Early recognition is key to improving the prognosis of ischemic stroke (IS), while available imaging methods tend to target events that have already undergone ischemia. A new method to detect early IS is urgently needed, as well as further study of its mechanisms. Viscosity and cysteine (Cys) levels of mitochondria have been associated with ferroptosis and IS. It is possible to identify IS and ferroptosis accurately and early by monitoring changes in mitochondrial Cys and viscosity simultaneously. In this work, a viscosity/Cys dual-responsive mitochondrial-targeted near-infrared (NIR) fluorescent probe ( NVCP ) was constructed for the precise tracking of IS using a two-dimensional design strategy. NVCP consists of a chromophore dyad containing diethylaminostyrene quinolinium rotor and chloro-sulfonylbenzoxadiazole (SBD-Cl) derivative with two easily distinguished emission bands ( lambda em = 592 and 670 nm). NVCP performs the way of killing two birds with one stone, that is, the probe exhibits excellent selectivity and sensitivity for detecting viscosity and Cys in living cells with excellent biocompatibility and accurate mitochondrial targeting capability by dual channel imaging mode. In addition, NVCP recognized that the viscosity increases and Cys level decreases in cells when undergoing ferroptosis and oxygen-glucose deprivation (OGD) stress by confocal imaging, flow cytometry, and Western blot experiments. Treatment of ferroptosis inhibitors (ferrostatin-1 (Fer-1) and deferoxamine (DFO)) could reverse the variation tendency of viscosity and Cys. This is the first time that the relationship between ferroptosis and IS was identified through an analysis of Cys and viscosity. More importantly, the ischemic area was also instantly distinguished from normal tissues through fluorescence imaging of NVCP in vivo . The developed NIR dual-responsive probe NVCP toward viscosity and Cys could serve as a sensitive and reliable tool for tracking ferroptosis-related pathological processes during IS. (c) 2025 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
Purpose: Postoperative adjuvant chemotherapy followed surgery is the standard management for localized advanced colorectal carcinoma (CRC). Mucinous adenocarcinoma (MAC) is a peculiar histological subtype of CRC, but the prognosis of MAC patients is controversial. The objective of this study is to assess the implication of MAC in survival of patients treated with surgery and firs-line adjuvant chemotherapy. Methods: Studies describing outcomes for advanced MAC and non-specific adenocarcinoma (AC) of CRC patients treated with first-line postoperative adjuvant chemotherapy followed surgery were searched in PubMed, Embase, Medline, EBSCO, Wiley, and Cochrane Library (January 1963eAugust 2021). Hazard ratios (HRs) of overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS) for MAC to AC were extracted. Random-effects model was used for calculating the pooled HRs and 95% confidence interval (CI). Results: This meta-analysis is comprised of 8 studies involving a total of 124,303 CRC patients treated with first-line adjuvant chemotherapy followed surgery. The pooled HR for MAC was 1.23 (95% CI, 1.07-1.41, p < 0.01, I-2 = 80%), and the DFS (HR, 2.95, 95% CI, 1.22-7.14) of MAC patients were significantly poorer than AC patients. Similar results were also observed in stage III and FOLFOX regimen subgroups. Conclusion: MAC was a risk factor for prognosis of localized advanced CRC patients treated with postoperative first-line adjuvant chemotherapy. Thus, the role of first-line adjuvant chemotherapy regimens should be further studied in these MAC patients.
Liver cancer is a malignant tumor with both high morbidity and mortality. The traditional treatment method is mainly based on hepatectomy for liver tumor. However, it is difficult to accurately distinguish the tumor tissue and its boundary with the naked eye and palpation, leading to an ambiguous resection result, finally causing high recurrence of liver cancer. Molecular fluorescent probes possessing numerous advantages, such as non-invasiveness, high sensitivity, and real-time imaging, have been extensively studied in liver cancer imaging and therapy. In this review, we briefly introduce the recent developments of always-on and activatable fluorescent probes in liver cancer imaging and therapy. Future potential challenges of the fluorescent probes for liver tumor imaging are also discussed. We expect that this review would improve the fluorescent probes development for real clinical application of liver cancer disease.
