Objective The Objective of this study was to analyze the disease burden trend of leukemia in children and adolescents aged 0-19 years in China from 1990 to 2021,and to provide a scientific evidence for the disease prevention and control strategy of this population. Methods The disease burden of leukemia in children and adolescents in China(excluding Taiwan)was analyzed using the Global Burden of Disease Database 2021(GBD 2021),including incidence,prevalence,mortality,and disability-adjusted life year(DALY).DALY consisted of two parts:years of life lost(YLL)and years lived with disability(YLD).The average annual percentage change(AAPC)was used to comprehensively evaluate the changing trends of various indicators from the disease burden of childhood leukemia in China from 1990 to 2021. Results In 2021,the age-standardized incidence,prevalence,mortality and DALY rates of the 0-19 years old population in China were 7.33/100,000,51.46/100,000,1.72/100,000,and 142.14/100,000,respectively.Among them,the age-standardized incidence,prevalence,mortality and DALY rates of males were higher than those of females.The incidence,prevalence,mortality and DALY rates of the 0- years old group were higher than those of other age groups.The age-standardized incidence,prevalence,mortality and DALY rates of acute lymphoblastic leukemia(ALL)were higher than those of other leukemia subtypes.From 1990 to 2021,the leukemia age-standardized incidence in the population aged 0 to 19 years did show a significant increase or decrease(AAPC=-0.32%,95% CI:-0.66%-0.02%);the age-standardized prevalence showed a significant increase(AAPC=3.05%,95% CI:2.68%-3.42%).While age-standardized mortality and DALY rates showed a downward trend(AAPC=-4.27%,95% CI:-4.53%-4.01%;AAPC=-4.3%,95% CI:-4.56%-4.05%). Conclusion From 1990 to 2021,the disease burden of leukemia in children and adolescents aged 0 to 19 years in China is increasing,the burden of death is decreasing,and the total DALY is decreasing.The burden of leukemia in this group varies greatly among different ages,genders,and leukemia subtypes.

Objective The aim of this study was to analyze the incidence and mortality of esophageal cancer and its trend in Lianyungang city from 2008 to 2019. Methods The data of esophageal cancer in all cancer registry areas in Lianyungang city were collected and sorted out,and the quality control reached the standards.The incidence,mortality,age-standardized rate of Chinese population(ASRC),age-standardized rate of World population(ASRW),cumulative rate at 0-74 years old,truncation rate of 35-64 years old,and composition ranking were calculated.The Joinpoint 4.7.0.0 software was used to analyze the average annual percentage change(AAPC)of the age-standardized incidence and mortality of esophageal cancer by the standard population(ASIRC and ASMRC). Results From 2008 to 2019,the incidence of esophageal cancer in Lianyungang city was 25.90/100,000,ASIRC was 17.95/100,000,ASIRW was 17.91/100,000,ranking the third in the incidence spectrum of malignant tumors.The mortality was 20.55/100,000,ASMRC was 13.86/100,000,and ASMRW was 13.71/100,000,ranking the third in the malignant tumor mortality spectrum.The incidence,mortality,ASIRC and ASMRC of esophageal cancer were higher in men than those in women,and higher in rural areas than those in urban areas.From 2008 to 2019,the change trend of incidence and mortality of esophageal cancer in Lianyungang city was the same,showing a downward trend.The AAPC of the ASIRC was-6.19%(95% CI:-7.08%-5.30%,P＜0.001),and the AAPC of the ASMRC was -4.03%(95% CI:-5.81%-2.22%,P＜0.001).Among them,the ASIRC and ASMRC of esophageal cancer in urban and rural areas showed a downward trend(P＜0.05).Among them,the ASIRC and ASMRC of esophageal cancer in urban women decreased the most,with an average annual decline of-7.99%(95% CI:-10.86%-5.03%,P＜0.001)and-9.19%(95% CI:-12.35%-5.93%,P＜0.001). Conclusion The incidence and mortality of esophageal cancer in Lianyungang city have shown a downward trend,a rural areas and male populations are the key prevention and control populations for esophageal cancer.

