showed that cEPC level positively correlated with the stage of the disease, but not with the age and gender of the patients. Moreover, patients with higher serum CEA levels had higher cEPC levels. These results provide clinical evidence for a correlation between two commonly used biomarkers. Further understanding the role of serum CEA in cEPC-mediated tumor vascularization may improve clinical CRC diagnosis and provide useful insights into the design of therapeutic interventions that target tumor vasculature.

Copper-Catalyzed Cross-Dehydrogenative N2-Coupling of NH-1,2,3-Triazoles with N,N -Dialkylamides: N-Amidoalkylation of NH-1,2,3-Triazoles.

An efficient copper-catalyzed C-N bond formation by N-H/C-H cross-dehydrogenative coupling (CDC) between NH-1,2,3-triazoles and N,N-dialkylamides has been developed. The method provided N-amidoalkylated 1,2,3-triazoles with moderate to high yields, and the reactions showed high N2-selectivities when 4,5-disubstituted NH-1,2,3-triazoles served as the substrates.

A Learnable and Explainable Wavelet Neural Network for EEG Artifacts Detection and Classification.

Electroencephalography (EEG) artifacts are very common in clinical diagnosis and can heavily impact diagnosis. Manual screening of artifact events is labor-intensive with little benefit. Therefore, exploring algorithms for automatic detection and classification of EEG artifacts can significantly assist clinical diagnosis. In this paper, we propose a learnable and explainable wavelet neural network (WaveNet) for EEG artifact detection and classification. The model is powered by the wavelet decomposition block based on invertible neural network, which can extract signal features without information loss, and a tree generator for building wavelet tree structure automatically. They provide the model with good feature extraction capabilities and explainability. To evaluate the model's performance more fairly, we introduce the base point level matching score (BASE) and the Event-Aligned Compensation Scoring (EACS) at the event level as two metrics for model performance evaluation. On the challenging Temple University EEG Artifact (TUAR) dataset, our model outperforms other baselines in terms of F1-score for both artifact detection and classification tasks. The case study also validates the model's ability to offer explainability for predictions based on frequency band energy, suggesting potential applications in clinical diagnosis.

SpatialDeX is a Reference-Free Method for Cell Type Deconvolution of Spatial Transcriptomics Data in Solid Tumors.

The rapid development of spatial transcriptomics (ST) technologies has enabled transcriptome-wide profiling of gene expression in tissue sections. Despite the emergence of single-cell resolution platforms, most ST sequencing studies still operate at a multi-cell resolution. Consequently, deconvolution of cell identities within the spatial spots has become imperative for characterizing cell type-specific spatial organization. To this end, we developed SpatialDeX, a regression model-based method for estimating cell type proportions in tumor ST spots. SpatialDeX exhibited comparable performance to reference-based methods and outperformed other reference-free methods with simulated ST data. Using experimental ST data, SpatialDeX demonstrated superior performance compared with both reference-based and reference-free approaches. Additionally, a pan-cancer clustering analysis on tumor spots identified by SpatialDeX unveiled distinct tumor progression mechanisms both within and across diverse cancer types. Overall, SpatialDeX is a valuable tool for unraveling the spatial cellular organization of tissues from ST data without requiring scRNA-seq references.

Clinical value of serum tumor markers in assessing the efficacy of neoadjuvant chemotherapy in advanced ovarian cancer: single-center prospective clinical study.

Objective: This study aimed to assess the clinical importance of various biomarkers, including NLR, CEA, CA199, CA125, CA153, and HE4, through dynamic testing to evaluate the effectiveness of neoadjuvant chemotherapy (NACT) for individuals facing advanced ovarian cancer. This provides valuable information for tailoring treatment plans to individual patients, thereby leading to a more personalized and effective management of individuals facing ovarian cancer. Methods: The levels of NLR, CA125, CA199, CEA, CA153, and HE4 were detected before chemotherapy and after 3 courses of chemotherapy. Patients were categorized into ineffective and effective groups according to the effectiveness of NACT. To evaluate the factors influencing NACT's effectiveness in individuals facing advanced ovarian cancer, receiver operating characteristic (ROC) curves, predictive modeling, and multifactorial regression analysis were employed. Results: In the effective group, the patients' age, maximum tumor diameter, and CEA and HE4 levels of the patients were significantly higher compared to those in the ineffective group (P <.05). Additionally, the difference in HE4 levels before and after treatment between the effective and ineffective groups was statistically significant (P<.05). Multifactorial analysis showed that age and maximum tumor diameter were independent risk factors impacting the effectiveness of NACT in individuals facing advanced ovarian cancer (P<.05). The ROC curve for predicting the effectiveness of NACT in individuals facing advanced ovarian cancer showed a sensitivity of 93.3% for NLR and a specificity of 92.3% for CA199. HE4 emerged as the most reliable predictor, demonstrating a specificity of 84.6% and a sensitivity of 75.3%. The area under the curve of the combined CA125 and HE4 assays for predicting the ineffectiveness of NACT in individuals facing advanced ovarian cancer was 0.825, showcasing a specificity of 74.2% and a sensitivity of 84.6%. Conclusion: The predictive capacity for the effectiveness of NACT in individuals facing advanced ovarian cancer is notably high when considering the sensitivity of NLR and the specificity of CA199. Additionally, the combination of CA125 and HE4 assays can obtain a better predictive effect, which can accurately select patients suitable for NACT, determine the appropriate timing of the interval debulking surgery (IDS) surgery, and achieve a satisfactory tumor reduction effect.

