Chinese herbal medicine for the treatment of intestinal cancer: preclinical studies and potential clinical applications.

Intestinal cancer (IC) poses a significant global health challenge that drives continuous efforts to explore effective treatment modalities. Conventional treatments for IC are effective, but are associated with several limitations and drawbacks. Chinese herbal medicine (CHM) plays an important role in the overall cancer prevention and therapeutic strategies. Recent years have seen a growing body of research focus on the potential of CHM in IC treatment, showing promising results in managing IC and mitigating the adverse effects of radiotherapy and chemotherapy. This review provides updated information from preclinical research and clinical observation on CHM's role in treatment of IC, offering insights into its comprehensive management and guiding future prevention strategies and clinical practice.

Enhancing Sensitivity in Detecting Severe Fever With Thrombocytopenia Syndrome Virus: Development of a Reverse Transcription-Droplet Digital Polymerase Chain Reaction.

Severe fever with thrombocytopenia syndrome (SFTS) is a highly fatal disease. Droplet digital polymerase chain reaction (ddPCR) presents unparalleled sensitivity and enables absolute quantification of viral load. In this prospective study, we enrolled 111 patients with SFTS and collected 259 continuous samples. Our findings unveil a robust reverse transcription (RT)-ddPCR method for SFTS with a limit of detection of 2.46 copies/µL (95% CI, 1.50-11.05), surpassing the sensitivity of RT-quantitative polymerase chain reaction at 103.29 copies/µL (95% CI, 79.69-216.35). Longitudinal cohort analysis revealed significantly higher RT-ddPCR detection rates at days 10 to 11, 13 to 14, and ≥15 of the disease course as compared with RT-quantitative polymerase chain reaction (P < .05). Positive RT-ddPCR results were associated with declined platelet and elevated aspartate aminotransferase and lactate dehydrogenase on the same day vs negative RT-ddPCR samples. RT-ddPCR exhibits commendable diagnostic efficacy in SFTS, and it remains detectable in blood samples from patients with an extended disease course. Furthermore, RT-ddPCR correlates with clinical laboratory tests, furnishing valuable reference data for clinical diagnosis.

[Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines].

Oral Chinese patent medicine is the essence of effective prescriptions created and summarized by Chinese medical scientists through thousands of years of medical practice. It is portable and convenient, with an obvious curative effect and other characteristics. However, at present, oral Chinese patent medicine is rich in dosage forms, various in types, complex in mechanism of action, and broad in clinical positioning. In clinical application, there are often cases of drug use without reference to instructions,repeated drug use, and prolonged drug use, which highlights safety problems such as adverse reactions and hepatorenal toxicity. Oral Chinese patent medicine pharmacovigilance is facing challenges. World Health Organization(WHO) has issued the WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems, and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use(ICH) has issued the ICH E2 pharmacovigilance guidelines. The United States has issued the Pharmacovigilance management standards and pharmacoepidemiological assessment guidelines, and the European Union has issued the Guidelines on good pharmacovigilance practices. Japan, South Korea, and other countries in the Asia Pacific region have established their own pharmacovigilance systems, but currently, there are no pharmacovigilance guidelines related to oral Chinese patent medicine in China. Therefore, experts from many disciplines and fields in China were invited to jointly develop the Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines, which aims to develop pharmacovigilance guidelines for clinical application that are consistent with China's national conditions and highlight the characteristics of oral Chinese patent medicine, and provide guidance for clinically safe and rational drug application in medical institutions.

[Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use].

