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.

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.

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 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.

OBJECTIVE: To detect pathogenic variant in a juvenile with severe type Cornelia de Lange syndrome (CdLS). METHODS: A 12-year-old female presented with comprehensive developmental retardation and deformity of lower limbs. Genomic DNA was extracted from peripheral blood sample of the patient. Whole exome sequencing was performed to identify pathogenic variants. Putative variant was verified by Sanger sequencing. The impact of variants was predicted and validated by bioinformatic analysis. RESULTS: A de novo missense variant, c.1507A>G (p. Lys503Glu), was found in the NIPBL gene of the proband. The variant was unreported previously and predicted to be pathogenic by PolyPhen-2, MutationTaster and SIFT. Using HomoloGene system, the 503 loci in the NIPBL protein are highly conserved. The change of amino acid (Glu), locating in 503 locus, was found to cause the Neuromodulin_N superfamily domain destroyed, resulting in severe damage to the function of NIPBL protein. CONCLUSION The de novo missense variant c.1507A>G (p. Lys503Glu) of the NIPBL gene probably underlies the disease in this patient.
Cell Cycle Proteins ; genetics ; Child ; De Lange Syndrome ; genetics ; Developmental Disabilities ; genetics ; Female ; Humans ; Mutation, Missense ; Phenotype

Objective: To evaluate the efficacy of lung cancer screening in urban areas of Henan province by low-dose computed tomography (LDCT) from 2013 to 2017. Methods: A cluster sampling method was used to select the residents of 40-74 years old in Henan province to investigate the risk factors and conduct lung cancer risk assessment. Subjects with high risk of lung cancer received LDCT for screening. Results: A total of 179 002 residents completed the lung cancer risk assessment, and 35 672 subjects were identified as high risk of lung cancer, with a high risk rate of 19.93%. A total of 13 383 subjects with high risk received LDCT, and the screening rate was 37.52%. There were 786 cases diagnosed as positive nodules, and the detection rate was 5.87%. Among them, 755 cases of solid/partial solid nodule were ≥5 mm, 23 cases of non-solid nodules were ≥8 mm, 8 cases were intratracheal nodules, and 115 cases were diagnosed as suspicious lung cancer. The detection rate in males was 6.74%, which was higher than 5.02% in females. The detection rate was positively related with age (P<0.05). Conclusions The application of LDCT is a useful screening method which can elevate the early detection rate of positive nodules and other related diseases in lungs. In the future, males and older populations should be paid more attention to improve screening efficacy.

Objective:To evaluate the compliance of low-dose computed tomography (LDCT) screening for high-risk groups of lung cancer and influencing factors in urban area of Henan province during 2013-2017.Methods:Cluster sampling method was used to select the residents of 40-74 years old in Henan for cancer risk factor investigation and lung cancer risk assessment. Subjects with high risk of lung cancer received LDCT screening. The differences of LDCT receiving rates between groups were compared with χ2 tests, and the time trend of rates were tested with the Cochran- Armitage trend test. The potential factors correlating to the compliance of LDCT screening were identified with multivariate logistic regression models. Results:Overall, 35 672 participants who met the inclusion criteria were included in this analysis, and 13 383 of them received LDCT screening, the receiving rate was 37.52%. The receiving rate varied greatly across cities, ranging from 38.47% to 26.73% ( P<0.05). Moreover, the receiving rate varied greatly across periods, ranging from 29.22% during 2013-2014 to 43.30% during 2014-2015, and the receiving rate increases gradually as the screening year increases ( P<0.001). The multivariate logistic regression analyses showed that: being female, age 45-69 years, with education level of junior high school/high school, previous smoking, drinking or previous drinking, infrequent physical exercise, history of tuberculosis, history of chronic bronchitis, history of emphysema, history of asthma bronchiectasis and family history of lung cancer were positive factors for receiving LDCT screening (All P<0.05). Conclusions:The overall compliance of LDCT screening in high-risk population of lung cancer was still not high in urban area of Henan. Implementation of effective interventions targeting the specific high-risk populations might improve the overall compliance of LDCT screening in the future.