Pan-cancer discovery of somatic mutations from RNA sequencing data.

Identification of somatic mutations (SMs) is essential for characterizing cancer genomes. While DNA-seq is the prevalent method for identifying SMs, RNA-seq provides an alternative strategy to discover tumor mutations in the transcribed genome. Here, we have developed a machine learning based pipeline to discover SMs based on RNA-seq data (designated as RNA-SMs). Subsequently, we have conducted a pan-cancer analysis to systematically identify RNA-SMs from over 8,000 tumors in The Cancer Genome Atlas (TCGA). In this way, we have identified over 105,000 novel SMs that had not been reported in previous TCGA studies. These novel SMs have significant clinical implications in designing targeted therapy for improved patient outcomes. Further, we have combined the SMs identified by both RNA-seq and DNA-seq analyses to depict an updated mutational landscape across 32 cancer types. This new online SM atlas, OncoDB ( https://oncodb.org ), offers a more complete view of gene mutations that underline the development and progression of various cancers.

Understanding apoptotic induction by Sargentodoxa cuneata-Patrinia villosa herb pair via PI3K/AKT/mTOR signalling in colorectal cancer cells using network pharmacology and cellular studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Sargentodoxa cuneata (Sargentodoxa cuneata (Oliv.) Rehder & E.H.Wilson, DXT)-Patrinia villosa(Patrinia villosa (Thunb.) Dufr, BJC) constitutes a commonly employed herb pair in Chinese medicine for colorectal cancer (CRC) treatment. Modern pharmacological investigations have revealed the anticancer activities of both Sargentodoxa cuneata and Patrinia villosa. Nevertheless, comprehensive studies are required to discern the specific antitumor active ingredients and mechanism of action when these two herbs are used in combination. AIM OF THE STUDY: Through the integration of network pharmacology, molecular docking techniques, experimental assays, and bioinformatics analysis, our study aims to forecast the active ingredients, potential targets, and molecular mechanisms underlying the therapeutic efficacy of this herb pair against CRC. MATERIALS AND METHODS: Plant names (1, Sargentodoxa cuneata (Oliv.) Rehder & E.H.Wilson; 2, Patrinia villosa (Thunb.) Dufr.) have been verified through WorldFloraOnline (www.worldFloraonline.org) and MPNs (http://mpns.kew.org). The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) were utilized for screening the active ingredients of the herb pair. The PharmMapper database was employed to predict the target proteins for each active ingredient. CRC-related targets were obtained from the Genecards database, Online Mendelian Inheritance in Man (OMIM) database, Disease Gene Network (DisGeNET) database, and Therapeutic Target Database (TTD). Common targets were identified by intersecting the target proteins of all active ingredients with CRC-related targets. Protein-protein interactions (PPI) for the common target proteins were constructed using the String database and Cytoscape 3.9.1 software. Network topology analysis facilitated the identification of core targets. These core targets were subjected to enrichment analysis of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) using the Metascape database. Molecular docking was performed using Discovery Studio 2019 to investigate the interactions between the active ingredients and core target proteins. The core targets were validated through bioinformatics analysis using GEPIA, HPA, and the cBioPortal database. Finally, a series of experiments were conducted to further validate the results in vitro. RESULT: A total of 15 active ingredients and 255 herb targets were identified, resulting in 66 common targets in conjunction with 6113 disease targets. The PPI analysis highlighted AKT1, EGFR, CASP3, SRC, and ESR1 as core targets. KEGG enrichment analysis indicated significant enrichment in the PI3K-AKT signaling pathway, a pathway associated with cancer. Molecular docking experiments confirmed favorable interactions between dihydroguaiaretic acid and the core target proteins (AKT1, EGFR, CASP3, and ESR1). Bioinformatics analysis revealed differential expression of EGFR and CASP3 in normal and CRC tissues. Cellular experiments further verified that dihydroguaiaretic acid induces apoptosis in colorectal cancer cells through the PI3K-AKT signaling pathway. CONCLUSION: Our network pharmacology study has elucidated that the Sargentodoxa cuneata-Patrinia villosa herb pair exerts the negative regulation of the PI3K/AKT/mTOR signaling pathway, ultimately leading to the induction of apoptosis in colorectal cancer cells. This research has predicted and validated the active ingredients, potential targets, and molecular mechanisms of Sargentodoxa cuneata-Patrinia villosa in the treatment of CRC, providing scientific evidence for the use of traditional Chinese medicine in managing CRC.

