Acute liver failure (ALF) is lack of broadly approved therapeutic strategy except liver transplantation. As a glycogen metabolic intermediate, UDP-glucose (UDP-G) has been considered to accelerate liver repairment. Nevertheless, the role of UDP-G and its receptor P2Y purinoceptor 14 (P2Y₁₄R) in ALF remains unknown. The present study aims to investigate the role and underlying mechanisms of UDP-G/P2Y₁₄R axis in ALF. In this study, hepatic P2Y₁₄R is significantly increased in TAA-induced and partial hepatectomy-induced ALF, while knockout of whole-body P2Y₁₄R aggravates liver failure, manifested by inhibiting β-Catenin-mediated liver regeneration. Consistently, P2Y₁₄R deficiency exhibits impaired liver regeneration in mice suffer partial hepatectomy. Importantly, only hepatocellular specific deletion of P2Y₁₄R (P2Y₁₄R ^flox/flox Alb ^cre/+ ) mice shows a similar phenomenon, rather than stellate cell specific deletion of P2Y₁₄R (P2Y₁₄R ^flox/flox Lrat ^cre/+ ) mice. Mechanistically, P2Y₁₄R induction regulates methylation of Dact-2 through CREB/DNMT3b signals in hepatocytes, subsequently inhibiting the expression of Dact-2 which is a stabilizer of β-Catenin degradation complex, leading to the activation of β-Catenin -mediated liver regeneration. Interestingly, the administration of exogenous UDP-G can accelerate liver regeneration and liver function recovery after partial hepatectomy in hepatocellular carcinoma mice. Together, the findings propose an unrecognized role of P2Y₁₄R in ALF and provide an effective adjuvant strategy for treatment of ALF.

Objective To analyze the characteristics of real-world adverse drug events(ADEs)of trabectedin based on the FDA Adverse Event Reporting System(FAERS)database in order to provide references for clinical drug safety management.Methods A total of 1 349 trabectedin-related reports were extracted from the FAERS database from Q1 2007 to Q4 2024.Using the MedDRA coding classification system for system organ class(SOC)and preferred term(PT),signal detection was performed through 4 proportional imbalance methods,including reporting odds ratio(ROR)and proportional reporting ratio(PRR).Subgroup analyses by gender,age,and temporal trends were also conducted.Results Hematological and lymphatic system disorders and hepatobiliary system disorders were the primary SOCs involved.High-frequency PTs included neutropenia(123 cases)and anemia(117 cases).Eight potential ADEs that have not been listed in the drug product instruction were identified.The median onset time of ADEs was 21 d,showing an early failure pattern,with differences observed by gender(females more prone to hematological toxicity)and age(elderly more susceptible to febrile neutropenia).Conclusion Trabectedin requires close attention to hematological toxicity,hepatotoxicity,and newly identified multi-system potential risks.Clinically,monitoring should be strengthened based on time windows and population characteristics to optimize drug regimens.Countermeasure It is recommended to strengthen the full cycle monitoring of anti-tumor drugs,standardize the reporting of adverse reactions,and establish a multi-departmental collaborative research platform.

This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.

