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The past few decades have witnessed the rise of immunotherapy for Gastrointestinal (GI) tract cancers. The role of immune checkpoint inhibitors (ICIs), particularly programmed death protein 1 (PD-1) and PD ligand-1 antibodies, has become increasingly pivotal in the treatment of advanced and perioperative GI tract cancers. Currently, anti-PD-1 plus chemotherapy is considered as first-line regimen for unselected advanced gastric/gastroesophageal junction adenocarcinoma (G/GEJC), mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC), and advanced esophageal cancer (EC). In addition, the encouraging performance of claudin18.2-redirected chimeric antigen receptor T-cell (CAR-T) therapy in later-line GI tract cancers brings new hope for cell therapy in solid tumour treatment. Nevertheless, immunotherapy for GI tumour remains yet precise, and researchers are dedicated to further maximising and optimising the efficacy. This review summarises the important research, latest progress, and future directions of immunotherapy for GI tract cancers including EC, G/GEJC, and CRC. [ABSTRACT FROM AUTHOR]

More and more in-depth tumor mechanism research and clinical precision treatment have put forward higher requirements for the technology for the establishment of tumor models.More and more tumor organoids have been applied. This model is able to reproduce the genomic, transcriptome, proteome and other omics features of parental tumors without heterogeneity found in cell line models. Based on these characteristics, tumor organoids have gradually become a representative preclinical model, facilitating the translation of new research results and precision treatment of patients. This article summarizes the latest progress of tumor organoids on R&D of technology and application, focusing on the current methods of establishing tumor organoids, opportunities and challenges in clinical and research application.

Abstract The past few decades have witnessed the rise of immunotherapy for Gastrointestinal (GI) tract cancers. The role of immune checkpoint inhibitors (ICIs), particularly programmed death protein 1 (PD-1) and PD ligand-1 antibodies, has become increasingly pivotal in the treatment of advanced and perioperative GI tract cancers. Currently, anti-PD-1 plus chemotherapy is considered as first-line regimen for unselected advanced gastric/gastroesophageal junction adenocarcinoma (G/GEJC), mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC), and advanced esophageal cancer (EC). In addition, the encouraging performance of claudin18.2-redirected chimeric antigen receptor T-cell (CAR-T) therapy in later-line GI tract cancers brings new hope for cell therapy in solid tumour treatment. Nevertheless, immunotherapy for GI tumour remains yet precise, and researchers are dedicated to further maximising and optimising the efficacy. This review summarises the important research, latest progress, and future directions of immunotherapy for GI tract cancers including EC, G/GEJC, and CRC.

Fluorescence imaging with high spatiotemporal resolution and sensitivity is employed for in vivo visualization and detection applications. Compared with visible light and the first near-infrared window (700–900 nm), the second near-infrared window (1 000–1 700 nm) imaging has a lower auto-background fluorescence, deeper tissue penetration, and a higher signal-to-noise ratio, thus highlighting its broad prospects in the biomedical field. Currently, reported second near-infrared region probes include single-walled carbon nanotubes, rare-earth nanoparticles, quantum dots, metal materials, and organic molecular dyes. Multimodal imaging can overcome the limitations of single imaging and provide more comprehensive information on the anatomical structure, tissue composition, and cellular and molecular quantification of lesions to achieve multi-level visualization. Therefore, second near-infrared window nanoprobes must be engineered for multimodal imaging. Moreover, these nanoprobes can be actively targeted by modification with antibodies, peptides, nucleotides, or biofilms to obtain detailed and accurate information on biological systems. This review describes the active targeting capabilities of various second near-infrared window nanoprobes in multimodal imaging, diagnosis, and treatment of different diseases by carrying different ligands and the common features and future application prospects of second near-infrared window fluorescent nanoprobes with targeting ability.

Cell mechanotransduction signals are important targets for physical therapy. However, current physiotherapy heavily relies on ultrasound, which is generated by high‐power equipment or amplified by auxiliary drugs, potentially causing undesired side effects. To address current limitations, a robotic actuation‐mediated therapy is developed that utilizes gentle mechanical loads to activate mechanosensitive ion channels. The resulting calcium influx precisely regulated the expression of recombinant tumor suppressor protein and death‐associated protein kinase, leading to programmed apoptosis of cancer cell line through caspase‐dependent pathway. In stark contrast to traditional gene therapy, the complete elimination of early‐ and middle‐stage tumors (volume ≤ 100 mm3) and significant growth inhibition of late‐stage tumor (500 mm3) are realized in tumor‐bearing mice by transfecting mechanogenetic circuits and treating daily with quantitative robotic actuation in a form of 5 min treatment over the course of 14 days. Thus, this massage‐derived therapy represents a quantitative strategy for cancer treatment. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions Patient‐derived organoids are potent pre‐chemotherapy models. Due to limited research on diverse types of oral squamous cell carcinoma (OSCC) and construction efficiency, our goal was to optimize OSCC organoid models from various sites and assess drug responsiveness.We screened and optimized culture media, employing three‐dimensional techniques to construct human‐derived oral squamous cell carcinoma (OSCC) organoid models in vitro. Morphological validation, immunofluorescence analysis, tissue origin verification, and Short Tandem Repeat (STR) sequencing confirmed the consistency between organoids and source tissues. These organoid models were then subjected to varying concentrations of anticancer drugs, with subsequent assessment of cell viability to calculate IC50 values.Twenty‐nine surgical specimens yielded an 86.2% success rate in culturing 25 organoids in vitro. Morphological consistency confirmed nuclear atypia and positive expression of K5, P40, and E‐cadherin, indicating squamous epithelial origin. Cultured complex organoids included α‐SMA+ tumour‐associated fibroblasts and tumour stem cells expressing CD44 and Ki67. STR sequencing affirmed genomic homogeneity between cultured organoids and source tissues. Drug sensitivity testing revealed diverse responses among organoids, highlighting their value for assessing drug sensitivity.An efficient OSCC organoid culture system for personalized in vitro drug sensitivity screening was established, laying the foundation for precise treatment development. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common malignant tumors recorded worldwide. This condition has high morbidity and mortality and seriously endangers people's health. Traditional diagnostic models fail to meet people's current needs for real-time monitoring of tumors. Compared with traditional detection methods, ctDNA detection is not only noninvasive but can also attain real-time detection of comprehensive genomic information of tumors. The advancement of detection technology has gradually highlighted the potential of ctDNA detection in the clinical treatment of CRC. This article reviews the advancements on the clinical application of ctDNA in early screening, minimal residual disease detection, and guidance on individualized treatment of CRC patients.

Colorectal cancer (CRC) is one of the most common malignant tumors recorded worldwide. This condition has high morbidity and mortality and seriously endangers people’s health. Traditional diagnostic models fail to meet people’s current needs for real-time monitoring of tumors. Compared with traditional detection methods, ctDNA detection is not only noninvasive but can also attain real-time detection of comprehensive genomic information of tumors. The advancement of detection technology has gradually highlighted the potential of ctDNA detection in the clinical treatment of CRC. This article reviews the advancements on the clinical application of ctDNA in early screening, minimal residual disease detection, and guidance on individualized treatment of CRC patients. [ABSTRACT FROM AUTHOR]

Abstract Cell mechanotransduction signals are important targets for physical therapy. However, current physiotherapy heavily relies on ultrasound, which is generated by high‐power equipment or amplified by auxiliary drugs, potentially causing undesired side effects. To address current limitations, a robotic actuation‐mediated therapy is developed that utilizes gentle mechanical loads to activate mechanosensitive ion channels. The resulting calcium influx precisely regulated the expression of recombinant tumor suppressor protein and death‐associated protein kinase, leading to programmed apoptosis of cancer cell line through caspase‐dependent pathway. In stark contrast to traditional gene therapy, the complete elimination of early‐ and middle‐stage tumors (volume ≤ 100 mm3) and significant growth inhibition of late‐stage tumor (500 mm3) are realized in tumor‐bearing mice by transfecting mechanogenetic circuits and treating daily with quantitative robotic actuation in a form of 5 min treatment over the course of 14 days. Thus, this massage‐derived therapy represents a quantitative strategy for cancer treatment.

