Lymph node metastasis (LNM) is a crucial risk factor influencing an unfavorable prognosis in specific cancers. Fundamental research illuminates our understanding of tumor behavior and identifies valuable therapeutic targets. Nevertheless, the exploration of fundamental theories and the validation of clinical therapies hinge on preclinical experiments. Preclinical models, in this context, serve as the conduit connecting fundamental theories to clinical outcomes. In vivo models established in animals offer a valuable platform for comprehensively observing interactions between tumor cells and organisms. Using various experimental animals, including mice, diverse methods, such as carcinogen-induced tumorigenesis, tumor cell line or human tumor transplantation, genetic engineering, and humanization, have been used effectively to construct numerous models for tumor LNM. Carcinogen-induced models simulate the entire process of tumorigenesis and metastasis. Transplantation models, using human tumor cell lines or patient-derived tumors, offer a research platform closely mirroring the histology and clinical behavior of human tumors. Genetically engineered models have been used to delve into the mechanisms of primary tumorigenesis within an intact microenvironment. Humanized models are used to overcome barriers between human and murine immune systems. Beyond mouse models, various other animal models have unique advantages and limitations, all contributing to exploring LNM. This review summarizes existing in vitro and animal preclinical models, identifies current bottlenecks in preclinical research, and offers an outlook on forthcoming preclinical models.
Animals ; Humans ; Mice ; Lymphatic Metastasis/pathology* ; Disease Models, Animal ; Cell Line, Tumor

Objective: To investigate the molecular mechanism and identify potential drugs for subthreshold depression (SD), and elucidate the detalied mechanism of Danzhi Xiaoyao powder (DZXY) in SD. Methods: Using RNA-sequencing, we identified differentially expressed genes (DEGs) in leukocytes of SD compared to healthy controls, deciphered their functions and pathways, and identified the hub genes of SD. We also assessed changes in leukocyte transcription factor activity in patients with SD using the TELiS platform. The Connectivity Map database was retrieved to screen candidate drugs for SD. Based on network pharmacology, we elucidated the “multi-component, multi-target, and multi-pathway” mechanism of DZXY in the treatment of SD. Results: We identified 1080 DEGs (padj <0.05 and |log2 (fold change)| ≥ 1 & protein coding) in the leukocytes of patients with SD. These DEGs, including hub genes, were primarily involved in immune and inflammatory response-related processes. Transcription factor activity analysis revealed similarities between the leukocyte transcriptome profile in SD and the conserved transcriptional response to adversities in immune cells. Connectivity Map analysis identified 28 potential drugs for SD treatment, particularly SB-202190 and TWS-119. Constructing the “Direct Compounds-Direct Targets-Pathways” network for DZXY and SD revealed the curative mechanisms of DZXY in SD, primarily including inflammatory response, lipid metabolism, immune response, and other processes. Conclusion These results provide new insights into the characteristics and functional changes of leukocytes in SD, partially illustrate the pathogenesis of SD, and suggest potential drugs for SD. The curative mechanisms of DZXY in SD are also partially elucidated.

Objective To evaluate the effect of manual massage on complications after endoscopic foam sclerotherapy injection for the treatment of internal hemorrhoids.Methods Consecutive 113 patients with grade Ⅰinternal hemorrhoids were prospectively enrolled and completed endoscopic foam sclerotherapy.The patients were randomly divided into a massage group(n=65)and a control group(n=68).Massage group performed manual perianal massage,Visual analogue scale(VAS)was used to evaluate perianal pain.The postoperative bleeding,short-term and long-term efficacy were also compared.Results The median VAS of 24 h postoperation was 1.0(0.0,3.0)in massage group,which was significantly lower than 2.0(1.0,4.0)in control group,the difference was statistically significant(P=0.014).The no bleeding rate of one week postoperation was 84.6％in massage group,which was significantly higher than 64.7％in control group,the difference was statistically significant(P=0.009).After 12 weeks,6 months and 12 months of follow-up,there were no significant differences in cure rate and remission rate between the two groups(P＞0.05).Conclusion Manual massage after endoscopic sclerosing agent injection is beneficial to relieve postoperative pain of grade Ⅰ internal hemorrhoids and reduce bleeding.