There are many kinds and dosage forms of Chinese patent medicines for external use on the market, which are widely used in clinical departments. The common adverse reactions of Chinese patent medicines for external use are skin reactions, and those for the rare severe diseases include palpitation, chest tightness, dyspnea, and anaphylactic shock. At present, World Health Organization(WHO), International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH),the United States, the European Union, and Asia-Pacific countries(such as Japan and South Korea) have not issued any pharmacovigilance guideline of Chinese patent medicines for external use. China has not issued any pharmacovigilance guideline for these medicines, only releasing the standard Evaluation of skin adverse reactions caused by Chinese patent medicines for external use(T/CACM 005-2017). To standardize the safe and reasonable use of Chinese patent medicines for external use, Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use was developed with the joint efforts of experts in diverse disciplines. The guideline provides guidance on the monitoring and reporting of adverse reactions/events, identification and assessment of risk signals, and risk control measures in the clinical application of Chinese patent medicines for external use to guide the rational use of these medicines in clinical practice. At the same time, the possible risks and risk control measures in clinical application of Chinese patent medicines for external use are listed for clinical reference. In addition, the guideline provides guidance for risk minimization plans and the standardization of activities related to pharmacovigilance of Chinese patent medicines for external use in China.

Discussion on clinical application and regularity of the theory of "mind-regulating" in clinical acupuncture and moxibustion treatment. / "调神"思想在针灸临床中的运用概况及规律探讨.

The active role of "Shen" (mind) in the process of disease treatment has always been valued by scholars of traditional Chinese medicine (TCM). "Tiaoshen" (mind-regulating) is regarded as the fundamental component of TCM therapy. "Mind-regulating" acupuncture and moxibustion therapy, as a treatment method for both body and mind, is consistent with the present bio-psycho-social medical model. In recent years, a large number of clinical studies have confirmed the exact efficacy of "mind-regulating" acupuncture and moxibustion therapy. This article reviewed the clinical applications of that in psychosomatic diseases, neurological diseases, and digestive diseases over the last decade. This article also summarized the research progress of various "mind-regulating" acupuncture and moxibustion methods, investigated the theoretical connotations of "Tongdu Tiaoshen" (dredging Governor Vessel and regulating mind) acupuncture, "Shugan Tiaoshen" (soothing liver and regulating mind) acupuncture, and the "Tiaoshen needling technique" (mind-regulating needling technique), and generalized the main acupoint selection rules. Lastly, future development directions were provided for the theoretical basis of clinical application of "mind-regulating" acupuncture and moxibustion therapy for further improvement.

Establishment and clinical application of a droplet digital PCR method for the detection of Edwardsiella tarda.

Edwardsiella tarda (E. tarda) can infect humans and a variety of animals, including fish, amphibians, reptiles, birds, and mammals. However, a more highly sensitive, specific, and repeatable test for its detection is lacking. The objective of this study was to develop a highly sensitive, specific, and repeatable droplet digital polymerase chain reaction (ddPCR)-based method for the quantitative detection of E. tarda. The gyrB gene was selected as the target gene, and primers and probe were designed and synthesized. Using E. tarda genomic DNA as templates, the reaction method was optimized to establish a linear relationship with real-time PCR detection methods. The sensitivity, specificity, and repeatability of the method were analyzed, and clinical samples were tested. When the primer and probe concentrations were 900 and 300 nM, respectively, and the annealing temperature was 57°C, the efficiency of the ddPCR amplification reaction was highest and the boundary between positive and negative droplet distribution was clearest. The sensitivity was high, with detection limit being as low as 0.56 copies·µL-1; additionally, and a good linear relationship (R 2 = 0.9962) between ddPCR and real-time PCR detection, within the range of 1-25,000 copies·µL-1, was evident. The repeatability was good, with a detection coefficient of variation of 2.74%. There was no cross-reactivity with 15 other common pathogenic microorganisms in aquatic animals (Streptococcus agalactiae, Streptococcus iniae, Streptococcus suis type 2, Nocardia seriolae, Vibrio parahaemolyticus, Aeromonas sobria, red sea bream iridovirus, decapod iridescent virus 1, enterocytozoon hepatopenaei, carp edema virus, Koi herpesvirus, goldfish hematopoietic necrosis virus, tilapia lake virus, viral nervous necrosis virus, or grass carp reovirus) in positive samples. Among the 48 clinical samples, including Bahaba taipingensis and its live food fish, pond water samples, and routine monitoring samples (Koi), 21 were positive for E. tarda, consistent with the bacterial isolation and identification results. The E. tarda ddPCR detection method has high specificity, sensitivity, and repeatability, can more accurately quantify E. tarda, and provides a useful reference for research related to this bacterium.

