BACKGROUND: Leukocyte telomere length (LTL) shortening, a biomarker of telomere attrition, has been linked to multiple diseases. However, the relationship between LTL and digestive diseases remains uncertain. This study aimed to investigate the association between LTL and the risk of digestive diseases. METHODS: A cohort analysis of over 500,000 participants from the UK Biobank (UKB) between 2006 and 2021 was conducted to estimate the associations of LTL with more than 90 common digestive diseases. LTL was quantified using multiplex quantitative polymerase chain reaction, and cases of each disease were determined according to inpatient and primary care data. Multivariable Cox proportional hazards regression analysis was used to evaluate the associations of LTL with the risk of digestive diseases. Furthermore, such associations were also evaluated after stratification by sex and ethnicity. RESULTS: After a mean follow-up time of 11.8 years, over 20 International Classification of Diseases, 10th Revision ( ICD-10 ) codes were showed to be associated with telomere attrition. LTL shortening is associated with an increased risk of several digestive diseases, including gastroesophageal reflux disease (K21: hazard ratio [HR] = 1.30, 95% confidence interval [95% CI]: 1.19-1.42), esophageal ulcer (K221: HR = 1.81, 95% CI: 1.22-2.71), Barrett's esophagus (K227: HR = 1.58, 95% CI: 1.14-2.17), gastritis (K29: HR = 1.39, 95% CI: 1.26-1.52), duodenal ulcer (K26: HR = 1.55, 95% CI: 1.14-2.12), functional dyspepsia (K30X: HR = 1.36, 95% CI: 1.06-1.69), non-alcoholic fatty liver disease (NAFLD) (K760: HR = 1.39, 95% CI: 1.09-1.78), liver cirrhosis (K74: HR = 4.73, 95% CI: 3.27-6.85), cholangitis (K830: HR = 2.55, 95% CI: 1.30-5.00), and hernia (K43: HR = 1.50, 95% CI: 1.17-1.94; K44: HR = 1.29, 95% CI: 1.17-1.42). The risk of rectal polyps (K621: HR = 0.77, 95% CI: 0.63-0.92) decreased per unit shortening of LTL. CONCLUSIONS This study suggests that LTL shortening is associated with an increased risk of most digestive diseases except for rectal polyps. These findings may provide some clues for understanding the pathogenesis of digestive diseases.
Humans ; Male ; Female ; Middle Aged ; Cohort Studies ; Leukocytes/metabolism* ; Telomere/genetics* ; Proportional Hazards Models ; Adult ; Digestive System Diseases/genetics* ; Aged ; Risk Factors ; Telomere Shortening

Background/Aims: Galectin-3 plays a key pathogenic role in cardiac hypertrophy and heart failure. The present study aimed to investigate the effects of galectin-3 on cardiomyopathy – related factors and cardiac contractility in a rat model of cirrhotic cardiomyopathy. Methods: Rats were divided into two sets, one for a functional study, the other for cardiac contractile-related protein evaluation. There were four groups in each set: sham operated and sham plus N-acetyllactosamine (N-Lac, a galectin-3 inhibitor; 5 mg/kg); bile duct ligated (BDL) and BDL plus N-Lac. Four weeks after surgery, ventricular level of galectin-3, collagen I and III ratio, tumor necrosis factor alpha (TNFα), and brain natriuretic peptide (BNP) were measured either by Western blots or immunohistochemistry or enzyme-linked immunosorbent assay. Blood pressure was measured by polygraph recorder. Cardiomyocyte contractility was measured by inverted microscopy. Results: Galectin-3 and collagen I/III ratio were significantly increased in cirrhotic hearts. TNFα and BNP were significantly increased in BDL serum and heart compared with sham controls. Galectin-3 inhibitor significantly decreased galectin-3, TNFα, and BNP in cirrhotic hearts but not in sham controls. N-Lac also significantly improved the blood pressure, and systolic and diastolic cardiomyocyte contractility in cirrhotic rats but had no effect on sham controls. Conclusion Increased galectin-3 in the cirrhotic heart significantly inhibited contractility via TNFα. Inhibition of galectin-3 decreased the cardiac content of TNFα and BNP and reversed the decreased blood pressure and depressed contractility in the cirrhotic heart. Galectin-3 appears to play a pathogenic role in cirrhotic cardiomyopathy.