Mucinous histology is generally considered as a risk factor of prognosis in stage II colon cancer, but there is no appropriate model for prognostic evaluation and treatment decision in patients with stage II colon mucinous adenocarcinoma (C-MAC) Thus, it is urgent to develop a comprehensive, individualized evaluation tool to reflect the heterogeneity of stage II C-MAC. Patients with stage II C-MAC who underwent surgical treatment in the Surveillance, Epidemiology, and End Results Program were enrolled and randomly divided into training cohort (70
Background Endoscopy biopsy (EB) is the standard diagnostic method for colorectal cancer (CRC), whereas its accuracy and efficiency in mucinous adenocarcinoma (MAC) initial diagnosis is unclear. Methods The initial EB and postoperative specimen (PS) pathological diagnosis of MAC from two centers were retrospectively collected and analyzed. The accuracy and efficiency of initial EB compared with PS pathological diagnosis were analyzed. The potential factors which would affect the initial EB diagnosis of MAC were analyzed. Results 280 and 78 eligible cases were enrolled in this study from two centers respectively. The initial EB diagnosis accuracy for MAC were 84.62% and 83.33%. However, among the cases of PS diagnosis with MAC, the diagnostic efficiency of initial EB was only 36.49% and 32.50% respectively. Lower tumor differentiation and more EB number were associated with an increased probability for the EB diagnosis of MAC, but only tumor differentiation was an independent diagnositic factor for EB in the two cohorts. Conclusions The accuracy of initial EB with MAC is high, but the diagnostic efficiency was extremely low. Tumor differentiation and EB number were associated with the diagnosis efficiency of MAC before surgery.
Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and the third leading cause of cancer death worldwide. The incidence of HCC accounts for more than 90% of primary HCC. Like most solid malignancies, the occurrence and development of HCC are closely related to the Warburg effect. The Warburg effect of HCC is mainly manifested as increased glucose uptake by HCC cells, increased glycolysis, restricted mitochondrial oxidative phosphorylation, increased pentose phosphate pathway in HCC cells, and increased glutamine decomposition. As the contribution of glycolysis to the total ATP of tumor cells generally does not exceed 50% to 60%, oxidative phosphorylation (OXPHOS) still makes a considerable contribution to the ATP of tumor cells. In some cases, there will be an anti-Warburg effect. HCC Warburg effect is closely related to HCC cell proliferation, apoptosis, immune escape, migration and invasion, chemotherapy resistance, and treatment failure. The mechanism of the Warburg effect in HCC is complex, involving the expression of stimulating the key glycolysis enzymes by hypoxia-inducible factor-1(HIF-1), the activation of oncogenes and the inactivation of tumor suppressor genes, the continuous activation of related signaling pathways, the participation of noncoding RNA, and the rate of metabolism gene mutation of enzyme. This article synthetically discusses the characteristics of glucose metabolism in HCC cells, the mechanism of Warburg effect, clinical significance, and corresponding treatment strategies and provides new perspectives for the prevention and treatment of HCC.
Background The extent of bowel resection is widely debated in colon cancer surgery. Right hemicolectomy (RHC) and partial colectomy (PC) are the most common operation options for right-sided colon cancer (RCC). However, there are still no treatment guidelines or published studies to guide surgical options for mucinous adenocarcinoma (MAC) of RCC. Methods Patients with MAC and non-specific adenocarcinoma (AC) of RCC who underwent RHC and PC from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were retrieved. The general characteristics and survival were compared and analyzed. Results A total of 27,910 RCC patients were enrolled in this study, among them 3,413 were MAC. The results showed that race, carcinoembryonic antigen (CEA) level, perineural invasion (PNI), tumor size, tumor location, TNM stage, liver metastasis, chemotherapy were significantly different between MAC and AC groups. The MAC group had similar dissected lymph nodes, but more positive lymph nodes than the AC group. The overall survival (OS) of the MAC group was poorer than that of the AC group, but cancer-specific survival (CSS) was similar between the two groups. The RHC subgroup of the MAC group had more patients of age ≤60 years, larger tumor size, cecum/ascending colon location and dissected lymph nodes than the PC subgroup, but similar positive lymph nodes, perioperative mortality, OS and CSS as the PC subgroup. Moreover, the univariate and multivariable analyses for the survival of RCC patients with MAC showed that RHC might not be a superior predictor for OS and CSS compared with PC. Conclusions RHC could not dissect more positive lymph nodes or provide long-term survival benefits for RCC patients with MAC compared with PC. This study could provide some evidence for surgery treatment selection for MAC of RCC, which has important clinical value in individual management of colon cancer patients.