Corneal densitometry: A new evaluation indicator for corneal diseases.

Corneal densitometry (CD) uses the biological properties of the cornea to visualize the morphology of the cornea and determine the degree of corneal transparency. At present, it is an emerging metric that has shown promise in various clinical diagnosis and evaluation of eye diseases and surgeries. We introduce the different methodologies used to measure CD. Furthermore, we systematically categorize the diagnostic value of CD into high, medium, and low levels based on its clinical significance. By analyzing a wide range of conditions, including keratoconus, postrefractive surgery changes, and other corneal pathologies, we assess the utility of CD in each context. We also discuss the potential implications of these classifications for disease monitoring and prognosis evaluation. Our review underscores the importance of integrating CD assessments into routine clinical practice to enhance the accuracy and effectiveness of diagnostic processes for corneal disorders.

Effects, methods and limits of the cryopreservation on mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are a type of cell capable of regulating the immune system, as well as exhibiting self-renewal and multi-lineage differentiation potential. Mesenchymal stem cells have emerged as an essential source of seed cells for therapeutic cell therapy. It is crucial to cryopreserve MSCs in liquid nitrogen prior to clinical application while preserving their functionality. Furthermore, efficient cryopreservation greatly enhances MSCs' potential in a range of biological domains. Nevertheless, there are several limits on the MSC cryopreservation methods now in use, necessitating thorough biosafety assessments before utilizing cryopreserved MSCs. Therefore, in order to improve the effectiveness of cryopreserved MSCs in clinical stem cell treatment procedures, new technological techniques must be developed immediately. The study offers an exhaustive analysis of the state-of-the-art MSC cryopreservation techniques, their effects on MSCs, and the difficulties encountered when using cryopreserved MSCs in clinical applications.

Clinical application of cluster analysis in patients with newly diagnosed type 2 diabetes.

AIMS: Early prevention and treatment of type 2 diabetes mellitus (T2DM) is still a huge challenge for patients and clinicians. Recently, a novel cluster-based diabetes classification was proposed which may offer the possibility to solve this problem. In this study, we report our performance of cluster analysis of individuals newly diagnosed with T2DM, our exploration of each subtype's clinical characteristics and medication treatment, and the comparison carried out concerning the risk for diabetes complications and comorbidities among subtypes by adjusting for influencing factors. We hope to promote the further application of cluster analysis in individuals with early-stage T2DM. METHODS: In this study, a k-means cluster algorithm was applied based on five indicators, namely, age, body mass index (BMI), glycosylated hemoglobin (HbA1c), homeostasis model assessment-2 insulin resistance (HOMA2-IR), and homeostasis model assessment-2 ß-cell function (HOMA2-ß), in order to perform the cluster analysis among 567 newly diagnosed participants with T2DM. The clinical characteristics and medication of each subtype were analyzed. The risk for diabetes complications and comorbidities in each subtype was compared by logistic regression analysis. RESULTS: The 567 patients were clustered into four subtypes, as follows: severe insulin-deficient diabetes (SIDD, 24.46%), age-related diabetes (MARD, 30.86%), mild obesity-related diabetes (MOD, 25.57%), and severe insulin-resistant diabetes (SIRD, 20.11%). According to the results of the oral glucose tolerance test (OGTT) and biochemical indices, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2hBG), HbA1c, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride-glucose index (TyG) were higher in SIDD and SIRD than in MARD and MOD. MOD had the highest fasting C-peptide (FCP), 2-hour postprandial C-peptide (2hCP), fasting insulin (FINS), 2-hour postprandial insulin (2hINS), serum creatinine (SCr), and uric acid (UA), while SIRD had the highest triglycerides (TGs) and TyG-BMI. Albumin transaminase (ALT) and albumin transaminase (AST) were higher in MOD and SIRD. As concerms medications, compared to the other subtypes, SIDD had a lower rate of metformin use (39.1%) and a higher rate of α-glucosidase inhibitor (AGI, 61.7%) and insulin (74.4%) use. SIRD showed the highest frequency of use of sodium-glucose cotransporter-2 inhibitors (SGLT-2i, 36.0%) and glucagon-like peptide-1 receptor agonists (GLP-1RA, 19.3%). Concerning diabetic complications and comorbidities, the prevalence of diabetic kidney disease (DKD), cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and hypertension differed significantly among subtypes. Employing logistic regression analysis, after adjusting for unmodifiable (sex and age) and modifiable related influences (e.g., BMI, HbA1c, and smoking), it was found that SIRD had the highest risk of developing DKD (odds ratio, OR = 2.001, 95% confidence interval (CI): 1.125-3.559) and dyslipidemia (OR = 3.550, 95% CI: 1.534-8.215). MOD was more likely to suffer from NAFLD (OR = 3.301, 95%CI: 1.586-6.870). CONCLUSIONS: Patients with newly diagnosed T2DM can be successfully clustered into four subtypes with different clinical characteristics, medication treatment, and risks for diabetes-related complications and comorbidities, the cluster-based diabetes classification possibly being beneficial both for prevention of secondary diabetes and for establishment of a theoretical basis for precision medicine.

