Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

ObjectiveTo investigate and explore the characteristics and influencing factors of glucose metabolism in children with β-thalassemia major （β-TM） after allogeneic hematopoietic stem cell transplantation （allo-HSCT）. MethodsThe follow-up data of 41 patients with β-TM who underwent HSCT at Hematopoietic Stem Cell Transplantation Department of Children's Medical Center of Sun Yat-sen Memorial Hospital， Sun Yat-sen University were retrospectively analyzed. Their glucose metabolism characteristics were evaluated through laboratory tests and the related influencing factors were analyzed. ResultsIn the study， 41.46% （17/41） of patients developed abnormal glucose homeostasis after HSCT. Among them， 82.35% （14/17） characterized by insulin resistance， but no cases of diabetes mellitus were found. The results of insulin releasing test and oral glucose tolerance test（OGTT） showed that 45.00% （9/20） of patients had abnormal insulin releasing curve and 40.0% （8/20） had delayed serum glucose peak. The average age of HSCT in abnormal glucose homeostasis group was significantly older than that in the normal glucose homeostasis group ［（8.8±3.9） years old vs （6.0±3.1） years old， P=0.015］. ConclusionsPatients with β-TM after HSCT may develop abnormal glucose homeostasis， consists largely of insulin resistance. The elder age of HSCT （≥7 years old） is a risk factor for abnormal glucose homeostasis in β-TM patients after HSCT. It is recommended to regularly monitor glucose metabolism indicators in β-TM children after HSCT， especially in elderly transplant recipients.

ObjectiveTo explore the clinical features and causative genes of short stature children with unknown etiology， providing evidence for precise clinical diagnosis and treatment. MethodsThe study recruited children with suspected but undiagnosed short stature from the pediatric endocrinology department in our hospital between January 2018 and August 2022. A retrospective analysis was performed on the clinical manifestations， laboratory test and whole exome sequencing （WES） results. Causative genes were classified and analyzed according to different pathogenic mechanisms. ResultsA total of 48 children （30 boys and 18 girls） were enrolled， aged 7.73 ± 3.97 years， with a height standard deviation score （ HtSDS） of -3.63 ± 1.67. Of the patients， 33 （68.8%） suffered from facial anomalies， 31 （64.6%） from skeletal abnormalities， 26 ［54.2%， 61.5% of whom born small for gestational age （SGA）］ from perinatal abnormalities， 24 ［50.0%， 87.5% of whom with growth hormone （GH） peak concentration below normal］ from endocrine disorders and 21（43.8%） had a family history of short stature. Laboratory tests showed that GH peak concentration following stimulation test was （9.72 ± 7.25） ng/mL， IGF-1 standard deviation score was -0.82 ± 1.42， the difference between bone age and chronological age was -0.93 ± 1.39 years. Of the 25 cases with mutant genes found by WES， 14 （56.0%） had pathogenic mutation， 6 （24.0%） likely pathogenic mutation， and 5 （20.0%） mutation of uncertain significance. Pathogenic and likely pathogenic variants were identified in 14 genes， including 10 affecting intracellular signaling pathways （PTPN11， RAF1， RIT1， ARID1B， ANKRD11， CSNK2A1， SRCAP， CUL7， SMAD4 and FAM111A） and 4 affecting extracellular matrix （ECM） components or functions （ACAN， FBN1， COL10A1 and COMP）. ConclusionsA rare monogenic disease should be considered as the possible etiology for children with severe short stature accompanied by facial anomalies， disproportionate body types， skeletal abnormalities， SGA， GH peak concentration below normal and a family history of short stature. WES played an important role in identifying the monogenic causes of short stature. This study indicated that affecting growth plate cartilage formation through intracellular signaling pathways and ECM components or functions was the main mechanism of causative genes leading to severe short stature in children. Further research may help discover and study new pathogenic variants and gene functions.

Cholelithiasis, a prevalent disease of the digestive system, is characterized by its intricate and diverse mechanisms, which are influenced by a complex interplay of genetic, environmental, lifestyle, and other factors. Recently, with the widespread application of molecular biology techniques, the role of the biliary tract microecological environment in the pathogenesis of gallstones has garnered increasing attention. This review includes the most recent and pertinent literature on the association between biliary tract microecology and gallstones, summarizing the latest research advancements in this field. Furthermore, it delves into the role of the biliary tract microecology in the formation of both cholesterol and pigment gallstones.