Nonselective beta-adrenergic blocker (NSBB) therapy for the prevention of initial and recurrent gastrointestinal bleeding in cirrhotic patients with gastroesophageal varices has been used for the past four decades. NSBB therapy is considered the cornerstone of treatment for varices, and has become the standard of care. However, a 2010 study from the group that pioneered β-blocker therapy suggested a detrimental effect of NSBBs in decompensated cirrhosis, especially in patients with refractory ascites. Since then, numerous additional studies have incompletely resolved whether NSBBs are deleterious, although more recent evidence weighs against a harmful effect. The possibility of a “therapeutic window” has also been raised. We aimed to review the literature to analyze the pros and cons of using NSBBs in patients with cirrhosis, not only with respect to bleeding or mortality but also to other potential benefits and risks. β-blockers are highly effective in preventing first bleeding and recurrent bleeding. Furthermore, NSBBs improve congestion/ischemia of the gut mucosa, decrease intestinal permeability, and therefore indirectly alleviate systemic inflammation. β-blockers shorten the electrocardiographic prolonged QTc interval and may also decrease the incidence of hepatocellular carcinoma. On the other hand, the possibility of deleterious effects in cirrhosis has not been completely eliminated. NSBBs may be associated with an increased risk of portal vein thrombosis, although this could be correlational artifact. Overall, we conclude that β-blockers in cirrhosis are much more of a friend than enemy.

Nonselective beta-adrenergic blocker (NSBB) therapy for the prevention of initial and recurrent gastrointestinal bleeding in cirrhotic patients with gastroesophageal varices has been used for the past four decades. NSBB therapy is considered the cornerstone of treatment for varices, and has become the standard of care. However, a 2010 study from the group that pioneered β-blocker therapy suggested a detrimental effect of NSBBs in decompensated cirrhosis, especially in patients with refractory ascites. Since then, numerous additional studies have incompletely resolved whether NSBBs are deleterious, although more recent evidence weighs against a harmful effect. The possibility of a “therapeutic window” has also been raised. We aimed to review the literature to analyze the pros and cons of using NSBBs in patients with cirrhosis, not only with respect to bleeding or mortality but also to other potential benefits and risks. β-blockers are highly effective in preventing first bleeding and recurrent bleeding. Furthermore, NSBBs improve congestion/ischemia of the gut mucosa, decrease intestinal permeability, and therefore indirectly alleviate systemic inflammation. β-blockers shorten the electrocardiographic prolonged QTc interval and may also decrease the incidence of hepatocellular carcinoma. On the other hand, the possibility of deleterious effects in cirrhosis has not been completely eliminated. NSBBs may be associated with an increased risk of portal vein thrombosis, although this could be correlational artifact. Overall, we conclude that β-blockers in cirrhosis are much more of a friend than enemy.