Clinical application value of long non-coding RNAs signatures of genomic instability in predicting prognosis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) presents challenges due to its high recurrence and metastasis rates and poor prognosis. While current clinical diagnostic and prognostic indicators exist, their accuracy remains imperfect due to their biological complexity. Therefore, there is a quest to identify improved biomarkers for HCC diagnosis and prognosis. By combining long non-coding RNA (lncRNA) expression and somatic mutations, Duan et al identified five representative lncRNAs from 88 lncRNAs related to genomic instability (GI), forming a GI-derived lncRNA signature (LncSig). This signature outperforms previously reported LncSig and TP53 mutations in predicting HCC prognosis. In this editorial, we comprehensively evaluate the clinical application value of such prognostic evaluation model based on sequencing technology in terms of cost, time, and practicability. Additionally, we provide an overview of various prognostic models for HCC, aiding in a comprehensive understanding of research progress in prognostic evaluation methods.

Advancements in Chronic Myeloid Leukemia detection: Development and evaluation of a novel QCM aptasensor for use in clinical practice.

Oncological diseases represent a significant global health challenge, with high mortality rates. Early detection is crucial for effective treatment, and aptamers, which demonstrate superior specificity and stability compared to antibodies, offer a promising avenue for diagnostic advancement. This study presents the design, development and evaluation of a quartz crystal microbalance (QCM) sensor functionalized with the T2-KK1B10 aptamer for the sensitive and specific detection of Chronic Myeloid Leukemia (CML) K562 cells. The research focuses on optimizing the biorecognition layer by adjusting the aptamer conditions, demonstrating the sensor's ability to detect these CML cells with high specificity and sensitivity. The aptamer-modified QCM sensor operates on the principle of mass change detection upon binding of target cells. By employing the Langmuir isotherm model, the performance of the sensor was optimized for the capture of CML cells from biological samples with LOD of 263 K562 cells. The sensor was also successfully regenerated multiple times without sensitivity loss. Validation of the sensor's performance was conducted under controlled laboratory settings, followed by extensive testing utilizing human lyophilized plasma and clinical samples from patients. The sensor exhibited high sensitivity and specificity in the detection of CML cells within clinical specimens, thereby illustrating its potential for practical clinical deployment. This research presents a novel approach to the early diagnosis of CML, facilitating timely intervention and enhanced patient outcomes. The developed aptasensor demonstrates potential for broader application in cancer diagnostics and personalized medicine.