Objective The Objective of this study was to analyze the mortality and changing trend of head and neck cancer(nasopharyngeal cancer,laryngeal cancer,thyroid cancer,and oral cancer)in cancer registry areas of Inner Mongolia Autonomous Region from 2010 to 2020,and to provide a scientific basis for the prevention and control of head and neck cancer in Inner Mongolia Autonomous Region. Methods The mortality data for head and neck cancers(nasopharyngeal cancer,laryngeal cancer,thyroid cancer,and oral cancers)in the tumor registration database of Inner Mongolia Autonomous Region from 2010 to 2020 were sorted out,and the China standard mortality of head and neck were calculated by gender,urban and rural areas,and cancer types.The average annual percentage change(AAPC)was analyzed using Joinpoint 4.9.1.0 software to assess the trend of China standard mortality of head and neck cancers and cancer types. Results The China standard mortality of head and neck cancers in cancer registry areas of Inner Mongolia was 2.85/100,000.The China standard mortality of males(4.24/100,000)was higher than that of females(1.53/100,000),and the China standard mortality in rural areas(2.93/100,000)was higher than that in urban areas(2.79/100,000).The China standard mortality of oral cancer was the highest at 1.16/100,000,and the China standard mortality of nasopharyngeal cancer was the lowest at 0.42/100,000.From 2010 to 2020,the mortality of head and neck cancers increased by an average annual rate of 3.79%(95% CI:1.45%-6.17%),and the trend was statistically significant(P=0.005).The mortality of male head and neck cancer increased by an annual rate of 7.27%(95% CI:3.05%-11.65%),and the trend was statistically significant(P=0.003).The mortality of females decreased by an average annual rate of 1.08%(95% CI:-4.51%-2.47%),and the trend was not statistically significant(P=0.500).The mortality of oral cancer showed an upward trend with an AAPC of 7.35%(P=0.040),and the mortality of laryngeal cancer,thyroid cancer and nasopharyngeal cancer showed no statistically significant trend(AAPC was 3.36%,1.38% and-0.36%,respectively,P＞0.05). Conclusion The mortality of head and neck cancer in cancer registry areas of Inner Mongolia Autonomous Region showed an upward trend from 2010 to 2020.The prevention and treatment of head and neck cancer should be paid to attention,with rural areas and male groups as the key prevention and control targets.The control measures should be strengthened for high-risk behaviors such as occupational exposure and alcohol consumption,oral cancer prevention and control should be focused on,and HPV vaccination and tobacco control policies should be strengthened.

Objective The aim of this study was to investigate the inhibitory effect of dihydroactinidiolide(DHAc)on proliferation of gastric cancer cells and its possible mechanism. Methods Gastric cancer MKN45 cells and AGS cells were cultured and divided into the control group(culture medium without DHAc)and treatment groups with different concentrations of DHAc(50,100,200,400,600,800,and 1 000 μmol/L).MTT assay and methylene blue(MB)assay were used to detect the effect of DHAc on the viability of MKN45 cells and AGS cells.The changes of mitochondrial membrane potential and the cell cycle distribution of MKN45 cells treated with DHAc were detected by flow cytometry,and its effects on the cell cycle of AGS cells were also analyzed.The effects of DHAc on the expression of proteins related to the cell cycle and autophagy in MKN45 cells were detected by Western blot. Results DHAc at different concentrations of 50,100,200,400,600,and 800 μmol/L showed significant inhibitory effects on proliferation of MKN45 cells.Among them,DHAc at the concentration range of 50-400 μmol/L also arrested the cell cycle of MKN45 cells at the G0/G1 phase,down-regulated the expressions of cyclin D1 and CDK4,and significantly reduced the mitochondrial membrane potential(P＜0.05);In the lower concentration range of 50-200 μmol/L,DHAc could induce autophagy in MKN45 cells,as manifested by the upregulation of the LC3-II/LC3-I ratio(P＜0.05).In addition,different concentrations of DHAc(100,200,400,600,800,and 1 000 μmol/L)could also significantly inhibit the proliferation of AGS cells.Among them,DHAc at the concentration range of 100-400 μmol/L could arrest the cell cycle of AGS cells at the G0/G1 phase(P＜0.05). Conclusion DHAc can inhibit the proliferation of gastric cancer cells.The possible mechanism is that DHAc arrests the cell cycle and induces autophagy in gastric cancer cells.

