[Purpose]To analyze the incidence and mortality of malignant tumors in cancer regis-tration areas of Heilongjiang Province in 2019 and the trend from 2013 to 2019.[Methods]The incidence and mortality data of malignant tumors reported by the Heilongjiang provincial cancer registries from 2013 to 2019 were collected,and the quality of data was assessed.The crude in-cidence/mortality rate,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW),0～74 years old cumulative rate were calculated.Joinpoint 4.6.0 software was used to calculate the average annual percentage change(AAPC)of ASIRC/ASMRC for the trend analysis from 2013 to 2019.[Results]In 2019,there were 16 732 new cases of malignant tumors in the cancer registration areas of Heilongjiang Province,including 8 639 males and 8 093 females.The crude incidence rate was 295.37/105,with an ASIRC and ASIRW of 167.10/105 and 164.18/105,respectively.There were 10 988 malig-nant tumor deaths,including 6 540 males and 4 448 females.The crude mortality rate was 193.97/105,with an ASMRC and ASMRW of 101.22/105 and 101.66/105,respectively.The inci-dence and mortality of malignant tumors increased rapidly after the age of 55,and the incidence and mortality of males were slightly higher than those of females.The top five malignant tumors of high incidence were lung cancer,female breast cancer,colorectal cancer,liver cancer and thy-roid cancer,and the top five malignant tumors of high mortality were lung cancer,liver cancer,colorectal cancer,stomach cancer and female breast cancer.From 2013 to 2019,the ASIRC of malignant tumors in cancer registration areas increased from 153.08/105 in 2013 to 167.10/105 in 2019,and the ASMRC increased from 92.22/105 in 2013 to 101.22/105 in 2019,but there was no statistical difference in the change trend.[Conclusion]The incidence and mortality of malignant tumors in Heilongjiang Province remain high.Lung cancer,female breast cancer,colorectal can-cer,liver cancer and stomach cancer should be the focus of cancer prevention and control.

[Purpose]To analyze the incidence and mortality of malignant tumors in cancer regis-tration areas of Heilongjiang Province in 2019 and the trend from 2013 to 2019.[Methods]The incidence and mortality data of malignant tumors reported by the Heilongjiang provincial cancer registries from 2013 to 2019 were collected,and the quality of data was assessed.The crude in-cidence/mortality rate,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW),0～74 years old cumulative rate were calculated.Joinpoint 4.6.0 software was used to calculate the average annual percentage change(AAPC)of ASIRC/ASMRC for the trend analysis from 2013 to 2019.[Results]In 2019,there were 16 732 new cases of malignant tumors in the cancer registration areas of Heilongjiang Province,including 8 639 males and 8 093 females.The crude incidence rate was 295.37/105,with an ASIRC and ASIRW of 167.10/105 and 164.18/105,respectively.There were 10 988 malig-nant tumor deaths,including 6 540 males and 4 448 females.The crude mortality rate was 193.97/105,with an ASMRC and ASMRW of 101.22/105 and 101.66/105,respectively.The inci-dence and mortality of malignant tumors increased rapidly after the age of 55,and the incidence and mortality of males were slightly higher than those of females.The top five malignant tumors of high incidence were lung cancer,female breast cancer,colorectal cancer,liver cancer and thy-roid cancer,and the top five malignant tumors of high mortality were lung cancer,liver cancer,colorectal cancer,stomach cancer and female breast cancer.From 2013 to 2019,the ASIRC of malignant tumors in cancer registration areas increased from 153.08/105 in 2013 to 167.10/105 in 2019,and the ASMRC increased from 92.22/105 in 2013 to 101.22/105 in 2019,but there was no statistical difference in the change trend.[Conclusion]The incidence and mortality of malignant tumors in Heilongjiang Province remain high.Lung cancer,female breast cancer,colorectal can-cer,liver cancer and stomach cancer should be the focus of cancer prevention and control.

