Liquid biopsy can reflect the state of tumors in vivo non-invasively, thus providing a strong basis for the early diagnosis, individualized treatment monitoring and prognosis of tumors. Circulating tumor cells (CTCs) and tumor-derived extracellular vesicles (tdEVs) contain information-rich components, such as nucleic acids and proteins, and they are essential markers for liquid biopsies. Their capture and analysis are of great importance for the study of disease occurrence and development and, consequently, have been the subject of many reviews. However, both CTCs and tdEVs carry the biological characteristics of their original tissue, and few reviews have focused on their function in the staging and classification of cancer. In this review, we focus on state-of-the-art sensors based on the simultaneous detection of multiple biomarkers within CTCs and tdEVs, with clinical applications centered on cancer classification and subtyping. We also provide a thorough discussion of the current challenges and prospects for novel sensors with the ultimate goal of cancer classification and staging. It is hoped that these most advanced technologies will bring new insights into the clinical practice of cancer screening and diagnosis.

Screen printed electrode (SPE) on carbon-based inks exhibits promising applications in biosensing, environment protection and food safety. We report here a unique carbon-based material comprising Pt-CuO nanocrystal interfacially anchored on functionalized carbon nanofiber (Pt-CuO@FCNF) and its functional ink to build SPE for ultrasensitive detection of cell released H2O2. Pt-CuO@FCNF is fabricated using a one-pot and mass production method through direct pyrolysis of Pt and CuO precursors together with FCNF. FCNF with 1-D structure and high electrical conductivity can interfically anchor Pt-CuO nanocrystal, which synergically promotes rich active site and catalytic activity towards H2O2. Pt-CuO@FCNF exhibits a wide linear response of 0.4 μM-11 mM, a low detection limit of 17 nM, a fast response time of 1.0 s, and good selectivity. Eventually, Pt-CuO@FCNF SPE realizes real-time and ultrasensitive qualification of H2O2 released from both normal and cancer cells.

Timely identification of human papillomavirus (HPV) infection is crucial for the prevention of cervical cancer. Current HPV detection methods mainly rely on polymerase chain reaction (PCR), which often requires bulky equipment and a long assay time. In this work, we report a heating-membrane-assisted multiplexed microfluidics platform that couples recombinase polymerase amplification (RPA) and CRISPR technology (termed M3-CRISPR) for fast and low-cost detection of multiple HPV subtypes. The heating membrane can provide convenient temperature control for the on-chip RPA and CRISPR assays. This stand-alone system allows simultaneous detection of HPV16 and HPV18 with high specificity and detection sensitivity (0.5 nM and 1 × 10-18 M for unamplified and amplified plasmids, respectively) in 30 min with a fluorescence-based readout. Furthermore, we introduced an optimized lateral flow dipstick (LFD) into the portable system to allow visualized detection of HPV DNA. The LFD-based readout also reached a detection sensitivity of 1 × 10-18 M for amplified plasmids and realized successful detection of HPV subtypes in the clinical samples. Finally, we established an automatic microfluidic system that enables the sample-in-answer-out detection of HPV subtypes. We believe that this fast, convenient, and affordable molecular diagnostic platform can serve as a useful tool in point-of-care testing of HPV or other pathogens.

The surface-enhanced Raman scattering (SERS) bioprobe's strategy for identifying tumor cells always depended on the intensity difference of the Raman signal compared with that of normal cells. Hence, exploring novel SERS nanostructure with excellent spectra stability, a high enhancement factor (EF), and good biocompatibility is a primary premise for boosting SERS signal reliability and accuracy of tumor cells. Here, high SERS EF (5.52 × 106) is acquired by developing novel amorphous nitrogen-doped carbon (NDC) nanocages (NCs), whose EF value was in a leading position among carbon-based SERS substrates. In addition, a uniform SERS signal was obtained on NDC NCs due to homogeneous morphology and size. The delocalized carbon-conjugated systems of graphitic-N, pyrrole-N, and pyridine-N with lone pair electrons increase the electronic density of states and reduce the electron localization function of NDC NCs, thereby promoting the charge transfer process. The electron-donor platform of the NDC NCs facilitates the thermodynamic process of charge transfer, resulting in multimode vibrational coupling in the surface complexes, which greatly amplifies the molecular polarizability. Importantly, the good biocompatibility and signal stability endow these NDC NC SERS bioprobes unique superiority in distinguishing tumor cells, and quantitative recognition of two triple-negative breast cancer cells based on SERS detection mode has been successfully realized.

