Vitamin C, also known as ascorbic acid, has sparked controversy since it first emerged as a potential anti-cancer agent. However, an increasing number of preclinical studies have demonstrated that high-dose vitamin C exhibits selective anti-tumor effects, including “pro-oxidative cytotoxicity”, “anti-cancer epigenetic regulation”, and “immune modulation”. Consequently, vitamin C has reemerged as a promising anti-cancer therapy in the form of high-dose administration. Advancements in pharmacokinetic research have facilitated the development of clinical trials. Early clinical studies across various cancer types have confirmed the safety of high-dose vitamin C administered via intravenous injection. Moreover, its use as an adjuvant therapy in combination with standard treatments, such as chemotherapy and radiotherapy, has shown promising therapeutic potential. However, there remains a lack of consensus regarding optimal dosage, administration methods, tumor specificity, and patient selection. These factors have contributed to the inconsistent outcomes observed in phase II clinical trials and have hindered the widespread conduct of phase III trials. Without robust clinical evidence, high-dose vitamin C, despite being a non-toxic and promising anti-cancer agent, risks being “shelved” once again. In this review, we provide a comprehensive overview of the anti-tumor mechanisms of high-dose vitamin C and a detailed analysis of preclinical and clinical studies investigating its role as an anti-cancer agent. Additionally, we explore emerging trends in high-dose vitamin C therapy for cancer treatment and offer recommendations for future research in this field.

Messenger RNA(mRNA) CCT6A can encode chaperone proteins and plays an important role in malignant tumors such as colorectal cancer, lung cancer and breast cancer. CCT6A is highly expressed in malignant tumors, which can be used as a biomarker to assess patients' prognosis, and promote malignant biological behaviors such as tumor proliferation and metastasis by regulating transforming growth factor β signals, cell cycles, and other pathways. CCT6A can also modulate immune cell infiltration in the tumor microenvironment and may be a potential target for tumor immunotherapy. The paper reviews the expression and function of CCT6A in malignancies.

Abstract Objective Chemotherapy resistance and side effects are important reasons for the failure of lung cancer treatment. Therefore, finding new sensitizers for chemotherapeutic drugs is an urgent problem to be solved.Method In this study, A549 cells were given different pharmacological interventions, including control, cisplatin, DMY and the combination of cisplatin and DMY. The level of cell proliferation and apoptosis were detected by MTT assay and Flow cytometry AV/PI double staining. Transwell assay was adopted to detect the ability of migration and invasion of A549 cells. Western blot analyzed the expression of protein about proliferation, apoptosis, migration, and invasion.Results The present study denoted that DMY strengthened the effect of cisplatin on the inhibition of proliferation in lung cancer A549 cells. Meanwhile, DMY promoted cisplatin induced apoptosis of A549 cells. Further, DMY combined with cisplatin can synergistically inhibit the migration and invasion of A549 cells. Western blotting results showed that the expression of E-cadherin was significantly increased in the combination group compared to cisplatin group, while, the expression of N-cadherin, matrix metalloproteinase MMP 2, MMP 9 and Smads proteins (p-SMAD 3, t-SMAD 3, t-SMAD 4), were significantly decreased in the combination group.Conclusion Low dosage of DMY can significantly enhance the effect of cisplatin treatment in lung cancer cells, and its mechanism may be related to the induction of apoptosis, inhibition of proliferation, migration and invasion, which is expected to be a low-toxic and efficient chemosensitizer for lung cancer treatment.

The immunonutritional status has important effects on outcomes for cancer patients. Albumin-to-globulin ratio (AGR) and the prognostic nutrition index (PNI) are often used to assess the immunonutritional status of cancer patients. However, the clinical significance of these factors in colorectal cancer (CRC) remains unclear. We aimed to evaluate the clinical significance of the AGR and PNI in CRC. We reviewed the clinical data of 511 patients with CRC in two hospitals. Data from one institution was used as the training cohort. The optimal cutoff values for AGR and PNI in the training cohort were 1.4 and 48.65, respectively. Patients in both the low AGR and low PNI groups had poor overall survival (OS) and progression-free survival (PFS), while those in the low AGR-low PNI group had the lowest OS and PFS. Multivariate analysis revealed that preoperative AGR, preoperative PNI, gross type, and TNM stage were independent prognostic factors influencing OS in patients with CRC. Preoperative AGR, preoperative PNI, and TNM stage were independently associated with PFS in patients with CRC. According to the results of multivariate analysis in the training cohort, we developed the nomograms for OS and PFS and performed internal and external validation, which showed good prediction ability of the nomograms. In conclusion, preoperative AGR and PNI can be used as effective indicators to predict survival for patients with CRC. AGR and PNI may help develop effective adjuvant-therapy schedules.

