New insights into the potential of exosomal circular RNAs in mediating cancer chemotherapy resistance and their clinical applications.

Chemotherapy resistance typically leads to tumour recurrence and is a major obstacle to cancer treatment. Increasing numbers of circular RNAs (circRNAs) have been confirmed to be abnormally expressed in various tumours, where they participate in the malignant progression of tumours, and play important roles in regulating the sensitivity of tumours to chemotherapy drugs. As exosomes mediate intercellular communication, they are rich in circRNAs and exhibit a specific RNA cargo sorting mechanism. By carrying and delivering circRNAs, exosomes can promote the efflux of chemotherapeutic drugs and reduce intracellular drug concentrations in recipient cells, thus affecting the cell cycle, apoptosis, autophagy, angiogenesis, invasion and migration. The mechanisms that affect the phenotype of tumour stem cells, epithelial-mesenchymal transformation and DNA damage repair also mediate chemotherapy resistance in many tumours. Exosomal circRNAs are diagnostic biomarkers and potential therapeutic targets for reversing chemotherapy resistance in tumours. Currently, the rise of new fields, such as machine learning and artificial intelligence, and new technologies such as biosensors, multimolecular diagnostic systems and platforms based on circRNAs, as well as the application of exosome-based vaccines, has provided novel ideas for precision cancer treatment. In this review, the recent progress in understanding how exosomal circRNAs mediate tumour chemotherapy resistance is reviewed, and the potential of exosomal circRNAs in tumour diagnosis, treatment and immune regulation is discussed, providing new ideas for inhibiting tumour chemotherapy resistance.

Chinese Medicine's Effects Against Advanced Gastric Cancer: A Single-center, Randomized, Double-blind, Controlled Clinical Trial.

Context: At present, medical practitioners commonly use surgery and perioperative chemotherapy, radiotherapy, and biological targeted therapy in clinical treatment of gastric cancer. Western medicine treatment can quickly treat patients' lesions but may cause adverse reactions. TCM can prevent the occurrence of toxic side effects and alleviate the side effects of Western medicine. Objectives: The study intended to explore the clinical efficacy of traditional Chinese medicine (TCM) combined with Western medicine in the treatment of advanced gastric cancer. Design: The research team performed a randomized, double-blind, controlled clinical trial. Setting: The study took place at the Cangzhou Central Hospital in Hebei, China. Participants: Participants were 102 patients with advanced gastric cancer who had been admitted to the hospital between February 2021 and March 2023. Interventions: The research team randomly divided participants into two groups, with 51 participants in each group: (1) the TCM group, who received TCM only, and (2) the combination group, who received chemotherapy combined with TCM. Outcome Measures: The research team measured: (1) clinical efficacy; (2) TCM syndrome efficacy; (3) levels of the blood tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen Sialyl-Lewis a (CA199), and carbohydrate antigen 72-4 (CA72-4); (4) psychological status using the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS); and (5) incidence of adverse reactions. Results: At baseline, no significant differences existed between the two groups in the clinical indicators. Postintervention compared to the TCM group, the combination group had significantly: (1) higher clinical efficacy (P = .003), (2) higher TCM syndrome efficacy (P = .003), (3) higher level of CEA and lower levels of CA199, and CA72-4 (all P = .000); (4) lower SAS scores and SDS scores (both P = .000); and (5) lower incidence of adverse reactions (P = .007). Conclusions: TCM, in the treatment of patients with advanced gastric cancer, can achieve good therapeutic effects. Combined with chemotherapy, patients' clinical efficacy can improve, level of blood tumor markers can decrease, psychological state can improve, and incidence of adverse reactions can decrease. Its clinical use had significant effects, and physicians can promote and use them.

Clinical Study of 32 Patients with Advanced Pancreatic Cancer Treated with Traditional Chinese Medicine Combined with Chemotherapy.

