Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.

Objective:To investigate the role of dynamic changes in liver stiffness measurement (LSM) in predicting liver-related end-point events (LREs) occurrence in patients with chronic hepatitis B (CHB) with liver fibrosis during long-term antiviral therapy.Methods:Data were collected from CHB patients whose liver biopsy results showed Metavir fibrosis stage F2～F4 or clinically diagnosed cirrhosis. Entecavir antiviral therapy was mainly administered. Follow-up was conducted once every six months. Clinical data such as demographic information, blood routine tests, liver biochemical parameters, HBV virological and serological test results, and LSM were collected. Dynamic changes in LSM were categorized into four types based on LSM levels before treatment (0y) and following two years of antiviral therapy (2y) : (1) LSM 0y < 10 kPa and LSM 2y < 10 kPa, i.e., LSM persisted < 10 kPa; (2) LSM 0y < 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM increased to ≥ 10 kPa; (3) LSM 0y ≥ 10 kPa and LSM 2y < 10 kPa, i.e., LSM decreased to < 10 kPa; (4) LSM 0y ≥ 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM persisted ≥ 10 kPa. The predictive role of the dynamic changes of LSM in the occurrence of LREs was analyzed. The Wilcoxon rank-sum test was used for quantitative data. Fisher's exact test was used for categorical data. Multivariate analysis was performed using the Cox proportional hazards regression model. Survival curves were plotted and compared using the Kaplan-Meier. Results:A total of 713 CHB cases with liver fibrosis were included, among whom 512 had cirrhosis. The cumulative incidence of LREs following two years of antiviral therapy was low in patients with LSM 0y < 10 kPa during follow-up (all patients: LSM persisted < 10 kPa 1.6% vs. LSM increased to ≥ 10 kPa 0%; cirrhosis subgroup: LSM persisted < 10 kPa 0% vs. LSM increased to ≥ 10 kPa 0%). The 5-year cumulative incidence of LREs following two years of antiviral treatment was significantly higher in patients with LSM0y ≥ 10 kPa than in those with LSM persisting ≥ 10 kPa and those with LSM decreasing to < 10 kPa during follow-up (all patients: LSM persisted ≥ 10 kPa 12.4% vs. LSM decreased to < 10 kPa 3.6%; cirrhosis subgroup: LSM persisted ≥ 10 kPa 12.6% vs. LSM decreased to < 10 kPa 4.3%). Patients with LSM persisting at ≥ 10 kPa had a significantly increased risk of LREs following two years of antiviral treatment compared with those whose LSM decreased to <10 kPa during follow-up after adjusting for age, gender, baseline body mass index, platelet count, and alanine aminotransferase (all patients, aHR=2.96, 95% CI: 1.41～6.24, P=0.005; cirrhosis subgroup, aHR=2.74, 95% CI:1.26～5.95, P=0.011). Conclusions:LSM<10 kPa before antiviral treatment had a lower risk of liver-related endpoint events following two years of treatment among CHB patients with liver fibrosis. LSM ≥10 kPa before antiviral treatment and LSM persisted ≥10 kPa two years following treatment had a significantly higher occurrence risk of liver-related endpoints than LSM<10 kPa following treatment among CHB patients with liver fibrosis.

[Objective]To analyze the clinical characteristics,efficacy of growth hormone(GH)therapy,and follow-up of a child with Rauch-Steindl syndrome(RAUST)caused by NSD2 gene mutation,aiming to enhance pediatricians'understanding of this disorder.[Methods]We summarized the clinical features,gene test results,outcomes of GH therapy,and follow-up data of a child with RAUST syndrome caused by NSD2 mutation admitted to the Pediatric Endocrinology Department of Sun Yat-sen Memorial Hospital in April 2017,and then conducted a comparative analysis with relevant literature.[Results]The 2.9-year-old boy at initial visit was born prematurely at 36 weeks of gestation,with a birth weight of 1.7 kg and a body length of 42.0 cm.Clinical manifestations included intrauterine growth retardation,delayed language and motor development,extreme short stature(82.0 cm,-3.7 SD),emaciation,and distinctive facial features(triangular face,narrow jaw,prominent forehead,arched eyebrows,sparse eyebrows,high anterior hairline,crowded dentition),accompanied by bilateral cryptorchidism.Bone age was delayed by 1.4 years.Karyotyping and chromosomal microarray analysis were normal.GH therapy initiated at 3.8 years old yielded annual growth rates of 4.9-6.6 cm/year.When the treatment was discontinued at the age of 8.0,the boy's height was 113.7 cm(-3.0 SD),with subsequent decline in growth velocity.Whole exome sequencing in July 2024 identified a frameshift variant c.4028del(p.Pro1343Glnfs*49)in NSD2,which was confirmed as de novo pathogenic variation by parental Sanger sequencing.[Conclusions]This study reports the clinical features of RAUST syndrome caused by NSD2 mutation and explores the long-term efficacy of GH therapy.The findings contribute to a better understanding of this rare syndrome and further optimize its diagnosis and management.

