In the ever-evolving landscape of cancer therapy, while cancer treatments such as chemotherapy, radiotherapy, and targeted therapy aim to eradicate malignant cells, they also inadvertently trigger cellular senescence in both cancerous and microenvironmental tissues. Therapy-induced senescence (TIS) can act as a barrier against tumor growth by halting cell proliferation in the short term, but the long-term persistence of therapy-induced senescent (TISnt) cells may pose a significant challenge in cancer management. Their distinct characteristics, like senescence-associated secretory phenotype (SASP), metabolic dysregulation, and immune evasion, make them exhibit remarkable heterogeneity to orchestrate the tumor microenvironment (TME), resulting in therapy resistance. However, how these TISnt cells functioning differently in cancer progression, and the intricate mechanisms by which they remodel the senescence-associated immunosuppressive microenvironment present challenges for improving anticancer therapy. Therefore, this review summarizes the heterogeneous TISnt cell phenotypes contributing to an accumulated senescent state, outlines their multidimensional interactions in the senescent microenvironment, and discusses current senescence-targeting strategies. Building on the current understanding of TIS, we propose potential avenues for improving TIS-targeting methodologies in the context of head and neck cancer, a representative heterogeneous malignancy, which can substantially enhance the efficacy of the "one-two punch" sequential treatment approach for head and neck cancer.
Humans ; Cellular Senescence/drug effects* ; Tumor Microenvironment ; Neoplasms/pathology* ; Senescence-Associated Secretory Phenotype

AIM:To investigate the role of ClC-3 chloride channel in the promotion of radio sensitization of na-sopharyngeal carcinoma CNE-2Z cells by dihydroartemisinin(DHA).METHODS:MTT was used to detect the inhibito-ry effect of DHA on the viability of CNE-2Z cells and normal nasopharyngeal epithelial NP69-SV40T cells,the radio sensi-tization effect of DHA on CNE-2Z cells was detected by cloning assay,the expression of ClC-3 protein was detected by Western blot,the expression of ClC-3 protein was down-regulated by siRNA technology,and the chlorine current of cells was recorded by whole cell patch-clamp technology.RESULTS:(1)Compared with NP69-SV40T cells,DHA selective-ly inhibited the proliferation of CNE-2Z cells,with IC10 values of(13.020±4.831)μmol/L and(5.244±1.050)μmol/L,respectively(P＜0.01).(2)The results of clonal formation experiments showed that DHA had a radio sensitizing effect on CNE-2Z cells,with a radio sensitization ratio of 1.9.(3)DHA could activate the chlorine channel of CNE-2Z cells and produce an outward chlorine current,but had no effect on the chlorine channel of NP69-SV40T cells.(4)DHA promoted the expression of ClC-3 chloric channel protein in CNE-2Z cells(P＜0.01).(5)Chlorine channel blocker NPPB could in-hibit the radio sensitizing effect of DHA on CNE-2Z cells by 1.84 times,and also inhibited the chlorine current activated by DHA.(6)the down-regulation of CNE-2Z ClC-3 protein could inhibit the radio sensitization effect of DHA on CNE-2Z cells by 4.19 times,and the activation of chlorine current by DHA on CNE-2Z cells was no longer produced.CONCLU-SION:DHA has a radio sensitizing effect on nasopharyngeal carcinoma CNE-2Z cells,which is likely to be related to the activation of ClC-3 chloride channel.

Objective To investigate the impact of Yanghe-patch acupoint in the treatment of impaired glucose tolerance(IGT)with Yang-deficiency constitution and its influence on serum metabolites.Methods The study enrolled a total of 63 patients with IGT were randomly selected and stratified into two groups:The control group(32 cases)and the treatment group(31 cases)at Ningbo Municipal Hospital of TCM Affliated to Zhejiang Chinese Medical University from October 2022 to January 2024,blood glucose,blood lipids,tumor necrosis factor-α(TNF-α),Yang-deficiency body mass score,and infrared thermal imaging temperature before and after treatment were compared between two groups.Furthermore,29 healthy individuals were selected as healthy negative controls,and their serum metabolites were analyzed by using liquid chromatograph-mass spectrometer(LC-MS)among three groups.Principal component analysis and orthogonal projections to latent structures-discriminate analysis were employed to identify characteristic differential metabolites.Additionally,key metabolic pathways were screened through network analysis by using MetaboAnalyst software.Results The treatment group after Yanghe-patch showed significant reductions in fasting blood glucose,glycosylated hemoglobin,triglycerides,low-density lipopro-tein and TNF-α levels(P＜0.05).Additionally,Yang-deficiency constitution conversion points significantly decreased within the treatment group(P＜0.05),while there were significant increases in the temperatures of Ren channel,Du channel,middle-Jiao and lower-Jiao(P＜0.05).However,there was a notable decrease in upper-Jiao temperature(P＜0.05).Metabolomics analysis identified varying levels of serum metabolites in IGT patients with Yang-deficiency constitution,such as 4-acetylaminobutyric acid,3-dehydrocholic acid,citric acid,and cystine etc.16 metabolites.Treatment group exhibited distinct expression patterns for 16 metabolites(including diaminoheptadecic acid,acetyl-L-carnitine and monobutyl phthalate etc.).The analysis by MetaboAnalyst shows that Yang-deficiency constitution with IGT was linked to dysregulation in the tricarboxylic acid cycle,aminoacyl bioanabolic pathway,and Gly-Ser-Thr metabolic axis.Additionally,Yanghe-patch intervention affects the glycine,serine and threonine(Gly-Ser-Thr)metabolic axis and sphingolipid metabolism.Conclusion The application of Yanghe-patch on acupoints shows potential in alleviating chronic systemic inflammation and improving symptoms associated with Yang-deficiency constitution in individuals with IGT.Metabolomics analysis has revealed a range of metabolites involved in their mechanism,among which the Gly-Ser-Thr metabolic pathway is considered crucial for regulating the constitution of Yang-deficiency constitution in individuals with IGT.