Atopic dermatitis (AD) is nowadays entering a new era of more targeted treatments. However, to make personalized medicine, which we are currently striving for, a reality, a reliable set of validated biomarkers is needed. The most practical seem to be biomarkers that can be obtained easily and minimally invasively. Tape stripping (TS) is a method that provides such an opportunity. This review summarizes the potential biomarkers of AD identified by the minimally invasive TS method. Thymic stromal lymphopoietin (TSLP), interleukin (IL)-13, CC chemokine ligand 17 (CCL17)/thymus and activation-regulated chemokine (TARC) and stratum corneum (SC) lipids can be used as predictive biomarkers for AD occurrence. CCL17/TARC also holds great promise for being reliable biomarkers for AD severity as well as treatment response.Nitric oxide synthase 2 (NOS2)/inducible nitric oxide synthase (iNOS) which high expression is specific for psoriasis may be a good biomarker for differential diagnosis between psoriasis and AD in challenging clinical situations.AD children with food allergy (FA) have a unique endotype characterized by selectively altered expression of various molecules in the skin that can indicate FA coexistence. Unfortunately, although numerous potential biomarkers have been found, none of these candidates have been validated and implemented into routine clinical practice, which still separates us from the possibility of a precise approach to AD patients.

This document is an editorial published in Frontiers in Oncology titled "Multi-omics analysis of programmed cell death-mediated tumor microenvironment heterogeneity." The editorial discusses the importance of programmed cell death in tumor initiation, progression, and therapeutic responsiveness. It emphasizes the role of multi-omics data in understanding tumor microenvironment heterogeneity and its implications for cancer subtyping and individualized treatment. The editorial also highlights several research articles included in the topic, which explore biomarkers, therapeutic targets, and treatment strategies related to programmed cell death in cancer. Overall, the editorial aims to contribute to the study of programmed cell death in cancer and its potential applications in research and clinical practice. [Extracted from the article]

Abstract Background Cholangiocarcinoma (CCA) refers to a collection of malignant tumors that develop from the biliary epithelium. Extensive clinical evidence and epidemiological observations indicate a concerning increase in both the incidence and mortality rates of CCA. Surgical resection is currently the sole available cure for CCA. However, it is unfortunate that only a fraction of patients has access to surgery at the time of diagnosis. Moreover, there is a high incidence of cancer recurrence after resection, and systemic treatments have limited efficacy. Therefore, the identification of novel biomarkers for CCA-targeted molecular therapy remains a crucial task in oncology research. Results Our study demonstrated that low expression of RSPO3 was associated with poorer survival rates in patients with CCA. We found that the RSPO3 promoter DNA was hypermethylated in CCA, which was correlated with the low expression of RSPO3. The expression of RSPO3 was influenced by the balance between the DNA methyltransferase DNMT3a and the DNA demethylase TET1 in CCA. In vitro and in vivo experiments showed that targeting RSPO3 promoter DNA methylation using dCas9DNMT3a promoted tumorigenicity of CCA, while targeted RSPO3 promoter DNA demethylation using dCas9TET1CD inhibited CCA tumorigenicity. Additionally, in our primary CCA model, knockdown of Rspo3 promoted CCA progression, whereas overexpression of Rspo3 inhibited CCA progression. Conclusions Our findings suggest that increased methylation and decreased expression of RSPO3 may indicate a poor prognosis in CCA. Restoring RSPO3 expression by targeting promoter DNA demethylation could offer insights for precise treatment of CCA.

Magnetic particle imaging (MPI) is a novel quantitative imaging technique using the nonlinear magnetization behavior of magnetic nanoparticles (MNPs) to determine their local concentration. Magnetic fluid hyperthermia (MFH) is a promising non-invasive therapy using the heating effects of MNPs. MPI-MFH is expected to enable real-time MPI guidance, localized MFH, and non-invasive temperature monitoring, which shows great potential for precise treatment of cancer. In this review, we introduce the fundamentals of MPI and MFH and their applications in the treatment of cancer. Also, we discuss the challenges and prospects of MPI-MFH. [ABSTRACT FROM AUTHOR]

Superlattices have considerable potential as sonosensitizers for cancer therapy because of their flexible and tunable band gaps, although they have not yet been reported. In this study, a Ti‐based organic–inorganic superlattice with good electron–hole separation was synthesized, which consisted of orderly layered superlattices of 2,2′‐bipyridine‐5,5′‐dicarboxylic acid (BPDC) and Ti−O layers. In addition, the superlattice was coordinated with Fe(III) and encapsulated doxorubicin (DOX) to prepare Ti‐BPDC@Fe@DOX@PEG (TFDP) after biocompatibility modification. TFDP can realize the simultaneous generation of reactive oxygen species and release of DOX under ultrasound irradiation. Moreover, adjusting the Fe(III) content can effectively modulate the band gap of the superlattice and increase the efficiency of sonodynamic therapy (SDT). The mechanisms underlying this modulation were explored. TFDP with Fe(III) can also be used as a contrast agent for magnetic resonance imaging (MRI). Both in vitro and in vivo experiments demonstrated the ability of TFDP to precisely treat cancer using MRI‐guided SDT/chemotherapy. This study expands the applications of superlattices as sonosensitizers with flexible and tailored modifications and indicates that superlattices are promising for precise and customized treatments. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinoma (CCA) refers to a collection of malignant tumors that develop from the biliary epithelium. Extensive clinical evidence and epidemiological observations indicate a concerning increase in both the incidence and mortality rates of CCA. Surgical resection is currently the sole available cure for CCA. However, it is unfortunate that only a fraction of patients has access to surgery at the time of diagnosis. Moreover, there is a high incidence of cancer recurrence after resection, and systemic treatments have limited efficacy. Therefore, the identification of novel biomarkers for CCA-targeted molecular therapy remains a crucial task in oncology research. Results: Our study demonstrated that low expression of RSPO3 was associated with poorer survival rates in patients with CCA. We found that the RSPO3 promoter DNA was hypermethylated in CCA, which was correlated with the low expression of RSPO3. The expression of RSPO3 was influenced by the balance between the DNA methyltransferase DNMT3a and the DNA demethylase TET1 in CCA. In vitro and in vivo experiments showed that targeting RSPO3 promoter DNA methylation using dCas9DNMT3a promoted tumorigenicity of CCA, while targeted RSPO3 promoter DNA demethylation using dCas9TET1CD inhibited CCA tumorigenicity. Additionally, in our primary CCA model, knockdown of Rspo3 promoted CCA progression, whereas overexpression of Rspo3 inhibited CCA progression. Conclusions: Our findings suggest that increased methylation and decreased expression of RSPO3 may indicate a poor prognosis in CCA. Restoring RSPO3 expression by targeting promoter DNA demethylation could offer insights for precise treatment of CCA. [ABSTRACT FROM AUTHOR]