With the medical model shifting from a single biomedical model to a biopsychological-social model, the impact of psychosocial factors on cancer patients has attracted attention.Studies have shown that chronic stress caused by long-term psychological stress, such as anxiety and depression, can promote the malignant progression of tumors by acting on β2-adrenergic receptor (β2-AR).β2-AR can promote tumor migration by activating epithelial-mesenchymal transition (EMT).However, the underlying mechanisms in the regulation of EMT by β2-AR are still unclear.In this study, we established a chronic stress model by treating MGC-803 and SGC-7901 human gastric cancer cells with isoproterenol (ISO), a β2-AR agonist.EMT in the two gastric cancer cell lines was enhanced after ISO treatment.Thereafter, we found that the interaction between β2-AR and PlexinA1 was involved in the process by which chronic stress affects EMT in both MGC-803 and SGC-7901 cells.Moreover, the activation of β2-AR by ISO increased the expression of PlexinA1, activated JAK-STAT3 signaling and further promoted EMT in human gastric cancer cells.Importantly, the knockdown of PlexinA1 by small hairpin RNAs inhibited JAK-STAT3 signaling and abolished the EMT induced by β2-AR.In conclusion, PlexinA1 was an important downstream target of β2-AR, through which β2-AR promoted EMT in human gastric cancer cells by activating JAK-STAT3 signaling.

应激是机体内环境稳态被破坏,或者面临破坏威胁时产生的适应性反应;根据应激源的持续时间分为急性应激和慢性应激.急性应激是指机体面对紧急危险情况下产生的非特异性适应性改变,通常有积极的影响,比如可以提高记忆力,暂时改善大脑的功能.慢性应激则是机体长期处于失稳状态,如生活、社会、职场压力和逆境等持续产生的负面影响,不仅会产生抑郁、不安和焦虑等负面情绪,还会影响睡眠质量和食欲、胃肠道功能,更有极端者会对自己的躯体造成伤害籍此缓解应激情绪、逃避应激源;此外慢性应激还会增加动脉粥样硬化、心血管疾病、精神障碍和肿瘤的发病风险.

1 概 述 结直肠癌( CRC)是世界上发病率第三、死亡率第二的常见恶性肿瘤之一,近年来发病率正在上升[1].结直肠癌发生的确切机制尚不清楚,然而,与结直肠癌密切相关的危险因素包括遗传、饮食、吸烟、酗酒和年龄等.环状RNA( circRNA)由一组具有环状结构的非编码RNA组成,这种环状结构是由经典剪接体介导的或套索类型的剪接构建的.根据环状RNA的来源可分为外显子环状RNA、内含子环状RNA和外显子-内含子环状RNA,它们分别来源于单个或多个外显子、内含子以及内含子和外显子.不同类别的环状RNA有不同的亚细胞定位.

炎性肠病(IBD)是发生于肠道的慢性非特异性炎症,其发病与多种因素相关.其中,微生态失调与IBD密切相关,但具体机制目前尚未完全阐明.随着现代医学的发展,传统的科赫法则已不再适用于所有感染性疾病的病因学研究."生态"科赫法则和"共生微生物"科赫法则是对传统科赫法则的改良,其中"生态"科赫法将单一致病原扩展至肠道微生态系统,为阐明IBD病因提供了更全面的证据,而"共生微生物"为重建IBD患者肠道微生态平衡提供了新的治疗思路.基于改良科赫法则探讨更加复杂的现代疾病,将有助于从整体水平阐明疾病病因并提高治疗策略的针对性.