The patient was a 70s man, whose chief complaint of Hematochezia. He visited neighborhood hospital and was diagnosed with lower rectal cancer by colonoscopy. Preoperative CT showed a mass in the bladder, which led to a diagnosis of multiple early stage bladder cancer after a thorough urological examination. We diagnosed that very low anterior resection was necessary for rectal cancer and total bladder resection was necessary for bladder cancer. The patient underwent robotic- assisted total pelvic exenteration with anal preservation. One year and three months have passed since the surgery, and no signs of recurrence have been observed.

Situs inversus totalis(SIT)is a rare congenital condition that causes complete transposition of thoracic and abdominal viscera. Due to associated anatomical abnormalities and low frequency, surgery for affected patients is considered to be difficult. A 72-year-old man was referred to our hospital with a chief complaint of narrow stools. The diagnosis was anal canal cancer(cT1bN0M0)accompanied by SIT. A trans-perineal minimally invasive surgical procedure with laparoscopic abdominoperineal resection(Tp-APR)was performed. When mobilizing the sigmoid colon, the surgeon changed their position in consideration of anatomical abnormalities. On the other hand, manipulation around the rectum was possible using the same technique as in patients with normal anatomy. The postoperative course was uneventful, and he had no recurrence 18 months after surgery. This is the first case that showed Tp-APR for anal canal cancer with SIT performed safely and feasibly. Preoperative simulation of associated abnormal anatomical structures is considered crucial for a case of SIT.

To clarify the function of the puborectalis muscle(PM)in fecal incontinence(FI)prevention after low anterior resection (LAR)for lower rectal cancer(LRC), PM function at 3 years after LAR was studied. A total of 29 patients aged 40-79 years (19 men and 10 women, mean age: 63.9 years)who underwent LAR for LRC were enrolled in the present study. Based on the presence of postoperative FI, these patients were divided into 2 groups[group A: patients with FI(n=13), 11 men and 2 women aged 43-75 years(mean age: 64.8 years)and group B: patients without FI(continence, n=16), 8 men and 8 women aged 41-79 years(mean age: 62.9 years)]. These groups were compared with group C of control subjects[n=38; 28 men and 10 women aged 42-76 years(mean age: 64.5 years)]. Magnetic stimulation at the S2-4 sacral levels has been shown to activate the sacral motor nerve(SMN)root of the cauda equina. SMN latency(SMNL)was determined on the right, left, and posterior sides of the upper anal canal. FI after LAR was also evaluated using the Wexner score(WS), with a score of 8 or more being associated with FI according to our data. All patients had pathological Stage Ⅰ disease(19 patients: T1, N0, M0; 10 patients: T2, N0, M0). Group A had a larger proportion of men than group B(p<0.1). The distance of anastomosis from the anal verge(DAAV)was significantly shorter in group A(2.2±1.2 cm)than in group B(4.6 ±1.3 cm)(p<0.001). Regarding WS of group A, 23.1% patients had a score of 8-10(mean: 9.0), 53.8% of 11-15 (mean: 13.4), and 30.7% of 16-20(mean: 17.0). All patients in group A(WS: 8 or more)were incontinent. In contrast, all patients in groups B(WS: 0)and C(WS: 0)were continent. Patients with preoperative defecation ability(WS: 0)were also continent. As for SMNL on the right(9 o'clock), left(15 o'clock), and posterior(18 o'clock)sides of the PM located in the upper anal canal, conduction delay was significantly longer in group A(8.4±0.6 ms, 8.2±1.9 ms, and 8.3±0.9 ms, respectively)than in groups B(4.4±0.5 ms, 4.3±0.7 ms, and 4.4±0.9 ms, respectively)and C(4.1±0.5 ms, 4.0±0.5 ms, and 4.2±0.7 ms, respectively)(p<0.001, all). FI after LAR with a short DAAV, especially in men, may cause PM dysfunction due to operative damage of the SMN.