Oxymatrine induces apoptosis in non-small cell lung cancer cells by downregulating TRIM46.

Sophora flavescens Aiton, a traditional Chinese medicine that was supposed to predominantly play an anti-inflammatory role, has been used to treat multiple diseases, including cancer, for over two thousand years. Recently, it has attracted increasing attention due to the anti-tumor properties of Oxymatrine, one of the most active alkaloids extracted from S. flavescens. This study aims to explore it's anti-tumor effects in non-small cell lung cancer (NSCLC) and the underlying mechanisms. We first investigated the effects of oxymatrine on cell apoptosis in lung cancer cell lines A549 and PC9 as well as explored related genes in regulating the apoptosis by transcriptome analysis. Subsequently, to further study the role of TRIM46, we constructed two types of TRIM46 over-expression cells (A549TRIM46+ and PC9TRIM46+ cells) and then investigated the effect of TRIM46 on oxymatrine-induced apoptosis. Moreover, we explored the effect of TRIM46 on downstream signaling pathways. Transcriptome analysis suggested that shared differentially expressed genes (DEGs) in A549 and PC9 cells treated with oxymatrine were CACNA1I, PADI2, and TRIM46. According to TCGA database analysis, the abundance of TRIM46 expression was higher than CACNA1I, and PADI2 in lung cancer tissues, then was selected as the final DEG for subsequent studies. We observed that oxymatrine resulted in down-expression of TRIM46 as well as induced the apoptosis of the cancer cells in a dose- and time-dependent manner. Meanwhile, we found that apoptosis induced by oxymatrine was inhibited by over-expressing TRIM46. Furthermore, our study indicated that the NF-κB signaling pathway was involved in apoptosis suppressed by TRIM46. We conclude that TRIM46 is the direct target of oxymatrine to induce anti-tumor apoptosis and may activate the downstream NF-κB signaling pathway.

Th1 cell immune response in Talaromyces marneffei infection with anti-interferon-γ autoantibody syndrome.

Anti-interferon-γ autoantibody (AIGA) syndrome may be the basis of disseminated Talaromyces marneffei infection in human immunodeficiency virus (HIV)-negative adults. However, the pathogenesis of Th1 cell immunity in T. marneffei infection with AIGA syndrome is unknown. A multicenter study of HIV-negative individuals with T. marneffei infection was conducted between September 2018 and September 2020 in Guangdong and Guangxi, China. Patients were divided into AIGA-positive (AP) and AIGA-negative (AN) groups according to the AIGA titer and neutralizing activity. The relationship between AIGA syndrome and Th1 immune deficiency was investigated by using AP patient serum and purification of AIGA. Fifty-five HIV-negative adults with disseminated T. marneffei infection who were otherwise healthy were included. The prevalence of AIGA positivity was 83.6%. Based on their AIGA status, 46 and 9 patients were assigned to the AP and AN groups, respectively. The levels of Th1 cells, IFN-γ, and T-bet were higher in T. marneffei-infected patients than in healthy controls. However, the levels of CD4+ T-cell STAT-1 phosphorylation (pSTAT1) and Th1 cells were lower in the AP group than in the AN group. Both the serum of patients with AIGA syndrome and the AIGA purified from the serum of patients with AIGA syndrome could reduce CD4+ T-cell pSTAT1, Th1 cell differentiation and T-bet mRNA, and protein expression. The Th1 cell immune response plays a pivotal role in defense against T. marneffei infection in HIV-negative patients. Inhibition of the Th1 cell immune response may be an important pathological effect of AIGA syndrome.IMPORTANCEThe pathogenesis of Th1 cell immunity in Talaromyces marneffei infection with anti-interferon-γ autoantibody (AIGA) syndrome is unknown. This is an interesting study addressing an important knowledge gap regarding the pathogenesis of T. marneffei in non-HIV positive patients; in particular patients with AIGA. The finding of the Th1 cell immune response plays a pivotal role in defense against T. marneffei infection in HIV-negative patients, and inhibition of the Th1 cell immune response may be an important pathological effect of AIGA syndrome, which presented in this research could help bridge the current knowledge gap.