Objective:To evaluate the compliance rate and its impact factors of liver cancer screening for high-risk groups in urban areas of Henan Province from 2013 to 2019.Methods:Residents of 40-74 years old in 8 cities of Henan province were selected to investigate the risk factors and liver cancer risk assessment. Subjects with high risk of liver cancer received AFP combined ultrasonography for screening. Chi-square tests were used to compare the differences in liver cancer screening participation rates between groups. Multivariate logistic regression models were applied to explore the potential factors correlating to the compliance of liver cancer screening.Results:Overall, 3 6781 participants who met the inclusion criteria were included in this analysis, and 17 241 of them took the following liver cancer screening, yielding a participation rate of 46.87%. The participation rate varied greatly across cities, ranging from 62.50% to 38.59%. Moreover, the participation rate varied greatly across periods, ranging from 52.77% in 2014-2015 to 38.14% in 2013-2014. The multivariate Logistic regression analyses showed that: female, older, high education degree, cigarette and alcohol intake, infrequent physical exercise, chronic hepatitis B, chronic hepatitis C, fatty liver, gallstones and a family history of liver cancer were inclined to accept liver cancer screening ( P<0.05). Conclusions:The overall participation rate of liver cancer screening among high-risk population is less than 50% in urban areas of Henan Province. Implement of effective interventions targeting the specific high-risk populations might improve the overall compliance rate of liver cancer screening in the future.

Objective:To evaluate the compliance of colonoscopy screening and the detection rate of colorectal lesions with colonoscopy in urban areas of Henan province from 2013 to 2019.Methods:The study objects were derived from the Cancer Screening Program in Urban Henan Province, China. From October 2013 to October 2019, 282 377 residents, who had lived in the local area for more than three years, were recruited from Zhengzhou, Zhumadian, Anyang, Luoyang, Nanyang, Jiaozuo, Puyang and Xinxiang. The cancer risk assessment questionnaire was used to collect basic demographic characteristics, eating habits, living environment and habits, psychology and emotions, past disease history and family history of cancer, and women′s physiological and reproductive history. The cancer risk assessment model was used for evaluating the risk of colorectal cancer. The data related to colonoscopy screening was obtained from the participating hospitals. Chi-square test was used to analyze the compliance rate among different groups.Results:The 282 377 subjects were (55.26±8.68) years old, of which 44.80% (126 505) were males, and 67.63% (190 694) had junior/senior/tertiary education background. A total of 39 834 (14.11%) subjects were assessed to be at high risk for colorectal cancer, of which 7 454 took the following colonoscopy screening, yielding a participation rate of 18.71%. The screening rate was higher in those aged 50 to 54 (20.42%) and 55 to 59 (20.43%) years, and lowest in those aged 70 years and older (12.30%) ( P<0.001). A total of 17 colorectal cancer cases were detected, with a detection rate of 0.23% (17/7 454). Conclusion:Colonoscopy as a means of screening for colorectal cancer is helpful for early detection of colorectal lesions, but the participation rate is poor.

Objective:To evaluate the compliance rate and its impact factors of liver cancer screening for high-risk groups in urban areas of Henan Province from 2013 to 2019.Methods:Residents of 40-74 years old in 8 cities of Henan province were selected to investigate the risk factors and liver cancer risk assessment. Subjects with high risk of liver cancer received AFP combined ultrasonography for screening. Chi-square tests were used to compare the differences in liver cancer screening participation rates between groups. Multivariate logistic regression models were applied to explore the potential factors correlating to the compliance of liver cancer screening.Results:Overall, 3 6781 participants who met the inclusion criteria were included in this analysis, and 17 241 of them took the following liver cancer screening, yielding a participation rate of 46.87%. The participation rate varied greatly across cities, ranging from 62.50% to 38.59%. Moreover, the participation rate varied greatly across periods, ranging from 52.77% in 2014-2015 to 38.14% in 2013-2014. The multivariate Logistic regression analyses showed that: female, older, high education degree, cigarette and alcohol intake, infrequent physical exercise, chronic hepatitis B, chronic hepatitis C, fatty liver, gallstones and a family history of liver cancer were inclined to accept liver cancer screening ( P<0.05). Conclusions:The overall participation rate of liver cancer screening among high-risk population is less than 50% in urban areas of Henan Province. Implement of effective interventions targeting the specific high-risk populations might improve the overall compliance rate of liver cancer screening in the future.