As a highly differentiated haploid germ cell in male body, sperm is an important carrier of life genetic information transmission, and its structural integrity is the condition of normal insemination, and also the basis of normal metabolism to produce energy and complete epigenetic inheritance. Sperm metabolism is considered to be the "energy supply station" of sperm movement, which ensures the normal life activities such as spermatogenesis, maturation, over-activation and sperm-egg union. Abnormal metabolism will directly affect the sperm vitality and cause male infertility. Sperm epigenetic inheritance is a process that affects the embryonic development and reproduction of offspring through paternal inheritance, including DNA methylation, chromatin remodeling and small RNA carried by sperm and other regulatory modes, which can also affect energy production to a certain extent, thereby leading to the decline of sperm motility and male fertility. Therefore, sperm metabolism and epigenetics are inextricably related to the maintenance of sperm motility. In this paper, the structure, metabolism and epigenetic regulation of human sperm are reviewed in order to provide theoretical reference for the research on male infertility caused by abnormal sperm motility.

As a highly differentiated haploid germ cell in male body, sperm is an important carrier of life genetic information transmission, and its structural integrity is the condition of normal insemination, and also the basis of normal metabolism to produce energy and complete epigenetic inheritance. Sperm metabolism is considered to be the "energy supply station" of sperm movement, which ensures the normal life activities such as spermatogenesis, maturation, over-activation and sperm-egg union. Abnormal metabolism will directly affect the sperm vitality and cause male infertility. Sperm epigenetic inheritance is a process that affects the embryonic development and reproduction of offspring through paternal inheritance, including DNA methylation, chromatin remodeling and small RNA carried by sperm and other regulatory modes, which can also affect energy production to a certain extent, thereby leading to the decline of sperm motility and male fertility. Therefore, sperm metabolism and epigenetics are inextricably related to the maintenance of sperm motility. In this paper, the structure, metabolism and epigenetic regulation of human sperm are reviewed in order to provide theoretical reference for the research on male infertility caused by abnormal sperm motility.

Objective To analyze the mortality characteristics and trends and the cause-eliminated life expectancy of gastric cancer in Harbin City from 1987 to 2019. Methods Mortality data of residents with gastric cancer from 1987 to 2019 in Harbin was analyzed to describe the mortality characteristics and trends of gastric cancer. Abridged life table and cause-eliminated life table were applied to calculate life expectancy and cause-eliminated life expectancy. Average annual percentage change (AAPC) was calculated with Joinpoint 4.2 software to evaluate the trends of mortality and cause-eliminated life expectancy of gastric cancer. Results From 1987 to 2019, the crude mortality, ASMRC and ASMRW and the truncated rate (35-64) were 14.3/10⁵, 10.9/10⁵, 10.9/10⁵, and 13.5/10⁵, respectively. The ASMRC showed an obvious decreasing trend at an average annual rate of 2.9% from 1987 to 2019 (95%CI: -4.4%--1.4%). Significant decreasing trends were observed for males (AAPC=-3.0%, 95%CI: -4.4%--1.7%) and females (AAPC=-3.1%, 95%CI: -5.3%--0.9%). An obvious decreasing trend in the ASMRW was also observed. The truncated rate (35-64) showed a downward trend (AAPC=-2.8%, 95%CI: -3.1%--2.5%). The average life expectancy of residents from 1987 to 2019 in Harbin were 76.78 years (male: 74.41 years, female: 79.33 years). After eliminating the causes of death of gastric cancer, the life expectancy increased by 0.25 years (male: 0.31 years, female: 0.18 years). Significant decreasing trends were found in the proportion of gastric cancer in all malignant cancer cases (AAPC=-0.18%, 95%CI: -2.0%--1.7%). Conclusion The mortality of gastric cancer decreases gradually from 1987 to 2019 in Harbin. After eliminating the causes of death of gastric cancer, the life expectancy increases by 0.25 years. Therefore, prevention and control should be strengthened.