Testicular germ cell tumors (TGCT) are the most common reproductive system malignancies in men aged 15–44 years, accounting for 95 % of all testicular tumors. Our previous studies have been shown that long non-coding RNAs (lncRNAs), such as LINC00313, TTTY14 and RFPL3S, were associated with development of TGCT. Subgrouping TGCT according to differential expressed lncRNAs and immunological characteristics is helpful to comprehensively describe the characteristics of TGCT and implement precise treatment. In this study, the TGCT transcriptome data in The Cancer Genome Atlas Program (TCGA) database was used to perform consensus clustering analysis to construct a prognostic model for TGCT. TGCT was divided into 3 subtypes C1, C2, and C3 based on the differentially expressed lncRNAs. C1 subtype was sensitive to chemotherapy drugs, while the C2 subtype was not sensitive to chemotherapy drugs, and C3 subtype may benefit from immunotherapy. We defined the C1 subtype as epidermal progression subtype, the C2 subtype as mesenchymal progression subtype, and the C3 subtype as T cell activation subtype. Subgrouping based on differentially expressed genes (DEGs) and immunological characteristics is helpful for the precise treatment of TGCT.

Wanyi Chen,1,* Po-Han Fang,2,* Bin Zheng,3 Yue Liang,1 Yiwen Mao,1 Xuefeng Jiang,1 Qionglan Tang4 1Department of Obstetrics and Gynecology, the First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 2International School, Jinan University, Guangzhou, People’s Republic of China; 3Guangdong Research Center for Organoid Engineering and Technology, Guangzhou, People’s Republic of China; 4Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qionglan Tang, Email qionglantang@126.comAbstract: So far, ovarian cancer has still been the most lethal gynecological malignancy. The chemotherapy and targeted medication are the mainstay for the recurrent ovarian cancer treatment. About 70% of the advanced-stage cases will relapse. Ascites-derived organoid is a pre-clinical model for the precise prediction of the therapeutic effectiveness for the ovarian cancer: it can be used to assess the drug sensitivity, to guide individualized precise treatment, and to improve advanced stage as well as recurrent ovarian cancer patient’ survival and prognosis. Until now, there has been no report concerning the establishment of the organoid out of the patient’s ascites and the concurrent usage of drug sensitivity test to guide the individualized precise treatment for the ovarian cancer. Here, we report a case of recurrent ovarian cancer of a 59-year-old female patient whose CA125 at its peak increased to 4523.4 U/mL. Then, patient’s own ovarian cancer organoid was constructed from the ascites by the abdominocentesis; concurrently, medication sensitivity test was performed on the organoid to guide individualized precise treatment. After the treatment, CA125 decreased to 33.7 U/mL, and the patient’s condition relieved effectively. This is the first published case report using ascites-derived organoid and the drug sensitivity test thereof to guide the precise treatment of recurrent ovarian cancer.Keywords: ascites-derived organoid, ovarian cancer organoid, recurrent ovarian cancer, drug sensitivity test, precise treatment

Abstract Objective Capsular characteristics of pleomorphic adenoma (PA) has various forms. Patients without complete capsule has a higher risk of recurrence than patients with complete capsule. We aimed to develop and validate CT-based intratumoral and peritumoral radiomics models to make a differential diagnosis between parotid PA with and without complete capsule. Methods Data of 260 patients (166 patients with PA from institution 1 (training set) and 94 patients (test set) from institution 2) were retrospectively analyzed. Three Volume of interest (VOIs) were defined in the CT images of each patient: tumor volume of interest (VOItumor), VOIperitumor, and VOIintra-plus peritumor. Radiomics features were extracted from each VOI and used to train nine different machine learning algorithms. Model performance was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC). Results The results showed that the radiomics models based on features from VOIintra-plus peritumor achieved higher AUCs compared to models based on features from VOItumor. The best performing model was Linear discriminant analysis, which achieved an AUC of 0.86 in the tenfold cross-validation and 0.869 in the test set. The model was based on 15 features, including shape-based features and texture features. Conclusions We demonstrated the feasibility of combining artificial intelligence with CT-based peritumoral radiomics features can be used to accurately predict capsular characteristics of parotid PA. This may assist in clinical decision-making by preoperative identification of capsular characteristics of parotid PA.

Objective Ankle arthroscope is the preferred tool for ankle surgeons to treat ankle impingement. However, there is no relevant report on how to improve the accuracy of arthroscopic osteotomy through preoperative planning. The aims of this study were to investigate a novel method to obtain the bone morphology in anterior and posterior ankle bony impingement through computed tomography (CT) calculation model, use this method to guide surgical decision‐making, and compare the postoperative efficacy and actual bone cutting volume with conventional surgery. Methods This retrospective cohort study includes 32 consecutive cases with anterior and posterior ankle bony impingement by arthroscopy from January 2017 to December 2019. Mimics software was utilized to calculate the bony morphology and measure the volume of the osteophytes by two trained software engineers. The patients were divided into the precise group (n = 15) and the conventional group (n = 17) according to whether obtain and quantify the osteophytes' morphology with CT based calculation model preoperative. All patients were evaluated clinically using visual analog scale (VAS) score, American Orthopaedic Foot and Ankle Society (AOFAS) score, active dorsiflexion and plantarflexion angle before and after surgery at both 3 months and 12 months postoperatively. We obtained the shape and volume of bone cutting through Boolean calculation. Clinical outcomes and radiological data were compared between the two groups. Results The VAS score, AOFAS score, active dorsiflexion angle and plantarflexion angle were significantly improved in both groups postoperatively. In comparison of the VAS score, AOFAS score, and active dorsiflexion angle, the precise group were higher than the conventional group in the follow‐up at 3 and 12 months postoperatively with statistical difference. The difference between the virtual bone cutting volume and the actual bone cutting volume of the anterior edge of distal tibia in the conventional group and precise group were 244.20 ± 147.66 mm3 and 76.53 ± 168.51 mm3, respectively, there was statistical difference between the two groups (t = −2.927, p = 0.011). Conclusion Using a novel method of obtaining and quantifying the bony morphology with CT‐based calculation model for anterior and posterior ankle bony impingement can help guide surgical decision‐making preoperatively and assist precise bone cutting during the operation, which can improve the efficacy and evaluate the accuracy of osteotomy postoperatively.

Breast cancer (BRCA) is a common neoplasm characterized by high levels of molecular heterogeneity. Previous studies have noted the importance of mitophagy for the progression and prognosis of BRCA. However, little was found in the similarity and difference of mitophagy-related gene expression patterns of BRCA. This study intended to investigate the differences in functional activation, somatic mutation, and immune-related characteristics among different subtypes of BRCA associated with mitophagy. Based on bioinformatics analysis, we systematically examined the heterogeneity of breast cancer concerning mitophagy and observed two distinct subtypes with different tumor microenvironments and prognoses. BRCA samples from TCGA database were divided into two subtypes based on the expression of 29 mitophagy-related genes by ConsensusClusterPlus algorithm. Two mitophagy-related subtypes with marked prognostic discrepancies were significantly correlated with race, intrinsic subtype grouped based on PAM50 subtype purity and BRCA Pathology. The results of GSVA and immune microenvironment analysis showed significant differences in cancer-related and immune-related features between the two subtypes. METABRIC datasets were extracted to validate the immune characteristics scoring and the expression of immune checkpoints between different subtypes based on the medium value of TCGA-Mitophagy score. It is noteworthy that the present study is the first to demonstrate a new classification based on the mitophagy of breast cancer, which comes up with a new perspective for the assessment and prognoses of BRCA.