The mechanism of action and chemical synthesis of FDA newly approved drug molecules.

In 2023, the U.S. Food and Drug Administration has approved 29 small molecule drugs. These newly approved small molecule drugs possess the distinct scaffolds, thereby exhibiting diverse mechanisms of action and binding modalities. Moreover, the marketed drugs have always been an important source of new drug development and creative inspiration, thereby fostering analogous endeavors in drug discovery that potentially extend to the diverse clinical indications. Therefore, conducting a comprehensive evaluation of drug approval experience and associated information will facilitate the expedited identification of highly potent drug molecules. In this review, we comprehensively summarized the relevant information regarding the clinical applications, mechanisms of action and chemical synthesis of 29 small molecule drugs, with the aim of providing a promising structural basis and design inspiration for pharmaceutical chemists.

Digital robot-assisted minimally invasive impacted tooth extraction: A case report.

Objective: This study investigated the clinical effects and applicability of minimally invasive impacted teeth extraction using digital robots. Methods: A marker was bonded to the non-surgical area before surgery. A Cone-Beam Computed Tomography (CBCT) scan was obtained and uploaded to the robot software to determine the drilling position of the ring drill. During the surgery, the robot arm automatically navigated to a predetermined position, and the ring drill removed part of the bone tissue and exposed and extracted the impacted teeth. Finally, the surgeon tightly sutured the wounds to the surgical area. Results: Three minimally invasive extractions of impacted teeth with robotic assistance were performed without complications. The surgical area showed good healing during the one-month follow-up examination. Conclusions: Digital robot-assisted minimally invasive extraction of impacted teeth is a highly feasible clinical procedure as it minimises trauma to the surgical area and protects the surrounding blood vessels and nerve bundles, making it a safe and valuable technique with significant potential for clinical application.

Clinical efficacy and future application of indigo naturalis in the treatment of ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by non-specific inflammation. Managing UC presents significant challenges due to its chronic nature and high recurrence rates. Indigo naturalis has emerged as a potential therapeutic agent in clinical UC treatment, demonstrating advantages in alleviating refractory UC and maintaining remission periods compared to other therapeutic approaches. AIM OF REVIEW: This review aims to elucidate the potential mechanisms underlying the therapeutic effects of indigo naturalis in UC treatment, assess its clinical efficacy, advantages, and limitations, and provide insights into methods and strategies for utilizing indigo naturalis in UC management. MATERIALS AND METHODS: Comprehensive data on indigo naturalis were collected from reputable online databases including PubMed, GreenMedical, Web of Science, Google Scholar, China National Knowledge Infrastructure Database, and National Intellectual Property Administration. RESULTS: Clinical studies have demonstrated that indigo naturalis, either alone or in combination with other drugs, yields favorable outcomes in UC treatment. Its mechanisms of action involve modulation of the AHR receptor, anti-inflammatory properties, regulation of intestinal flora, restoration of the intestinal barrier, and modulation of immunity. Despite its efficacy in managing refractory UC and prolonging remission periods, indigo naturalis treatment is associated with adverse reactions, quality variations, and inadequate pharmacokinetic investigations. CONCLUSION: The therapeutic effects of indigo naturalis in UC treatment are closely linked to its ability to regulate the AHR receptor, exert anti-inflammatory effects, mcodulate intestinal flora, restore the intestinal barrier, and regulate immunity. Addressing the current shortcomings, including adverse reactions, quality control issues, and insufficient pharmacokinetic data, is crucial for optimizing the clinical utility of indigo naturalis in UC management. By refining patient-centered treatment strategies, indigo naturalis holds promise for broader application in UC treatment, thereby alleviating the suffering of UC patients.