Objective:To evaluate the compliance of colonoscopy screening and the detection rate of colorectal lesions with colonoscopy in urban areas of Henan province from 2013 to 2019.Methods:The study objects were derived from the Cancer Screening Program in Urban Henan Province, China. From October 2013 to October 2019, 282 377 residents, who had lived in the local area for more than three years, were recruited from Zhengzhou, Zhumadian, Anyang, Luoyang, Nanyang, Jiaozuo, Puyang and Xinxiang. The cancer risk assessment questionnaire was used to collect basic demographic characteristics, eating habits, living environment and habits, psychology and emotions, past disease history and family history of cancer, and women′s physiological and reproductive history. The cancer risk assessment model was used for evaluating the risk of colorectal cancer. The data related to colonoscopy screening was obtained from the participating hospitals. Chi-square test was used to analyze the compliance rate among different groups.Results:The 282 377 subjects were (55.26±8.68) years old, of which 44.80% (126 505) were males, and 67.63% (190 694) had junior/senior/tertiary education background. A total of 39 834 (14.11%) subjects were assessed to be at high risk for colorectal cancer, of which 7 454 took the following colonoscopy screening, yielding a participation rate of 18.71%. The screening rate was higher in those aged 50 to 54 (20.42%) and 55 to 59 (20.43%) years, and lowest in those aged 70 years and older (12.30%) ( P<0.001). A total of 17 colorectal cancer cases were detected, with a detection rate of 0.23% (17/7 454). Conclusion:Colonoscopy as a means of screening for colorectal cancer is helpful for early detection of colorectal lesions, but the participation rate is poor.

Objective:To study the compliance of endoscopic screening for high-risk population of upper gastrointestinal cancer and relevant factors in urban areas of Henan Province, 2013-2017.Methods:The study participants were from the Cancer Screening Program in Urban Henan Province, China. From October 2013 to October 2017, 43 423 residents, who were evaluated as high-risk population for upper gastrointestinal cancer, were recruited from Zhengzhou, Zhumadian and Anyang. The cancer risk assessment questionnaire was used to collect basic demographic characteristics, dietary habits, living environment and habits, psychology and emotions, disease history and family history of cancer, and women's physiological and reproductive history. The data of endoscopic screening was obtained from hospitals participating in the Cancer Screening Program. Multivariate logistic regression model was applied to explore potential factors related to the compliance of endoscopic screening.Results:The age of study participants was(55.49±8.15) years old, and 44.00% (19 105) were male. About 18.41% of study subjects (7 996) took the endoscopic screening. The multivariate logistic regression analysis showed that females, individuals aged 45-64 years old, with junior high school education or above, unmarried/divorced/widowed, previous smoking, alcohol drinking, infrequent physical exercise, history of reflux esophagitis, history of superficial gastritis, history of gastric ulcer, history of duodenal ulcer, history of gastric polyps and family history of upper gastrointestinal cancer were more likely to accept endoscopic screening.Conclusion:The overall participation rate of endoscopic screening among high-risk population of upper gastrointestinal cancer was still low in urban areas of Henan Province. Gender, age, education, marital status, smoking, alcohol consumption, physical activity, history of upper gastrointestinal disease and family history of upper gastroin testinal cancer were associated with the compliance of endoscopic screening.

OBJECTIVE: To analyze pathogenic variant of CSNK2A1 gene in a boy with Okur-Chung neurodevelopmental syndrome (OCNS). METHODS: The 8-year-old boy presented with growth retardation, intellectual disability and spells of breath holding. With genomic DNA extracted from peripheral blood samples of the patient and his parents, whole exome sequencing was carried out. Putative pathogenic variants were verified with Sanger sequencing. The nature and impact of detected variants were predicted through bioinformatic analysis. RESULTS: A novel de novo missense variant c.149A>G (p.Tyr50Cys) of the CSNK2A1 gene was identified, which was unreported previously. The variant was predicted to be pathogenic by PolyPhen-2, Mutation Taster and SIFT software. Based on a HomoloGene system, 50 loci within the CK2alpha protein are highly conserved. The change of amino acid (Cys) at position 50 has destroyed the ATP binding loop domain, causing serious damage to its function. As predicted by a Swiss PDB viewer, the variant can significantly alter the spatial structure of CK2alpha, resulting in loss of protein function. CONCLUSION The patient's condition may be attributed to the novel de novo missense variant c.149A>G (p.Tyr50Cys) of the CSNK2A1 gene.