Objective The Objective of this study was to investigate the effect of DCPIB(4-[(2-butyl-6,7-dichloro-2-cyclopentyl-1-oxo-3H-inden-5-yl)oxy]butanoic acid),a selective reversible volume-regulated anion channel inhibitor,on the proliferation capacity of melanoma cells and its mechanism of action. Methods CCK-8 assay and EdU assay were used to detect the effect of DCPIB on the proliferation capacity of A375 cells and RPMI-7951 cells.Transcriptome sequencing was conducted to analyze the differentially expressed genes(DEGs)between the control group(A375 cells treated with absolute ethanol)and the DCPIB-treated group(A375 cells treated with 10 μM of DCPIB)to find the significantly changed signaling pathways.qRT-PCR was used to detect the changes in the mRNA levels of DEGs.Western blot was used to detect the changes in the expression of proteins related to relevant signaling pathways. Results DCPIB significantly inhibited the proliferation of A375 cells and RPMI-7951 cells(P＜0.01).The results of transcriptome sequencing revealed that DNA damage-inducible transcript 3(DDIT3)was significantly upregulated in the DCPIB-treated group(t=161.800,P＜0.001),and the levels of multiple key genes mRNA related to DNA damage repair pathway,including Ku70,Ku80,RAD51,MLH1,MSH6,PARP1,FANCD2 were downregulated.qRT-PCR verified that the levels of key genes mRNA in the above DNA damage repair pathways were significantly reduced after DCPIB treatment in A375 cells for 36 h(P＜0.05).GO functional enrichment and KEGG pathway analyses revealed that after DCPIB treatment,the mRNA levels of endoplasmic reticulum stress-related genes,including HSPA5,DDIT3,ATF4,XBP1,ERN1,EIF2AK3 were upregulated,and the downstream PI3K-Akt signaling pathway was abnormally expressed.qRT-PCR verified that the expression of TRIB3,a downstream molecule of DDIT3 was upregulated in A375 cells treated with DCPIB(t=2.819,P=0.048),and the downstream Akt-mTOR signaling pathway was inhibited,and the levels of p-Akt(t=7.638,P=0.002)and p-mTOR proteins(t=4.898,P=0.008)were significantly decreased. Conclusion DCPIB can significantly inhibit the proliferation of melanoma cells,and its mechanism may be related to the DDIT3-TRIB3-Akt-mTOR signaling axis.

Objective The aim of this study was to investigate the expression of nuclear pore membrane protein 121(POM121)in head and neck mucosal melanoma(HNMM)and its effect on the migration and invasion of HNMM cells. Methods The cancer tissues from 63 patients with HNMM and 20 adjacent normal oral epithelial tissues who were treated in the Harbin Cancer Hospital of Harbin Medical University from March 1,2011 to March 30,2015 were collected,and the expression of POM121 was detected by immunohistochemistry.The relationship between the expression of POM121 and the clinicopathological features of HNMM patients and its effect on the prognosis of patients were analyzed.Western blot was used to detect the expression of POM121 in HNMM cells(MM9H-1 cells)and human oral epithelial cells(human oral keratinocytes,HOK cells).After knocking down POM121 with small interfering RNA(siRNA),the effects on the migration and invasion of HNMM cells were detected by Scratch assay and Transwell assay. Results Immunohistochemistry showed that expression of POM121 was significantly higher in HNMM tissues than that in adjacent tissues(P＜0.001).The expression of POM121 was associated with tumor size and stage(P＜0.05).Kaplan-Meier analysis showed that the disease-free survival(DFS)and overall survival(OS)of patients with low expression of POM121 were significantly longer than those with high expression of POM121.Cox regression analysis showed that POM121 expression,AJCC stage and lymph node metastasis were influencing factors for OS and DFS of HNMM patients(P＜0.05).Western blot results showed that the expression of POM121 protein in MM9H-1 cells was significantly higher than that in HOK cells(P＜0.05).After knocking down POM121,the cell migration rate and cell invasion ability were significantly reduced(P＜0.001). Conclusion POM121 is highly expressed in HNMM tissues and cells,and down-regulation of POM121 significantly inhibits the migration and invasion of HNMM cells.