Objective: Our aim was to investigate the effect of the clinical application of Traditional Chinese Medicine (TCM) combined with chemotherapy in the treatment of advanced pancreatic cancer. Methods: The study participants were divided into 2 groups: the combined treatment group, comprised of 32 patients with advanced pancreatic cancer admitted to Zhejiang Provincial People's Hospital in China between June 2021 and June 2022 who received TCM combined with chemotherapy; and the control group: 32 patients with advanced pancreatic cancer admitted to Zhejiang Provincial People's Hospital in China between June 2021 and June 2022 who received chemotherapy alone. The TCM symptom score, TCM clinical efficacy, Western medicine clinical efficacy, patient quality of life (QoL) and incidence of adverse events (AEs) were compared in the 2 groups. Results: Prior to treatment, there was no significant difference in the patients' general clinical condition in the 2 groups (P > .05); after treatment, the TCM symptom score in the combined treatment group (16.62±2.77) was better than in the control group (21.44±2.53), with a P < .05. The TCM and Western medicine clinical efficacy was better than in the control group, with a P < .05; QoL score was higher than in the control group, P < .05; the incidence of AEs (3.12%) was lower than in the control group (28.12%); P < .05. Conclusion: In the treatment of patients with advanced pancreatic cancer, the application of TCM combined with chemotherapy can achieve good therapeutic results, improve the patients' prognosis, effectively reduce the occurrence of AEs and continuously restore patients' QoL.

Toxic epidermal necrolysis after injection of sclerosing agent and medical adhesive into oesophageal variceal ligation in a patient with a malignant liver tumour: A case report.

Chronic liver disease can cause an increase in portal sinus pressure, which may lead to rupture and bleeding of esophageal and gastric varices. Oesophageal variceal ligation, with use of sclerosing agent and tissue glue injection is commonly used in clinical practice to address oesophageal bleeding. A 58-year-old male patient with chronic liver disease was treated with oesophageal variceal ligation, sclerosing agent and tissue glue injection due to oesophageal and gastric variceal bleeding. After 2 days, the skin of the patient exhibited erythema to different degrees. After 10 days of dexamethasone treatment, the whole-body rash worsened, and a severe skin reaction appeared that was suggestive of toxic epidermal necrolysis (TEN). Strict mucosal care was provided, and corticosteroids, γ globulin and adalimumab were concurrently used for treatment. After 20 days, the patient recovered from the skin problems. To the best of our knowledge, TEN after endoscopic surgery has rarely been reported in the relevant literature. Furthermore, when patients being treated with multiple drugs have erythema multiforme, physicians should be alert to the possibility of its development into TEN. The present case report summarizes the treatment methods for patients with TEN, providing a practical clinical basis and direction for the future diagnosis and treatment of the condition.

Novel receptor, mutation, vaccine, and establishment of coping mode for SARS-CoV-2: current status and future.

Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant pneumonia in December 2019, the cumulative number of infected people worldwide has exceeded 670 million, with over 6.8 million deaths. Despite the marketing of multiple series of vaccines and the implementation of strict prevention and control measures in many countries, the spread and prevalence of SARS-CoV-2 have not been completely and effectively controlled. The latest research shows that in addition to angiotensin converting enzyme II (ACE2), dozens of protein molecules, including AXL, can act as host receptors for SARS-CoV-2 infecting human cells, and virus mutation and immune evasion never seem to stop. To sum up, this review summarizes and organizes the latest relevant literature, comprehensively reviews the genome characteristics of SARS-CoV-2 as well as receptor-based pathogenesis (including ACE2 and other new receptors), mutation and immune evasion, vaccine development and other aspects, and proposes a series of prevention and treatment opinions. It is expected to provide a theoretical basis for an in-depth understanding of the pathogenic mechanism of SARS-CoV-2 along with a research basis and new ideas for the diagnosis and classification, of COVID-19-related disease and for drug and vaccine research and development.

Whole-transcriptome sequencing with ceRNA regulation network construction and verification in glioblastoma.