Objective: In this study, we evaluated the role of a multidisciplinary team (MDT) in clinical practice for cervical cancer by analyzing the development of a singlecase multidisciplinary consultation for cervical cancer. Methods: Patients in MDT consultations for cervical cancer were retrospectively analyzed for clinical information, decision content of MDT discussion, implementation, and follow-up results. Results: Of the 392 patients who met the inclusion criteria, 359 had a first episode, of which 284 were stage IA-IIA2 (79.11%) and 75 were stage IIB-IVB (20.89%). Of these 392, 33 had a recurrence (8.42%). A total of 416 cases were analyzed, and neoadjuvant chemotherapy with surgery was recommended in 43 cases, of which 40 cases were implemented, and 36 of the 40 achieved the expected outcome. Surgical treatment was recommended in 241 cases, of which 226 underwent surgery, and 215 of them achieved the expected outcome. Radiotherapy was recommended in 31 cases, of which 26 cases underwent it, and 22 of them achieved the expected efficacy. Concurrent chemoradiotherapy was recommended in 57 cases, of which 49 underwent it, and 39 of them achieved the expected efficacy. Other treatments were recommended in 44 cases, of which 23 cases were implemented, and 10 of them achieved the expected efficacy, with statistically significant differences compared with cases without implementation (P <0.05). MDT decisions were correlated with age; the younger the patients, the higher the implementation efficiency (P <0.05). The difference between MDT expectation in all implementation and partial implementation and age was statistically significant (P <0.05). No significant difference was found between age and MDT expectation in all not fully implemented decisions (P >0.05). Some decisions were not fully implemented due to economic status and fear of certain treatments of the patient.Conclusion: The MDT plays an important role in clinical practice such as clinical staging, treatment plan, and the complete treatment management of patients with cervical cancer, which can significantly improve the near-term treatment effect, whereas its effect on a long-term prognosis needs further clinical observation and active exploration. [ABSTRACT FROM AUTHOR]

Background: At present, radiotherapy (RT) is widely used in cancer treatment, but traditional RT methods using ionizing radiation cannot avoid damage to normal tissues. Therefore, the development of a more precise RT is an important research direction for relevant researchers. Concurrently, research on radiosensitizers (RSs) using nanotechnology is developing rapidly, and RSs that are selective for cancerous tissues or cancer cells may become an important part of future precision RT. Methods: Using RSs and RT as keywords, the relevant papers in the PubMed database from 2013 to 2022 were summarized. Articles on RS with selectivity to cancer tissue were collected. Among the selected articles, RSs were classified into “active selectivity”, “passive selectivity” and “others” according to the different selectivity principles of RSs. Results: A total of 771 articles were retrieved from PubMed. After screening, the research content of the remaining 79 articles was found to be related to the selectivity of RSs to cancer tissues. Among them, 28 articles were classified as “active selectivity”, and most of the sensitizers in this category could target specific targets in cancer tissues. There were 30 papers classified as “passive selectivity” and the selectivity principles were mainly the enhanced permeability and retention (EPR) effect, aggregation caused by pH sensitivity, and aggregation in anoxic environments. There were 21 papers classified as “others”. The sensitizers in these studies showed selectivity for cancer tissue, but the mechanism was not clear. This review attempts to summarize studies on RSs that are selective for cancer tissues. Conclusions: We reviewed nearly ten years of literature on selective RSs and classified the selectivity of different RSs into active and passive selectivities.

Colorectal Cancer (CRC) is one of the most common gastrointestinal tumors, and its high tumor heterogeneity makes traditional sequencing methods incapable of obtaining information about the heterogeneity of individual cancer cells in CRC. Therefore, single-cell sequencing technology can be applied to better analyze the differences in genetic and protein information between cells, to obtain genomic sequence information of single cells, and to more thoroughly analyze the cellular characteristics and interactions in the CRC microenvironment. This will provide a more comprehensive understanding of colorectal cancer development and metastasis and indicate the treatment plan and prognosis. In this study, we review the application of single-cell sequencing to analyze the tumor microenvironment of CRC, explore the mechanisms involved in CRC metastasis and progression, and provide a reference for potential treatment options. [ABSTRACT FROM AUTHOR]

Cervical adenocarcinomas (ADCs), including human papillomavirus (HPV)‐associated (HPVA) and non‐HPVA (NHPVA), though exhibiting a more malignant phenotype and poorer prognosis, are treated identically to squamous cell carcinoma (SCC). This clinical dilemma requires a deeper investigation into their differences. Herein a transcriptomic atlas of SCC, HPVA, and NHPVA‐ADC using single‐cell RNA (scRNA) and T‐cell receptor sequencing (TCR‐seq) is presented. Regarding structural cells, the malignancy origin of epithelial cells, angiogenic tip cells and two subtypes of fibroblasts is revealed. The promalignant properties of the structural cells using organoids are further confirmed. Regarding immune cells, myeloid cells with multiple functions other than antigen presentation and exhausted T lymphocytes contribute to immunosuppression. From the perspective of HPV infection, not only is HPV‐dependent and independent cervical cancer oncogenesis proposed but also three immune reaction patterns mediated by T cells (coordinated/inactive/imbalanced) are identified. Strikingly, diagnostic biomarkers to distinguish ADC from SCC are discovered and prognostic biomarkers with marker genes for malignant epithelial cells, tip cells, and SPP1/C1QC macrophages are generated. Importantly, the efficacy of anti‐CD96 and anti‐TIGIT, not inferior to anti‐PD1, in animal experiments is confirmed and targeted therapies specifically for HPV‐positive SCC, HPVA and NHPVA‐ADC, providing essential clues for further clinical trials, are proposed. [ABSTRACT FROM AUTHOR]

