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.

Objective To describe and analyze the incidence and mortality of malignant tumors in Daoli District of Harbin from 2008 to 2012. Methods The tumor registration data of 2008—2012 reported by the Daoli District Cancer Registry was collect-ed. The crude incidence and mortality,China standardization rate,World standardization rate,cumulative rate and truncated incidence rate of major malignant tumors were calculated and trends of the incidence and mortality of malignant tumors in 5 years were analyzed. Results From 2008 to 2012,there were 10 893 cases of malignant tumors in Daoli District of Harbin,including 5879 males and 5 014 females. The incidence rate increased first and then stabilized. Incidence of malignancy,China standardization rate,world standardiza-tion rate,cumulative rate and truncated incidence rate in men were higher than those in women. The incidence rates were at a low level in the 0~25 age group,rising rapidly in the 25~80 age group,reaching a peak at the age of 80,and then beginning to decline. From 2008 to 2012,there were 6 801 cases of malignant tumor deaths in Daoli District of Harbin,including 4 069 males and 2 732 females. There was no significant change in mortality over five years. Malignancy mortality,China standardization rate,world standardization rate,cumulative rate and truncated incidence rate in men were higher than those in women. The mortality rates were at a low level in the 0~30 age group,rising rapidly in the 30~75 age group,reaching a peak at the age of 75,and then beginning to decline. The high-est incidence of malignant tumors in Daoli District from 2008 to 2012 was lung cancer,followed by liver cancer,colorectal cancer, stomach cancer and breast cancer. The highest mortality rate of malignant tumors was lung cancer,followed by liver cancer,colorectal cancer,stomach cancer and pancreatic cancer. Conclusion The incidence of malignant tumors in Daoli District of Harbin City in-creased first and then stabilized in 2008-2012,and there was no significant change in mortality. Lung cancer,digestive system malig-nant tumors,and female breast cancer are the main cancer types of malignant tumors incidence and death in Daoli District of Harbin.

Objective To analyze the malignant tumor incidence and mortality in Heilongjiang province in 2013.Methods Tumor registration data of Heilongjiang province cancer registries in 2013 were collected.The malignant tumor incidence and mortality of registration data from 7 cancer registries were analyzed according to the criteria of quality control from National Central Cancer Registry (NCCR).Results The crude incidence rate of cancer in Heilongjiang province was 234.34/105.Age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population were 153.08/105 and 149.33/105 with the cumulative incidence rate (0-74 years old) of 17.17％.The cancer incidence and ASIRC were 258.42/105 and 157.00/105 in urban areas,whereas in rural areas,they were 190.95/105 and 145.44/105,respectively.The cancer mortality in Heilongjiang province was 147.62/10s.Age-standardized mortality rates by ASIRC and by world standard population were 92.22/105 and 91.41/105 with the cumulative incidence rate (0-74 years old) of 10.44％.The cancer mortality and ASIRC were 171.85/105 and 97.85/105 in urban areas,whereas in rural areas,they were 103.95/105 and 78.48/105,respectively.Lung cancer,breast cancer,liver cancer,colorectal cancer and gastric cancer were the high-incidence cancers in Heilongjiang province.Lung cancer,liver cancer,gastric cancer,colorectal cancer and breast cancer were the most death causes.Conclusion The morbidity and mortality of lung cancer are the highest in Heilongjiang province in 2013.Lung cancer and digestive system malignancies are the most common cancers in Heilongjiang province.Dynamic monitoring tumor morbi-dity and mortality in Heilongjiang province is the basis of the cancer prevention and control work.The active and effective comprehensive control measures should be taken to curb the rising trend of malignant tumor burden.

Objective To investigate TCM resources in Changshou District of Chongqing based on the fourth national census of TCM resources; To provide theoretical references for the protection and exploitation of TCM resources. Methods Sample-plot survey, line survey and interview survey were used in this study. Results Totally 142 families, 482 genera and 639 species (including subspecies and varieties) were collected from the general survey of TCM resources in this region. There were a total of 575 species of medicinal plants, including 456 kinds of ordinary medicinal plants and 119 species of national key medicinal plant which were recorded in the Chinese Pharmacopoeia (2015 Edition). But there was no department leader of the Chinese medicine industry and TCM cultivation was almost blank. Nowadays there was no TCM processing enterprise, and the quality could not be controlled. The continual increase of production cost restricted the development of TCM industry. Conclusion TCM resources in Changshou District of Chongqing are abundant, while the TCM industry is almost blank. The support and guidance from government are needed to develop TCM industry in this area.

Objective To construct the recombinant eukaryotic expression plasmids of human adenylyl cyclase-associated protein 1 (CAP1)and to explore its intracellular location and functions.Methods By using Hela cDNA as the template,the cDNAs encoding CAP1 was amplified by PCR and inserted into pCMV-Myc vector to construct the recombinant plasmid.The recombinant plasmid was transfected into 293 cells using lipofectamine 2000.The protein expression and the intracellular location of the inserted gene were confirmed by Western blotting and immunofluorescence,respectively.Scratch-repair experiment was used to detect the cancer cells’ migration ability.Results The recombinant eukaryotic expression plasmid of human CAP1 was successfully constructed and transfected into eukaryote cells.The recombinant plasmid was successfully expressed in eukaryote cells.CAP1 was located in the cytoplasm.The results of scratch-repair experiment showed that the overexpression of CAP1 could significantly inhibit the cells’ migration.Conclusion CAP1 recombinant plasmid was successfully expressed in eukaryotic cells.CAP1 protein was located in the cytoplasm.The overexpression of CAP1 inhibited cell migration. The present study provides important experimental evidence for further study on CAP1.