Objective A targeted nanopeptides(VEGF/TIE-2 targeted nanopeptides,VTN)that simultaneously inhibits vascular endothelial growth factor(VEGF)/ tyrosine kinase with immunoglobulin-like and EGF-like domains-2(TIE-2)signaling pathways were designed and synthesized,and explore its inhibitory effect on angiogenesis in renal clear cell carcinoma(ccRCC). Methods VTN and non-self-assembling control VTN-C were prepared by solid-phase peptide synthesis technology,and the molecular structures of VTN and VTN-C were analyzed by electrospray ionization mass spectrometry(ESI-MS).The CCK-8 method was used to evaluate the effect of VTN on the cell viability of human umbilical vein endothelial cells(HUVEC).The cell scratch assay,Transwell invasion assay and angiogenesis assay were used to detect the inhibitory effects of VTN on migration,invasion and angiogenesis of HUVEC.Western blot was used to detect the effect of VTN on the phosphorylation of downstream proteins of VEGF and TIE-2 signaling pathways.A 786-O cell mouse model was established,and the effects of VTN on tumor angiogenesis and tumor progression were observed through animal experiments. Results ESI-MS showed that the main charge state peaks of both synthesized VTN and VVTN-C pointed to the same molecular weight,which was highly consistent with the corresponding theoretical molecular mass.Immunofluorescence showed that VTN co-localized with VEGF and TIE-2.VTN combined with MMP-2 could significantly inhibit the activity of HUVEC(P＜0.001).The cell invasion rate and scratch closure rate in the VTN group were reduced by(78.30±1.35)% and(37.09±3.49)% compared those in the PBS group,respectively(P＜0.001).Angiogenesis experiments showed that VTN could significantly inhibit the angiogenesis of HUVEC(P＜0.001).Western blot showed that VTN significantly inhibited the phosphorylation of Akt and ERK(P＜0.001).The results from animal experiments showed that tumor volume in the VTN group was decreased by(87.16±1.30)% compared with the control group,and the CD31-positive area was reduced(P＜0.001). Conclusion VTN significantly blocks ccRCC angiogenesis and delays tumor progression by inhibiting VEGF and TIE-2 signaling pathways and downregulating Akt and ERK phosphorylation.

Objective The aim of this study was to investigate the key genes that regulate colorectal cancer(CRC)metastasis,evaluate the effects of exosomal miR-151A-3P derived from CRC on the proliferation and migration,and explore the possibility of exosomal miR-151A-3P as a prognostic biomarker for CRC patients. Methods High-throughput sequencing was performed to screen the differentially expressed miRNAs in serum exosomes of metastatic CRC patients.RT-qPCR was used to verify the expression of differentially expressed miRNAs in CRC specimens.After mimics overexpression or knockdown of miR-151A-3P,CCK-8 and EdU assays were used to detect cell proliferation,and Scratch wound healing and Transwell assays were used to detect cell migration and invasion capability.A BALB/c nude mouse model was used to evaluate the effect of exosomal miR-151A-3P on the metastatic ability of CRC cells. Results The sequencing results showed that compared with non-metastatic CRC patients,the expression of miR-151A-3P was significantly increased in serum exosomes of metastatic CRC patients(P＜0.001).The results were validated by RT-qPCR and found that miR-151A-3P was highly expressed in both serum exosomes and tumor tissues of metastatic CRC patients(P＜0.001).The overall survival of CRC patients with high expression of serum exosomal miR-151A-3P was shorter than that of CRC patients with low expression(P=0.029).After silencing miR-151A-3P,the cell proliferation,migration,and invasion abilities of CRC cells were decreased(P＜0.05),while overexpression of miR-151A-3P could promote the proliferation,migration and invasion of CRC cells(P＜0.05).In the BALB/c nude mouse colorectal cancer model,the administration of exosomal miR-151A-3P led to an increase in the number of lung metastases in BALB/c nude mice(P＜0.05). Conclusion CRC-derived exosomal miR-151A-3P promotes the proliferation and migration of CRC cells,and is associated with poor prognosis of CRC patients.

