Objective To explore the relationship between insulin resistance (IR) indexes and hyperuricemia (HUA) among the people with hypertension. Methods From July to August in 2018,hypertension screening was carried out in Wuyuan county,Jiangxi province,and the data were collected through questionnaire survey,physical measurement,and biochemical test.Logistic regression was performed to analyze the relationship between HUA and IR indexes including metabolic score for IR (METS-IR),triglyceride-glucose (TyG) index,TyG-body mass index (BMI),TyG-waist circumference (WC),visceral adiposity index (VAI),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and lipid accumulation product (LAP).The penalty spline method was used for the curve fitting between IR indexes and HUA.The area under the receiver operating characteristic curve (AUC) was employed to reveal the correlation between each index and HUA. Results The 14 220 hypertension patients included 6 713 males and 7 507 females,with the average age of (63.8±9.4) years old,the average uric acid level of (418.9±120.6) mmol/L,and the HUA detection rate of 44.4%.The HUA group had higher proportions of males,current drinking,current smoking,diabetes,and using antihypertensive drugs,older age,higher diastolic blood pressure,WC,BMI,homocysteine,total cholesterol,TG,low-density lipoprotein cholesterol,blood urea nitrogen,creatinine,aspartate aminotransferase,alanine aminotransferase,total protein,albumin,total bilirubin,direct bilirubin, METS-IR, TyG, TyG-BMI, TyG-WC, VAI, TG/HDL-C, and LAP, and lower systolic blood pressure and HDL-C than the normal uric acid group (all P<0.05).Multivariate Logistic regression showed that METS-IR (OR=1.049,95%CI=1.038-1.060, P<0.001), TyG (OR=1.639,95%CI=1.496-1.797, P<0.001), TyG-BMI (OR=1.008,95%CI=1.006-1.010, P<0.001), TyG-WC (OR=1.003,95%CI=1.002-1.004, P<0.001), lnVAI (OR=1.850, 95%CI=1.735-1.973, P<0.001), ln(TG/HDL-C) (OR=1.862,95%CI=1.692-2.048, P<0.001),and lnLAP (OR=1.503,95%CI=1.401-1.613,P<0.001) were associated with the risk of HUA.Curve fitting indicated that METS-IR,TyG,TYG-BMI,TYG-WC,lnVAI,ln(TG/HDL-C),and lnLAP were positively correlated with HUA (all P<0.001),and the AUC of TyG index was higher than that of other IR indexes (all P<0.05). Conclusion Increased IR indexes,especially TyG,were associated with the risk of HUA among people with hypertension.
Male ; Female ; Humans ; Middle Aged ; Aged ; Insulin Resistance ; Hyperuricemia ; Uric Acid ; Hypertension/complications* ; Glucose ; Obesity, Abdominal/epidemiology* ; Triglycerides ; Bilirubin ; Cholesterol ; Blood Glucose/metabolism*

OBJECTIVES: Hereditary spherocytosis (HS) is the most common hereditary defect of the red cell membrane, mainly characterized by anemia, jaundice, and splenomegaly. Due to the atypical clinical manifestations and negative family history of some patients, as well as the low sensitivity and specificity of traditional laboratory examinations, it is easy for it to escape diagnosis or be misdiagnosed. At present, it has been confirmed that the mutation of ANK1, SPTB, SPTA1, SLC4A1 and EPB42 genes can cause the deletion of their corresponding coding proteins, and thus lead to the defect of erythrocyte membrane. This study aims to analyze the feasibility and clinical application value of HS gene diagnosis. METHODS: Data of 26 patients from Hunan, China with HS admitted to the Department of Hematology, Second Xiangya Hospital of Central South University from January 2018 to September 2021 were retrospectively collected, and their clinical manifestations and results of laboratory examinations were analyzed. Next-generation sequencing (NGS) combined with Sanger sequencing were applied. The mutation of HS pathogenic gene and the variation of uridine diphosphate-glucuronosyl transferase 1 family polypeptide A1 (UGT1A1), a key enzyme in the regulation of bilirubin metabolism, were detected. The results of pathogenic gene variations were interpreted pathogenic gene variations in accordance with the Standards and guidelines for the interpretation of sequence variants published by the American College of Medical Genetics and Genomics (ACMG). The clinical characteristics of patients with different gene variants were analyzed, and the clinical diagnosis and genetic diagnosis were compared. RESULTS: Among the 26 patients with HS, there were 23 cases of anemia, 25 cases of jaundice, 24 cases of splenomegaly, and 14 cases of cholelithiasis. There were 16 cases with family history and 10 cases without family history. The results of HS mutation test were positive in 25 cases and negative in 1 case. A total of 18 heterozygous mutations of HS pathogenic genes were detected in 19 families, among which 14 were pathogenic, 1 was likely pathogenic and 3 were of unknown significance. SPTB mutations (12) and ANK1 mutations (4) were the most common. The main variation types were nonsense mutation (9). There were no significant differences in peripheral blood cell parameters and hemolysis indicators between the SPTB mutant group and the ANK1 mutant group (all P>0.05). The rate of splenectomy in ANK1 mutation group was higher than that in SPTB mutation group, and the difference was statistically significant (χ²=6.970, P=0.014). There were no significant differences in peripheral blood cell parameters and hemolysis indicators among different mutation types (nonsense mutation, frameshift mutation, splice site mutation and missense mutation) (all P>0.05). Among the 18 clinically confirmedpatients, there were 17 cases whose diagnosis is consistent with the genetic diagnosis. Eight patients were clinically suspected, and all of them were confirmed by detection of HS gene mutation. Twenty-four patients with HS underwent UGT1A1 mutation detection, among which 5 patients carried UGT1A1 mutation resulting in a decrease in enzyme activity, and 19 patients had normal enzyme activity. The level of total bilirubin (TBIL) in the group with reduced enzyme activity was higher than that in the group with normal enzyme activity, and the difference was statistically significant (U=22, P=0.038). CONCLUSIONS Most patients with HS have anemia, jaundice and splenomegaly, often accompanied by cholelithiasis. SPTB and ANK1 mutations are the most common mutations in HS pathogenic genes among patients in Hunan, China, and there was no significant correlation between genotype and clinical phenotype. Genetic diagnosis is highly consistent with clinical diagnosis. The decrease of UGT1A1 enzyme activity can lead to the aggravation of jaundice in HS patients. Clinical combined gene diagnosis is beneficial for the rapid and precision diagnosis of HS. The detection of UGT1A1 enzyme activity related gene variation plays an important role in evaluation of HS jaundice.
Humans ; Codon, Nonsense ; Hemolysis ; Retrospective Studies ; Splenomegaly ; Bilirubin