Recent progress on triterpenoid derivatives and their anticancer potential.

Cancer poses a significant global public health challenge, with commonly used adjuvant or neoadjuvant chemotherapy often leading to adverse side effects and drug resistance. Therefore, advancing cancer treatment necessitates the ongoing development of novel anticancer agents with diverse structures and mechanisms of action. Natural products remain crucial in the process of drug discovery, serving as a primary source for pharmaceutical leads and therapeutic advancements. Triterpenoids are particularly compelling due to their complex structures and wide array of biological activities. Recent research has demonstrated that naturally occurring triterpenes and their derivatives have the potential to serve as promising candidates for new drug development. This review aims to comprehensively explore the anticancer properties of triterpenoids and their synthetic analogs, with a focus on recent advancements. Various aspects, such as synthesis, phytochemistry, and molecular simulation for structure-activity relationship analyses, are summarized. It is anticipated that triterpenoid derivatives will emerge as notable anticancer agents following further investigation into their mechanisms of action and in vivo studies.

Development of a clinical scoring model to predict the overall and relapse­free survival of patients with hepatocellular carcinoma following a hepatectomy.

Hepatocellular carcinoma (HCC) is a highly lethal disease, and surgical resection is one of the major treatment methods used. However, to date, at least to the best of our knowledge, there is no effective prognostic scoring system for the overall survival (OS) and relapse-free survival (RFS) of patients following hepatectomy. The present study developed a low-cost and easy-to-use model based on the clinicopathological characteristics of patients with HCC for assessment of outcome prediction and risk stratification. A total of 690 patients with HCC undergoing surgery were included and randomly divided into two cohorts (n=345). Cox regression analysis was conducted to investigate the association between the clinicopathological and treatment features, and patient survival. Multivariate analysis revealed that ascites, vascular tumor thrombus, low tumor differentiation and extrahepatic metastasis were independent risk factors for OS. Extrahepatic metastasis and multiple tumors were independent risk factors to predict tumor recurrence. These variables were weighted to construct the ascites, vascular tumor thrombus, low tumor differentiation, extrahepatic metastasis and multiple tumors (AVLEM) score based on the cumulative incidence (CuI) of the aforementioned variables, and the patients were classified into grade 0 (CuI=0), grade 1 (CuI=1 for OS and CuI ≥1 for RFS), and grade 2 (CuI ≥2) subgroups, respectively. Kaplan-Meier analysis revealed that the OS and RFS differed significantly among the subgroups; however, the survival rate between the two cohorts did not exhibit any marked differences. On the whole, the present study demonstrates that with this AVLEM scoring system, patients with HCC with a high score had a poor OS and RFS; thus, it is suggested that such patients undergo imaging examinations following a hepatectomy more frequently.

Serum sphingolipids aid in diagnosing adult HIV-negative patients with pulmonary cryptococcosis: a clinical cohort study.

Background: Pulmonary cryptococcosis (PC) contributes to the ongoing global disease burden in human immunodeficiency virus (HIV)-negative populations. Since some PC patients are misdiagnosed under existing diagnostic guidelines, new diagnostic markers are needed to improve diagnostic accuracy and therapeutic efficacy and reduce disease risk. Methods: Our previously established sphingolipidomic approach was employed to explore the use of serum sphingolipids (SPLs) in diagnosing HIV-negative patients with PC. A clinical cohort of PC, pulmonary aspergillosis (PA), and tuberculosis (TB) patients and healthy controls was assessed to identify SPL biomarkers. Results: A total of 47 PC, 27 PA, and 18 TB patients and 40 controls were enrolled. PC and TB patients had similar clinical features, laboratory test results and radiological features, excluding plural effusion. The serum ceramide [Cer (d18:1/18:0)] level showed a significant increase in PC patients compared to controls and PA and TB patients (P<0.05). Cer (d18:1/18:0) was identified as a specific diagnostic biomarker for PC. The optimal cut-off value of greater than 18.00 nM showed a diagnostic sensitivity of 76.60% and a specificity of 95.00% and better distinguished PC patients from PA and TB patients. Furthermore, the serum Cer (d18:1/18:0) level gradually decreased after 3 and 6 months of treatment, suggesting the prediction potential for therapeutic efficacy of this biomarker. In addition, Cer (d18:1/18:0) analysis presented a higher sensitivity than the cryptococcal antigen (CrAg) assay. Conclusions: This is the first study to report the use of the SPL Cer (d18:1/18:0) as a serum biomarker for diagnosing Cryptococcus spp. infection in HIV-negative patients.