Objective:To explore the effects of smart cloud follow-up platform in home care for elderly patients with pacemakers.Methods:Totally 120 elderly patients who received pacemaker implantation in a ClassⅢ Grade A hospital in Henan province between August 2018 and August 2019 were selected by convenient sampling. The 60 patients admitted from August 2018 to February 2019 were included into the control group, while the 60 patients admitted from March to August 2019 were selected into the experimental group. Patients in the experimental group received home care based on the cloud follow-up platform, while patients in the control group received routine continuing care at home. After 3 months of intervention, the complication rate, functional exercise compliance and quality of life were compared between the two groups using χ 2 test and t test. Results:Totally 59 patients in the experimental group and 58 patients in the control group completed the study. After intervention, the complication rate in the experimental group was 32.2% (19/59) , lower than 89.7% (52/58) in the control group, and the difference was statistically significant (χ 2=9.307, P< 0.05) ; the scores of physical exercise compliance after pacemaker implantation, postoperative precautions compliance and compliance of initiative advice seeking in the experimental group were (26.05±3.07) , (15.42±1.24) and (11.85±1.96) , higher than those in the control group (18.53±2.93) , (9.66±2.40) and (6.05±1.58) in the control group, and the differences were statistically significant ( t=13.548, 16.331, 17.558; P< 0.01) ; the total quality of life score in the experimental group was (161.12±9.94) , higher than (132.50±9.20) in the control group, and the difference was statistically significant ( t=16.149, P < 0.01) . Conclusions:The home management model based on the smart cloud follow-up platform improves home follow-up experience of elderly patients with pacemaker, the compliance of home functional exercises, and their quality of life.

Objective To investigate the nutritional support of hospitalized patients with advanced lung cancer in Shanghai. Methods From July 2018 to May 2020, hospitalized patients with advanced lung cancer in our hospital were selected. Patients were assessed using general situation questionnaire and patient subjective evaluation scale. The experimental indicators of patients were detected, the nutritional support was analyzed, and the risk factors of nutritional status of patients with lung cancer were analyzed. Results Among the 106 patients, 75 were male and 31 were female, 74 were under 64 years old and 32 were over 65 years old; PG-SGA results revealed that 37 cases (34.91%) scored 0~1, 48 cases (45.28%) scored 2-8, and 21 cases (19.81%) scored equal to or above 9; According to PG-SGA classification, patients were divided into good nutrition group (n=37) and malnutrition group (n=69). The proportion of patients of ≤64-year-old, TNM stage IV, WBC and neutrophil count in good nutrition group was lower than that of malnutrition group (P<0.05), meanwhile, the KPS, body mass index, red blood cell count, lymphocyte count, hemoglobin, serum protein, albumin, immunoglobulin IgG, IgM, IgA, CD4 +, CD3 +, and CD8 + were higher than those of malnutrition group (P<0.05). Logistic analysis showed that age ≥ 64 years old, TNM stage IV, KPS and BMI were risk factors of nutritional status (P<0.05). Conclusion Among the patients with advanced lung cancer in Shanghai, the incidence of malnutrition is 65.09%, and 19.81% of those with severe malnutrition are in urgent need of nutritional support. Logistic analysis results yield that age over 64 years old, TNM stage Ⅳ, KPS, body mass index are risk factors affecting nutritional status of patients.

Objective: To investigate the prognostic impact of alterations of epidermal growth factor receptor(EGFR) and MGMT in glioblastoma. Methods: The retrospective study included 161 supratentorial glioblastomas diagnosed in the Department of Pathology, Xuanwu Hospital, Capital Medical University from 2009 to 2015. EGFR and EGFRvⅢ protein expression was detected by immunohistochemistry; EGFR amplification was detected by fluorescence in situ hybridization; MGMT promoter methylation was detected by pyrosequencing. The change of molecular genetics EGFR and MGMT and outcome were assessed statistically. Results: There were 161 patients, including 85 (52.8%) males and 76 (47.2%) females. The mean age was 53 years, and the median overall survival was 13 months. The integrated classification of glioblastoma included 16 IDH-mutant, 134 wild type, and 11 NOS. The rate of overexpression of EGFR protein was 32.9%(53/161), and that of EGFR amplification was 37.5%(18/48). There was high concordance between immunohistochemistry and FISH(85.4%, Kappa=0.475, P<0.01) and between the level of EGFR protein and EGFR amplification (P<0.01). Twelve cases showed EGFRvⅢ expression, and all also showed EGFR protein overexpression; 149 cases were EGFRv Ⅲ wild type, and EGFR protein overexpression was seen in 27.5%(41/149) of cases. There was no correlation between EGFR and EGFRv Ⅲ expression. Of all cases, 70.2%(106/151) showed MGMT promoter methylation by pyrosequencing. The changes of molecular genetics of EGFR and MGMT were not related. EGFR amplification and protein overexpression had no significant relationship with prognosis. Patients with EGFRv Ⅲ-mutant had shorter survival time than the EGFRv Ⅲ-wild type(P=0.014); patients with MGMT promoter methylation had better prognosis than without (PFS:P=0.002,OS:P=0.006),and MGMT promoter methylation was an independent predictor for overall survival (HR=0.269, 95%CI 0.124-0.583, P=0.001). Conclusions EGFR protein expression by immunohistochemistry correlates with the status of EGFR amplification. Patients with EGFRv Ⅲ-mutant tumors have poorer prognosis than that with EGFRv Ⅲ-wild type tumors. MGMT promoter methylation is closely associated with prognosis and an independent predictor for overall survival.