Abstract Background: Aggressive angiomyxoma is a rare, locally invasive mesenchymal neoplasm with a high recurrence rate. However, our current research on the clinical characteristics, therapeutic strategies and prognosis of aggressive angiomyxoma is limited. This study aimed to improve the management of aggressive angiomyxoma by evaluating the clinicopathological characteristics, therapeutic strategies, and prognostic factors associated with aggressive angiomyxomas. Methods: Retrospectively analyzed the medical records of patients histopathologically diagnosed with aggressive angiomyxomas from May 2005 to January 2022. Data related to clinicopathological characteristics, therapeutic strategies, and survival time were recorded and analyzed. Survival and prognosis analyses were carried out to identify variables significantly associated with the outcomes. Results: fourteen patients were included in the study with a median follow-up of 78.8 months. Univariate Cox regression analysis identified tumor margin (P=0.012) and initial treatment site (P=0.039) as associated with disease-free survival (DFS). The Kaplan-Meier survival curve showed that tumor margin had a greater effect on the prognosis of patients. Patients with positive tumor margins had a significantly lower probability of survival with DFS than those with negative margins (HR= 3.41, CI:2.73-15.74, P=0.012). Meanwhile, we found that patients who underwent surgery in other hospitals had a lower probability of survival with DFS. This difference in survival was statistically significant (HR=1.48, CI:1.09-2.50, P=0.039). To further demonstrate the results of this study, we constructed a Nomogram model. The results showed that the tumor margin and initial treatment site had the greatest effect on patient prognosis and the greatest contribution to risk score, which confirmed the results of Kaplan-Meier survival curve analysis. Conclusion: Tumor margin and initial treatment site are closely associated with prognosis in aggressive angiomyxomas. Radical resection with negative tumor margins is the first choice of treatment for aggressive angiomyxomas. Patients with aggressive angiomyxomas should go to the comprehensive authoritative hospitals to obtain definitive diagnosis and effective treatment in in earlier stage. Furthermore, Patients with aggressive angiomyxomasrequire long-term follow-up, especially within three years after surgery.

The intestinal tract is composed of different cell lineages with distinct functions and gene expression profiles, providing uptake of nutrients and protection against insults to the gut lumen. Changes in or damage to the cellulosity or local environment of the intestinal tract can cause various diseases. Single-cell RNA sequencing (scRNA-seq) is a powerful tool for profiling and analyzing individual cell data, making it possible to resolve rare and intermediate cell states that are hardly observed at the bulk level. In this review, we discuss the application of intestinal tract scRNA-seq in identifying novel cell subtypes and states, targets, and explaining the molecular mechanisms involved in intestinal diseases. Finally, we provide future perspectives on using single-cell techniques to discover molecular and cellular targets and biomarkers as a new approach for developing novel therapeutics for intestinal diseases.

Chronic stress induced by long-term anxiety and depression can promote the malignant progression of gastric cancer. β2-adrenergic receptor (β2-AR) is a critical mediator for chronic stress-induced multiple processes of tumor cells. However, the function of chronic stress in gastric cancer and its potential mechanisms in vivo and in vitro, especially at the cellular level, remain unknown. Here, we provide further evidence that chronic stress affected behavior and hypothalamus pituitary adrenal axis related hormone levels in mice. Furthermore, immunofluorescence showed that emotion affected the expression of epithelial-mesenchymal transition (EMT) markers in patients' tissues. To address this, salbutamol, a specific agonist of β2-AR, was utilized for simulating chronic stress and demonstrating the mechanism of stress in tumor progression at the molecular level both in vivo and in vitro. Salbutamol significantly induced EMT, migration and invasion via ERK (Extracellular-signal-regulated kinase) phosphorylation, and the effects were reversed by the β2-AR antagonist ICI-118,551. The promoting effects of salbutamol on EMT, migration and invasion were inhibited by phosphorylation inhibitor of ERK PD98059 in vitro. Analysis of xenograft models revealed that salbutamol significantly promoted tumor growth and adrenal volume, while ICI-118,551 inhibited these effects. In addition, salbutamol increased the expression of mesenchymal marker N-cadherin and decreased epithelial marker E-cadherin in transplanted tumor tissue. In conclusion, salbutamol simulates a chronic stress model, which promotes tumorigenesis of gastric cancer cells through β2-AR/ERK/EMT pathway.

ObjectiveWe investigated the clinical significance of preoperative pan-immune-inflammation value (PIV) in patients with colorectal cancer (CRC).MethodsIn this retrospective study, 366 cases who underwent surgery for CRC were enrolled. Their clinical data were collected. PIV was calculated with the formula PIV = [neutrophil count (109/L)× platelet count (109/L) × monocyte count (109/L) /lymphocyte count (109/L). Patients were divided into high PIV (> median PIV) and low PIV (< median PIV) groups. The relationship between PIV and clinicopathological features of CRC was investigated. Receiver operating characteristic (ROC) curve was plotted to indicate the value of immune-inflammatory biomarkers (IIBs) in predicting the TNM stage of CRC, and the area under the curve (AUC) was calculated to evaluate the actual clinical value of IIBs. AUC > 0.5 and closer to 1 indicated the better predictive efficacy. The influencing factors of PIV in CRC were analyzed.ResultsWe found that PIV was positively correlated with tumor size (r = 0.300, p < 0.05), carcinoembryonic antigen (CEA) (r = 0.214, p < 0.05) and carbohydrate antigen 125 (CA-125) (r = 0.249, p < 0.05), but negatively correlated with albumin (Alb) (r = −0.242, p < 0.05). PIV was significantly different in patients with different tumor locations (left or right), surgical methods (laparotomy versus laparoscopic surgery) (p < 0.05), and patients with different pathological T stages, N-stage and TNM stages (p < 0.05). ROC curve analysis of IIBs showed the AUC of PIV was greater than other markers when combined with CEA or carbohydrate antigen 19–9 (CA19–9). Multivariate regression analysis identified T stage, CEA, Alb, and tumor size as the independent influential factors of PIV in CRC.ConclusionPIV is associated with the tumor stage in patients with CRC, which may be useful in preoperative assessment of CRC.