Objective: To explore the relationship between different serum albumin and lymphocyte levels in patients with 2019-novel coronavirus (2019-nCoV) pneumonia (COVID-19). Methods: A retrospective study was performed to identify the characteristics of the clinical data of 205 COVID-19 patients who were hospitalized in the Happy Street of Hanchuan People's Hospital, Xiaogan, Hubei Province from January 24 to February 12, 2020, including their general information, serum albumin (ALB) levels, lymphocyte counts (LYM), percentage of lymphocytes (LYM%) and other laboratory parameter levels. Low ALB group and normal ALB group were demarcated by the concentration of 35g/L, further to identify the differences of LYM and LYM% levels and the incidence of LYM and LYM% decline at different ALB levels between groups,as well as the correlation between ALB and LYM, LYM% levels in hypoalbuminemia conditions . Results: 17.5% of COVID-19 patients were associated with hypoalbuminemia. The levels of LYM and LYM% in the low ALB group were significantly lower than those in the normal ALB group (P <0.001). The incidence of LYM and LYM% decline in the low ALB group was significantly higher than those in the normal ALB group (P <0.001). The levels of LYM and LYM% in the low ALB group were significantly positively correlated with serum ALB concentrations (P <0.05). Conclusions The decrease of lymphocyte levels in COVID-19 patients may be correlated to hypoalbuminemia. COVID-19 patients complicated by hypoalbuminemia should be actively intervened to maintain serum albumin in the normal range.

Objective:To investigate the features, changing trend, and rules of pneumoconiosis in Jiangsu Province, China, as well as the health status of patients with pneumoconiosis.Methods:From July to October 2019, the patients with pneumoconiosis, reported up to the end of 2018 in Jiangsu Province, were enrolled as respondents, and follow-up and retrospective investigation were performed. A total of 24405 patients with pneumoconiosis were investigated, and related data were collected from the monitoring system of cause of death for residents, pneumoconiosis network reporting system, occupational disease diagnosis institution, management institutions for the reporting of occupational diseases, and related residents' committee or village committee. The patients with pneumoconiosis, who had been reported, were followed up by telephone or on-site visit to obtain the information on their conditions. A descriptive analysis was performed for age of onset, working years, sex, category of industry, type of pneumoconiosis, annual disease onset, geographic distribution, and medical security.Results:Among the 24405 patients, a male/female ratio was 16.81∶1. Of all 24405 patients, 15948 (65.35%) had stage 1 pneumoconiosis, 5289 (21.67%) had stage 2 pneumoconiosis, and 1637 (6.71%) had stage 3 pneumoconiosis. The mean working years for dust exposure was 16.25±9.95 years for all patients, and the mean working years for dust exposure was 15.80±9.95 years for patients with stage 1 pneumoconiosis, 17.82±9.80 years for patients with stage 2 pneumoconiosis, and 16.31±9.90 years for patients with stage 3 pneumoconiosis. The highest number of cases of pneumoconiosis was reported in Wuxi (5744 cases, accounting for 23.54%) , followed by Zhenjiang (4160 cases, accounting for 17.05%) , Xuzhou (3851 cases, accounting for 15.78%) , Yancheng (3340 cases, accounting for 13.69%) , and Suzhou (2948 cases, accounting for 12.08%) . Major types of pneumoconiosis included silicosis (15392 cases, accounting for 63.07%) and coal workers' pneumoconiosis (5253 cases, accounting for 21.52%) . In this survey, 21115 completed follow-up, among whom 15924 survived and 5191 died, 15924 patients with pneumoconiosis survived, among whom 7461 (46.85%) had an age of ≥70 years and 2515 (15.79%) were exposed to dust for 5-9 years. The industries involved were mainly coal mining and washing industry (5687 cases, accounting for 35.71%) and public management, social security, and social organization (3349 cases, accounting for 21.03%) ; in terms of security, 7999 patients (50.23%) were covered by occupational injury insurance, 946 (5.94%) were compensated by employers, 4537 (28.49%) were covered by basic medical insurance for urban and rural residents, 1590 (9.98%) were covered by critical illness insurance, and 5458 (34.28%) were covered by other types of social security, such as medical assistance and poverty relief.Conclusion:Silicosis and coal worker's pneumoconiosis are the key points for the prevention and treatment of pneumoconiosis in Jiangsu Province, and supervision should be strengthened for industries and regions with serious dust hazards.