Objective: Ankle arthroscope is the preferred tool for ankle surgeons to treat ankle impingement. However, there is no relevant report on how to improve the accuracy of arthroscopic osteotomy through preoperative planning. The aims of this study were to investigate a novel method to obtain the bone morphology in anterior and posterior ankle bony impingement through computed tomography (CT) calculation model, use this method to guide surgical decision‐making, and compare the postoperative efficacy and actual bone cutting volume with conventional surgery. Methods: This retrospective cohort study includes 32 consecutive cases with anterior and posterior ankle bony impingement by arthroscopy from January 2017 to December 2019. Mimics software was utilized to calculate the bony morphology and measure the volume of the osteophytes by two trained software engineers. The patients were divided into the precise group (n = 15) and the conventional group (n = 17) according to whether obtain and quantify the osteophytes' morphology with CT based calculation model preoperative. All patients were evaluated clinically using visual analog scale (VAS) score, American Orthopaedic Foot and Ankle Society (AOFAS) score, active dorsiflexion and plantarflexion angle before and after surgery at both 3 months and 12 months postoperatively. We obtained the shape and volume of bone cutting through Boolean calculation. Clinical outcomes and radiological data were compared between the two groups. Results: The VAS score, AOFAS score, active dorsiflexion angle and plantarflexion angle were significantly improved in both groups postoperatively. In comparison of the VAS score, AOFAS score, and active dorsiflexion angle, the precise group were higher than the conventional group in the follow‐up at 3 and 12 months postoperatively with statistical difference. The difference between the virtual bone cutting volume and the actual bone cutting volume of the anterior edge of distal tibia in the conventional group and precise group were 244.20 ± 147.66 mm3 and 76.53 ± 168.51 mm3, respectively, there was statistical difference between the two groups (t = −2.927, p = 0.011). Conclusion: Using a novel method of obtaining and quantifying the bony morphology with CT‐based calculation model for anterior and posterior ankle bony impingement can help guide surgical decision‐making preoperatively and assist precise bone cutting during the operation, which can improve the efficacy and evaluate the accuracy of osteotomy postoperatively. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of this study was to identify the ferroptosis induced tumor microenvironment (FeME) landscape in bladder cancer (BCa) for mRNA vaccine development and selecting suitable patients for precision treatment. Methods Gene expression profiles and clinical information of 1216 BCa patients were extracted from TCGA-BLCA, three GEO databases and IMvigor210 cohort. We comprehensively established the FeME landscape of 1216 BCa samples based on 290 ferroptosis related genes (FRGs), and systematically correlated these regulation patterns with TME cell-infiltrating characteristics. Besides, we identified the patients’ ferroptosis risk index (FRI) to predict the prognosis of BCa for precise treatment. Results Six over-expressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in BCa. Furthermore, we demonstrated the evaluation of FeME within individual tumors could predict stages of tumor inflammation, subtypes, genetic variation, and patient prognosis. Then, 5-lncRNA signature was mined to produce the FRI. Low FRI was also linked to increased mutation load, better prognosis and enhanced response to anti-PD-L1 immunotherapy. Besides, an immunotherapy cohort confirmed patients with lower FRI demonstrated significant therapeutic advantages and clinical benefits. Conclusions TFRC, SCD, G6PD, FADS2, SQLE, and SLC3A2 are potent antigens for developing anti-BCa mRNA vaccine. Establishment of FRI will contribute to enhancing our cognition of TME infiltration characterization and guiding more effective immunotherapy strategies and selecting appropriate patients for tumor vaccine therapy.

Several studies have shown that the dysregulation of the oral microbiota plays a crucial role in human health conditions, such as dental caries, periodontal disease, oral cancer, other oral infectious diseases, cardiovascular diseases, diabetes, bacteremia, and low birth weight. The use of traditional detection methods in conjunction with rapidly advancing molecular techniques in the diagnosis of harmful oral microorganisms has expanded our understanding of the diversity, location, and function of the microbiota associated with health and disease. This review aimed to highlight the latest knowledge in this field, including microbial colonization; the most modern detection methods; and interactions in disease progression. The next decade may achieve the rapid diagnosis and precise treatment of harmful oral microorganisms. [ABSTRACT FROM AUTHOR]

Abstract Cervical adenocarcinomas (ADCs), including human papillomavirus (HPV)‐associated (HPVA) and non‐HPVA (NHPVA), though exhibiting a more malignant phenotype and poorer prognosis, are treated identically to squamous cell carcinoma (SCC). This clinical dilemma requires a deeper investigation into their differences. Herein a transcriptomic atlas of SCC, HPVA, and NHPVA‐ADC using single‐cell RNA (scRNA) and T‐cell receptor sequencing (TCR‐seq) is presented. Regarding structural cells, the malignancy origin of epithelial cells, angiogenic tip cells and two subtypes of fibroblasts is revealed. The promalignant properties of the structural cells using organoids are further confirmed. Regarding immune cells, myeloid cells with multiple functions other than antigen presentation and exhausted T lymphocytes contribute to immunosuppression. From the perspective of HPV infection, not only is HPV‐dependent and independent cervical cancer oncogenesis proposed but also three immune reaction patterns mediated by T cells (coordinated/inactive/imbalanced) are identified. Strikingly, diagnostic biomarkers to distinguish ADC from SCC are discovered and prognostic biomarkers with marker genes for malignant epithelial cells, tip cells, and SPP1/C1QC macrophages are generated. Importantly, the efficacy of anti‐CD96 and anti‐TIGIT, not inferior to anti‐PD1, in animal experiments is confirmed and targeted therapies specifically for HPV‐positive SCC, HPVA and NHPVA‐ADC, providing essential clues for further clinical trials, are proposed.

Objective: This review aims to provide some theoretical guidance for the precise treatment of ovarian cancer and the development of estrogen-related drugs. Mechanism: Ovarian cancer is one of the leading causes of death in gynecological cancer patients, mainly affecting middle-aged and elderly women. It has the characteristics of hidden location, strong heterogeneity and lack of specific symptoms in the early stage. Numerous studies have shown that estrogen receptor (ER) plays an important role in different types of cancer, including ovarian cancer. Accordingly, the study of ER signaling pathways and related regulatory factors in ovarian cancer cells should help us understand the pathogenesis of ovarian cancer. Findings in Brief: The expression of estrogen receptor subtypes is related to ovarian cancer gene and leads to ovarian cancer. Estrogen receptor modulators appear to be an important factor in the prognosis of patients with ovarian cancer after hormone therapy. Conclusions: This review summarizes the regulatory mechanism of ER in the occurrence and development of ovarian cancer and outlines the specific role of estrogen receptor modulators (SERMs) in the treatment and prevention of ovarian cancer.

Despite extensive use of radiotherapy in nasopharyngeal carcinoma (NPC) treatment because of its high radiosensitivity, there have been huge challenges in further improving therapeutic effect, meanwhile obviously reducing radiation damage. To this end, synergistic chemoradiotherapy has emerged as a potential strategy for highly effective NPC therapy. Here, we developed RGD-targeted platinum-based nanoparticles (RGD-PtNPs, denoted as RPNs) to achieve targeted chemoradiotherapy for NPC. Such nanoparticles consist of an RGD-conjugated shell and a cis-platinum (CDDP) crosslinking core. Taking advantage of RGD, the RPNs may effectively accumulate in tumor, penetrate into tumor tissues and be taken by cancer cells, giving rise to a high delivery efficiency of CDDP. When they are fully enriched in tumor sites, the CDDP loaded RPNs can act as radiotherapy sensitizer and chemotherapy agents. By means of X-ray-promoted tumor cell uptake of nanoparticle and CDDP-induced cell cycle arrest in radiation-sensitive G2/M phases, RPNs may offer remarkable therapeutic outcome in the synergistic chemoradiotherapy for NPC.

Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disease with a wide range of heterogeneity. Accurate biomarkers or predictors are the keys to instructing personalized tailored precise treatment. The development of technology such as transcriptomics, genomics, and proteomics provides novel insights into the possibility to find potential biomarkers. Meanwhile, emerging minimally invasive methods such as tape stripping were used to reveal different profiles of patients’ skin without biopsy. Several potential biomarkers or predictors have been found. In this review, we summarized the current development of potential biomarkers of AD. Nitric oxide synthase 2/inducible nitric oxide synthase (NOS2/iNOS), human beta-defensin-2 (hBD-2), and matrix metalloproteinases 8/9 (MMP8/9) may be the candidate biomarkers for AD diagnosis. Filaggrin (FLG) gene mutation increased the occurrence risk of AD. Fatty-acid-binding protein 5 (FABP5) may serve as an effective biomarker for the atopic march (AM). Squamous cell carcinoma antigen 2 (SCCA2), serum thymus and activation-regulated chemokine (TARC), cutaneous T-cell-attracting chemokine (CTACK), eosinophil-derived neurotoxin (EDN), macrophage-derived chemokine (MDC), lactate dehydrogenase (LDH), and interleukin (IL)-18 can be the candidate biomarkers for disease severity monitoring. IL-17, IL-23, IL-33, and indoleamine 2,3-dioxygenase (IDO1) can be used as predictive biomarkers for AD comorbidities. LDH, TARC, pulmonary and activation-regulated chemokine (PARC), periostin, IL-22, eotaxin-1/3, and IL-8 may be the candidate biomarkers for monitoring treatment effects. There are still unmet needs and a long way to go for more convenient, non-invasive, and effective predictors and biomarkers to better guide personalized precise treatment.