Objective:To describe the distribution characteristics of alcohol consumption in adult twins in the Chinese National Twin Registry (CNTR), and further explore the influence of genetic factors on alcohol consumption in adult twins.Methods:The subjects of the study were twins registered by CNTR in 11 project areas across China from 2010 to 2018. A total of 56 966 twins (28 483 pairs) aged 18 years and above who answered questions about drinking behavior were included, and the random effect model was used to describe the population and regional distribution characteristics of alcohol consumption. Intra-pair analysis was performed to calculate the concordance rate and heritability of their alcohol consumption.Results:The age of all subjects was (36.6±12.0) years, and current drinkers accounted for 16.6% (9 461/56 966) of all subjects. In men, those aged 50-59 years, those in northern China, those living in rural area, those with low education level and those with high BMI, the proportions of current drinkers were higher. After excluding 468 pairs of twins who had stopped alcohol use and 21 764 pairs of twins who had no drink or had small amount drink, an intra-pair analysis was conducted in 4 929 pairs of same-sex twins, and found that the concordance rate of alcohol consumption was 64.0% (2 059/3 215) in monozygotic twins, and 52.6% (902/1 714) in dizygotic twins, the difference was significant ( P<0.001), and the heritability of alcohol consumption was 24.1% (95% CI: 18.9%- 29.3%). The further stratified analysis found that in southern men, the heritability was highest in those aged 40-49 years (36.1%, 95% CI: 21.6%-50.7%), while in northern men, the heritability was highest in those aged 50-59 years (34.2%, 95% CI: 18.1%-50.3%). Conclusions:In adult twins in China, there were population and regional differences in the distribution of alcohol consumption behavior, and alcohol consumption was influenced by genetic factors, and gender, age and region had potential modifying effects.

This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.

Objective:To describe the distribution characteristics of alcohol consumption in adult twins in the Chinese National Twin Registry (CNTR), and further explore the influence of genetic factors on alcohol consumption in adult twins.Methods:The subjects of the study were twins registered by CNTR in 11 project areas across China from 2010 to 2018. A total of 56 966 twins (28 483 pairs) aged 18 years and above who answered questions about drinking behavior were included, and the random effect model was used to describe the population and regional distribution characteristics of alcohol consumption. Intra-pair analysis was performed to calculate the concordance rate and heritability of their alcohol consumption.Results:The age of all subjects was (36.6±12.0) years, and current drinkers accounted for 16.6% (9 461/56 966) of all subjects. In men, those aged 50-59 years, those in northern China, those living in rural area, those with low education level and those with high BMI, the proportions of current drinkers were higher. After excluding 468 pairs of twins who had stopped alcohol use and 21 764 pairs of twins who had no drink or had small amount drink, an intra-pair analysis was conducted in 4 929 pairs of same-sex twins, and found that the concordance rate of alcohol consumption was 64.0% (2 059/3 215) in monozygotic twins, and 52.6% (902/1 714) in dizygotic twins, the difference was significant ( P<0.001), and the heritability of alcohol consumption was 24.1% (95% CI: 18.9%- 29.3%). The further stratified analysis found that in southern men, the heritability was highest in those aged 40-49 years (36.1%, 95% CI: 21.6%-50.7%), while in northern men, the heritability was highest in those aged 50-59 years (34.2%, 95% CI: 18.1%-50.3%). Conclusions:In adult twins in China, there were population and regional differences in the distribution of alcohol consumption behavior, and alcohol consumption was influenced by genetic factors, and gender, age and region had potential modifying effects.

Objective:To investigate the clinicopathological features, classification, and genetic characteristics of common lymphatic malformation (CLM) in superficial soft tissue.Methods:A retrospective study of 110 patients with the diagnosis of CLM at the Henan Province People′s Hospital, China from August 2019 to August 2022 was performed. The clinicopathological features, relevant immunohistochemical (IHC) staining results, and fluorescence quantitative PCR of PIK3CA mutation were analyzed, and patients were followed up.Results:Among the 110 CLM patients, there were 53 males and 57 females; 65 cases (65/110, 59.1%) were first detected when the patients were≤2 years old. The most common location was the head and neck in 41 cases (41/110, 37.3%). Clinically, 102 cases (102/110, 92.7%) were solitary, 83 cases (83/110, 75.5%) were skin-colored, 69 cases (69/110, 62.7%) had indistinct borders, and 10 cases (10/110, 9.1%) had diffuse and severe macroscopic manifestations. There were 52 macrocystic type (52/110, 47.3%), 23 microcystic type (23/110, 20.9%), and 35 combined type (35/110, 31.8%). The macrocystic CLM presented as soft, translucent masses with large cystic cavities on the cut surface, and histologically they were composed of large, irregularly dilated channels that were thicker with irregular smooth muscle and lymphocytic infiltration. Microcystic CLM showed wartlike projections or translucent blisters on the skin, with small honeycomb structures on the cut surface, and histologically consisted of round or angular dilated small lymphatic vessels with little or no smooth muscle. The combined CLM had both macrocystic and microcystic morphologies. IHC staining showed that the lymphatic endothelial cells were positive for LYVE-1, D2-40, PROX1, CD31, and VEGFR3 but negative for CD34; in the macrocystic and combined CLM vessel walls were positive for SMA. Eight of 13 CLM had PIK3CA mutation. All patients were followed up, and 24 (24/110, 21.8%) had relapses, which more frequently occurred in combined type, followed by microcystic type.Conclusions:CLM is a congenital vascular malformation composed of dilated, abnormal lymphatic channels, with PIK3CA mutation. There are significant differences in clinicopathological characteristics among the different types. Since microcystic and combined CLM are prone to recurrence, accurate pathological subtyping is necessary to guide treatment and to predict prognosis.