Objective To understand the effectiveness of peroral endoscopic myotomy(POEM)for achalasia and secondary severe malnutrition in children and the effectiveness of nutrition support before and after POEM.Method Treatment of POEM,nutrition support(tube feeding by percutaneous endoscopic gastrostomy three months before operation)in one case were recorded and analyzed.Results POEM was successful without any complication such as perforation,bleeding,and pneumoderm.The child suffered from fever after surgery,which was dissolved after symptomatic treatment three days later.Chest pain was relieved after changing position.The diet was changed from liquid to semifluid,and then to normal diet.The child did not have dysphagia.During the 6-month follow-up,the patient had normal diets by oral route.The weight was 32 kg before achalasia and decreased to 18 kg after 9 months(at admission);it then increased to 29 kg after short-time(12 days)parenteral nutrition and long-time(3 months)enteral nutrition by percutaneous endoscopic gastrostomy,and then the patient received POEM.His weight was 30,31,31,29,and 31 kg 1,4,6,9,and 13 months,respectively,after POEM.Conclusion POEM can effectively cure achalasia in pediatric patients and improve the quality of life.Rational enteral nutrition can improve nutrition status and facilitate a successful POEM.

Objective: To investigate the usefulness of loss of CIC expression as the prescreening detection of 1p/19q co-deletion in the diagnosis of oligodendroglial tumors and its prognostic implication. Methods: The retrospective study included 113 oligodendroglial tumors diagnosed in the Department of Pathology, Xuanwu Hospital, Capital Medical University. Expression of CIC protein was detected by immunohistochemistry, and the 1p/19q co-deletion by fluorescence in situ hybridization in all the tumors; and the correlation of the loss of protein and 1p/19q co-deletion with prognosis was assessed. Results: The rate of negative CIC protein expression was 59.3% (67/113) in 113 oligodendroglial tumors. CIC protein expression was differentially lost in various gliomas, 85.7% (42/49) in pure oligodendrogliomas and 39.1% (25/64) in mixed oligodendroglial tumors (P<0.01). The loss of CIC protein expression showed a sensitivity of 76.1% (54/71), specificity 71.1% (27/38), false positive rate of 16.9% (11/65), and a false negative rate of 38.6% (17/44). In 63 cases integrated diagnosis as oligodendroglial tumors with mutant IDH and 1p/19q co-deletion, the loss of CIC protein expression was 81.0% (51/63); the sensitivity and specificity were increased to 81.0% (51/63) and 76.9% (20/26), and the false positive rate and false negative rate decreased to 10.5% (6/57) and 37.5% (12/32), respectively. By using Kaplan-Meier analysis, the CIC negative group showed a trend towards better outcome than the CIC positive group, but there was no statistical difference (overall survival: P=0.218; progression free survival: P=0.249). Conclusions Detection of the lost CIC protein expression can predict the chromosome 1p/19q co-deletion. In oligodendroglial tumors with IDH mutant and 1p/19q co-deletion, there is no relation between prognosis and CIC protein expression.

Objective: To investigate the diagnostic and prognostic implications of ATRX mutation and p53 mutation in patients with glioma. Methods: The clinicopathologic and molecular features of Chinese adult glioma patients, including diffuse and anaplastic astroastrocytoma with IDH mutation, oligodendroglioma and anaplastic oligodendroglioma with IDH mutation and 1p/19q co-deletion and diffuse astroastrocytoma with IDH wild type were reviewed and tested for ATRX loss expression and p53 overexpression. Results: Loss of ATRX expression was seen in 85.19% (23/27) diffuse and anaplastic astroastrocytoma with IDH mutation, higher than that of oligodendroglial tumors (0/53; P<0.01). Loss of ATRX expression was strongly linked to p53 overexpression(69.57%, 16/23). The patients who lost ATRX expression combined with normal p53 expression survived longer(P=0.013). Conclusions ATRX mutation is a molecular marker for astrocytic tumors. ATRX mutation combined with p53 mutation can predict prognosis of patients with glioma.

Aortic Valve ; Fibroma ; Heart Neoplasms ; Humans