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC₅₀ values and achieved picomolar DC₅₀ values and >99% of maximum degradation (D_max) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^Y1230H and c-MET^D1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.

Background::The clinical characteristics of patients with the comorbidities of hypertension and coronary artery disease (HT-CAD) and atrial fibrillation (AF) are largely unknown. This study aimed to investigate the prevalence of AF in patients with HT-CAD and clinical characteristics of patients with both HT-CAD and AF.Methods::This cross-sectional study was conducted in Chinese People’s Liberation Army General Hospital in Beijing, China, and included 20,747 inpatients with HT-CAD with or without AF from August 2008 to July 2018. We examined the overall prevalence, clinical characteristics, comorbidity profiles, treatment patterns, and blood pressure (BP) control of patients with both HT-CAD and AF. Multivariate logistic regression was used to investigate the associations of cardiovascular risk factors with AF in patients with HT-CAD.Results::The overall prevalence of AF in patients with HT-CAD was 4.87% (1011/20,747), and this increased with age; to be specific, the prevalence in women and men increased from 0.78% (2/255) and 1.02% (26/2561) at the age of <50 years to 8.73% (193/2210) and 10.28 % (298/2900) at the age of ≥70 years, respectively. HT-CAD patients who had AF had a higher prevalence of cardiovascular-related comorbidities than those without AF. Multivariate logistic regression showed that age, gender (male), body mass index, heart failure, and chronic kidney disease were independently associated with the risk of AF in patients with HT-CAD. For those with both HT-CAD and AF, 73.49% (743/1011) had a CHA 2DS 2-VASc score of ≥4, and only about half of them had the BP controlled at <140/90 mmHg, which indicated a high risk of thromboembolism and stroke. The use of oral anticoagulation increased during the study period (10.00% [20/200] in 2008 to 2011 vs. 30.06% [159/529] in 2015 to 2018, P < 0.01), but remained at a relatively low level. Conclusions::AF is highly prevalent among patients with HT-CAD. Patients with both HT-CAD and AF have a higher prevalence of cardiovascular-related comorbidities, lower BP control rate, and lower use of oral anticoagulation.

Objective:To explore the clinical characteristics of Diamond-Blackfan anemia (DBA) in children caused by RPL5 gene mutation, thus improving the understanding of the etiology of DBA.Methods:The clinical data and sequencing results of a child with DBA caused by RPL5 gene mutation treated in the Children′s Hospital of Fudan University were analyzed.In addition, through literature review of reported DBA cases at domestic and home, summarized the clinical features of DBA.Results:The patient was an 8-year-old male child.Bone marrow puncture examination of the child showed DBA, and a heterozygous mutation of RPL5 gene c. 657C>G, p.Y219X was identified for the first time in the DBA case.A total of 47 cases of DBA were retrieved from the online databases plus the one reported in this study (48 cases in total), and their clinical features were summarized as follows: the incidence of DBA was similar in men and women.The number of DBA patients in Asia was lower than that in Europe and the United States.DBA was mainly a sporadic disease.Among the exon mutations in European and American cases of DBA, 43.0% of them had mutations in Exon3.The malformation rate of DBA patients with RPL5 mutation was 81.3% (39/48 cases, excluding short stature cases), which was higher than that of patients with other mutation types.The response rate of glucocorticoid therapy for DBA was 46.0%, which was lower than that of the overall response rate.Conclusions:chr1: 93303142(c.657 C>G, p.Y219X) is a newly detected mutation of RPL5 gene in the DBA case, which expands the pathogenic gene spectrum of DBA.Patients with RPL5 mutation have higher rates of teratogenicity and multiple teratogenicity, and a lower response rate to hormone therapy.

