Objective The Objective of this study was to investigate the changing trend of esophageal cancer mortality in Beijing from 1990 to 2019,and to provide evidence for the prevention and treatment of esophageal cancer. Methods Based on the surveillance data of death causes in Beijing from 1990 to 2019,the age-period-cohort(APC)model and endogenous estimator factor(IE)method were used to estimate the age,period and cohort effect of death risk of esophageal cancer in Beijing. Results The mortality of esophageal cancer in Beijing from 1990 to 2019 decreased in a fluctuating manner,with the minimum value of 7.12/100,000(2000—2004),rising to 7.93/100,00(2010—2014)and then began to decline.The standardized mortality showed a downward trend,from 12.53/100,000(1990)to 4.04/100,000(2019),a drop of 67.78%.In 1990,the standardized mortality of male in Beijing was 2.4 times than that of female,and this ratio increased to 4.9 times in 2019.The APC model analysis showed that the age effect of the death risk of esophageal cancer in Beijing increased with age,and the death risk of 80-84 years old group was the highest,with a mortality risk coefficient of 1.957;the period effect was relatively flat,and the relative risk from 2015 to 2019 was 0.852.The birth cohort effect showed an overall downward trend,and the rate of change fluctuated greatly.Compared with those born in 1910—1914,the relative risk of esophageal cancer death for people born in 1980—1984 was 0.032. Conclusion The mortality of esophageal cancer showed a downward trend from 1990 to 2019 in Beijing.The death risk of esophageal cancer is related to age and birth cohort effects.The older the age,the higher the death risk,and the later the birth,the lower the death risk.It is necessary to focus on strengthen the prevention and treatment of esophageal cancer in men and middle-aged and elderly people.

Objective To analyze the long-term trend of mortality and years of life lost(YLL)of stomach cancer in Nanjing from 2007 to 2019. Methods From January 1,2007 to December 31,2019,the date of stomach cancer deaths was collected from the Nanjing Surveillance System for all causes of death.The crude and age-standardized mortality rate of stomach cancer was calculated according to Chinese standard population in 2000.The Joinpoint regression was used to calculate the average annual percentage change(AAPC)to indicate the trend of mortality and YLL rates of stomach cancer. Results From 2007 to 2019,there were 32 187 deaths of stomach cancer in Nanjing,22 296 in male and 9 891 in female,the crude rates of male were higher than female(52.64/10⁵ vs. 23.61/10⁵,u=2.281,P＜0.05),10 591 in urban areas and 21 596 in rural areas,the crude rates of urban areas were lower than rural areas(26.02/10⁵ vs. 49.56/10⁵,u=55.257,P＜0.05).The mortality rates of stomach cancer increased from the age of 40 years and peaked in age group of 80-years in males,peaked in age group of 85-years in females.From 2007 to 2019,the crude mortality and age-standardized mortality were decreased with year(AAPC,crude mortality:-2.65%,age-standardized mortality:-7.69%,P＜0.05).The total YLL numbers were 681,511 person-years and the rates were 8.09 person-years per thousand.From 2007 to 2019 was,YLL rates were decreased with year(AAPC was-3.86%,P＜0.05),and increased with age(the AAPC was 52.43%,P＜0.05),and the rates of males increased faster than those of females(AAPC,males:54.90%,females:49.70%,P＜0.05). Conclusion The mortality of stomach cancer varied with sex,age and areas(urban area and rural area).The present analysis provides the character of stomach cancer in Nanjing,which can help optimize the screening and prevention strategies of stomach cancer to improve life quality and reduce the disease burden.