Pro-inflammatory cytokines selectively induce specific signals to regulate host responses. Since the immunological imbalance caused by abnormal release of cytokines is involved in the development of many diseases, cytokine-specific detections are of great clinical significance for disease diagnosis and efficacy monitoring. Aptamers are single-stranded nucleic acid sequences which can bind to the target with high selectivity and affinity. It has attracted much attention in the development of novel aptamers-based methods for the detection of specific biomarkers of inflammatory diseases. This paper reviewed recent advances in electrochemical and optical aptasensors for the detection of tumor necrosis factor-α, interleukin-6, transforming growth factor-β, interferon-γ and interleukin-8. The findings offered valuable insights into the clinical application potential and challenges of nucleic acid aptamers in the detection of key inflammatory cytokines, providing a meaningful reference for the development of aptamer-based cytokines sensitive detection point-of-care testing equipment and novel diagnostic strategies for inflammatory disorders.

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

As an important component of the tumor microenvironment, cancer-associated fibroblasts (CAFs) secrete energy metabolites to supply energy for tumor progression. Abnormal regulation of long noncoding RNAs (lncRNAs) is thought to contribute to glucose metabolism, but the role of lncRNAs in glycolysis in oral CAFs has not been systematically examined. In the present study, by using RNA sequencing and bioinformatics analysis, we analyzed the lncRNA/mRNA profiles of normal fibroblasts (NFs) derived from normal tissues and CAFs derived from patients with oral squamous cell carcinoma (OSCC). LncRNA H19 was identified as a key lncRNA in oral CAFs and was synchronously upregulated in both oral cancer cell lines and CAFs. Using small interfering RNA (siRNA) strategies, we determined that lncRNA H19 knockdown affected proliferation, migration, and glycolysis in oral CAFs. We found that knockdown of lncRNA H19 by siRNA suppressed the MAPK signaling pathway, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and miR-675-5p. Furthermore, the lncRNA H19/miR-675-5p/PFKFB3 axis was involved in promoting the glycolysis pathway in oral CAFs, as demonstrated by a luciferase reporter system assay and treatment with a miRNA-specific inhibitor. Our study presents a new way to understand glucose metabolism in oral CAFs, theoretically providing a novel biomarker for OSCC molecular diagnosis and a new target for antitumor therapy.
Cancer-Associated Fibroblasts/metabolism* ; Carcinoma, Squamous Cell/genetics* ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glycolysis ; Head and Neck Neoplasms ; Humans ; MicroRNAs/metabolism* ; Mouth Neoplasms/genetics* ; Phosphofructokinase-2/genetics* ; RNA, Long Noncoding/genetics* ; Signal Transduction ; Tumor Microenvironment

Objective:To investigate the clinical pathological and epidemiological characteristics of primary esophageal malignant melanoma (PMME).Methods:The clinical pathology data of 180 PMME patients in the esophageal cancer database of the key laboratory of esophageal cancer research in Henan Province from 1973 to 2016 were collected, of which 136 were male, aged (58.5±9.0) years, 44 were female, aged (56.7±12.2) years. Kaplan-Meier and Log rank test were used for survival analysis, Cox regression scale model was used for risk factor analysis.Results:The incidence of PMME is 0.036% (180/500, 000), mostly were male (about 3∶1 for men: female). The common sites of PMME were the lower part of the esophagus (48.9%, 85/174), followed by the middle section of the esophagus (46.0%, 80/174) and the upper part of the esophagus (5.2%, 9/174). No black particles were seen in the PMME cells of 3 patients under microscope, and strong positive expressions of Melan-A and HMB453 were observed in these 3 patients by immunohistochemical results. Of the 129 patients who had a routine preoperative esophageal biopsy, 69 were undiagnosed with PMME (53.5%). The medium survival time of the whole group was 7.9 months, and the survival rates of 1, 2, 3, 5 years were 25.0%, 7.9%, 6.6% and 1.3%, respectively. The univariate analysis showed that N, M, TNM phase and radiotherapy were related to the overall survival of patients ( P<0.05). Multivariate analysis showed that TNM phase and radiotherapy were the independent risk factors for overall survival of patients ( P<0.05). Conclusions:PMME is more common in men, the common site of the disease is the lower part of the esophagus. The preoperatively missed diagnosis rate of Chinese PMME is high. TNM phase and radiotherapy are the independent risk factors for overall survival of patients.