Dysregulated glycolysis is one of the mechanisms employed by cancer cells to facilitate growth and metastasis. Here we aimed to characterize the PPFIA4 gene, as a glycolysis-related oncogene in promoting the proliferation and migration of colon cancer cells. Using bioinformatical tools including The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA), we found that PPFIA4 expression and methylation levels were higher in colon cancer tissues of different stages than in normal tissues. Higher PPFIA4 level was also positively correlated with poorer survival of patients. PPFIA4 upregulation also correlated with poor prognosis and higher clinical stages of colon cancer patients. Colon cancer cell viability, migration and migration were enhanced after PPFIA4 overexpression. EMT markers and glycolysis were upregulated after PPFIA4 overexpression. PPFIA4 expression was found to be positively correlated with PFKFB3 and ENO2 levels, while knockdown of PFKFB3 and ENO2 reduced cell proliferation, migration, invasion and glycolysis. PPFIA4 upregulation is a potential biomarker in colon cancer which promotes proliferation, migration, invasion and glycolysis. The upregulation of PFKFB3/ENO2 signaling by PPFIA4 is a potential mechanism underlying the oncogenic effects of PPFIA4.
Lynch syndrome is the most prevalent form of familial colorectal cancer (CRC) and is caused by pathogenic germline mismatch repair (MMR) gene mutations. MLH1, MSH2 and MSH6 mutations have been well studied, but the rate and characteristics of PMS2 mutations are rare, especially in China. This study enrolled 1706 unselected patients with CRC who underwent colorectal resection from June 2016 to November 2018, the MMR status and clinicopathological features were analysed. A total of 11.8% of patients with CRC had defects in at least one MMR-related protein. Among them, 8.3% were identified with PMS2 defects, and 3.1% of patients had isolated PMS2 defects. Compared with MMR-proficient CRC, PMS2-defect CRC occurred more frequently in the right colon and less frequently in the rectum, had more poorly differentiated and mucinous carcinoma cases, and had fewer perineural invasions and a lower pN stage but a more advanced pT stage and a larger tumour size. In the cases with PMS2 defect, there were fewer tumours in the right colon, fewer poorly differentiated cases and smaller tumour sizes than in the cases with both MLH1 and PMS2 defects. In addition, in cases with isolated PMS2 defects, there were more tumours in the right colon and, more mucinous carcinoma cases than in cases with MMR-proficient CRCs, but had a similar cancer onset age. This study identified the rate, clinicopathological and age characteristics of PMS2 defects in CRCs in China and highlighted the importance of universal screening and germline detection of PMS2 in CRC.
Background: Mucinous adenocarcinoma (MC) is the second most common pathological type of colon carcinoma (CC). Colon cancer liver metastases (CLMs) are common and lethal, and complete resection of the primary tumour and metastases for CLM patients would be beneficial. However, there is still no consensus on the role of surgery for MC with liver metastases (M-CLM). Methods: Patients diagnosed with M-CLM or classical adenocarcinoma with CLM (A-CLM) from 2010 to 2013 in the Surveillance, Epidemiology, and End Results (SEER) database were retrieved. The clinicopathological features and overall survival (OS) and cancer-specific survival (CSS) data were compared and analysed. Results: The results showed that the M-CLM group had a larger tumour size, more right colon localizations, higher pT and pN stages, more female patients, and more retrieved and positive lymph nodes and accounted for a higher proportion of surgeries than the A-CLM group. The OS and CSS of M-CLM patients who underwent any type of surgery were significantly better than those of patients who did not undergo any surgery, but poorer than those of A-CLM patients who underwent surgery. Meanwhile, the OS and CSS of M-CLM and A-CLM patients who did not undergo any surgery were comparable. Compared with hemicolectomy, partial colectomy led to similar or better OS and CSS for M-CLM, and surgery was an independent protective factor for long-term survival in M-CLM. Conclusions: M-CLM had distinct clinicopathological characteristics from A-CLM, and surgery could improve the survival and is an independent favourable prognostic factor for M-CLM. In addition, partial colectomy might be a non-inferiority choice as hemicolectomy for M-CLM according to the results from this study.