Inflammatory bowel disease (IBD) is a chronic non-specific inflammatory disease that occurs in the intestinal tract. It is mainly divided into two subtypes, i.e., the Crohn's disease (CD) and ulcerative colitis (UC). At present, its pathogenesis has not been fully elucidated, but it has been generally believed that the environment, immune disorders, genetic susceptibility, and intestinal microbes are the main factors for the disease pathogenesis. With the development of the sequencing technology, microbial factors have received more and more attention. The gut microbiota is in a state of precise balance with the host, in which the host immune system is tolerant to immunogenic antigens produced by gut commensal microbes. In IBD patients, changes in the balance between pathogenic microorganisms and commensal microbes lead to changes in the composition and diversity of gut microbes, and the balance between microorganisms and the host would be disrupted. This new state is defined as dysbiosis. It has been confirmed, in both clinical and experimental settings, that dysbiosis plays an important role in the occurrence and development of IBD, but the causal relationship between dysbiosis and inflammation has not been elucidated. On the other hand, as a classic research method for pathogen identification, the Koch's postulates sets the standard for verifying the role of pathogens in disease. With the further acknowledgment of the disease pathogenesis, it is realized that the traditional Koch's postulates is not applicable to the etiology research (determination) of infectious diseases. Thus, many researchers have carried out more comprehensive and complex elaboration of Koch's postulates to help people better understand and explain disease pathogenesis through the improved Koch's postulates. Therefore, focusing on the new perspective of the improved Koch's postulates is of great significance for deeply understanding the relationship between dysbiosis and IBD. This article has reviewed the studies on dysbiosis in IBD, the use of microbial agents in the treatment of IBD, and their relationship to the modified Koch's postulates.

由于左、右半结肠癌在胚胎来源、解剖与生理、遗传变异、肿瘤微生态等方面存在着很大的差异，故在临床与科研中不能将左、右半结肠癌一视同仁，而应该充分考虑到这些差异所在。对左、右半结肠癌的治疗方式、疗效、预后等方面的研究进展进行系统性阐述，希冀实现未来研究的针对性和治疗的精准化。

It is known that chronic stress modulates multiple processes in a complex microenvironment, such as angiogenesis and immune function. However, the role of chronic stress inducing tumor angiogenesis and how it contributes to tumor progression are not quite clear. The following study assess psychological state from numerous ambulatory cancer cases (n=332), and chronic stress-related hormone levels were further measured. Here, we show that chronic stress not only causes behavioral changes in human, most importantly attributed to an elevated level of stress-related hormones. To address this, isoprenaline, the agonist of β2-adrenergic receptor (β2-AR), was utilized for simulating chronic stress and demonstrating the mechanism of stress in tumor angiogenesis at molecular level both in vivo and in vitro. As suggested by this study, isoprenaline promote VEGF autocrine of HUVECs, which can induce plexinA1 and VEGFR2 expression. Moreover, we show that isoprenaline promoted the expression of p-JAK2 and p-STAT3 in vitro. The results reveal that, isoprenaline enhances the autocrine of VEGF in HUVECs and up-regulating plexinA1 and VEGFR2 levels, thus activating the phosphorylation of JAK2-STAT3 pathway, the two essential parts during angiogenesis. The present work indicates that, the mechanism of chronic stress in enhancing angiogenesis is probably achieved through activating the plexinA1/VEGFR2-JAK2-STAT3 signal transduction pathway within HUVECs, and this is probably a candidate target for developing a strategy against angiogenesis in cancer.

结肠癌是一种异质性疾病,结肠肿瘤位置是影响结肠癌病情进展、治疗方式选择和生存预后的重要因素,左半结肠癌与右半结肠癌在解剖生理、能量代谢、组织病理学、肠道菌群构成、分子生物学等方面均存在显著差异.利用结肠癌偏侧性差异的特点,不仅能够探寻左半结肠癌与右半结肠癌差异存在的根本原因,而且可以制定相应个体化精准化的治疗策略,为不同部位的结肠癌患者提供更加有效的治疗.