[Cancer survival analysis in Tianjin, 2010 to 2016].

Objective: Survival analysis of cancers' incidence data in Tianjin from 2010 to 2016 was conducted to provide the basis for formulating and evaluating regional health policies on cancer prevention and treatment. Methods: Registration data in Tianjin were used between January 1, 2010 to December 31, 2016 and patients were followed-up till 31 December, 2021. Life-table method was used to calculate the observed survival rate and Edered Ⅱ was used to calculate the relative survival rate. The data were stratified by year, gender, age group and cancer sites. Difference in survival curves between group was analyzed by Kaplan-Meier method and Log rank test. Joinpoint regression model was used to analyze the trend change. Results: The 5-year relative survival rates of cancer were 41.92% to 53.65% from 2010 to 2016 for residents in Tianjin, with an increasing trend (t=4.81, P=0.005), and the average was 48.56%. The survival rate of females was higher than that of males (57.71%vs. 39.20%), and the survival rate of urban residents was higher than that of rural residents (49.38% vs. 47.24%). The 5-year relative survival rates were 63.14%, 78.39%, 58.25% and 32.67% in 0-14, 15-44, 45-64 and 65 and above age groups, respectively. The median relative survival times of all cancer were 2.34 to 6.00 years from 2010 to 2016 in Tianjin, with an increasing trend (t=3.86, P=0.012). The average of median relative survival times was 4.11 years. The median survival time of females was longer than that of males (11.99 years vs. 2.03 years), and the time of urban residents were longer than that of rural residents (4.60 years vs. 3.43 years). The median relative survival time were 12.07, 11.92 and 1.34 years in 15-44, 45-64 and 65 and above age groups, respectively. Conclusions: The cumulative survival rate of cancer increased significantly from 2010 to 2016 in Tianjin, indicating that the prevention and treatment effect of cancer is obvious. The focus should be on male, rural areas, higher age group, and targeted prevention and treatment measures should be taken to lung, esophagus, liver, gallbladder and pancreatic cancer.

[Endovascular therapy accompanied by spontaneous portosystemic shunts for overt hepatic encephalopathy].

Objective: To preliminarily evaluate the safety and efficacy of shunt-related interventional therapy accompanied with spontaneous portosystemic shunts (SPSS) in patients with hepatic encephalopathy (HE). Methods: Case data on six patients who underwent interventional therapy accompanied by SPSS for HE from January 2017 to March 2021 were collected to evaluate the efficacy and postoperative complications. Results: All six patients underwent SPSS. Four patients had hepatitis B cirrhosis; one had alcoholic cirrhosis; and one had hepatic arterioportal fistula-induced portal hypertension. Child-Pugh liver function scores were C and B in three and three cases, respectively. The SPSS type was gastrorenal shunt in two cases; portal-thoracic-azygos venous in two cases; portal-umbilical-iliac venous in one case; and portal-splenic venous - inferior vena cava in one case. Two of them had previously had a transjugular intrahepatic portosystemic shunt (TIPS), and there were SPSS prior to TIPS. Five cases (5/6) successfully underwent shunt embolization, and one case (1/6) underwent stent implantation for flow restriction (portal-umbilical-iliac vein). The technical success rate was 100%. HE did not recur during hospitalization or the three-month follow-up period. However, one case had a recurrence of HE within a year after surgery and was treated symptomatically, while another experienced gastrointestinal bleeding a year after surgery.. Conclusion: SPSS embolization or flow restriction is effective and safe for improving HE patients' symptoms.

[Study on increase of average life expectancy of residents in Tianjin from 1999 to 2018].