Objective:To explore the incidence and mortality of esophageal cancer in the cancer registration areas of Heilongjiang province from 2013 to 2017 and their trends of change over time.Methods:The esophageal cancer incidence, mortality and population data reported by 12 cancer registration areas of Heilongjiang province were collected. Among them, the data of 11 areas met the check standards, including 7 cities above the prefecture level (abbreviated as urban area), 4 counties and county-level cities (abbreviated as rural area). The crude incidence and mortality rates of esophageal cancer in 11 cancer registration areas of Heilongjiang province from 2013 to 2017, and their standardized rates by Chinese population (adjusted according to the standard population composition of the 2000 census of China) and world population (adjusted using Segi world standard population composition), and the cumulative incidence or mortality rate from 0 to 74 years old (abbreviated as cumulative incidence or mortality rate) were calculated. Joinpoint regression was used to calculate the annual percentage change (APC) of the incidence and mortality rates, and the trend analysis was performed.Results:From 2013 to 2017, the crude incidence rate of esophageal cancer in the cancer registration areas of Heilongjiang province was 6.40/100 000, the standardized incidence rate by Chinese population was 3.63/100 000, and the cumulative incidence rate was 0.44%. The crude incidence rate of esophageal cancer in males (11.61/100 000) was higher than that in females (1.27/100 000). The crude incidence rate of esophageal cancer in rural area (6.27/100 000) was lower than that in urban area (6.71/100 000). From 2013 to 2017, the crude mortality rate of esophageal cancer in the cancer registration areas of Heilongjiang province was 5.32/100 000, the standardized mortality rate by Chinese population was 3.01/100 000, and the cumulative mortality rate was 0.35%. The crude mortality rate of esophageal cancer in males (9.56/100 000) was higher than that in females (1.15/100 000). The crude mortality rate of esophageal cancer in rural area (5.13/100 000) was lower than that in urban area (5.39/100 000). Joinpoint regression analysis showed that from 2013 to 2017, the incidence and mortality rates of esophageal cancer in the entire population and males had an increasing trend, but the differences were not statistically significant (all P > 0.05), and the standardized incidence rate by Chinese population in females had a downward trend, and the difference was statistically significant (APC = -7.92, 95% CI -11.52- -4.21, P < 0.01). Conclusions:The incidence and mortality rates of esophageal cancer in Heilongjiang province have been increasing in recent years, and the burden of disease is still heavy. In the male population, the primary prevention, early detection and early treatment of esophageal cancer should be paid more attention.

Objective To analyze the incidence, mortality and time trend of lung cancer in Heilongjiang Cancer Registries from 2013 to 2017. Methods We calculated the incidence (mortality) rate and age-standardized incidence (mortality) rate of lung cancer in Heilongjiang Cancer Registries from 2013 to 2017. Chinese population census in 2000 and World Segi's standard population were used for age-standardization. Annual percentage change (APC) was calculated using Joinpoint software. Results The incidence of lung cancer in Heilongjiang Cancer Registries from 2013 to 2017 was 63.44/10⁵ and ASR China was 36.14/10⁵. The incidence of lung cancer in males (78.08/10⁵) was higher than that in females (49.04/10⁵). The incidence of lung cancer in rural areas (65.54/10⁵) was higher than that in urban areas (58.20/10⁵). From 2013 to 2017, the mortality rate of lung cancer in Heilongjiang Cancer Registries was 57.02/10⁵, and ASR China was 32.53/10⁵. The mortality rate of lung cancer in males (69.92/10⁵) was higher than that in females (44.40/10⁵). The mortality rate of lung cancer in rural areas (60.68/10⁵) was higher than that in urban areas (48.02/10⁵). The incidence of lung cancer in the 55-year-old age group showed a downward trend (APC=-5.0%, t=-5.1, P < 0.05), and the mortality rate of lung cancer in the 70-year-old group showed a downward trend (APC=-4.9%, t=-5.0). Conclusion Heilongjiang Province is a high incidence area of lung cancer. The prevention and control of lung cancer should be further strengthened according to the epidemiological characteristics of lung cancer in this province.