A woman in her 60s had been aware of perianal erosions for 1 month. Skin biopsy showed Paget's cells in the stratified squamous epithelium, and immunohistochemistry showed negative staining for CK7 and positive staining for CK20. Colonoscopy revealed well-differentiated adenocarcinoma in the anal canal. Computed tomography showed neither regional lymph node metastasis nor distant metastasis. Hence, she was diagnosed with anal canal carcinoma with pagetoid spread. We determined the extent of resection of the skin lesion preoperatively by mapping biopsy, and performed laparoscopic abdominoperineal resection. The pathological findings revealed adenocarcinoma(tub1, tub2), and the skin resection margin was negative. Immunohistochemistry for Paget's cells in the stratified squamous epithelium showed negative staining for GCDFP-15 and CK7, and positive staining for CK20. Twenty-four months after surgery, we detected right inguinal lymph node metastasis and performed right inguinal lymphadenectomy. As of 4 months after the lymphadenectomy, no local recurrence or distant metastasis has been detected during follow-up examinations.

Perianal Pagetoid spread is a rare condition for which there is no proven therapy. We experienced a case of anal canal cancer with Pagetoid spread which exhibited a significant response to preoperative chemoradiotherapy(CRT). A 76-year-old man with anal stenosis was referred to our hospital. He was diagnosed with anal canal cancer with Pagetoid spread. No infiltration into the surrounding tissue was observed, but metastasis to the left inguinal lymph node was noted. The patient received preoperative CRT(oral S-1, 1.8 Gy×25 Fr, a total dose of 45 Gy)including the bilateral inguinal region. After CRT, the main tumor size was reduced and PET-CT showed disappearance of the abnormal accumulation in the left inguinal lymph nodes. Laparoscopic abdominoperineal resection and left inguinal trans lymphadenectomy were performed. The macroscopic findings of the surgical specimen confirmed no residual carcinoma or lymph node metastasis. Although more proof is needed, this case suggested that CRT may be effective for anal canal cancer with pagetoid spread.

The patient was an 83-year-old woman. CT scan showed a 20 mm mass in the surgical anatomy of the medial segment (S4)of the liver, but the patient refused to undergo surgery and continued periodic clinical follow-up. After 1 year and 3 months of initial examination, a CT scan showed an enlargement of 36 mm. Therefore, surgical treatment was adopted. Preoperative lower gastrointestinal endoscopy revealed a type 1 tumor of the sigmoid colon quarter circumference 30 mm from the anal verge, and the biopsy led to a diagnosis of adenocarcinoma equivalent to tub 1. The hepatic mass showed heterogeneous contrast effect centered on the arterial phase margins and prolonged contrast effect in the equilibrium phase. Since the liver tumor was a single S4 mass with a 36 mm diameter, laparoscopic sigmoidectomy and laparoscopic partial hepatic resection were performed subsequently. Pathology results showed that the sigmoid colon tumor and hepatic S4 mass were predominantly well-differentiated and moderately-differentiated adenocarcinomas, respectively. Immunohistochemical results were cytokeratin 7 antibody-positive and cytokeratin 20 antibody-negative, leading to a definitive diagnosis of intrahepatic cholangiocarcinoma. The patient's postoperative course was well and was discharged from the hospital on postoperative day 12. After 1 year postoperatively, the patient remains recurrence-free.

Computerized identification of lymph node metastasis of breast cancer (BCLNM) from whole-slide pathological images (WSIs) can largely benefit therapy decision and prognosis analysis. Besides the general challenges of computational pathology, like extra-high resolution, very expensive fine-grained annotation, etc., two particular difficulties with this task lie in (1) modeling the significant inter-tumoral heterogeneity in BCLNM pathological images, and (2) identifying micro-metastases, i.e., metastasized tumors with tiny foci. Towards this end, this paper presents a novel weakly supervised method, termed as Prototypical Multiple Instance Learning (PMIL), to learn to predict BCLNM from WSIs with slide-level class labels only. PMIL introduces the well-established vocabulary-based multiple instance learning (MIL) paradigm into computational pathology, which is characterized by utilizing the so-called prototypes to model pathological data and construct WSI features. PMIL mainly consists of two innovatively designed modules, i.e., the prototype discovery module which acquires prototypes from training data by unsupervised clustering, and the prototype-based slide embedding module which builds WSI features by matching constitutive patches against the prototypes. Relative to existing MIL methods for WSI classification, PMIL has two substantial merits: (1) being more explicit and interpretable in modeling the inter-tumoral heterogeneity in BCLNM pathological images, and (2) being more effective in identifying micro-metastases. Evaluation is conducted on two datasets, i.e., the public Camelyon16 dataset and the Zbraln dataset created by ourselves. PMIL achieves an AUC of 88.2% on Camelyon16 and 98.4% on Zbraln (at 40x magnification factor), which consistently outperforms other compared methods. Comprehensive analysis will also be carried out to further reveal the effectiveness and merits of the proposed method.