In modern society, sugary foods have become an integral part of many people′s lives. However, excessive sugar consumption has adverse effects on both overall health and oral health, serving as a contributing factor to the global increasing incidence in oral diseases, cardiovascular diseases, cancers, obesity, and diabetes. In response to the health risks related to high-sugar diets, the World Health Organization (WHO) and World Dental Federation (FDI) have proposed initiatives and recommendations, with various governments implementing different policies and strategies to reduce sugar intake. Chinese government has also taken proactive measures. The "Healthy China Action (2019-2030)" initiative introduced by the State Council in 2019 established a crucial benchmark in limiting the average daily intake of added sugar to 25 g per person forward to 2030. Experts from Chinese Center for Disease Control and Prevention and the field of oral health have meticulously examined the impacts of sugar reduction on oral health, as well as strategies, methods, and practical considerations related to reducing sugar intake through several meeting and wrote the "Expert consensus: reducing free-sugar for caries prevention", which was subsequently reviewed and revised based on the feedback from multiple stakeholders. They have conducted thorough analyses of global trends in sugar reduction and best practices to provide valuable insights to China for crafting effective policies and strategies on sugar reduction. This consensus mainly includes the classification of free sugars, the latest scientific evidence on dental caries, recommendations from WHO on sugar-sweetened beverage taxes, nutrition labeling, advertising, food reform, adjusting supply systems, education, and promotion strategies, as well as sugar reduction actions taken by various governments around the world. Combining the actual situation in China, policy recommendations and authoritative popular science knowledge on sugar reduction for caries prevention to public are proposed to advocate for experts in multiple fields to focus on sugar reduction for caries prevention, promote the work process, and provide the scientific basis for oral health educators.

ObjectiveTo investigate the value of Fried Frailty Phenotype （FFP）， liver frailty index （LFI）， and Short Physical Performance Battery （SPPB） in predicting 2-year all-cause mortality and decompensation events in patients with liver cirrhosis. MethodsA total of 277 patients with liver cirrhosis who were hospitalized in Beijing Friendship Hospital， Capital Medical University， from December 2020 to December 2021 were enrolled， and FFP， LFI， and SPPB were used to assess the state of frailty. Based on the scores of each tool， these patients were divided into frail and non-frail groups. These three tools were compared in terms of consistency and independent predictive performance. The primary endpoints were 2-year all-cause mortality rate and composite endpoints （death+decompensation events）， and the Cox regression analysis， the receiver operating characteristic （ROC） curve， net reclassification index （NRI）， and integrated discrimination improvement （IDI） index were used to analyze the predictive value of the three tools. Normally distributed continuous data were compared between two groups using the independent samples t-test， while non-normally distributed continuous data were compared using the Mann-Whitney U test. Categorical data were compared between groups using the chi-square test or Fisher’s exact test. The agreement among different frailty tools was evaluated using Cohen’s Kappa statistic. The Kaplan-Meier survival curve was plotted， and a survival analysis was performed using the log-rank test. ResultsThe prevalence rate of frailty assessed by FFP， LFI， and SPPB was 37.2%， 22.4%， and 20.2%， respectively， with a moderate consistency between FFP and LFI/SPPB （κ=0.57， 95% confidence interval ［CI］： 0.47 — 0.67； κ=0.51， 95%CI： 0.41 — 0.62） and a relatively high consistency between LFI and SPPB （κ=0.87， 95%CI： 0.80 — 0.94）. Compared with the non-frailty group， the frailty group had significantly higher all-cause mortality rate and incidence rate of composite endpoints （P0.001）. After multivariate adjustment， FFP， LFI， and SPPB had a hazard ratio of 2.42（95%CI： 1.51 — 5.11）， 2.21（95%CI： 1.11 — 4.42）， and 2.21（95%CI： 1.14 — 4.30）， respectively， in predicting all-cause mortality， as well as a hazard ratio of 2.51（95%CI： 1.61 — 3.91）， 2.40（95%CI： 1.51 — 3.80）， and 2.20（95%CI： 1.39 — 3.47）， respectively， in predicting composite endpoints. Compared with Child-Pugh score， FFP had a significantly greater area under the ROC curve （AUC） in predicting all-cause mortality （0.79 vs 0.69， P=0.032） and composite endpoints （0.75 vs 0.68， P=0.044）. Frailty assessment tools combined with Child-Pugh score significantly improved the performance in predicting all-cause mortality and composite endpoints， with an AUC of 0.81 — 0.82 and 0.77 — 0.78， respectively （P0.05）. NRI and IDI analyses further confirmed the improvement of the combined model in classification （all P0.001）. ConclusionFFP， LFI， and SPPB can independently predict adverse outcomes in patients with liver cirrhosis， among which FFP has the best predictive performance， and the combination of frailty assessment tools with Child-Pugh score can significantly enhance the accuracy of prognostic evaluation.