Objective:To investigate the features, changing trend, and rules of pneumoconiosis in Jiangsu Province, China, as well as the health status of patients with pneumoconiosis.Methods:From July to October 2019, the patients with pneumoconiosis, reported up to the end of 2018 in Jiangsu Province, were enrolled as respondents, and follow-up and retrospective investigation were performed. A total of 24405 patients with pneumoconiosis were investigated, and related data were collected from the monitoring system of cause of death for residents, pneumoconiosis network reporting system, occupational disease diagnosis institution, management institutions for the reporting of occupational diseases, and related residents' committee or village committee. The patients with pneumoconiosis, who had been reported, were followed up by telephone or on-site visit to obtain the information on their conditions. A descriptive analysis was performed for age of onset, working years, sex, category of industry, type of pneumoconiosis, annual disease onset, geographic distribution, and medical security.Results:Among the 24405 patients, a male/female ratio was 16.81∶1. Of all 24405 patients, 15948 (65.35%) had stage 1 pneumoconiosis, 5289 (21.67%) had stage 2 pneumoconiosis, and 1637 (6.71%) had stage 3 pneumoconiosis. The mean working years for dust exposure was 16.25±9.95 years for all patients, and the mean working years for dust exposure was 15.80±9.95 years for patients with stage 1 pneumoconiosis, 17.82±9.80 years for patients with stage 2 pneumoconiosis, and 16.31±9.90 years for patients with stage 3 pneumoconiosis. The highest number of cases of pneumoconiosis was reported in Wuxi (5744 cases, accounting for 23.54%) , followed by Zhenjiang (4160 cases, accounting for 17.05%) , Xuzhou (3851 cases, accounting for 15.78%) , Yancheng (3340 cases, accounting for 13.69%) , and Suzhou (2948 cases, accounting for 12.08%) . Major types of pneumoconiosis included silicosis (15392 cases, accounting for 63.07%) and coal workers' pneumoconiosis (5253 cases, accounting for 21.52%) . In this survey, 21115 completed follow-up, among whom 15924 survived and 5191 died, 15924 patients with pneumoconiosis survived, among whom 7461 (46.85%) had an age of ≥70 years and 2515 (15.79%) were exposed to dust for 5-9 years. The industries involved were mainly coal mining and washing industry (5687 cases, accounting for 35.71%) and public management, social security, and social organization (3349 cases, accounting for 21.03%) ; in terms of security, 7999 patients (50.23%) were covered by occupational injury insurance, 946 (5.94%) were compensated by employers, 4537 (28.49%) were covered by basic medical insurance for urban and rural residents, 1590 (9.98%) were covered by critical illness insurance, and 5458 (34.28%) were covered by other types of social security, such as medical assistance and poverty relief.Conclusion:Silicosis and coal worker's pneumoconiosis are the key points for the prevention and treatment of pneumoconiosis in Jiangsu Province, and supervision should be strengthened for industries and regions with serious dust hazards.

Objective: To study the main factors that influencing Pneumoconiosis patients' healthcare seeking behaviors. Methods: Conducting a descriptive analysis to analyze the relationship between the annual hospitalization rate and social security status (medical insurance, location of medical insurance, proportion of insurance used for reimbursement of pneumoconiosis, whether there is employment injury insurance at work, whether to apply for compensation after diagnosing pneumoconiosis, whether they receive social assistance and a minimum allowance) , social relationship status of patients (whether there is pneumoconiosis in the family or relatives, whether there is a pneumoconiosis in a friend or a colleague, and whether or not he/she has received financial assistance) , life quality of patients (subjective feelings) and living standard of patients (dietary level) based on data acquired from 120 pneumoconiosis patients. Results: The results of single factor analysis reveal that the location of medical insurance, the proportion of insurance for reimbursement of pneumoconiosis, whether there is employment injury insurance at work, whether to apply for compensation after diagnosing pneumoconiosis are statistically significant in pneumoconiosis patients' hospital utilization ratio (P<0.05) . The place where medical insurance is located is the current place of residence, the reimbursement ratio of medical insurance for pneumoconiosis is listed as 50%-70%, the work unit has medical insurance, those who have not applied for compensation for pneumoconiosis have a higher utilization rate of hospitalization services. The annual hospitalization rate was 73.3%, 80.0%, 60.6%, 63.0%, respectively. Conclusion The location of patient medical insurance, the proportion of insurance used for reimbursement of pneumoconiosis, whether there is employment injury insurance at work, and whether to apply for compensation after pneumoconiosis are the influencing factors of the patients' annual hospitalization rate.