Objective The Objective of this study was to analyze the changing trend of breast cancer disease burden attributable to metabolic risk factors in Chinese female population between 1990 and 2019,so as to provide scientific basis for formulating targeted prevention and control strategies. Methods Based on the global burden of disease study 2019(GBD 2019)database,mortality,disability adjusted life year(DALY),disability adjusted life year(DALY),years lived with disability(YLD),years of life lost(YLL),and population attributable fraction(PAF)were calculated to analyze the changing trend of breast cancer disease burden attributed to metabolic risk factors in Chinese female population. Results The age-standardized mortality and the DALY rate of breast cancer attributable to metabolic risk factors in China and the World both showed an upward trend between 1990 and 2019.The attributable age-standardized mortality and DALY rate in China increased by 1.79%(95% CI:1.51%-2.07%,P＜0.05)and 1.77%(95% CI:1.45%-2.09%,P＜0.05),the global attributable standardized mortality and DALY rate increased by 0.80%(95% CI:0.69%-0.92%,P＜0.05)and 0.97%(95% CI:0.91%-1.04%,P＜0.05),respectively,and the increase in China was higher than that in the World.There were differences in the PAF attributable to metabolic risk factors of breast cancer among Chinese women in different age groups between 1990 and 2019,and the PAF value was higher in the age group of 50-69 and over 70 years old.The attributable DALY rate was the highest in the age group of 50-69,and the attributable mortality increased with age,reaching the highest in the ≥70-year-old age group.Compared with 1990,the number of breast cancer deaths and DALY caused by high body mass index among metabolic risk factors in 2019 increased by 450.34% and 440.28%,respectively,and the mortality and DALY rate increased by 352.48% and 344.20%,respectively. Conclusion The burden of breast cancer in Chinese female population is heavy due to metabolic risk factors,and middle-aged and elderly female population is a high-risk group.In addition,high body mass index is an important risk factor among metabolic risk factors.

Objective The aims of this study were to analyze the effects of colorectal cancer screening in Jinshan district from 2013 to 2021,and to provide a basis for improving colorectal cancer screening strategies in the future. Methods Microsoft Access 2010 was used to establish a screening database of colorectal cancer in Jinshan district from 2013 to 2021,and the rate of primary screening,colonoscopy examination rate and resident colonoscopy diagnosis results of in different genders and age groups were calculated and compared. Results From 2013 to 2021,a total of 172,244 permanent residents aged 50-74 years old were carried out colorectal cancer screening in Jinshan district.The positive rate of primary screening was 24.28%,of which 25.73% was males and 23.34% was females.They had statistically significant(χ²=127.145,P＜0.001).A total of 16,714 residents with positive screening results underwent colonoscopy,and the colonoscopy rate was 39.97%,including 40.28% for males and 39.74% for females.There was no significant difference in colonoscopy rates between the two genders(χ²=1.258,P=0.262).In the past 9 years,a total of 90 cases of colorectal cancer were detected through colonoscopy,with a detection rate of 0.54%,and 2,974 cases of precancerous lesions were detected,with a detection rate of 17.79%.There was a significant difference in the distribution of colonoscopy diagnosis results between males and females(χ²=747.903,P＜0.001)and there were also significant differences in the distribution of colonoscopy diagnosis results among residents of different age groups(χ²=111.769,P＜0.001). Conclusion Colorectal cancer screening has achieved good results in Jinshan district,but it is necessary to further mobilize residents aged 50-74 to participate in the screening,continuously increase the rate of colonoscopy examination,and strengthen the capabilities of colonoscopy examination and pathological diagnosis in designated hospitals.

Objective The aim of this study was to analyze the correlation between the expression of programmed death ligand 1(PD-L1)and clinical pathological features and common driver gene mutation in patients with non-small cell lung cancer(NSCLC),so as to provide theoretical basis for immunotherapy of NSCLC patients. Methods Retrospective inclusion of NSCLC patients who underwent PD-L1 immunohistochemistry staining and epidermal growth factor receptor(EGFR),Kirsten rat sarcoma viral oncogene(KRAS),anaplastic lymphoma kinase(ALK),RET proto-oncogene(RET),v-Raf murine sarcoma viral oncogene homolog(BRAF),ROS proto-oncogene 1(ROS1),human epidermal growth factor receptor-2(HER2),cellular-mesenchymal to epithelial transition factor(MET)gene testing from the Pathology Department of Beijing Thoracic Hospital Affiliated to Capital Medical University from January 2018 to December 2021.Analysis of the impact of different pathological features and driver gene variants on PD-L1 protein expression in NSCLC patients. Results PD-L1 protein expression was detected in 2 386 cases,with a positive rate of 45.8%(1 093/2 386).Among them,the low expression group(1%≤TPS≤49%)was 62.0%(678/1 093),while the high expression group(TPS≥50%)was 38.0%(415/1 093).There were differences in PD-L1 expression among different clinical and pathological features.Multivariate logistic regression analysis showed that smoking history,lymph node metastasis,pathological subtypes,EGFR mutations,KRAS mutations,ALK and MET mutations were independent risk factors for PD-L1 expression in NSCLC patients(P＜0.05),while lymph node metastasis and EGFR mutations were independent risk factors for PD-L1 expression levels in NSCLC patients(P＜0.05). Conclusion The PD-L1 protein has a high positive rate in patients with smoking,squamous cell carcinoma,KRAS mutant,ALK positive,and MET mutant,and is highly expressed in patients with lymph node metastasis and EGFR wild-type.Different from NSCLC patients with EGFR positive,NSCLC patients with KRAS,and MET positive are expected to benefit from the treatment of immune checkpoint inhibitors.