Objective:To understand the characteristics and trends of acute myocardial infarction (AMI) in Shandong Province and to provide evidence for formulating prevention and control strategies.Methods:Data were derived from the AMI incidence reports of Shandong Province's Chronic Disease Surveillance Information Management System in 2012-2021. The crude and standardized incidence rates were used as indicators to describe the incidence level of AMI. Joinpoint regression analysis was used to analyze the trends in the incidence and age of onset over the years. The contribution of population aging to the increase in AMI incidence was assessed using the rate difference decomposition method. The incidence of AMI in each district (county) in Shandong Province was visualized using ArcGIS 10.8 software, and global and local spatial autocorrelation analysis was performed using DeoDa 1.12 software.Results:From 2012 to 2021, 198 233 cases of AMI were reported from 19 provincial monitoring sites in Shandong Province, of which 53.13% were males and 97.12% were ≥45 years old. The reported crude incidence increased from 90.12 per 100 000 in 2012 to 176.54 per 100 000 in 2021, with an average annual increase of 7.01% ( Z=7.35 , P<0.001). There was no significant upward trend in standardized incidence ( Z=1.64 , P=0.140), but the standardized incidence of male residents showed an increasing trend ( Z=2.76 , P=0.028). Before 2014, the reported crude incidence of males was similar to that of females, but after 2014, the reported crude incidence of males was continuously higher than that of females. However, males' standardized incidence was higher than females in all years. Both crude and standardized incidence rates were higher in rural residents than in urban areas. The median onset of AMI increased from 71.6 years old in 2012 to 73.5 years old in 2021. The median age of onset in males was lower than that in females in all years, and in most years, the median age of onset in urban residents was lower than that in rural residents. The incidence of AMI in males showed a trend in younger age groups. According to the seasonal decomposition, the incidence peak of AMI was in January, and the trough was in September. The contribution of aging population to the increase in crude incidence of AMI increased from 8.63% in 2013 to 52.58% in 2021. The global spatial autocorrelation analysis showed that the incidence of AMI presented an obvious spatial clustering distribution. Local spatial autocorrelation analysis found that the high-incidence areas (counties) were mainly concentrated in Liaocheng City and Dezhou City in the northwest region of Shandong Province and Heze City in the southwest. Conclusions:The incidence of AMI among residents in Shandong Province was rising, with spatial clustering and seasonal clustering characteristics. People aged 45 years and older, male residents, and rural residents were at high risk of developing AMI. There was a certain trend of younger age at onset among men. Targeted prevention and control measures should be taken for high-incidence seasons, high-risk groups, and high-incidence clustering areas in northwestern Shandong Province.