Helicobacter pylori (H. pylori) is a class I carcinogen causing gastric cancer. Almost 50% of people on earth have been infected and it is worse in developing countries. Early diagnosis of H. pylori infection is the most important strategy for preventing the spread and worse consequences. H. pylori can be isolated from human saliva, and the sampling of saliva is easy and convenient. Therefore, we developed a visual denaturation bubble-mediated strand exchange amplification and RGB visual analysis-based assay for quantitative detection of H. pylori in saliva in this study. Under the optimized reaction temperature and time, the SEA reaction could be finished in 30 min with a simple reaction system and low dependency on equipment. The detection results could be qualitatively identified by the naked eye and quantitatively analyzed by a developed RGB visual analysis method. The limit of detection (LOD) of RGB visual analysis was 10.8 CFU/mL. This assay had good specificity and anti-interference capacity. In the artificial contamination test, the recovery rate of our assay was between 99.3% and 111.5%, with RSD values ranging from 1.7% to 3.5%. These indicated our assay also had good reliability in the detection of saliva. We believe this assay showed good potential for better non-invasive diagnosis of H. pylori infection.

Extracellular acidification indicates a metabolic shift in cancer cells and is, along with tissue hypoxia, a hallmark of tumor malignancy. Thus, non-invasive mapping of extracellular pH (pHe) is essential for researchers to understand the tumor microenvironment and to monitor tumor response to metabolism-targeting drugs. While electron paramagnetic resonance (EPR) has been successfully used to map pHe in mouse xenograft models, this method is not sensitive enough to map pHe with a moderate amount of exogenous pH-sensitive probes. Here, we show that a modified EPR system achieves twofold higher sensitivity by using the multiple harmonic detection (MHD) method and improves the robustness of pHe mapping in mouse xenograft models. Our results demonstrate that treatment of a mouse xenograft model of human-derived pancreatic ductal adenocarcinoma cells with the carbonic anhydrase IX (CAIX) inhibitor U-104 delays tumor growth with a concurrent tendency toward further extracellular acidification. We anticipate that EPR-based pHe mapping can be expanded to monitor the response of other metabolism-targeting drugs. Furthermore, pHe monitoring can also be used for the development of improved metabolism-targeting cancer treatments.

Circulating tumor cells (CTCs) have emerged as promising circulating biomarkers for non-invasive cancer diagnosis and management. Isolation and detection of CTCs in clinical samples are challenging due to the extreme rarity and high heterogeneity of CTCs. Here, we describe a poly(ethylene oxide) (PEO) concentration gradient-based microfluidic method for rapid, label-free, highly efficient isolation of CTCs directly from whole blood samples. Stable concentration gradients of PEO were formed within the microchannel by co-injecting the side fluid (blood sample spiked with 0.025% PEO) and center fluid (0.075% PEO solution). The competition between the elastic lift force and the inertial lift force enabled size-based separation of large CTCs and small blood cells based on their distinct migration patterns. The microfluidic device could process 1 mL of blood sample in 30 min, with a separation efficiency of >90% and an enrichment ratio of >700 for tumor cells. The isolated CTCs from blood samples were enumerated by immunofluorescence staining, allowing for discrimination of breast cancer patients from healthy donors with an accuracy of 84.2%. The concentration gradient-based microfluidic separation provides a powerful tool for label-free isolation of CTCs for a wide range of clinical applications.