Objective To explore the role and mechanism of survival-related lncRNA AP000487.1 in the occurrence and development of esophageal cancer. Methods qRT-PCR was used to verify the expression of lncRNA AP000696.1,LINC00689,LINC00900 and AP000487.1 that significantly associated with overall survival of esophageal cancer patients in esophageal cancer tissues and cell lines.Cell proliferation was detected by CCK-8 assay,cell invasion was evaluated by Transwell invasion assay,and cell migration was detected by scratch assay.The expression of TLR/NF-κB signaling pathway related proteins was detected by Western blot and qRT-PCR. Results The expression of AP000487.1 was significantly up-regulated in ECA109 cells,TE-1 cells,and ESCA tissues(P＜0.001).Silencing AP000487.1 in ECA109 cells and TE-1 cells significantly inhibited the proliferation,invasion and migration of ESCA cells.Overexpression of AP000487.1 significantly enhanced the proliferation,invasion and migration.Western blot was used to detect pathway-related proteins,and the results showed that silencing AP000487.1 could inhibit the TLR/NF-κB signaling pathway and down-regulate the expression of p-p65 and p-IκB in TE-1 cells;Compared with the Smart silencer-NC group,the expressions of TNF-α(P＜0.001),IL-1β(P＜0.01)and IL-6(P＜0.01)in the Smart silencer-AP000487.1 group were significantly down-regulated. Conclusion AP000487.1 is highly expressed in esophageal cancer cell lines and tissues,and its abnormal expression promotes the proliferation,invasion and migration of ESCA by regulating the TLR/NF-κB signaling pathway.AP000487.1 may be a potential therapeutic target for ESCA.

Objective The Objective of this study was to identify the feasibility of adoptive reinfusion in NK cells to treat colorectal cancer and to explore new therapeutic strategies by detecting the killing efficiency of NK cells and PD-1 monoclonal antibody(mAb)+ NK cells in five kinds of colorectal cancer cell lines. Methods NK cells were cultured by inducing peripheral blood mononuclear cells in vitro,and a CCK-8 assay was used to detect NK cells and PD-1 mAb + NK cells to kill the efficiency of five colorectal cancer LOVO,Caco-2,HT-29,HT-115 and HRT-18 cell lines,the ratio of effect-to-target,and compare the killing effects of the two effector groups on colorectal cancer cells through statistics. Results The killing efficiencies of NK cells against the five target cells were significantly different(P＜0.01).The killing efficiencies of NK cells against the same target cells were significantly different at different effect target ratios(P＜0.05).The killing efficiencies of PD-1 mAb combined with NK cells on Caco-2(effect-target-ratio 2∶1),HT-29(effect-target-ratio 5∶1 and 10∶1)and HT-115(effect-target-ratio 0.1∶1 and 0.5∶1)cells were significantly different from those of NK cells alone(P＜0.05),and there was no significant difference among other groups(P＞0.05). Conclusion When using NK cells adoptive transfusion to treat colorectal cancer,controlling the effect-target ratio at 2:1 may be a safe and effective ratio;Killing efficiency of NK cells on colorectal cancer has nothing to do with its degree of differentiation;PD-1 mAb can be combined with adoptive reinfusion of NK cells in the treatment of colorectal cancer and has certain therapeutic significance.