Objective: The objective of this study was to explore and verify the subtypes in hepatocellular carcinoma based on the immune (lymphocyte and myeloid cells), stem, and stromal cells in the tumor microenvironment and analyze the biological characteristics and potential relevance of each cluster. Methods: We used the xCell algorithm to calculate cell scores and got subtypes by k-means clustering. In the external validation sets, we verified the conclusion stability by a neural network model. Simultaneously, we speculated the inner connection between clusters by pseudotime trajectory analysis and confirmed it by pathway enrichment, TMB, CNV, etc., analysis. Result: According to the results of the consensus cluster, we chose k = 4 as the optimal value and got four different subtypes (C1, C2, C3, and C4) with different biological characteristics based on infiltrating levels of 48 cells in TME. In univariable Cox regression, the hazard ratio (HR) value of C3 versus C1 was 2.881 (95% CI: 1.572–5.279); in multivariable Cox regression, we corrected the age and TNM stage, and the HR value of C3 versus C1 was 2.510 (95% CI: 1.339–4.706). C1 and C2 belonged to the immune-active type, C3 and C4 related to the immune-insensitive type and the potential conversion relationships between clusters. We established a neural network model, and the area under the curves of the neural network model was 0.949 in the testing cohort; the same survival results were also observed in the external validation set. We compared the differences in cell infiltration, immune function, pathway enrichment, TMB, and CNV of four clusters and speculated that C1 and C2 were more likely to benefit from immunotherapy and C3 may benefit from FGF inhibitors. Discussion: Our analysis provides a new approach for the identification of four tumor microenvironment clusters in patients with liver cancer and identifies the biological differences and predicts the immunotherapy efficacy between the four subtypes. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to identify the ferroptosis induced tumor microenvironment (FeME) landscape in bladder cancer (BCa) for mRNA vaccine development and selecting suitable patients for precision treatment. Methods: Gene expression profiles and clinical information of 1216 BCa patients were extracted from TCGA-BLCA, three GEO databases and IMvigor210 cohort. We comprehensively established the FeME landscape of 1216 BCa samples based on 290 ferroptosis related genes (FRGs), and systematically correlated these regulation patterns with TME cell-infiltrating characteristics. Besides, we identified the patients' ferroptosis risk index (FRI) to predict the prognosis of BCa for precise treatment. Results: Six over-expressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in BCa. Furthermore, we demonstrated the evaluation of FeME within individual tumors could predict stages of tumor inflammation, subtypes, genetic variation, and patient prognosis. Then, 5-lncRNA signature was mined to produce the FRI. Low FRI was also linked to increased mutation load, better prognosis and enhanced response to anti-PD-L1 immunotherapy. Besides, an immunotherapy cohort confirmed patients with lower FRI demonstrated significant therapeutic advantages and clinical benefits. Conclusions: TFRC, SCD, G6PD, FADS2, SQLE, and SLC3A2 are potent antigens for developing anti-BCa mRNA vaccine. Establishment of FRI will contribute to enhancing our cognition of TME infiltration characterization and guiding more effective immunotherapy strategies and selecting appropriate patients for tumor vaccine therapy. [ABSTRACT FROM AUTHOR]

Abstract Background Breast cancer (BC) is a complex disease with high heterogeneity, which often leads to great differences in treatment results. Current common molecular typing method is PAM50, which shows positive results for precision medicine; however, room for improvement still remains because of the different prognoses of subtypes. Therefore, in this article, we used lncRNAs, which are more tissue-specific and developmental stage-specific than other RNAs, as typing markers and combined single-cell expression profiles to retype BC, to provide a new method for BC classification and explore new precise therapeutic strategies based on this method. Methods Based on lncRNA expression profiles of 317 single cells from 11 BC patients, SC3 was used to retype BC, and differential expression analysis and enrichment analysis were performed to identify biological characteristics of new subtypes. The results were validated for survival analysis using data from TCGA. Then, the downstream regulatory genes of lncRNA markers of each subtype were searched by expression correlation analysis, and these genes were used as targets to screen therapeutic drugs, thus proposing new precision treatment strategies according to the different subtype compositions of patients. Results Seven lncRNA subtypes and their specific biological characteristics are obtained. Then, 57 targets and 210 drugs of 7 subtypes were acquired. New precision medicine strategies were proposed according to the different compositions of patient subtypes. Conclusions For patients with different subtype compositions, we propose a strategy to select different drugs for different patients, which means using drugs targeting multi subtype or combinations of drugs targeting a single subtype to simultaneously kill different cancer cells by personalized treatment, thus reducing the possibility of drug resistance and even recurrence.

Nocardia is an opportunistic pathogen that mainly involves immunosuppressed patients and causes a high mortality rate. As an emerging approach to detect infectious pathogens, metagenomic next-generation sequencing (mNGS) was reported in the detection of Nocardia. However, there is no evidence demonstrating the effect of mNGS on the prognosis of Nocardia infection. In this retrospective study, we included 18 nocardiosis patients. Nocardia species were detected by mNGS from their clinical samples. All the patients were diagnosed with nocardiosis by clinical experts through a comprehensive evaluation. Of these 18 patients, fever is the most frequent initial symptom. Compared to traditional culture methods, mNGS provides a faster turnaround time (TAT) and higher sensitivity. Pulmonary nocardiosis was the most common clinical presentation in the study. mNGS detected 13 types of Nocardia species, of which Nocardia abscessus and Nocardia cyriacigeorgica were the most common species. The study’s most noteworthy discovery is that mNGS outperforms culture at detecting mixed infections (more than one pathogen detected in one clinical specimen, including bacteria, fungi, and excluding virus), and number of infectious species was an independent risk factor for nocardiosis patients’ prognostics after adjusting age, ICU days, gender and underlying diseases (adjusted HR = 1.47, 95% CI: 1.09-1.98, p = 0.011). As a result, we believe that by detecting mixed infections (more than one pathogenic species), mNGS can provide a clinical risk warning for the prognosis of nocardiosis.

The fight against Mycobacterium tuberculosis (MTB) has been going on for thousands of years, while it still poses a threat to human health. In addition to routine detections, metagenomic next-generation sequencing (mNGS) has begun to show presence as a comprehensive and hypothesis-free test. It can not only detect MTB without isolating specific pathogens but also suggest the co-infection pathogens or underlying tumor simultaneously, which is of benefit to assist in comprehensive clinical diagnosis. It also shows the potential to detect multiple drug resistance sites for precise treatment. However, considering the cost performance compared with conventional assays (especially Xpert MTB/RIF), mNGS seems to be overqualified for patients with mild and typical symptoms. Technology optimization of sequencing and analyzing should be conducted to improve the positive rate and broaden the applicable fields.