Objective:To investigate the role of dynamic changes in liver stiffness measurement (LSM) in predicting liver-related end-point events (LREs) occurrence in patients with chronic hepatitis B (CHB) with liver fibrosis during long-term antiviral therapy.Methods:Data were collected from CHB patients whose liver biopsy results showed Metavir fibrosis stage F2～F4 or clinically diagnosed cirrhosis. Entecavir antiviral therapy was mainly administered. Follow-up was conducted once every six months. Clinical data such as demographic information, blood routine tests, liver biochemical parameters, HBV virological and serological test results, and LSM were collected. Dynamic changes in LSM were categorized into four types based on LSM levels before treatment (0y) and following two years of antiviral therapy (2y) : (1) LSM 0y < 10 kPa and LSM 2y < 10 kPa, i.e., LSM persisted < 10 kPa; (2) LSM 0y < 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM increased to ≥ 10 kPa; (3) LSM 0y ≥ 10 kPa and LSM 2y < 10 kPa, i.e., LSM decreased to < 10 kPa; (4) LSM 0y ≥ 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM persisted ≥ 10 kPa. The predictive role of the dynamic changes of LSM in the occurrence of LREs was analyzed. The Wilcoxon rank-sum test was used for quantitative data. Fisher's exact test was used for categorical data. Multivariate analysis was performed using the Cox proportional hazards regression model. Survival curves were plotted and compared using the Kaplan-Meier. Results:A total of 713 CHB cases with liver fibrosis were included, among whom 512 had cirrhosis. The cumulative incidence of LREs following two years of antiviral therapy was low in patients with LSM 0y < 10 kPa during follow-up (all patients: LSM persisted < 10 kPa 1.6% vs. LSM increased to ≥ 10 kPa 0%; cirrhosis subgroup: LSM persisted < 10 kPa 0% vs. LSM increased to ≥ 10 kPa 0%). The 5-year cumulative incidence of LREs following two years of antiviral treatment was significantly higher in patients with LSM0y ≥ 10 kPa than in those with LSM persisting ≥ 10 kPa and those with LSM decreasing to < 10 kPa during follow-up (all patients: LSM persisted ≥ 10 kPa 12.4% vs. LSM decreased to < 10 kPa 3.6%; cirrhosis subgroup: LSM persisted ≥ 10 kPa 12.6% vs. LSM decreased to < 10 kPa 4.3%). Patients with LSM persisting at ≥ 10 kPa had a significantly increased risk of LREs following two years of antiviral treatment compared with those whose LSM decreased to <10 kPa during follow-up after adjusting for age, gender, baseline body mass index, platelet count, and alanine aminotransferase (all patients, aHR=2.96, 95% CI: 1.41～6.24, P=0.005; cirrhosis subgroup, aHR=2.74, 95% CI:1.26～5.95, P=0.011). Conclusions:LSM<10 kPa before antiviral treatment had a lower risk of liver-related endpoint events following two years of treatment among CHB patients with liver fibrosis. LSM ≥10 kPa before antiviral treatment and LSM persisted ≥10 kPa two years following treatment had a significantly higher occurrence risk of liver-related endpoints than LSM<10 kPa following treatment among CHB patients with liver fibrosis.