Objective The aim of this study was to explore the role of lncRNA DUXAP8 in the occurrence and development of endometrial cancer(EC). Methods The Cancer Genome Atlas(TCGA)database was used to analyze the expression level of lncRNA DUXAP8 in EC tissues and the association between DUXAP8 and prognosis of patients.qRT-PCR was used to detect the expression of DUXAP8 in EC cells lines.HEC-1A cell lines with DUXAP8 overexpressed or knockdown were constructed by transfection.CCK-8,colony forming,transwell,scratch healing assay,and flow cytometry were used to detect the abilities of proliferation,invasion,migration,cell cycle,and cell apoptosis in endometrial cancer cells after different treatments,and Western blot was used to detect the levels of epithelial-mesenchymal transition(EMT)-related protein. Results DUXAP8 was significantly upregulated in endometrial cancer,and endometrial cancer patients with high DUXAP8 expression had a relatively poor prognosis.Inhibition of DUXAP8 hinder cell proliferation,invasion,migration and EMT process,cell cycle arrested at the G0/G1 phase,and induced apoptosis.While overexpression DUXAP8 enhanced the proliferation,invasion,migration and EMT process of tumor cells,cell cycle arrested at the S phase,and apoptosis level significantly reduced. Conclusion These results suggested that DUXAP8 functions regard as a pro-oncogene in endometrial cancer and may be a new target for EC therapy.

Malignant melanoma is a highly malignant solid tumor with strong invasiveness and poor prognosis.With marketing of immunotherapy drugs,the overall survival rate of malignant melanoma patients has been greatly improved.However,some patients progress rapidly and deteriorate rapidly after immunotherapy,which is called hyperprogressive disease.The survival rate of hyperprogressive patients is lower and their prognosis is worse.In order to detect and prevent the occurrence of hyperprogressionin time and reduce the mortality of patients,this article reviews the research status immunotherapy for hyperprogression of malignant melanoma.

Interleukin-6(IL-6)is a pleiotropic potent proinflammatory cytokine presenting in the tumor microenvironment.The hexamer complex and its receptor IL-6R and glycoprotein 130(IL-6/IL-6R/gp130)activate JAK/STAT3,PI3K-Akt and other signal pathways,leading to the occurrence and development of tumors.Therefore,IL-6 can be used as an important target for the treatment of malignant tumors.At present,there are many methods for treating breast cancer clinically,but the overall treatment effect is still unsatisfactory,which is mainly due to the drug resistance of cancer cells to traditional anti-cancer therapies.Inflammatory factors in tumor microenvironment can promote tumor growth and induce resistance to chemoradiotherapy.Therefore,an in-depth study of IL-6 mediated cell effects and its signal pathways can provide ideas for the future research on the treatment of IL-6 in breast cancer.The latest research reviews the role of inhibiting IL-6 and its signal pathways in the treatment of breast cancer,in order to provide effective therapeutic methods for the treatment of breast cancer.

The emergence of trastuzumab has greatly improved the prognosis of patients with HER2-positive breast cancer,but some patients still develop primary or secondary trastuzumab resistance during treatment.In recent years,the drug resistance mechanism of trastuzumab has attracted more and more attention,but the drug resistance phenomenon has not been fully elucidated.Lipid metabolism,as a basic physiological activity to maintain cell survival,is closely related to the resistance of HER2-positive breast cancer cells to targeted therapy,and is expected to become a new target for the treatment of trastuzumab resistance.This article reviews the relationship between lipid metabolism and the mechanism of trastuzumab resistance.

Exosomes are small vesicles with a diameter of 30~150 nm secreted by various cells.They play an important role in cell communication and epigenetic regulation by transporting critical proteins and genetic materials such as miRNA,mRNA,and DNA.Long non-coding RNA(lncRNA)is an RNA transcript that is more than 200 nucleotides in length and does not encode a protein.Current studies have found that lncRNA is an important nucleic acid molecule contained in exosomes.It plays an important role in the occurrence and development of tumors,and the regulation of tumor biological function through exosome mediation.This paper reviews the development,early diagnosis,treatment and prognosis of exosome lncRNAs in squamous cell carcinoma(SCC)in recent years,as well as its application prospects,in order to provide reference for follow-up studies.