OBJECTIVES: To explore the key genes involved in the occurrence and development of glioblastoma (GBM) by analyzing whole-transcriptome sequencing and biologic data from GBM and normal cerebral cortex tissues and to search for important noncoding RNA (ncRNA) molecular markers based on the competitive endogenous RNA (ceRNA) network. METHODS: Ten GBM and normal cerebral cortex tissues were collected for full transcriptome sequencing, screened for differentially expressed (DE) mRNAs, miRNAs, lncRNAs, and circRNAs, and subjected to bioinformatic analysis. We constructed a Protein-Protein Interaction (PPI) network and a circRNA/lncRNA-miRNA-mRNA regulatory network and identified them using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Finally, The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases were used to validate and conduct a survival analysis of the target genes. RESULTS: A total of 5341 DEmRNAs, 259 DEmiRNAs, 3122 DElncRNAs, and 2135 DEcircRNAs were identified. Enrichment analysis showed that target genes regulated by DEmiRNA, DElncRNA, and DEcircRNA were closely related to chemical synaptic transmission and ion transmembrane transport. A PPI network analysis screened 10 hub genes that directly participate in tumor cell mitosis regulation. In addition, the ceRNA composite network showed that hsa-miR-296-5p and hsa-miR-874-5p were the central nodes of the network, and the reliability of relevant key molecules was successfully verified through RT-qPCR identification and the TCGA database. The CGGA database survival analysis produced 8 DEmRNAs closely related to GBM patient survival prognosis. CONCLUSIONS: This study revealed the important regulatory functions and molecular mechanisms of ncRNA molecules and identified hsa-miR-296-5p and hsa-miR-874-5p as key molecules in the ceRNA network. They may play an important role in GBM pathogenesis, treatment, and prognosis.

Exosomal circWDR62 promotes temozolomide resistance and malignant progression through regulation of the miR-370-3p/MGMT axis in glioma.

Exosome-mediated delivery of circular RNAs (circRNAs) is implicated in cancer progression. However, the role of exosomal circRNAs in the chemotherapy resistance of tumours remains poorly understood. Here we identified a novel circRNA, circWDR62. It was found that circWDR62 expression was upregulated in TMZ-resistant glioma cells and TMZ-resistant glioma cell-derived exosomes compared with their controls by using high-throughput microarray analysis and quantitative real-time polymerase chain reaction, and high circWDR62 expression was associated with poor prognosis of glioma. Functionally, downregulation of circWDR62 expression could significantly inhibit the TMZ resistance and malignant progression of glioma. Further mechanistic studies showed that circWDR62 plays a role by sponging miR-370-3p as a competing endogenous RNA. Rescue experiments confirmed that MGMT is the downstream target of the circWDR62/miR-370-3p axis in glioma. In addition, circWDR62 could be transported between TMZ-resistant and TMZ-sensitive glioma cells via exosomes. Exosomal circWDR62 from TMZ-resistant cells conferred TMZ resistance in recipient sensitive cells while also enhancing the proliferation, migration and invasion of these cells. A series of clinical and in vivo trials corroborated that exosomal circWDR62 could promote TMZ chemoresistance and malignant progression of glioma. Our results demonstrate for the first time that exosome-mediated delivery of circWDR62 can promote TMZ resistance and malignant progression via targeting of the miR-370-3p/MGMT axis in vitro and in vivo in glioma, providing a new therapeutic strategy. Moreover, exosomal circWDR62 in human serum may serve as a promising therapeutic target and prognostic marker for glioma therapy.

NcRNAs: Multi­angle participation in the regulation of glioma chemotherapy resistance (Review).

As the most common primary tumour of the central nervous system, gliomas have a high recurrence rate after surgical resection and are resistant to chemotherapy, particularly high­grade gliomas dominated by glioblastoma multiforme (GBM). The prognosis of GBM remains poor despite improvements in treatment modalities, posing a serious threat to human health. At present, although drugs such as temozolomide, cisplatin and bevacizumab, are effective in improving the overall survival of patients with GBM, most patients eventually develop drug resistance, leading to poor clinical prognosis. The development of multidrug resistance has therefore become a major obstacle to improving the effectiveness of chemotherapy for GBM. The ability to fully understand the underlying mechanisms of chemotherapy resistance and to develop novel therapeutic targets to overcome resistance is critical to improving the prognosis of patients with GBM. Of note, growing evidence indicates that a large number of abnormally expressed noncoding RNAs (ncRNAs) have a central role in glioma chemoresistance and may target various mechanisms to modulate chemosensitivity. In the present review, the roles and molecular mechanisms of ncRNAs in glioma drug resistance were systematically summarized, the potential of ncRNAs as drug resistance markers and novel therapeutic targets of glioma were discussed and prospects for glioma treatment were outlined. ncRNAs are a research direction for tumor drug resistance mechanisms and targeted therapies, which not only provides novel perspectives for reversing glioma drug resistance but may also promote the development of precision medicine for clinical diagnosis and treatment.