Objective: To assess the trend and the factors responsible for the increase of life expectancy of residents in Tianjin over the past two decades. Methods: Abridged Life Table and Arriaga's decomposition method was applied to quantify the influence of the age structure and the leading causes of death on the increase of life expectancy of residents in Tianjin from 1999 to 2018. Results: In the past 20 years, the life expectancy of residents in Tianjin increased by 4.97 years, the life expectancy of men and women increased by 4.11 years and 5.86 years, respectively. The decrease of mortality rate in 0-year-old group contributed 19.17% to the increase of the life expectancy, while the decrease of mortality rate in residents aged ≥55 years contributed more to the increase of life expectancy, with the cumulative contribution rate of 67.38%. The major contribution to the increase of life expectancy was the mortality reduction of cerebrovascular disease, respiratory disease, cardiovascular disease, perinatal diseases, congenital malformations and injury, with the contribution percentage of 27.27%, 21.37%, 15.76%, 12.22%, 6.44% and 4.86%, respectively. The increase of mortality of malignant tumor, injury and poisoning, diabetes and nervous system diseases and others had a negative effect on the increase of life expectancy of people aged ≥75 years. From 1999 to 2018, the life expectancy increased from 76.72 years to 81.46 years (t=9.11, P<0.001), the annual percent change (APC) was 0.58%. From 2011 to 2018, it was stable, ranging from 81.46 years to 81.69 years (t=0.89, P=0.387, APC=0.13%). Conclusion: From 1999 to 2018, the increase of life expectancy was attributed to the decrease of mortalities in infants and the elderly and the decrease of mortalities of cerebro-cardiovascular disease, respiratory disease, perinatal disease, congenital malformations and injury. However, these positive contributions were partly offset by the negative contribution of malignant tumor, injury, diabetes and nervous system disease in those aged ≥75 years. Comprehensive prevention and control of key diseases should be strengthened in key population in order to further improve the life expectancy of the population.

[Study on the diet balance index and its relationship with blood uric acid of smoking adults in Tianjin].

Objective: Diet balance index (DBI_16) was used to evaluate the dietary status of smoking adults in Tianjin, and the relationship between DBI_16 and serum uric acid was analyzed. Methods: A total of 1 478 inhabitants aged 18 and above were enrolled. The dietary status was obtained with a 3-day dietary recall and condiment weighing method. And their fasting venous blood was collected to detect uric acid. Food intake and DBI_16 scores of smokers and non-smokers were described, and the relationship among smoking, diet quality distance (DQD-DBI), and serum uric acid was analyzed. Results: The intake of vegetables, fruits, and milk of smokers in Tianjin was lower than while the salt, oil, cereals, and aquatic products were higher than that of non-smokers. The DBI_16 scores of vegetables and fruits, food types, milk, and beans of smokers were lower than those of non-smokers in Tianjin, and the scores of pure energy foods and condiments were higher than those of the non-smokers. The DQD-DBI, high bound score and low bound score of smokers in Tianjin were 42.0, 14.0, and 29.0 respectively, which were all higher than those of non-smokers. The main problems appeared as moderately inadequate intake (accounting for 67.0%), low, excessive intake (accounting for 70.9%), and moderate imbalance of intake (accounting for 67.2%). The serum uric acid of smokers was higher than in the non-smokers, and there the same result appeared under the conditions of "not suitable" in DQD-DBI. Conclusions: In Tianjin, the dietary imbalance was more evident in smokers than the non-smokers, and the serum uric acid was significantly higher than the non-smokers. Strategies as strengthening the nutrition education and intervention targeted for smokers were in urgent need.

[Study of influence of birth weight on risk of chronic diseases and blood uric acid in adulthood].

Objective: To understand the influence of birth weight on the risk of chronic diseases, such as hypertension and diabetes, and the relationship between birth weight and serum uric acid in adulthood. Methods: According to the Chinese Adult Chronic Disease and Nutrition Surveillance Program, a total of 1 131 residents aged 18 years and above were enrolled from Hexi, Nankai, Hongqiao, Wuqing, Jinnan, Baodi and Jizhou districts of Tianjin. The data of birth weight and blood pressure of the residents were collected, and fasting venous blood samples were collected from them to detect uric acid, blood glucose and blood lipids levels. The distribution of birth weight of the surveyed population was described, and the relationship between birth weight and chronic diseases, such as hypertension and diabetes, and the blood uric acid level in adulthood were analyzed. Results: The average birth weight of the surveyed population in Tianjin was 3.37 kg, which was higher in males than in females. No matter overweight/obesity, hypertension or diabetes, the prevalence rate of normal birth weight was the lowest in adulthood. After univariate logistic regression analysis and adjusting for age, sex, smoking and drinking status, it was found that compared with normal birth weight, low birth weight had a stronger correlation with diabetes (OR=2.91,95%CI:1.46-5.76) and dyslipidemia (OR=1.79,95%CI:1.01-3.19) in adulthood. Macrosomia was strongly associated with overweight/obesity in adulthood (OR=1.47, 95%CI:1.08-2.01). There was no significant difference in serum uric acid level among the residents with different birth weights. Conclusions: The low birth weight of the surveyed population in Tianjin was closely related to the risk of diabetes and dyslipidemia in adulthood, and the macrosomia was closely related to the risk of overweight/obesity in adulthood.