Lung cancer is the second most common cancer worldwide after breast cancer,due to increasing morbidity and mortality from diseases related to smoking,air pollution and lung infections,as well as increasing awareness of cancer screening.However,due to the lack of obvious clinical features of early-stage lung cancer,most patients are diagnosed at an advanced stage.Therefore,the early and accurate diagnosis of benign and malignant pulmonary lesions is very necessary for the treatment and prognosis of patients.Peripheral pulmonary lesions(PPLs)are located in a special location,close to or even close to the chest wall,which enables ultrasound to break the “taboo” of lung examination and exert its unique advantages.With the continuous development of ultrasound technology,multimodal ultrasound diagnosis technology has been gradually applied to the examination of PPLs to improve the accuracy of disease diagnosis.This article will review the application progress of multimodal ultrasound in the diagnosis of benign and malignant peripheral pulmonary lesions.

N6-methyladenosine(m6A)is the most abundant internal chemical modifications in eukaryotic mRNA and long non-coding RNAs(lncRNAs),and its process is controlled by methyltransferase,demethylase and reader proteins are involved in the completion and rely on the three dynamic regulation.Among them,the YT521-B homology domain(YTH)protein is a kind of mature m6A reading protein,which can specifically recognize m6A-containing RNA and mediate its function,and is related to the occurrence and development of various tumors.However,little is known about the role of YTH proteins in colorectal cancer.This article reviews the structure,function and related pathway mechanism of the YTH protein in colorectal cancer,so as to provide the reference for the personalized treatment for colorectal cancer.

Diffuse large B-cell lymphoma(DLBCL)is a common form of non-Hodgkin′s lymphoma.Currently,the 5-year overall survival rate of patients treated with R-CHOP first-line therapy is 60% to 70%.The heterogeneous and aggressiveness of DLBCL may lead some patients to relapse or progress to refractory disease after receiving treatment.As a nuclear export receptor protein,exportin 1(XPO1)can transports more than 220 proteins and RNAs from the nucleus to the cytoplasm,and preferentially transport oncoproteins and mRNAs encoding oncoproteins,which may be involved in the occurrence and development of tumors.Related studies have shown that XPO1 is overexpressed in many malignant tumors such as leukemia and lymphoma,and mutates in B-cell malignancies such as DLBCL.XPO1 inhibitors can target XPO1 and block the nuclear output of oncoproteins;they can also limit the combination of XPO1 and its target proteins such as tumor suppressor protein(TSP),reduce the nuclear export of TSP,and play an anti-inflammatory role in malignant tumors.This article reviews the research progress of XPO1 inhibitors in DLBCL.

SYT13 is an atypical synaptotagmins located on chromosome 11.It is expressed in the heart,lung,testis,brain,kidney,spleen,pancreas and other organs.More and more studies have confirmed that SYT13 is abnormally expressed in a variety of cancers.This article reviews the research progress of SYT13 in the occurrence and development of malignant tumors.

Copper is a metal element involved in a variety of biological processes.Maintaining the balance of copper ions is an important condition for maintaining the health of body.Copper is related to the occurrence and development of many diseases,including malignant tumors."Cuprotosis" is a newly proposed cell death mode that depends on the accumulation of intracellular copper.Studies have shown that the dynamic balance of copper is related to the occurrence and development of breast cancer,and the research on copper in the treatment of breast cancer is also rising.This article mainly summarizes the mechanism of copper-dependent cell death and the research status of copper in breast cancer.

Gastric cancer(GC)is a complex heterogeneous disease with high morbidity and mortality all year round.Molecular targeted therapy is expected to become a more effective treatment strategy with limited or nonexistent side effects on normal cells of the body.Wingless-Type MMTV Integration Site Family/beta-catenin(β-catenin)(Wnt for short)signaling pathway is involved in the regulation of embryoic development and cell proliferation,differentiation,migration,apoptosis and so on.It is one of the main pathways involved in the occurrence,progression and metastasis of cancer.Dysregulation of the Wnt pathway is observed in approximately 50% of GC patients and thus may provide a new therapeutic target.In recent years,more and more evidence has shown that the Wnt pathway plays a central role in the occurrence and progression of GC,and some inhibitors targeting this pathway at the ligand/receptor level are being studied in preclinical or clinical trials.Finding new useful targets may become a potential marker for early diagnosis and treatment of GC.This article reviews the relationship between Wnt signaling pathway and GC,and the research progress of the pathway inhibitors in GC,in order to provide a new strategy for the diagnosis and treatment of GC.