Identification and characterization of N6-methyladenosine modification of circRNAs in glioblastoma.

This research systematically profiled the global N6-methyladenosine modification pattern of circular RNAs (circRNAs) in glioblastoma (GBM). Based on RNA methylation sequencing (MeRIP sequencing or N6-methyladenosine sequencing) and RNA sequencing, we described the N6-methyladenosine modification status and gene expression of circRNAs in GBM and normal brain tissues. N6-methyladenosine-related circRNAs were immunoprecipitated and validated by real-time quantitative PCR. Bioinformatics analysis and related screening were carried out. Compared with those of the NC group, the circRNAs from GBM exhibited 1370 new N6-methyladenosine peaks and 1322 missing N6-methyladenosine peaks. Among the loci associated with altered N6-methyladenosine peaks, 1298 were up-regulated and 1905 were down-regulated. The N6-methyladenosine level tended to be positively correlated with circRNA expression. Bioinformatics analysis was used to predict the biological function of N6-methyladenosine-modified circRNAs and the corresponding signalling pathways. In addition, through PCR validation combined with clinical data mining, we identified five molecules of interest (BUB1, C1S, DTHD1, F13A1 and NDC80) that could be initial candidates for further study of the function and mechanism of N6-methyladenosine-mediated GBM development. In conclusion, our findings demonstrated the N6-methyladenosine modification pattern of circRNAs in human GBM, revealing the possible roles of N6-methyladenosine-mediated novel noncoding RNAs in the origin and progression of GBM.

Molecular Characteristics, Prognostic Value, and Immune Characteristics of m6A Regulators Identified in Head and Neck Squamous Cell Carcinoma.

N6-methyladenosine (m6A) plays crucial roles in a diverse range of physiological and pathological processes, and it is believed that it tremendously promotes neoplasia and progression. However, knowledge of the molecular characteristics of m6A modification, its prognostic value, and the infiltration of immune cell populations in head and neck squamous cell carcinoma (HNSCC) is still insufficient. Therefore, a pan-cancer genomic analysis was systematically performed here by examining m6A regulators at the molecular level within 33 multiple cancer types, and the correlations between the expression of m6A molecules were researched using datasets from The Cancer Genome Atlas (TCGA). Based on the above analysis, insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is upregulated in HNSCC and may serve as an independent prognostic factor of overall survival, thus showing potential as a prognostic biomarker in HNSCC. Genetic alteration analyses elucidated the reasons for the abnormal upregulation of IGF2BP2 in HNSCC. As a result, IGF2BP2 was selected for further univariate and multivariate analyses. The functions of the related genes were annotated through gene set enrichment analysis, and the activation states of multiple biological pathways were shown by gene set variation analysis. We found that LRRC59 and STIP1 may act as IGF2BP2-associated genes to have a regulatory function in the m6A modification. In addition, we found that the status of immune cell infiltration was correlated with the level of IGF2BP2 gene expression. Our results provide supplementation at the molecular level for epigenetic regulation in HNSCC and insight into effective immunotherapy targets and strategies.

Screening and functional prediction of differentially expressed circular RNAs in human glioma of different grades.