Objective:To evaluate the relationship between blood transfusion factors (massive transfusion, transfusion of stored red blood cells and anhepatic transfusion) and early postoperative outcomes in the patients undergoing orthotopic liver transplantation.Methods:Patients with end-stage liver disease who underwent orthotopic liver transplantation and intraoperative blood transfusion from January 2021 to March 2022 in our hospital were retrospectively selected, and their clinical data were collected. The patients were divided into massive transfusion group (M group, total red blood cell transfusion ≥10 U) and non-massive transfusion group (NM group) according to the amount of intraoperative blood transfused. The patients were divided into fresh blood group (NS group) and stored blood group (S group, red blood cell storage time > 2 weeks) according to the storage time of red blood cells transfused. The patients were divided into transfusion in anhepatic stage group (group T) and nontransfusion in anhepatic stage group (group NT) according to whether blood was transfused in the anhepatic stage. Multivariate logistic regression, generalized linear model and generalized linear mixed model were used to analyze the relationship between blood transfusion factors and primary outcome measures (postoperative pulmonary complications, circulation overload, acute kidney injury, abdominal infection, thrombosis) and between blood transfusion factors and secondary outcome measures (duration of ICU stay, postoperative hospitalization, postoperative temperature ≥38.5 ℃ at any time point after surgery, postoperative liver and kidney function index, coagulation function index, platelet count and preoperative difference).Results:One hundred and six patients were enrolled in this study. The results of multivariate logistic regression analysis: Massive blood transfusion and infusion of stored blood were risk factors for postoperative pulmonary complications, massive blood transfusion was a risk factor for abdominal infection, Child-Turcotte-Pugh score for liver function and time of anhepatic phase were risk factors for postoperative acute kidney injury, Child-Turcotte-Pugh score was a risk factor for circulatory overload, and age and massive blood transfusion were risk factors for thrombosis ( P<0.05). The results of generalized linear model analysis: Intraoperative stored blood transfusion and blood transfusion during the anhepatic phase were risk factors for prolonged duration of ICU stay, massive blood transfusion, intraoperative stored blood transfusion and blood transfusion during the anhepatic phase were risk factors for prolonged hospitalization ( P<0.05), and there was no correlation between massive blood transfusion, intraoperative stored blood transfusion and blood transfusion during the anhepatic phase and temperature ≥38.5 ℃ at any time point after surgery ( P>0.05). The results of generalized linear mixed model analysis: There was statistically significant difference in the difference between preoperative and postoperative liver and kidney function indexes, coagulation function indexes and platelet counts in the patients with or without massive transfusion, stored blood transfusion or blood transfusion during the anhepatic phase ( P<0.05). Conclusions:Massive blood transfusion and infusion of stored blood are the main risk factors for early adverse outcomes after orthotopic liver transplantation in the patients.

The current organ allocation rules prioritize elderly and urgent patients on the lung transplantation (LT) waiting list. A steady increase in the threshold at which age is taken into consideration for LT has been observed. This retrospective cohort study recruited 166 lung transplant recipients aged ≽ 65 years between January 2016 and October 2020 in the largest LT center in China. In the cohort, subgroups of patients aged 65-70 years (111 recipients, group 65-70) and ≽ 70 years (55 recipients, group ≽ 70) were included. Group D restrictive lung disease was the main indication of a lung transplant in recipients over 65 years. A significantly higher percentage of coronary artery stenosis was observed in the group ≽ 70 (30.9% vs. 14.4% in group 65-70, P = 0.014). ECMO bridging to LT was performed in 5.4% (group 65-70) and 7.3% (group ≽ 70) of patients. Kaplan-Meier estimates showed that recipients with cardiac abnormalities had a significantly increased risk of mortality. After adjusting for potential confounders, cardiac abnormality was shown to be independently associated with the increased risk of post-LT mortality (HR 6.37, P = 0.0060). Our result showed that LT can be performed in candidates with an advanced age and can provide life-extending benefits.
Aged ; Humans ; East Asian People ; Heart Diseases/etiology* ; Lung Transplantation/adverse effects* ; Retrospective Studies