[Analysis on long-term trend of mortality and years of life lost of breast cancer in women in Tianjin, 1999-2017].

Objective: To analyze the trends of mortality and years of life lost (YLL) of breast cancer in women in Tianjin and provide references for the development of intervention strategies. Methods: The crude mortality rate, standard mortality rate, cumulative rate (0-74 years old) and truncated rate (35-64 years old) of breast cancer in women in Tianjin from 1999 to 2017 were calculated. The annual percentage change of the mortality rate and YLL rate were analyzed by Joinpoint regression. Results: From 1999 to 2017, a total of 8 356 deaths of breast cancer were reported in Tianjin, resulting in a YLL of 262 835.53 person-years. The average crude mortality rate was 9.15/100 000. The average age standardized rate(ASR) (World) was 6.14/100 000. The ratio of ASR (World) between urban and rural areas was 1.73∶1. The peak mortality ratio of age groups between urban area and rural area was 3.13∶1. From 1999 to 2017, both the crude mortality rate and ASR of breast cancer in Tianjin had rising trends. In 2017, the crude mortality rate and the ASR of breast cancer increased by 113.7% and 44.4% respectively compared with 1999. The increase of urban mortality mainly came from elderly group aged ≥75 years, and the mortality of young age groups in rural area showed an fast increases, which was most obvious in age group 45-59 years (average annual percentage change=3.6%, P<0.01). Conclusions: The mortality rate of breast cancer and disease burden in women in Tianjin are still in rapid increase. We should continue to implement the prevention and control strategies such as lifestyle intervention and screening of key groups. More attention need to be paid to the increase of breast cancer incidence in rural area.

[Analysis of the long-term trend of mortality and years of life lost of gastric cancer in Tianjin from 1999 to 2015].

Objective: To analyze the long-term trend of mortality and years of life lost (YLL) of gastric cancer in Tianjin from 1999 to 2015. Methods: From January 1, 1999 to December 31, 2015, the data of gastric cancer deaths was collected from the Tianjin death surveillance system. The inclusion criteria of death due to gastric cancer were coded by using 151 in the 9(th) edition of the international classification of diseases (ICD) (1999-2002) and C16 in the 10(th) edition of ICD (2003-2015). The crude and age-standardized mortality rate (ASR) of gastric cancer was calculated according to Segi's world standard population. YLL was calculated according to the standard method of the disease burden of WHO. The Joinpoint regression was used to calculate the average annual percentage change (AAPC) to indicate the trend of mortality and YLL of gastric cancer. Results: From 1999 to 2015, there were 20 000 deaths of gastric cancer in Tianjin. The proportion of gastric cancer death in the population aged 0-44 years old, 45-64 years old, and 65 years old and above was 4.9%, 30.4%, and 64.8%, respectively. The proportion of males and urban was 67.1% and 67.5%, respectively. From 1999 to 2015, the crude mortality rate was from 12.10/100 000 to 12.58/100 000. The ASR was from 11.04/100 000 to 7.24/100 000. The average annual YLL number was 29 625.83 person-years and the rate was 3.09 person-years per thousand people. From 1999 to 2015, the crude mortality rate and the PYLL of gastric cancer in Tianjin were stable (the AAPC was 0.34% and -0.24%, all P values >0.05). The ASR showed a downward trend (AAPC=-2.58%, P<0.001). Conclusion: From 1999 to 2015, the ASR of gastric cancer in Tianjin showed a downward trend, and the YLL of gastric cancer was stable.