Objective: To understand the situation and characteristics of out-patient utilization of urban and rural pneumoconiosis patients in Jiangsu province, and to provide a reference for the formulation of relevant policies. Methods: Using a questionnaire on patients with pneumoconiosis and their influencing factors, 120 patients with pneumoconiosis were randomly selected in Nanjing, Wuxi, Suzhou, Yancheng Vocational Defense Institute or CDC. The rate of outpatients with pneumoconiosis in urban and rural areas and the choice of out-patient hospitals were analyzed. Results: Of the 75 patients with severe pneumoconi-related symptoms such as chest tightness and dyspnea in the first two weeks of the survey, 36 (48.0%) lived in cities and 39 (52.0%) lived in rural areas. Patients with pneumoconiosis who live in urban and rural areas have different aggravating conditions within two weeks. Two weeks of aggravated symptoms in outpatient consultations accounted for36 (48.0%) . Of the 36 patients who used outpatient treatment, rural residents mainly chose 8 people from a hospital and a township health hospital, accounting for 34.8%, while 10 people from urban residents chose a nursing home or nursing home, accounting for 40.0%. The main reason why urban and rural pneumoconiosis patients did not go to the doctor is "conscious symptoms are lighter" and "feel that the doctor is useless." Conclusion The rate of outpatients with pneumoconiosis in Jiangsu province within two weeks is lower than that of ordinary elderly residents. There may be differences in treatment behavior patterns of urban and rural pneumoconiosis patients.Economic factors have a certain influence on the outpatient treatment behavior of pneumoconiosis patients. The recognition of outpatient service is the main factor affecting the outpatient treatment of pneumoconiosis patients. It is very important to popularize the knowledge of pneumoconiosis and do a good job in propaganda of occupational diseases and health education for pneumoconiosis patients. Focusing on the outpatient treatment of pneumoconiosis patients and making targeted medical policies is very important to standardize and improve the rehabilitation of pneumoconiosis patients.

Carenoprazan has the similar structure and mechanism with the potassium-competitive blocker vonoprazan. Howerver, its safety during the pregnancy remains uncertain. To study the embryo-fetal development toxicity and toxicokinetics of carenoprazan hydrochloride via oral administration, time-mated Sprague-Dawley rats were divided into 5 groups, treated with normal saline, cyclophosphamide for injection(3. 8 mg/kg), and carenoprazan hydrochloride(20, 60, 200 mg/kg), respectively. Administrated orally from gestation day(GD)6 - 15. At the termination(GD 20), pregnant dams were sacrificed, and concentrations of carenoprazan hydrochloride as well as its metabolite in plasma and issues of both maternal and fetus were examined. As a result, the body weight gain of maternal in both high(200 mg/kg)and medium(60 mg/kg)dose as well as the food consumption of high-dose were decreased during GD 10-16. At the high dose group, decrease of crown rump length of fetuses were significant. Also, skeletal malformation/variations of fetus increased obviously at both high- and medium- dosage. The toxcicokinetics of carenoprazan hydrochloride are linear after single treatment between 20-200 mg/kg. The placental barrier was penetrated by carenoprazan hydrochloride and metabolite, and the distribution of metabolite in organs were similar in both maternal and fetus, with the highest concentration in livers. Therefore might resulted in the development toxicity. The No Observed Adverse Effect Level(NOAEL)of carenoprazan hydrochloride for both maternal and fetal was 20 mg/kg.