Chinese Medicine in Colorectal Cancer Treatment: From Potential Targets and Mechanisms to Clinical Application.

Colorectal cancer (CRC) is a global health challenge necessitating innovative therapeutic strategies. There is an increasing trend toward the clinical application of integrative Chinese medicine (CM) and Western medicine approaches. Chinese herbal monomers and formulations exert enhanced antitumor effects by modulating multiple signaling pathways in tumor cells, including inhibiting cell proliferation, inducing apoptosis, suppressing angiogenesis, reversing multidrug resistance, inhibiting metastasis, and regulating immunity. The synergistic effects of CM with chemotherapy, targeted therapy, immunotherapy, and nanovectors provide a comprehensive framework for CRC treatment. CM can mitigate drug toxicity, improve immune function, control tumor progression, alleviate clinical symptoms, and improve patients' survival and quality of life. This review summarizes the key mechanisms and therapeutic strategies of CM in CRC, highlighting its clinical significance. The potential for CM and combination with conventional treatment modalities is emphasized, providing valuable insights for future research and clinical practice.

A Comprehensive Overview of Postbiotics with a Special Focus on Discovery Techniques and Clinical Applications.

The increasing interest in postbiotics, a term gaining recognition alongside probiotics and prebiotics, aligns with a growing number of clinical trials demonstrating positive outcomes for specific conditions. Postbiotics present several advantages, including safety, extended shelf life, ease of administration, absence of risk, and patentability, making them more appealing than probiotics alone. This review covers various aspects, starting with an introduction, terminology, classification of postbiotics, and brief mechanisms of action. It emphasizes microbial metabolomics as the initial step in discovering novel postbiotics. Commonly employed techniques such as NMR, GC-MS, and LC-MS are briefly outlined, along with their application principles and limitations in microbial metabolomics. The review also examines existing research where these techniques were used to identify, isolate, and characterize postbiotics derived from different microbial sources. The discovery section concludes by highlighting challenges and future directions to enhance postbiotic discovery. In the second half of the review, we delve deeper into numerous published postbiotic clinical trials to date. We provide brief overviews of system-specific trial applications, their objectives, the postbiotics tested, and their outcomes. The review concludes by highlighting ongoing applications of postbiotics in extended clinical trials, offering a comprehensive overview of the current landscape in this evolving field.

Paeonia genus: a systematic review of active ingredients, pharmacological effects and mechanisms, and clinical applications for the treatment of cancer.

The main active constituents of plants of the Paeonia genus are known to have antitumor activity. Hundreds of compounds with a wide range of pharmacological activities, including monoterpene glycosides, flavonoids, tannins, stilbenes, triterpenoids, steroids, and phenolic compounds have been isolated. Among them, monoterpenes and their glycosides, flavonoids, phenolic acids, and other constituents have been shown to have good therapeutic effects on various cancers, with the main mechanisms including the induction of apoptosis; the inhibition of tumor cell proliferation, migration, and invasion; and the modulation of immunity. In this study, many citations related to the traditional uses, phytochemical constituents, antitumor effects, and clinical applications of the Paeonia genus were retrieved from popular and widely used databases such as Web of Science, Science Direct, Google Scholar, and PubMed using different search strings. A systematic review of the antitumor constituents of the Paeonia genus and their therapeutic effects on various cancers was conducted and the mechanisms of action and pathways of these phytochemicals were summarised to provide a further basis for antitumor research.

Research Progress of γδT Cells in Tumor Immunotherapy.