[Status quo on smoking and related change pattern of smoking related behavior in past 20 years in urban residents in Tianjin].

Objective: To understand the status quo of smoking and change pattern of smoking related behaviors in the past 20 years in the urban adults in Tianjin. Methods: Data was from the study of Chinese Chronic Disease and Risk Factors (2015). Multi stage stratified random sampling method was used to conduct a questionnaire survey in 7 surveillance sites in Tianjin. Results: in the urban residents aged>20 years were compared with those in surveys in 1996 and 2010. Results In 2015, the smoking rate in men and women aged>20 years in Tianjin were 41.1% and 4.5% respectively. The average age of starting smoking was (19.2±4.7) years for men and (24.8±10.9) years for women, showing a younger age trend. Compared with the data from 1996 and 2010, the smoking rate in the urban residents was in decrease, but the rate of successful smoking cessation was in increase in 2015, the differences were significant. Conclusions: Since 1996, the rate of smoking in the urban residents of Tianjin has been in decline, however it is still at a high level, especially in women. The average age of starting smoking remains to be younger. It is necessary to strengthen the health education about harm of smoking in adolescents.

[Analysis on long-term trends of cervical cancer mortality and years of life lost in Tianjin, 1999-2015].

Objective: To analyze the mortality and years of life lost (YLL) trends of cervical cancer in Tianjin, and provide references for the research and prevention programs of cervical cancer. Methods: Mortality rate, standard mortality rate, cumulative rate (0-74 years-old) and truncated rate (35-64 years-old) of cervical cancer from 1999 to 2015 were calculated. The annual percentage change of the mortality rate and YLL rate were analyzed by using Joinpoint regression analysis, and the trend in different age-groups were analyzed. Results: From 1999 to 2015, 1 741 cases died of cervical cancer in Tianjin, the average crude mortality rate was 2.15/100 000. The average age-standardized rate of (ASR) China and ASR world were 1.47/100 000 and 1.50/100 000 respectively. The average YLL was 3 347.97 person-years. Deaths occurred in those aged 0-34 years, 35-64 years and 65 years and over accounted for 3.10%, 57.84% and 39.06% of the total, respectively. The mortality rate of cervical cancer in urban area was higher than that in rural area, with a ratio of 1.37∶1 between urban area and rural area. The age-specific mortality rate of cervical cancer during 1999-2015 increased with age. Two peaks of mortality rate were observed in those aged 50 years and aged 75 years, during 2014-2015. From 1999 to 2011, the mortality rate of cervical cancer was stable (APC=-0.2%, P=0.80), but there was a rapid increase from 2011 to 2015 (APC=21.6%, P<0.01). But group aged 20-49 years, it showed an upward trend from 1999 to 2015 (APC=6.9%, P<0.01). For group aged 50-69 years, it showed a downward trend from 1999 to 2007 (APC=-9.2%, P<0.01), and an upward trend from 2007 to 2015 (APC=14.5%, P<0.01). For group aged 70 years and over, it showed a downward trend from 1999 to 2009 (APC=-10.2%, P<0.01), but the difference in the mortality were not significant from 2009 to 2015 (APC=7.8%, P=0.10). Since 2008, the YLL rate of cervical cancer in group aged 50-70 years had exceeded that in group aged >70 years and the gap gradually widened. Conclusions: There had been a rapid increase trend of cervical cancer mortality since 2011 in Tianjin. Women aged 50-70 years were the main group of life loss.

[Bioinformatics analysis of microRNA comprehensive regulatory network in B- cell acute lymphoblastic leukemia].