Objective:To investigate the clinical pathological and epidemiological characteristics of primary esophageal malignant melanoma (PMME).Methods:The clinical pathology data of 180 PMME patients in the esophageal cancer database of the key laboratory of esophageal cancer research in Henan Province from 1973 to 2016 were collected, of which 136 were male, aged (58.5±9.0) years, 44 were female, aged (56.7±12.2) years. Kaplan-Meier and Log rank test were used for survival analysis, Cox regression scale model was used for risk factor analysis.Results:The incidence of PMME is 0.036% (180/500, 000), mostly were male (about 3∶1 for men: female). The common sites of PMME were the lower part of the esophagus (48.9%, 85/174), followed by the middle section of the esophagus (46.0%, 80/174) and the upper part of the esophagus (5.2%, 9/174). No black particles were seen in the PMME cells of 3 patients under microscope, and strong positive expressions of Melan-A and HMB453 were observed in these 3 patients by immunohistochemical results. Of the 129 patients who had a routine preoperative esophageal biopsy, 69 were undiagnosed with PMME (53.5%). The medium survival time of the whole group was 7.9 months, and the survival rates of 1, 2, 3, 5 years were 25.0%, 7.9%, 6.6% and 1.3%, respectively. The univariate analysis showed that N, M, TNM phase and radiotherapy were related to the overall survival of patients ( P<0.05). Multivariate analysis showed that TNM phase and radiotherapy were the independent risk factors for overall survival of patients ( P<0.05). Conclusions:PMME is more common in men, the common site of the disease is the lower part of the esophagus. The preoperatively missed diagnosis rate of Chinese PMME is high. TNM phase and radiotherapy are the independent risk factors for overall survival of patients.

Objective:To observe the effect of nocturnal nutritional support on the improvement of nutritional status and liver function in patients with hepatitis B cirrhosis.Methods:A total of 60 patients with hepatitis B cirrhosis who were treated at the Affiliated Hospital of Guizhou Medical University from April 2011 to August 2018 were selected, and they were divided into nutritional intervention group and control group according to the random digital table method, with 30 cases in each group.The two groups were given basic medical treatment, and the nutritional intervention group was given basic treatment plus 30g of complex functional nutrients, once per night, for 12 weeks.The changes of liver function and nutritional status of the two groups were observed every 4 weeks, and the occurrence of complications was recorded.Results:Before intervention, the ALB, PA, TBIL, body mass index, triceps cutaneous fold thickness and grip strength had no statistically significant differences between the two groups(all P>0.05). After 12 weeks of intervention, the albumin [(32.61±1.78) g/L], pre-albumin [(116.65±11.92) g/L], total bilirubin [(36.6±5.86)μmol/L], body mass index [(22.23±2.92) kg/m 2], skinfold [(17.34±1.31) mm], the grip strength [(23.36±2.44)kg] in the intervention group were superior to the control group[(30.38±1.58)g/L, (101.22±7.76)g/L, (47.75±4.83)μmol/L, (21.07±2.11)kg/m 2, (16.07±1.40)mm, (20.01±2.70)kg], the differences were statistically significant between the two groups( t=4.946, 5.105, 5.881, 2.407, 2.272, 3.805, all P<0.05). The incidence of the complications in the intervention group was 10%(3/30), which in the control group was 33%(10/30), the difference was statistically significant between the two groups(χ 2=4.381, P=0.033). Conclusion:Providing nutritional support at night can improve the nutritional status of patients with hepatitis B cirrhosis, promote the repair of liver function, and reduce the incidence of complications.

Esophageal cancer is a unique malignant disease in China. A fundamental difference exists between the Chinese population and the western population on esophageal cancer in terms of epidemiology, histogenesis, and carcinogenic risk factors. Therefore, ap-plying the western academic achievements to Chinese is difficult. Thus, Chinese scientists have the responsibility to conquer esopha-geal cancer in China. This article reviews the progress of esophageal cancer focused on the molecular mechanism for interactions of ge-netic and environmental risk factors and human esophageal multistage carcinogenesis.