Recently, large, high-quality public datasets have led to the development of convolutional neural networks that can detect lymph node metastases of breast cancer at the level of expert pathologists. Many cancers, regardless of the site of origin, can metastasize to lymph nodes. However, collecting and annotating high-volume, high-quality datasets for every cancer type is challenging. In this paper we investigate how to leverage existing high-quality datasets most efficiently in multi-task settings for closely related tasks. Specifically, we will explore different training and domain adaptation strategies, including prevention of catastrophic forgetting, for breast, colon and head-and-neck cancer metastasis detection in lymph nodes. Our results show state-of-the-art performance on colon and head-and-neck cancer metastasis detection tasks. We show the effectiveness of adaptation of networks from one cancer type to another to obtain multi-task metastasis detection networks. Furthermore, we show that leveraging existing high-quality datasets can significantly boost performance on new target tasks and that catastrophic forgetting can be effectively mitigated.Last, we compare different mitigation strategies.

ATP and reactive oxygen species (ROS) are considered significant indicators of cell apoptosis. However, visualizing the interplay between apoptosis-related ATP and ROS is challenging. Herein, we developed a metal-organic framework (MOF)-based nanoprobe for an apoptosis assay using duplex imaging of cellular ATP and ROS. The nanoprobe was fabricated through controlled encapsulation of gold nanorods with a thin zirconium-based MOF layer, followed by modification of the ROS-responsive molecules 2-mercaptohydroquinone and 6-carboxyfluorescein-labeled ATP aptamer. The nanoprobe enables ATP and ROS visualization via fluorescence and surface-enhanced Raman spectroscopy, respectively, avoiding the mutual interference that often occurs in single-mode methods. Moreover, the dual-modal assay effectively showed dynamic imaging of ATP and ROS in cancer cells treated with various drugs, revealing their apoptosis-related pathways and interactions that differ from those under normal conditions. This study provides a method for studying the relationship between energy metabolism and redox homeostasis in cell apoptosis processes.

Formalin-fixed, paraffin-embedded (FFPE) tissues are an invaluable resource for retrospective studies, but protein extraction and subsequent sample processing steps have been shown to be challenging for mass spectrometry (MS) analysis. Streamlined high-throughput sample preparation workflows are essential for efficient peptide extraction from complex clinical specimens such as fresh frozen tissues or FFPE. Overall, proteome analysis has gained significant improvements in the instrumentation, acquisition methods, sample preparation workflows, and analysis pipelines, yet even the most recent FFPE workflows remain complex and are not readily scalable. Here, we present an optimized workflow for automated sonication-free acid-assisted proteome (ASAP) extraction from FFPE sections. ASAP enables efficient protein extraction from FFPE specimens, achieving similar proteome coverage as established methods using expensive sonicators, resulting in reduced sample processing time. The broad applicability of ASAP on archived pediatric tumor FFPE specimens resulted in high-quality data with increased proteome coverage and quantitative reproducibility. Our study demonstrates the practicality and superiority of the ASAP workflow as a streamlined, time- and cost-effective pipeline for high-throughput FFPE proteomics of clinical specimens.

Aim: pharmaceutical patenting activity in developing countries, including Mexico, is unknown. Objective: determine the activity of pharmaceutical patents by Mexican universities. Method: using 'university' as keyword and A61K, A61P and C07 as International Patent Classification codes, was searched to generate a perspective of pharmaceutical patent applications by Mexican universities. Results: 227 patents (186 granted patents + 41 not-granted patents) were claimed in the period 2000-2018. The leading university was the National Autonomous University of Mexico, followed by the Instituto Politecnico Nacional, Universidad Autonoma de Nuevo León, and Universidad Autonoma de Puebla. The pharmaceutical concerns addressed were led by the fields of infectious, cancer and diabetes. Conclusion: in Mexican universities, the licensing of pharmaceutical patents is still in its early stages.

The blood levels of cancer antigen 125 (CA125) and human epididymal secretory protein 4 (HE4) are measured in the diagnosis and progression monitoring of ovarian cancer (OC), and the Risk of Ovarian Malignancy Algorithm (ROMA) score% values are calculated for cancer risk assessment. For the first time, disposable dual screen-printed carbon electrodes modified with reduced graphene oxide, polythionine, and gold nanoparticles were used to fabricate label-free electrochemical dual CA125-HE4 immunosensors for the sensitive, fast, and practical simultaneous determination of CA125 and HE4. DPV and SWV methods were used to simultaneously determine antigens in two different linear ranges (1-100 pg mL-1 and 1-50 ng mL-1). High sensitivity, low LOD, and LOQ were obtained for two linear ranges with a correlation coefficient above 0.99. The application stability of the dual CA125-HE4 immunosensors was determined as 60 days, and the storage stability was determined as 16 weeks. The dual immunosensors exhibited high selectivity in eight different antigen mixtures. The reusability of the dual immunosensors has been tested up to 9 cycles. ROMA score% values for pre-menopausal and post-menopausal status were calculated using the concentration of CA125 and HE4 in the blood serum and assessing OC risk. The disposable dual immunosensors can be used in point-of-care tests for rapid and practical simultaneous determination of CA125 and HE4 with high selectivity, sensitivity, and repeatability.