Background: Hyzetimibe is a novel inhibitor of cholesterol that specifically targets the NPC1L1 gene. Significant inter-individual variability suggests the existence of an abundance of poor responders and non-responders. In addition, the current literature is inconsistent and controversial regarding the potential impact of the Niemann-Pick C1-Like 1 (NPC1L1) gene on low-density lipoprotein cholesterol (LDL-C) reduction. In light of these concerns, we performed a high-quality clinical trial to investigate the specific characteristics of NPC1L1 gene variation on LDL-C reduction. Methods: This was a multicenter, randomized, double-blind, placebo-controlled, clinical trial with a factorial design. Qualified patients were randomly assigned to one of six treatments: placebo, hyzetimibe (10 or 20 mg), atorvastatin, and atorvastatin plus hyzetimibe (10 or 20 mg). Fasting blood samples were collected and genotyped, and the concentrations of LDL-C and the targeted drug trough were determined to investigate the association between the NPC1L1 gene expression and the reduction of LDL-C. Results: In total, 727 individuals were initially recruited; of these, 444 were eligible to begin the trial. We identified one SNP (g1679C > G) that exerted significantly different impacts on LDL-C levels. As monotherapy, CC carriers experienced significantly higher reductions in the mean LDL-C (−23.99%) than either the GG (−16.45%, p < 0.01) or GC (−13.02%, p < 0.01) carriers in the hyzetimibe (20 mg) group. In contrast, when co-administered with atorvastatin, GC carriers experienced greater LDL-C reduction than non-GC carriers (-52.23% vs. −45.03%) in the hyzetimibe (20 mg) plus atorvastatin group. Furthermore, the proportions of individuals experiencing a reduction in LDL-C by >50% increased as the dose of hyzetimibe increased from 16.1% to 65.4%. Conclusion: The g1679C > G SNP in the NPC1L1 gene is critical and exerts a differential impact on the response to hyzetimibe treatment. Heterozygotic patients respond with poor efficacy when treated by monotherapy but show good responses in terms of LDL-C reduction when hyzetimibe was co-administered with atorvastatin. To treat hypercholesterolemia in a precise manner with hyzetimibe, it is necessary to identify genotype patients for the g1679C > G SNP. We also highlight the potential necessity for identifying the appropriate subjects to be treated with ezetimibe. Clinical Trial Registration: [https://clinicaltrials.gov/], identifier [CTR20150351] [ABSTRACT FROM AUTHOR]

Background: Hyzetimibe is a novel inhibitor of cholesterol that specifically targets the NPC1L1 gene. Significant inter-individual variability suggests the existence of an abundance of poor responders and non-responders. In addition, the current literature is inconsistent and controversial regarding the potential impact of the Niemann-Pick C1-Like 1 (NPC1L1) gene on low-density lipoprotein cholesterol (LDL-C) reduction. In light of these concerns, we performed a high-quality clinical trial to investigate the specific characteristics of NPC1L1 gene variation on LDL-C reduction.Methods: This was a multicenter, randomized, double-blind, placebo-controlled, clinical trial with a factorial design. Qualified patients were randomly assigned to one of six treatments: placebo, hyzetimibe (10 or 20 mg), atorvastatin, and atorvastatin plus hyzetimibe (10 or 20 mg). Fasting blood samples were collected and genotyped, and the concentrations of LDL-C and the targeted drug trough were determined to investigate the association between the NPC1L1 gene expression and the reduction of LDL-C.Results: In total, 727 individuals were initially recruited; of these, 444 were eligible to begin the trial. We identified one SNP (g1679C > G) that exerted significantly different impacts on LDL-C levels. As monotherapy, CC carriers experienced significantly higher reductions in the mean LDL-C (−23.99%) than either the GG (−16.45%, p < 0.01) or GC (−13.02%, p < 0.01) carriers in the hyzetimibe (20 mg) group. In contrast, when co-administered with atorvastatin, GC carriers experienced greater LDL-C reduction than non-GC carriers (-52.23% vs. −45.03%) in the hyzetimibe (20 mg) plus atorvastatin group. Furthermore, the proportions of individuals experiencing a reduction in LDL-C by >50% increased as the dose of hyzetimibe increased from 16.1% to 65.4%.Conclusion: The g1679C > G SNP in the NPC1L1 gene is critical and exerts a differential impact on the response to hyzetimibe treatment. Heterozygotic patients respond with poor efficacy when treated by monotherapy but show good responses in terms of LDL-C reduction when hyzetimibe was co-administered with atorvastatin. To treat hypercholesterolemia in a precise manner with hyzetimibe, it is necessary to identify genotype patients for the g1679C > G SNP. We also highlight the potential necessity for identifying the appropriate subjects to be treated with ezetimibe.Clinical Trial Registration: [https://clinicaltrials.gov/], identifier [CTR20150351]

Purpose: The study was to explore whether the 3-dimensional printing guiding plate system could facilitate the modified procedure for arthroscopic treatment of nondisplaced scaphoid nonunion. Methods: Patients, diagnosed with scaphoid nonunion without displacement, were randomly assigned into two groups. In Group A, the 3-dimensional printing guiding plate system was used for guiding fixation during the surgery. In Group B, fixation was performed with intra-operative fluoroscopy. The bone operation time was recorded during the surgery. The patients were evaluated before surgery and followed-up after six post-operative months, including motion ratio, strength ratio, Visual Analogue Scale, modified Mayo Scores, Patient Rated Wrist Evaluation scores, plain radiography and CT scan. Results: Sixteen patients were recruited for the study. The average bone operation time in Group A was statistically shorter than that in Group B. Conclusions: 3-dimensional printing technique-assisted arthroscopic bone graft and fixation of scaphoid nonunion constitute an effective and accurate clinical treatment option. The translational potential of this article: The concept and technique of 3D printing assisted percutaneous fixation introduced in this paper have the potential to be applied in a variety of operations requiring accurate percutaneous fixation, especially for the joint injuries.

Background: Breast cancer (BC) is a complex disease with high heterogeneity, which often leads to great differences in treatment results. Current common molecular typing method is PAM50, which shows positive results for precision medicine; however, room for improvement still remains because of the different prognoses of subtypes. Therefore, in this article, we used lncRNAs, which are more tissue-specific and developmental stage-specific than other RNAs, as typing markers and combined single-cell expression profiles to retype BC, to provide a new method for BC classification and explore new precise therapeutic strategies based on this method.Methods: Based on lncRNA expression profiles of 317 single cells from 11 BC patients, SC3 was used to retype BC, and differential expression analysis and enrichment analysis were performed to identify biological characteristics of new subtypes. The results were validated for survival analysis using data from TCGA. Then, the downstream regulatory genes of lncRNA markers of each subtype were searched by expression correlation analysis, and these genes were used as targets to screen therapeutic drugs, thus proposing new precision treatment strategies according to the different subtype compositions of patients.Results: Seven lncRNA subtypes and their specific biological characteristics are obtained. Then, 57 targets and 210 drugs of 7 subtypes were acquired. New precision medicine strategies were proposed according to the different compositions of patient subtypes.Conclusions: For patients with different subtype compositions, we propose a strategy to select different drugs for different patients, which means using drugs targeting multi subtype or combinations of drugs targeting a single subtype to simultaneously kill different cancer cells by personalized treatment, thus reducing the possibility of drug resistance and even recurrence. [ABSTRACT FROM AUTHOR]

Viral infection and environmental pollution make the incidence of lymphoma increase year by year. Early diagnosis and precise treatment are of great clinical significance. Exosomes are tiny vesicles of lipid bilayer membrane structure, which mediate cell to cell communication and information exchange. In recent years, many studies have proved that exosomes are the important mechanism of the occurrence, development and drug resistance of lymphoma. Nucleic acids and small molecules in exosomes can be used for early diagnosis and prognosis of lymphoma. Material modification can significantly enhance the targeting and therapeutic efficacy of exosomes. This paper summarized the biological characteristics of exosomes, the methods of isolation and identification, the relationship between exosomes and tumor, and the research progress of exosomes in lymphoma, to provide references for the early warning and treatment of lymphoma. [ABSTRACT FROM AUTHOR]