Background: γδT cells are special innate lymphoid cells, which are not restricted by major histocompatibility complex (MHC). γδT cells mainly exist in human epidermis and mucosal epithelium. They can secrete a variety of cytokines and chemokines involved in immune regulation, and produce effective cytotoxic responses to cancer cells. Purpose:  To investigate the role of γδT cells in tumor immunotherapy, to understand its anti-tumor mechanism, and to explore the synergistic effect with other treatment modalities. This therapy is expected to become an important means of cancer treatment. Research Design: In this review presents a comprehensive analysis of the existing literature, focusing on the efficacy of γδT cells in a variety of tumor types. Results: The mechanism of γδT cells recognizing tumor antigens and killing tumor was clarified. The tumor immunotherapy based on γδT cells and its application in clinical practice were summarized. Conclusions: γδT cells have shown promising potential in tumor immunotherapy, but the therapeutic effect varies according to the type of tumor, and some patients have poor response. There are still some challenges in the treatment of this disease, such as non-standard expansion regimens and different responses of patients, indicating that the existing treatment methods are not complete. Future research should focus on perfecting γδT cell expansion protocols, gaining a deeper understanding of its anti-tumor mechanisms, and exploring synergies with other treatment modalities. This multifaceted study will promote the development of γδT cells in the field of cancer immunotherapy.

γδT cells are innate lymphocytes that are not restricted by the major histocompatibility complex (MHC). This cell can secrete a number of substances, these substances can produce effective killing effect on cancer cells. γδT cells are one of the major components of human intraepithelial lymphocytes and mucosal intraepithelial lymphocytes (IEL). γδT cells, which are composed of γ and δ chains, play an important role in anti-infection. In recent years, a large number of studies have confirmed that γδT cells have shown good anti-tumor effects in tumors of the digestive system, urinary system, blood system, reproductive system, respiratory system and other systems. Therefore, γδT cell-based cellular immunotherapy is a powerful supplement to tumor immunotherapy. This review will focus on the recognition of tumor antigens by γδT cells, the mechanism of tumor killing, the tumor immunotherapy based on γδT cells and its application in clinical practice.

Engineering therapeutical extracellular vesicles for clinical translation.

Cell-based therapies are revolutionizing medicine by replacing or modifying dysfunctional cells with healthy cells or engineered derivatives, offering disease reversal and cure. One promising approach is using cell-derived extracellular vesicles (EVs), which offer therapeutic benefits similar to cell transplants without the biosafety risks. Although EV applications face challenges like limited production, inadequate therapeutic loading, and poor targeting efficiency, recent advances in bioengineering have enhanced their effectiveness. Herein, we summarize technological breakthroughs in EV bioengineering over the past 5 years, highlighting their improved therapeutic functionalities and potential clinical prospects. We also discuss biomanufacturing processes, regulation, and safety considerations for bioengineered EV therapies, emphasizing the significance of establishing robust frameworks to ensure translation capability, safety, and therapeutic effectiveness for successful clinical adoption.

Mutational Signatures in Colorectal Cancer: Translational Insights, Clinical Applications, and Limitations.

A multitude of exogenous and endogenous processes have the potential to result in DNA damage. While the repair mechanisms are typically capable of correcting this damage, errors in the repair process can result in mutations. The findings of research conducted in 2012 indicate that mutations do not occur randomly but rather follow specific patterns that can be attributed to known or inferred mutational processes. The process of mutational signature analysis allows for the inference of the predominant mutational process for a given cancer sample, with significant potential for clinical applications. A deeper comprehension of these mutational signatures in CRC could facilitate enhanced prevention strategies, facilitate the comprehension of genotoxic drug activity, predict responses to personalized treatments, and, in the future, inform the development of targeted therapies in the context of precision oncology. The efforts of numerous researchers have led to the identification of several mutational signatures, which can be categorized into different mutational signature references. In CRC, distinct mutational signatures are identified as correlating with mismatch repair deficiency, polymerase mutations, and chemotherapy treatment. In this context, a mutational signature analysis offers considerable potential for enhancing minimal residual disease (MRD) tests in stage II (high-risk) and stage III CRC post-surgery, stratifying CRC based on the impacts of genetic and epigenetic alterations for precision oncology, identifying potential therapeutic vulnerabilities, and evaluating drug efficacy and guiding therapy, as illustrated in a proof-of-concept clinical trial.