Herein, a chemiluminescence (CL) biosensor based on CRISPR-Cas12a and cation exchange reaction was constructed to detect the biomarker microRNA-21 (miRNA-21). The rolling circle amplification (RCA) reaction was introduced to convert each target RNA strand into a long single-stranded DNA with repeated sequences, which acted as triggers to initiate the transcleavage activity of CRISPR-Cas12a. The activated Cas12a could cleave the biotinylated linker DNA of CuS nanoparticles (NPs) to inhibit the binding of CuS NPs to streptavidin immobilized on the surface of the microplate, which strongly reduced the generation of Cu2+ from a cation exchange between CuS NPs and AgNO3, and thus efficiently suppressed the CL of Cu2+-luminol-H2O2 system, giving a "signal off" biosensor. With the multiple amplification, the detection limit of the developed sensor for miRNA-21 reached 16 aM. In addition, this biosensor is not only suitable for a professional chemiluminescence instrument but also for a smartphone used as a detection tool for the purpose of portable and low-cost assay. This method could be used to specifically detect quite a low level of miRNA-21 in human serum samples and various cancer cells, indicating its potential in ultrasensitive molecular diagnostics.

Dolichyl monophosphates (DolPs) are essential lipids in glycosylation pathways that are highly conserved across almost all domains of life. The availability of DolP is critical for all glycosylation processes, as these lipids serve as membrane-anchored building blocks used by various types of glycosyltransferases to generate complex post-translational modifications of proteins and lipids. The analysis of DolP species by reverse-phase liquid chromatography-mass spectrometry (RPLC-MS) remains a challenge due to their very low abundance and wide range of lipophilicities. Until now, a method for the simultaneous qualitative and quantitative assessment of DolP species from biological membranes has been lacking. Here, we describe a novel approach based on simple sample preparation, rapid and efficient trimethylsilyl diazomethane-dependent phosphate methylation, and RPLC-MS analysis for quantification of DolP species with different isoprene chain lengths. We used this workflow to selectively quantify DolP species from lipid extracts derived of Saccharomyces cerevisiae, HeLa, and human skin fibroblasts from steroid 5-α-reductase 3- congenital disorders of glycosylation (SRD5A3-CDG) patients and healthy controls. Integration of this workflow with global lipidomics analyses will be a powerful tool to expand our understanding of the role of DolPs in pathophysiological alterations of metabolic pathways downstream of HMG-CoA reductase, associated with CDGs, hypercholesterolemia, neurodegeneration, and cancer.

Increasing evidence indicates that angiogenesis plays a pivotal role in tumor progression. Formin-like 2 (FMNL2) is well-known for promoting metastasis; however, the molecular mechanisms by which FMNL2 promotes angiogenesis in colorectal cancer (CRC) remain unclear. Here, we found that FMNL2 promotes angiogenesis and metastasis of CRC in vitro and in vivo. The GDB/FH3 domain of FMNL2 directly interacts with epidermal growth factor-like protein 6 (EGFL6). FMNL2 promotes EGFL6 paracrine signaling via exosomes to regulate angiogenesis in CRC. Cytoskeleton associated protein 4 (CKAP4) is a downstream target of EGFL6 and is involved in CRC angiogenesis. EGFL6 binds to the N-terminus of CKAP4 to promote the migration of human umbilical vein endothelial cells (HUVECs) by activating ERK/MMP pathway. These findings suggest that FMNL2 promotes the migration of HUVECs and enhances angiogenesis and tumorigenesis in CRC by regulating the EGFL6/CKAP4/ERK axis. Therefore, the EGFL6/CKAP4/ERK axis may be a candidate therapeutic target for CRC treatment.