Circular RNAs (circRNAs) have a critical regulatory function in human glioma. However, novel circRNAs related to different pathological grades of glioma and their crucial potential function are worth screening and prediction. CircRNA expression profiling was performed for 6 paired high- and low-grade glioma tissues and 5 adjacent normal brain tissues through next-generation sequencing. Quantitative real-time PCR (qRT-PCR) was conducted to validate circRNA expression. Bioinformatics analysis was performed, and circRNA-miRNA-mRNA networks were constructed. The expression and survival data of miRNAs and target genes were examined by GEPIA, Chinese Glioma Genome Atlas (CGGA), ONCOMINE, and cBioPortal databases. The RNA binding proteins (RBPs), open reading frames (ORFs) and N6-methyladenosine (m6A) modifications of the identified circRNAs were also predicted. Through multilevel research screening, 4 circRNAs (hsa_circ_0000915, hsa_circ_0127664, hsa_circ_0008362, and hsa_circ_0001467) were associated with glioma of different pathological grades and could be preferred candidates for subsequent functional analysis. Therefore, circRNAs are associated with the different pathological grades of glioma and reveal their potential critical regulatory function. CircRNAs might provide vital molecular biomarkers and potential therapeutic targets for glioma.

m6A modification in RNA: biogenesis, functions and roles in gliomas.

The chemical modification of RNA is a newly discovered epigenetic regulation mechanism in cells and plays a crucial role in a variety of biological processes. N6-methyladenine (m6A) mRNA modification is the most abundant form of posttranscriptional RNA modification in eukaryotes. Through the development of m6A RNA sequencing, the relevant molecular mechanism of m6A modification has gradually been revealed. It has been found that the effect of m6A modification on RNA metabolism involves processing, nuclear export, translation and even decay. As the most common malignant tumour of the central nervous system, gliomas (especially glioblastoma) have a very poor prognosis, and treatment efficacy is not ideal even with the application of high-intensity treatment measures of surgery combined with chemoradiotherapy. Exploring the origin and development mechanisms of tumour cells from the perspective of tumour biogenesis has always been a hotspot in the field of glioma research. Emerging evidence suggests that m6A modification can play a key role in gliomas through a variety of mechanisms, providing more possibilities for early diagnosis and targeted therapy of gliomas. The aim of the present review is to focus on the research progress regarding the association between m6A modification and gliomas. And to provide a theoretical basis according to the currently available literature for further exploring this association. This review may provide new insights for the molecular mechanism, early diagnosis, histologic grading, targeted therapy and prognostic evaluation of gliomas.

New understanding of the damage of SARS-CoV-2 infection outside the respiratory system.

Since early December 2019, a number of pneumonia cases associated with unknown coronavirus infection were identified in Wuhan, China, and many additional cases were identified in other regions of China and in other countries within 3 months. Currently, more than 80,000 cases have been diagnosed in China, including more than 3000 deaths. The epidemic is spreading to the rest of the world, posing a grave challenge to prevention and control. On February 12, 2020, the International Committee on Taxonomy of Viruses and the World Health Organization officially named the novel coronavirus and associated pneumonia as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19), respectively. According to the recent research on SARS-CoV-2, the virus mainly infects the respiratory system but may cause damage to other systems. In this paper, we will systematically review the pathogenic features, transmission routes, and infection mechanisms of SARS-CoV-2, as well as any adverse effects on the digestive system, urogenital system, central nervous system, and circulatory system, in order to provide a theoretical and clinical basis for the diagnosis, classification, treatment, and prognosis assessment of SARS-CoV-2 infection.

Exosomal miRNA-34 from cancer-associated fibroblasts inhibits growth and invasion of gastric cancer cells in vitro and in vivo.

Gastric cancer (GC) is one of the most common malignancies worldwide manifesting high morbidity and mortality. Cancer-associated fibroblasts (CAFs), important components of the tumor microenvironment, are essential for tumorigenesis and progression. Exosomes secreted from CAFs have been reported as the critical molecule-vehicle in intercellular crosstalk. However, the precise mechanism underlying the effect of CAFs remains to be fully investigated. In this study, we aimed to determine the role of CAFs and their exosomes in the progression of GC and related mechanisms. The results revealed that miRNA-34 was downregulated in both GC fibroblasts (GCFs) and GC cell lines while the overexpression of miRNA-34 suppressed the proliferation, invasion, and motility of GC cell lines. Coculturing GC cells with miRNA-34-overexpressing GCFs led to the suppression of cancer progression. Also, exosomes derived from GCFs were taken up by GC cells in vitro and in vivo and exerted antitumor roles in GC. In addition, exosomal miRNA-34 inhibited GC cell proliferation and invasion in vitro and suppressed tumor growth in vivo. Furthermore, 16 genes were identified as potential downstream targeting genes of miRNA-34. Taken together, GCFs-derived exosomal miRNA-34 may be a promising targeting molecule for therapeutic strategies in GC.