BACKGROUND In December 2019, an ongoing outbreak of coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China. The characteristics of COVID-19 patients treated in local hospitals in Wuhan are not fully representative of patients outside Wuhan. Therefore, it is highly essential to analyze the epidemiological and clinical characteristics of COVID-19 in areas outside Wuhan or Hubei Province. To date, a limited number of studies have concentrated on the epidemiological and clinical characteristics of COVID-19 patients with different genders, clinical classification, and with or without basic diseases. AIM To study the epidemiological and clinical characteristics of COVID-19 patients in Hengyang (China) and provide a reliable reference for the prevention and control of COVID-19. METHODS From January 16 to March 2, 2020, a total of 48 confirmed cases of COVID-19 were reported in Hengyang, and those cases were included in this study. The diagnostic criteria, clinical classification, and discharge standard related to COVID-19 were in line with the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7) released by National Health Commission and National Administration of Traditional Chinese Medicine. The presence of SARS-CoV-2 in pharyngeal swab specimens was detected by quantitative reverse transcription polymerase chain reaction. All the data were imported into the excel worksheet and statistically analyzed by using SPSS 25.0 software. RESULTS A total of 48 cases of COVID-19 were collected, of which 1 was mild, 38 were moderate, and 9 were severe. It was unveiled that there were 31 (64.6%) male patients and 17 (35.4%) female patients, with a female-to-male ratio of 1.82:1. The range of age of patients with COVID-19 was dominantly 30-49 years old [25 (52.1%) of 48], followed by those aged over 60 years old [11 (22.9%)]. Besides, 29.2% (14 of 48) of patients had basic diseases, and 57.2% (8 of 14) of patients with basic diseases were aged over 60 years old. The occupations of 48 COVID-19 patients were mainly farmers working in agricultural production [15 (31.5%) of 48], rural migrant workers from Hengyang to Wuhan [15 (31.5%)], and service workers operating in the service sector [8 (16.7%)]. The mean latent period was 6.86 +/- 3.57 d, and the median was 7 [interquartile range (IQR): 4-9] d. The mean time from onset of symptoms to the first physician visit was 3.38 +/- 2.98 (95%CI: 2.58-9.18) d, with a median of 2 (IQR: 1-5) d, and the mean time from hospital admission to confirmed diagnosis was 2.29 +/- 2.11 (95%CI: 1.18-6.42) d, with a median of 2 (IQR: 1-3) d. The main symptoms were fever [43 (89.6%) of 48], cough and expectoration [41 (85.4%)], fatigue [22 (45.8%)], and chills [22 (45.8%)]. Other symptoms included poor appetite [13 (27.1%)], sore throat [9 (18.8%)], dyspnea [9 (18.8%)], diarrhea [7 (14.6%)], dizziness [5 (10.4%)], headache [5 (10.4%)], muscle pain [5 (10.4%)], nausea and vomiting [4 (8.3%)], hemoptysis [4 (8.3%)], and runny nose [1 (2.1%)]. The numbers of peripheral blood leukocytes, lymphocytes, and eosinophils were significantly reduced in the majority of the patients. The levels of C-reactive protein, fibrinogen, blood glucose, lactate dehydrogenase, D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (gamma-GT), myoglobin (MB), and creatine kinase (CK) were increased in 64.6%, 44.7%, 43.2%, 37.0%, 29.5%, 22.9%,20.8%, 21.6%, 13.6%, and 12.8% of patients, respectively. The incidence of ALT elevation in male patients was remarkably higher than that in females (P< 0. 01), while the incidences of AST, CK, and blood glucose elevations in severe patients were remarkably higher than those in moderate patients (P< 0.05, respectively). Except for the mild patients, chest computed tomography showed characteristic pulmonary lesions. All the patients received antiviral drugs, 38 (79.2%) accepted traditional Chinese medicine, and 2 (4.2%) received treatment of human umbilical-cord mesenchymal stem cells. On March 2, 2020, 48 patients with COVID-19 were all cured and discharged. CONCLUSION Based on our results, patients with COVID-19 often have multiple organ dysfunction or damage. The incidences of ALT elevation in males, and AST, CK, and blood glucose elevations in severe patients are remarkably higher.