[Objective]To analyze the clinical characteristics,efficacy of growth hormone(GH)therapy,and follow-up of a child with Rauch-Steindl syndrome(RAUST)caused by NSD2 gene mutation,aiming to enhance pediatricians'understanding of this disorder.[Methods]We summarized the clinical features,gene test results,outcomes of GH therapy,and follow-up data of a child with RAUST syndrome caused by NSD2 mutation admitted to the Pediatric Endocrinology Department of Sun Yat-sen Memorial Hospital in April 2017,and then conducted a comparative analysis with relevant literature.[Results]The 2.9-year-old boy at initial visit was born prematurely at 36 weeks of gestation,with a birth weight of 1.7 kg and a body length of 42.0 cm.Clinical manifestations included intrauterine growth retardation,delayed language and motor development,extreme short stature(82.0 cm,-3.7 SD),emaciation,and distinctive facial features(triangular face,narrow jaw,prominent forehead,arched eyebrows,sparse eyebrows,high anterior hairline,crowded dentition),accompanied by bilateral cryptorchidism.Bone age was delayed by 1.4 years.Karyotyping and chromosomal microarray analysis were normal.GH therapy initiated at 3.8 years old yielded annual growth rates of 4.9-6.6 cm/year.When the treatment was discontinued at the age of 8.0,the boy's height was 113.7 cm(-3.0 SD),with subsequent decline in growth velocity.Whole exome sequencing in July 2024 identified a frameshift variant c.4028del(p.Pro1343Glnfs*49)in NSD2,which was confirmed as de novo pathogenic variation by parental Sanger sequencing.[Conclusions]This study reports the clinical features of RAUST syndrome caused by NSD2 mutation and explores the long-term efficacy of GH therapy.The findings contribute to a better understanding of this rare syndrome and further optimize its diagnosis and management.

In modern society, sugary foods have become an integral part of many people′s lives. However, excessive sugar consumption has adverse effects on both overall health and oral health, serving as a contributing factor to the global increasing incidence in oral diseases, cardiovascular diseases, cancers, obesity, and diabetes. In response to the health risks related to high-sugar diets, the World Health Organization (WHO) and World Dental Federation (FDI) have proposed initiatives and recommendations, with various governments implementing different policies and strategies to reduce sugar intake. Chinese government has also taken proactive measures. The "Healthy China Action (2019-2030)" initiative introduced by the State Council in 2019 established a crucial benchmark in limiting the average daily intake of added sugar to 25 g per person forward to 2030. Experts from Chinese Center for Disease Control and Prevention and the field of oral health have meticulously examined the impacts of sugar reduction on oral health, as well as strategies, methods, and practical considerations related to reducing sugar intake through several meeting and wrote the "Expert consensus: reducing free-sugar for caries prevention", which was subsequently reviewed and revised based on the feedback from multiple stakeholders. They have conducted thorough analyses of global trends in sugar reduction and best practices to provide valuable insights to China for crafting effective policies and strategies on sugar reduction. This consensus mainly includes the classification of free sugars, the latest scientific evidence on dental caries, recommendations from WHO on sugar-sweetened beverage taxes, nutrition labeling, advertising, food reform, adjusting supply systems, education, and promotion strategies, as well as sugar reduction actions taken by various governments around the world. Combining the actual situation in China, policy recommendations and authoritative popular science knowledge on sugar reduction for caries prevention to public are proposed to advocate for experts in multiple fields to focus on sugar reduction for caries prevention, promote the work process, and provide the scientific basis for oral health educators.

Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.

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.