OBJECTIVE: To reveal the involvement of molecules in the pathogenesis of B-cell acute lymphoblastic leukemia (B-ALL) by bioinformatics analyses. METHODS: The microarray data of B-ALL were downloaded from the Gene Expression Omnibus (GEO) database and Qlucore Omics Explorer software was used to screen differentially expressed miRNA. Based on the differentially expressed miRNAs, we predicted the target genes, long non-coding RNAs (lncRNA) and transcription factors (TFs). Then we constructed the miRNAs-centered comprehensive regulatory network. In addition, we performed functional enrichment analysis to analyze the functions of target genes. RESULTS: Of all the 15 differentially expressed miRNAs, 7 miRNAs were of overexpression, 8 miRNAs underexpressed. From the miRNAs comprehensive regulatory network, we found that hsa-miR-486-3p and hsa-miR-126 regulated a large number of target genes, hsa-miR-126 including target genes MYC. The hsa-miR-29a, hsa-miR-130a and hsa-miR-181c regu- lated a lot of lncRNAs containing X-inactive-specific transcript (XIST). The hsa-miR-181a-2, hsa-miR- 181b-2 and hsa-miR-663 were regulated by a host of TFs including caudal- related homeobox transcription fact2 (CDX2). Additionally, the target genes of has-miR-126 were enriched in Wnt pathways. CONCLUSIONS: The expression of hsa-miR-29a , hsa-miR-126 and has-miR-181 family were significantly different in B-ALL. Target gene of MYC, TFs of CDX2 and lncRNA of XIST may play important roles in the development of B-ALL, serving as a potential therapeutic target.

Retinoic acid biosynthesis by normal human breast epithelium is via aldehyde dehydrogenase 6, absent in MCF-7 cells.

Retinoic acid (RA) is the form of vitamin A that controls differentiation and proliferation of epithelia. Our previous work established that normal breast epithelia synthesize RA from retinol, an ability retained by three immortalized but nontumorigenic cell lines but lost in five of six breast cell lines. In this work, we characterize the cause of this defect in one of the lines, the MCF-7 line. We have determined that the immortalized but nontumorigenic cell line, MTSV1.7, capable of synthesizing RA from both retinol and retinal, contains a retinaldehyde dehydrogenase activity for the second step in RA biosynthesis. We have identified it, after isolation, as a previously described enzyme, aldehyde dehydrogenase 6 (ALDH6). Immunohistochemical analysis of normal human breast with antibodies to ALDH6 showed expression of this enzyme in the glandular epithelia colocalized with cellular RA-binding protein type II, a possible marker for certain cells able to synthesize RA. ALDH6 was not present in MCF-7 cells, and these cells were unable to oxidize retinal to RA in culture. When MCF-7 cells were then transfected with ALDH6, they (re)gained the ability to oxidize retinal to RA as well as some ability to synthesize RA when provided with retinol. This suggests that loss of ALDH6 expression is the defect in RA biosynthesis in these cells. Identification of ALDH6 as the retinaldehyde dehydrogenase present in normal human breast epithelia provides the first tool necessary for studying the loss of RA synthetic ability in cancer cells and the relationship of this process to malignant transformation.

Retinol conversion to retinoic acid is impaired in breast cancer cell lines relative to normal cells.

The bioactivity of retinol (vitamin A) is in part dependent on its metabolism to retinoic acid (RA). We investigated the ability of breast epithelial cells to synthesize RA when challenged with a physiological retinol dose (2 microM). Normal human mammary epithelial cells (HMEC) cultured from reduction mammoplasties were competent in RA synthesis and the ability to synthesize RA was retained by immortal, nontumorigenic breast epithelial cell lines (MTSV1.7, MCF-10F, and 184B5). In contrast, most (five of six) breast cancer cell lines could not synthesize RA or did so at low rates relative to normal cells. A notable exception was the MDA-MB-468 cell line, which was fully competent in RA synthesis. Most (>/=68%) of the RA synthesized by breast cells was recovered from the culture medium. Cellular retinol binding protein and cellular RA binding protein II, both expressed in HMEC, had various expression patterns in the cell lines that did not correlate with the observed differences in RA synthesizing ability. Strong RA induction of the RA hydroxylase P450RAI (CYP26) was confined to ERalpha-positive T47D and MCF-7 breast cancer cells and did not appear to explain the lack of detectable RA levels in these cells since RA remained undetectable when the cells were treated with 5-10 microM liarozole, a P450RAI inhibitor. We hypothesize that retinol bioactivity is impaired in breast cancer cells that cannot synthesize RA. In preliminary support of this hypothesis, we found that retinol (0.5-2 microM) inhibited MCF-10F but not T47D or MCF-7 cell growth.