Objective This study aimed to investigate the association between chromatin remodeling-related genes(CRRGs)and overall survival(OS)of patients with skin cutaneous melanoma(SKCM),and to construct a risk score prognostic prediction model. Methods Based on the TCGA and GTEx databases,the differentially expressed CRRGs in SKCM were obtained,and the prognosis-related genes of SKCM were further screened by protein-protein interaction(PPI)network analysis,univariate Cox regression analysis,and LASSO regression analysis.A risk score prognostic model was constructed based on the prognosis-related genes.According to the median of the risk score,SKCM patients were divided into the high-risk and low-risk groups.The single sample gene set enrichment analysis(ssGSEA)algorithm was used to evaluate the immune cell infiltration of SKCM patients between the high-and low-risk groups. Results A total of 15 hub genes were screened out through the PPI network analysis.Univariate Cox regression and LASSO regression analysis screened out 5 CRRGs associated with OS in SKCM patients,namely MMP2,MMP9,SPP1,TNFSF11,and TIMP1.A risk score was constructed based on the 5 prognostic genes,and multivariate Cox regression analysis showed that the risk score was an independent prognostic factor for SKCM patients(P＜0.05).Survival analysis showed that SKCM patients in the high-risk group was shorter than that in the low-risk group(P＜0.05).The results of immune cell infiltration analysis showed that there were significant differences in the infiltration ratios of 16 immune cells between the high-and low-risk groups,among which the proportions of activated B cells,immature B cells,effector and memory CD8+T cells and activated CD8+T cells in the high-risk group were significantly reduced(P＜0.05).The proportion of CD56bright natural killer cells,CD56dim natural killer cells,γδT cells and immature dendritic cells in the high-risk group were significantly increased(P＜0.05).The drug sensitivity analysis showed that there were significant differences in the sensitivity of high-risk and low-risk SKCM patients to crizotinib,erlotinib,gefitinib and vinorelbine(P＜0.01).Conclusions This study constructed a prognosis model of SKCM composed of 5 CRRGs,further revealed the differences in the immune microenvironment and drug sensitivity in patients with different risk groups of SKCM,and provided an important reference for personalized treatment of SKCM patients.

Over the past decade,the new cases and deaths of breast cancer has rank first among malignant tumors in women,and its incidence is rising,with a younger age trend.Breast cancer demonstrates a high degree of heterogeneity and is prone to drug resistance to comprehensive treatment.As a newly discovered regulatory cell death form mediated by copper,cuproptosis is closely related to the occurrence and development of breast cancer.With the advancement of nano-medicine,metal-based drugs represented by copper can selectively deliver copper ions to tumor sites through the specific delivery system of nanomaterials.These metal drugs kill tumor cells by inducing copper overload,regulating the tumor microenvironment,and enhancing anti-tumor immune response.Therefore,copper-based drugs exhibit significant application potential in the treatment of breast cancer.This article reviews of the mechanism of cuproptosis in the occurrence and development of breast cancer and the application and progress of nanomedicine-mediated cuproptosis in the treatment of breast cancer.

Breast cancer is one of the most common cancers among women in the world,and the continuous progress of its diagnosis and treatment technology is crucial to improve the patient survival rates and quality of life.In recent years,the rapid development of nanotechnology has provided a new strategy for the diagnosis and treatment of breast cancer.This article summarizes the application progress of nanoparticles in the diagnosis and treatment of breast cancer,covering breast cancer imaging,drug delivery,gene therapy,and immunotherapy,and discusses the future development trend.

Early cervical cancer can be cured through surgery,but about half of patients are already locally advanced at the time of initial diagnosis.Cisplatin-based concurrent chemoradiotherapy is the standard treatment for locally advanced cervical cancer.However,the prognosis of these patients remains poor after completing simultaneous radiotherapy and chemotherapy.The emergence of immunotherapy has dramatically improved the prognosis of patients with advanced and recurrent cervical cancer,and is gradually being combined with conventional treatments such as chemotherapy,radiotherapy and targeted therapy.Recent studies have shown that the combination of pembrolizumab and concurrent radiotherapy significantly improves the progression-free survival rate of patients with locally advanced cervical cancer,without significantly increasing the incidence of toxic side effects;The combination of neoadjuvant chemotherapy with immune checkpoint inhibitors and surgery is expected to become a new treatment option for locally advanced cervical cancer;The use of nabumolizumab immunomaintenance therapy after synchronous radiotherapy and chemotherapy may improve the survival rate and treatment efficacy of patients with locally advanced cervical cancer.This article provides a review of the progress in immunotherapy for locally advanced cervical cancer.

The accurate prediction and evaluation of lymphatic vascular invasion(LVI)are extremely important for the prognosis of breast cancer patients.Postoperative histopathology has certain limitations in predicting lymphatic vascular invasion,and magnetic resonance imaging(MRI)technology,with its high resolution and multi-parameter imaging characteristics,provides a more effective non-invasive means for the prediction and evaluation of lymphatic vascular invasion.With the continuous development of the research field of radiomics,researchers have constructed a more accurate prediction model of lymphatic vascular invasion by deeply analyzing a large number of radiological features shown in MRI images and combining with the clinical data of patients.This article reviews the recent research progress of MRI in the field of predicting lymphatic vascular invasion of breast cancer.The purpose of this article is to provide a scientific basis for the clinical treatment of breast cancer patients through accurate identification of lymphatic vascular invasion status before surgery,and to assist clinicians in formulating more personalized treatment plans for patients.