Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Objective:To investigate the association between triglyceride-glucose (TyG) index and all-cause mortality in elderly patients with hypertension and coronary artery disease.Methods:This was a retrospective cohort study, a total of 5 640 elderly inpatients (≥65 years) with hypertension and coronary artery disease who were admitted to the Department of Cardiology, Liberation Army General Hospital from August 2008 to July 2018 were enrolled in this study. The baseline clinical data of the patients were collected and the TyG index was calculated. Patients were divided into four groups according to their TyG index quartiles: TyG index<8.31 ( Q1 group, n=1 392), 8.31≤TyG index<8.67 ( Q2 group, n=1 417), 8.67≤TyG index<9.07 ( Q3 group, n=1 427), and TyG index≥9.07 ( Q4 group, n=1 404). All patients were followed up by obtaining outpatient/rehospitalization records or by telephone. The primary endpoint was all-cause mortality. Log-rank test was used to compare the cumulative all-cause mortality among groups. Cox proportional hazard regression model was used to analyze the risk of all-cause mortality in each group (the Q2 group with the lowest all-cause mortality was used as a reference), after adjusting for confounding factors, Restricted cubic spline analysis (RCS) was used to determine the association between TyG index and risk of all-cause mortality. Results:During a follow-up of 6.44 (4.70, 8.85) years, 1 037 all-cause deaths (18.39 %) were documented. The cumulative all-cause mortality in Q1- Q4 groups was 16.52%, 16.51%, 17.59% and 22.93%, respectively, and the difference was statistically significant ( χ2=26.49, P<0.01). In the Cox regression model, compared with Q2 group (reference), the HR (95% CI) for all-cause mortality was 1.06 (0.88-1.28) in the Q1 group, 1.23 (1.02-1.48) in the Q3 group and 1.48 (1.23-1.77) in the Q4 group, respectively ( P for trend<0.01). RCS curve analysis showed that when the TyG index was greater than 8.67, the risk of all-cause mortality increased with the TyG index, and there was a linear relationship between TyG index and all-cause mortality in this patient cohort (non-linearity P=0.31). Conclusion:The elevated TyG index is significantly associated with a higher risk for all-cause mortality in elderly hypertension and coronary artery disease patients.

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.

Objective To prepare 4-sulfonylcalix[6]arene-modified cotton fibers for adsorption and removal of uranium based on the specific complexation of calix[6]arene with uranium (VI). Methods Chemical grafting was used for the modification of cotton, which reacted with α-bromoisobutyryl bromide, glycidyl methacrylate, and 4-sulfonylcalix[6]arene. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and infrared spectroscopy (FTIR) were used to characterize the structure of 4-sulfonylcalix[6]arene-modified cotton (Cotton S-C[6]a). A Franz diffusion cell was used to simulate uranium-contaminated skin. Laser fluorimetry was used to determine the uranium content. Results SEM, XPS, and FTIR showed that cotton fibers were successfully grafted with 4-sulfonylcalix[6]arene. The optimal conditions of Cotton S-C[6]a for the adsorption of uranium (VI) was pH 4.0, duration of 20 min, and 20 mg of adsorbent. The adsorption process fitted well with pseudo-secondary-order kinetics. The uranium removal efficiency of Cotton S-C[6]a was up to 78.46% in aqueous solution and 81.72% on skin. Conclusion The synthesized Cotton S-C[6]a is highly efficient in the removal of uranium (VI) in solution and on contaminated skin.

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 dendritic cells (DCs)-mediated antigen presentation for radiation-injured cells by using the in vitro cell co-culture technology to simulate the in vivo microenvironment of the lung tissue. Methods ⁶⁰Co γ-irradiated mouse lung epithelial cells (MLE-12) were cultured with bone marrow-derived DCs and/or splenic T lymphocytes for 48 hours. Flow cytometry was used to measure the expression levels of costimulatory molecules (CD80/86) and antigenic peptide recognition complexes (the major histocompatibility complex [MHC] class Ⅰ/Ⅱ) on DCs and T cell activation markers (CD69/28/152) as well as the numbers of CD4⁺ and CD8⁺ T cells. Results ⁶⁰Co γ irradiation significantly increased the apoptosis rate of MLE-12 cells in a dose-dependent manner, and significantly stimulated the expression of CD80/86 and MHC Ⅱ on DCs, without direct activation of T cells. After γ (6 Gy)-irradiated MLE-12 cells were co-cultured with DCs and T lymphocytes for 48 h, there were significant increases in the expression of CD69 and CD28 on T cells, the numbers of CD4⁺ and CD8⁺ T cells, and the expression of CD86 and MHC I on DCs, as compared with the control groups. Conclusion Radiation-injured cells can stimulate antigen presentation by DCs and activate T cells.

Objective To investigate the role of complement in radiation-induced lung injury in mice after chest irradiation with ⁶⁰Co γ-rays at a single dose of 20 Gy. Methods C57BL/6 mice underwent chest irradiation with ⁶⁰Co γ-rays at a single dose of 20 Gy, followed by observation for the inflammatory reaction of the lung tissue in the early stage (within 15 d) and pulmonary fibrosis in the later stage (30 and 180 d). Enzyme-linked immunosorbent assay was used to measure the levels of C2, C3a, C4, and C5b-9 in the lung tissues at 1, 3, 7, 15, 30, and 180 d after irradiation. The expression of complement mRNA in BEAS-2B cells after irradiation was determined using RT-PCR. Results Radiation-induced lung injury in micepresented as inflammatory response in the early stage and fibrosis in the late stage. Complement C2, C4, and C5b-9 complexes were increased in the early period (3 or 7 d) after irradiation (P < 0.05), which might be associated with the inflammatory response induced by irradiation. During 3 to 180 d, complement C3a was significantly higher in the irradiated mice than in the control mice, suggesting a close relationship between C3a and radiation-induced lung injury. The irradiated cells showed increased mRNA expression of C2 and C3, with no changes in the mRNA levels of C4 and C5. Conclusion Different complement proteins have varying responses to radiation-induced lung injury, among which C3a is closely related to radiation-induced lung injury, suggesting that regulating C3a and its receptors may be a new way to prevent and treat radiation-induced lung injury.

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 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.