Viral infection and environmental pollution make the incidence of lymphoma increase year by year. Early diagnosis and precise treatment are of great clinical significance. Exosomes are tiny vesicles of lipid bilayer membrane structure, which mediate cell to cell communication and information exchange. In recent years, many studies have proved that exosomes are the important mechanism of the occurrence, development and drug resistance of lymphoma. Nucleic acids and small molecules in exosomes can be used for early diagnosis and prognosis of lymphoma. Material modification can significantly enhance the targeting and therapeutic efficacy of exosomes. This paper summarized the biological characteristics of exosomes, the methods of isolation and identification, the relationship between exosomes and tumor, and the research progress of exosomes in lymphoma, to provide references for the early warning and treatment of lymphoma. Reset [ABSTRACT FROM AUTHOR]

Nocardia genus is an aerobic, gram-positive, and opportunistic pathogen, which mainly affects cell-mediated immunosuppressed patients. Early diagnosis and treatment greatly improve prognosis. However, the limitation of golden standard-bacterial culture exists. Here, we report a 61-year-old male with pneumonia, sepsis and intermuscular abscesses induced by Nocardia farcinica. Venous blood culture reported negative results. Former improper diagnosis and treatment did not improve his condition. With the assistant of metagenomic next-generation sequencing, the pathogen was identified as Nocardia farcinica. He was then applied with accurate treatment and had a remarkable clinical and radiological improvement.

Tumor tissues are often composed of not only tumor cells but also non-tumor cells such as immune cells, stromal cells and mesenchymal cells. They play an important role in tumor growth and progress together. Tumor purity is significantly associated with clinical features, gene expression and tumor biology, indicating that we need to fully consider the potential confounding effect of tumor purity on tumor analyses. This article reviews the concept, calculate methods and impact of tumor purity on genomic analysis.

Background: The high heterogeneity of acute respiratory distress syndrome (ARDS) contributes to paradoxical conclusions from previous investigations of rosuvastatin for ARDS. Identification of the population (phenotype) that could benefit from rosuvastatin is a novel exploration for the precise treatment.Methods: The patient population for this analysis consisted of unique patients with ARDS enrolled in the SAILS trial (rosuvastatin vs. placebo). Phenotypes were derived using consensus k-means clustering applied to routinely available clinical variables within 6 h of hospital presentation before the patients received placebo or rosuvastatin. The Kaplan–Meier statistic was used to estimate the 90-day cumulative mortality to screen for a specific population that could benefit from rosuvastatin, with a cutoff P < 0.05.Results: The derivation cohort included 585 patients with ARDS. Of the patients with the four derived phenotypes, those with phenotype 3 were classified as the “specific population who could benefit from rosuvastatin” as rosuvastatin resulted in a significant reduction in 90-day cumulative mortality from ARDS [hazard ratio (HR), 0.29; 95% confidence interval (CI), 0.09–0.93; P = 0.027]. Additionally, rosuvastatin markedly improved the days free of cardiovascular failure (10.08 ± 3.79 in the rosuvastatin group vs. 7.31 ± 4.94 in the placebo group, P = 0.01) and coagulation abnormalities (13.65 ± 1.33 vs. 12.15 ± 3.77, P = 0.02) up to day 14 in the phenotype 3 cohort. Phenotype 3 was summarized as Platelethigh & Creatlow phenotype because these patients have a relatively higher platelet count (390.05 ± 79.43 × 109/L) and lower creatinine (1.42 ± 1.08 mg/dL) than do patients classified as other phenotypes. In addition, rosuvastatin seemed to increase 90-day mortality for patients classified as phenotype 4 (HR, 2.76; 95% CI, 0.09–9.93; P = 0.076), with an adverse effect on reducing the days free of renal failure up to day 14 (4.70 ± 4.99 vs. 10.17 ± 4.69, P = 0.01). Patients in phenotype 4 showed relatively severe illness in terms of baseline features, particularly renal failure, with high serum glucose. Therefore, phenotype 4 was defined as APACHEhigh & Serum glucosehigh phenotype.Conclusions: This secondary analysis of the SAILS trial identified that rosuvastatin seems to be harmful for patients classified as APACHEhigh & Serum glucosehigh phenotype, but benefit patients in Platelethigh & Creatlow phenotype, thus uncovering the novel value of rosuvastatin for the precise treatment of ARDS.

Drugs targeting the cyclin-dependent kinase 4/6 (CDK4/6)–retinoblastoma 1 (RB1) axis have shown efficacy against multiple solid cancers, but their therapeutic potential in pancreatic cancer remains poorly defined. A recent report proposed that a “tailored” combination of first-line and second-line CDK4-targeting drugs would hold promise for pancreatic cancer treatment. Indeed, this therapeutic strategy exhibited significantly suppressive effects on pancreatic cancer patient-derived cell lines and tumor tissue in vitro. However, the study neglected immune involvement and the influence of CDK6 and RB1 in CDK4 inhibition-based treatment. Herein, we reveal multiple new facets of the CDK4/6–RB1 axis in pancreatic cancer, highlighting the complexity of this signaling axis for future prognostic and therapeutic targeting.

Background: Inflammatory myofibroblastic tumors (IMTs) are a spectrum of tumors that range in morphology and biological behavior from benign, intermediate, to apparently malignant and epithelioid inflammatory myofibroblastic sarcoma (EIMS) is one of the malignant subtypes. This study tried to provide experience and new ideas for treating this rare disease., Methods: This study retrospectively analyzed and followed up 12 children with EIMS admitted to Beijing Children's Hospital, Baoding Children's Hospital, and Children's Hospital of Chongqing Medical University from August 2016 to May 2022., Results: Of the 12 children, 7 were male and 5 were female, with a median age of 74.50 [interquartile range (IQR), 61.50-90.00] months. Of these patients, eight had a single lesion and four had multiple lesions. The maximum diameter of the single tumor foci was 19.30 cm, the full meridian of the multiple tumor foci target lesions was 32.67 cm, and the median maximum tumor size was 11.99 (IQR, 7.80-15.70) cm. The site of disease was the abdominopelvic cavity in eight cases, the thoracic cavity in two cases, the maxillofacial region in one case, and the larynx in one case. The clinical manifestations were predominantly elevated body temperature (n=8). There was one case of ROS1 fusion mutation and nine cases of ALK fusion mutation. Of the 12 children, 6 were biopsied at the initial diagnosis and 6 were surgically treated. Follow-up treatment included preoperative neoadjuvant chemotherapy (n=4), peritoneal thermal perfusion therapy (n=2), targeted therapy (n=3), postoperative chemotherapy (n=5), and radiotherapy (n=3). The follow-up time was 14.50 (IQR, 10.50-31.50) months, with eight cases of tumor-free survival, two cases of death, and two cases of loss of follow-up., Conclusions: EIMS in children is extremely rare and clinically aggressive. The clinical presentation is nonspecific, and the initial diagnosis of the tumor is often large. Mutations in the ALK gene are common in EIMS. Surgery is the mainstay of EIMS treatment, and patients benefit from a multidisciplinary combination that includes targeted therapies, with long-term prognosis remaining subject to ongoing follow-up., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-23-590/coif). The authors have no conflicts of interest to declare., (2024 Translational Pediatrics. All rights reserved.)