Exosomal circular RNA sorting mechanisms and their function in promoting or inhibiting cancer.

Exosomes are nanoscale phospholipid bilayer vesicles that can be artificially engineered into vectors for the treatment of cancer. Circular RNA (circRNA), a type of non-coding RNA, has crucial regulatory functions in various aspects of cancer, such as tumorigenesis, apoptosis, proliferation, invasion, metastasis and chemo- and radiotherapeutic resistance, as well as in cancer prognosis. Notably, the exosomal transfer of circRNAs may function to both promote and inhibit cancer. Numerous studies have addressed the importance of circRNAs in cancer and non-coding RNAs (such as microRNAs and long non-coding RNAs) in exosomes. However, little research has focussed on a class of RNAs called exosomal circRNAs. The present review discusses current studies regarding exosomal circRNAs, including their biogenesis and biological functions, their abundance in exosomes and possible sorting mechanisms and their potential roles in both promoting and inhibiting cancer. It is predicted that in the next five years there will be increasing research exploring the functional mechanisms of exosomal circRNA in various diseases, in particular their roles in cancer genesis and progression.

Advances in circular RNAs and their role in glioma (Review).

Glioma is the most common primary tumour of the central nervous system, and is associated with a high postoperative recurrence rate and resistance to chemotherapy. High­grade glioblastoma in particular has a very poor prognosis and poses a serious threat to human health. Related studies have confirmed that the occurrence and development of gliomas are closely associated with the abnormal expression and regulation of genes. Moreover, the number of studies on the association of the expression of non­coding RNAs [linear RNAs, microRNAs and circular RNAs (circRNAs)] in human cells with glioma has been gradually increasing in recent years. Among those, circRNAs, previously considered to be 'splicing errors', have been shown to be highly expressed in eukaryotic cells and regulate the biological behaviour of gliomas. circRNAs are highly abundant and stable, and have become a research hotspot in the field of glioma molecular biology. The aim of the present review was to focus on the research progress regarding the association between circRNA expression and gliomas, and to provide a theoretical basis according to the currently available literature for further exploring this association. The present study may be of value for the early diagnosis, pathological grading, targeted therapy and prognostic evaluation of gliomas.

Circular RNA: biogenesis, degradation, functions and potential roles in mediating resistance to anticarcinogens.

Aim: This review aims to systematically describe the biogenesis and degradation of circular RNAs (circRNAs), discusses the major functions of circRNAs, introduces the mechanisms by which circRNAs play a role in cancer, comprehensively summarize the relationship between circRNAs and anticarcinogen resistance as well as underlying specific mechanisms in multiple cancers. Materials & methods: We screened and analyzed large quantity of scientific papers which associated with circRNAs, noncoding RNAs, function, cancer, drug resistance and chemoresistance, and then summarized in Figures 1 & 2 & Table 1. Results & conclusion: The biogenesis, degradation and function of circRNAs are specially compared with other noncoding RNAs, it can affect cancer pathogenesis and progression and are implicated in mediating resistance to various anticarcinogens in various types of cancer.

[Autophagy mechanism of cerebral ischemia injury and intervention of traditional Chinese medicine].

OBJECTIVE: Autophagy is a process of degrading the damaged organelles and macromolecules by lysosomes in cells, which belongs to the programmed cell death. Cerebral ischemia is one of the important reasons for activation of autophagy. Studies have showed that autophagy plays a protective role in neuronal death induced by ischemia. However, it has also been found that excessive activation of autophagy could aggravate cerebral ischemia injury. In recent years, more and more Chinese medicine has been proved to regulate the autophagy level of brain neurons and reduce cerebral ischemia injury. In this paper, the main molecular mechanism of autophagy in the process of cerebral ischemic injury and the intervention effects of Chinese herbs on autophagy arereviewed in order to explore the basic principle of regulating autophagy by Chinese herbs and to play a better role in the clinical treatment of cerebral ischemic diseases.