Cellular retinoic acid-binding protein(II) presence in rat uterine epithelial cells correlates with their synthesis of retinoic acid.

Vitamin A (retinol) and retinoic acid are necessary for the maintenance of the female reproductive system of higher animals. Our previous work has demonstrated cell specific expression of cellular retinoic acid-binding protein (CRABP) and cellular retinoic-acid binding protein(II) [CRABP(II)] in the uterus of the rat. CRABP(II) expression was shown to be induced in the uterine surface epithelial cells by treatment of prepubertal rats with pregnant mare serum gonadotropin (PMSG). Here we report that, after PMSG treatment, collected uteri had markedly higher levels of retinoic acid than did the uteri of prepubertal rats treated with the control vehicle. Smooth muscle, stromal, and epithelial cells were then cultured from uteri from such animals and provided with retinol or with the retinol/retinol-binding protein complex. Retinoic acid production, analyzed by high-performance liquid chromatography, was observed for the epithelial cells from the uteri of prepubertal animals treated with PMSG, cells previously shown to express CRABP(II) and confirmed here to continue to express it in culture. Little or no retinoic acid was produced by cultured epithelial cells from the prepubertal uteri [shown previously to be negative for CRABP(II)] or by smooth muscle and stromal cells taken from uteri of prepubertal or PMSG-treated rats (shown previously to express CRABP). Retinoic acid production by uterine epithelial cells [and CRABP(II) expression] was also observed if the prepubertal rat was treated with estrogen before cell collection. At no time did cells expressing CRABP exhibit significant retinoic acid synthesis. Thus, this system revealed an important difference in retinoid metabolism between cells expressing CRABP and CRABP(II) and suggests CRABP(II) may participate in retinoic acid production and/or secretion.

Regulation and localization of cellular retinol-binding protein, retinol-binding protein, cellular retinoic acid-binding protein (CRABP), and CRABP II in the uterus of the pseudopregnant rat.

Three members of the superfamily of small intracellular carrier proteins for lipophilic compounds are cellular retinol-binding protein (CRBP), cellular retinoic acid-binding protein (CRABP), and cellular retinoic acid-binding protein II (CRABP II). Retinol-binding protein (RBP) is a secreted protein that binds and solubilizes vitamin A for transport. Here we report the coordinate regulation of RBP, CRBP, retinol, and CRABP II in the uterus of the pseudopregnant rat. In the proliferative stage of the uterus, which was induced by PMSG, the messenger RNA (mRNA) and protein levels of RBP and CRBP as well as retinol levels significantly decreased. This pattern of regulation was duplicated by estrogen treatment of prepubertal rats. In addition, CRBP and RBP were found to be colocalized to the stromal cells of the rat uterus by immunohistochemistry and [35S]methionine-labeled affinity chromatography, respectively, and were not detected in other cell populations. CRABP II mRNA and protein expression were up-regulated in the proliferative phase of the uterus brought about by PMSG injection or, alternatively, by estrogen treatment of prepubertal rats. CRABP II was localized to the surface epithelium, but was not seen elsewhere, including glandular epithelium. Immunolocalization of CRABP showed staining of the smooth muscle and stromal cells of the uterus. The appearance of CRABP in the stroma of the uterus also correlated with PMSG injection as well as estrogen treatment. Although estrogen induced the appearance of both binding proteins, CRABP mRNA levels peaked between 4-24 h postestrogen treatment, whereas CRABP II mRNA levels continued to rise 48 h postestrogen treatment. These data demonstrate an important role for vitamin A and retinoid-binding proteins in rat uterine physiology.

[Preliminary chromosomal localization of cloned DNA fragments from a highly metastatic human giant cell carcinoma of lung].

By using DNA transfecting and molecular cloning techniques, a 2.3 kb DNA fragment was isolated and subcloned into pUC-18 to generate pLC-2. Chromosome in situ hybridization was conducted between biotin-labelled pLC-2 and PG cell's chromosomes and the cloned gene fragment of 2.3 kb was preliminarily localized.