Colorectal cancer (CRC) is a common malignancy worldwide, and the gut microbiota and metabolites play an important role in its initiation and progression. In this study, we constructed a mouse model of inflammation-induced colorectal tumors, with fixed doses of azoxymethane/dextran sulfate sodium (AOM/DSS). We found that colorectal tumors only formed in some mice treated with certain concentrations of AOM/DSS (tumor group), whereas other mice did not develop tumors (non-tumor group). 16S rDNA amplicon sequencing and liquid chromatography-mass spectrometry (LC-MS)/MS analyses were performed to investigate the microbes and metabolites in the fecal samples. As a result, 1189 operational taxonomic units (OTUs) were obtained from the fecal samples, and the non-tumor group had a relatively higher OTU richness and diversity. Moreover, 53 different microbes were identified at the phylum and genus levels, including Proteobacteria, Cyanobacteria, and Prevotella. Furthermore, four bacterial taxa were obviously enriched in the non-tumor group, according to linear discriminant analysis scores (log10) > 4. The untargeted metabolomics analysis revealed significant differences between the fecal samples and metabolic phenotypes. Further, the heatmaps and volcano plots revealed 53 and 19 dysregulated metabolites between the groups, in positive and negative ion modes, respectively. Styrene degradation and amino sugar-nucleotide sugar metabolism pathways were significantly different in positive and negative ion modes, respectively. Moreover, a correlation analysis between the metabolome and microbiome was further conducted, which revealed the key microbiota and metabolites. In conclusion, we successfully established a tumor model using a certain dose of AOM/DSS and identified the differential intestinal microbiota and characteristic metabolites that might modulate tumorigenesis, thereby providing new concepts for the prevention and treatment of CRC.

High-risk human papillomavirus (HPV)-related cancers consist of cervical cancer, anal cancer, penile cancer, vulvar cancer, vaginal cancer, and head and neck cancer (HNC). Of these, the disease burden of HNC is second only to cervical cancer. HNC mostly originates from malignant lesions of squamous epithelial cells and mainly includes oral cavity cancer, pharyngeal cancer (including nasopharyngeal cancer, oropharyngeal cancer, and hypopharyngeal cancer), and laryngeal cancer. Tobacco use, alcohol abuse, and HPV infection are three primary risk factors. Recently, there is an upward trend of HNC incidence globally, especially in high-income countries. In China, the disease burden and trends of HPV-related HNC are still not clear. A few small sample size and single-center studies suggest a high HPV prevalence and increasing trend in HNC. Methodological differences in HPV testing and regional variabilities still exist among these studies. Among the anatomic sites, oropharyngeal cancer has been shown to be caused by HPV infection, but the association of HPV with other sites is still under debate. In addition, there is a paucity of relevant studies. Here, this review narrates the association between HPV infection and HNC, compares the differences between global and Chinese studies, and then explores the importance of HPV infection in various anatomical sites. The main objective is to highlight the research on HPV-related HNC and promote relevant prevention and treatment programs.

The HoloLens (Microsoft Corp., Redmond, WA), a head-worn, optically see-through augmented reality (AR) display, is the main player in the recent boost in medical AR research. In this systematic review, we provide a comprehensive overview of the usage of the first-generation HoloLens within the medical domain, from its release in March 2016, until the year of 2021. We identified 217 relevant publications through a systematic search of the PubMed, Scopus, IEEE Xplore and SpringerLink databases. We propose a new taxonomy including use case, technical methodology for registration and tracking, data sources, visualization as well as validation and evaluation, and analyze the retrieved publications accordingly. We find that the bulk of research focuses on supporting physicians during interventions, where the HoloLens is promising for procedures usually performed without image guidance. However, the consensus is that accuracy and reliability are still too low to replace conventional guidance systems. Medical students are the second most common target group, where AR-enhanced medical simulators emerge as a promising technology. While concerns about human-computer interactions, usability and perception are frequently mentioned, hardly any concepts to overcome these issues have been proposed. Instead, registration and tracking lie at the core of most reviewed publications, nevertheless only few of them propose innovative concepts in this direction. Finally, we find that the validation of HoloLens applications suffers from a lack of standardized and rigorous evaluation protocols. We hope that this review can advance medical AR research by identifying gaps in the current literature, to pave the way for novel, innovative directions and translation into the medical routine.