Objective: To investigate the lifespan of erythrocytes in megaloblastic anemia (MA) patients. Methods: A prospective cohort study analysis. Clinical data from 42 MA patients who were newly diagnosed at the Department of Hematology, Lanzhou University Second Hospital from January 2021 to August 2021 were analyzed, as were control data from 24 healthy volunteers acquired during the same period. The carbon monoxide breath test was used to measure erythrocyte lifespan, and correlations between erythrocyte lifespan and laboratory test indexes before and after treatment were calculated. Statistical analysis included the t-test and Pearson correlation. Results: The mean erythrocyte lifespan in the 42 newly diagnosed MA patients was (49.05±41.60) d, which was significantly shorter than that in the healthy control group [(104.13±42.62) d; t=5.13,P=0.001]. In a vitamin B₁₂-deficient subset of MA patients the mean erythrocyte lifespan was (30.09±15.14) d, and in a folic acid-deficient subgroup it was (72.00±51.44) d, and the difference between these two MA subsets was significant (t=3.73, P=0.001). The mean erythrocyte lifespan after MA treatment was (101.28±33.02) d, which differed significantly from that before MA treatment (t=4.72, P=0.001). In MA patients erythrocyte lifespan was positively correlated with hemoglobin concentration (r=0.373), and negatively correlated with total bilirubin level (r=-0.425), indirect bilirubin level (r=-0.431), and lactate dehydrogenase level (r=-0.504) (all P<0.05). Conclusions: Erythrocyte lifespan was shortened in MA patients, and there was a significant difference between a vitamin B₁₂-deficient group and a folic acid-deficient group. After treatment the erythrocyte lifespan can return to normal. Erythrocyte lifespan is expected to become an informative index for the diagnosis and treatment of MA.
Humans ; Longevity ; Clinical Relevance ; Prospective Studies ; Erythrocytes ; Anemia, Megaloblastic ; Folic Acid ; Bilirubin ; Vitamins

Objective: To investigate the factors influencing total bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt (TIPS). Methods: 104 cases with portal hypertension and esophageal variceal hemorrhage (EVB) treated with elective TIPS treatment were selected as the study subjects and were divided into a bilirubin-elevated group and a normal bilirubin group according to the total bilirubin elevation level during the early postoperative period. Univariate analysis and logistic regression were used to analyze the factors influencing total bilirubin elevation in the early postoperative period. PCR amplification and first-generation sequencing technology were used to detect the polymorphic loci of the UGT1A1 gene promoter TATA box, enhancer c.-3279 T > G, c.211G > A, and c.686C > A. Logistic regression was used to analyze the correlation of four locus alleles and genotypes with elevated total bilirubin in the early postoperative period. Results: Among the 104 cases, 47 patients were in the bilirubin elevated group, including 35 males (74.5%) and 12 females (25.5%), aged (50.72 ± 12.56) years. There were 57 cases in the normal bilirubin group, including 42 males (73.7%) and 15 females (26.3%), aged (51.63 ± 11.10) years. There was no statistically significant difference in age (t = -0.391, P = 0.697) and gender (χ(2) = 0.008, P = 0.928) between the two groups of patients. Univariate analysis revealed that preoperative alanine transaminase (ALT) level (χ(2) = 5.954, P = 0.015), total bilirubin level (χ(2) = 16.638, P < 0.001), MELD score (χ(2) = 10.054, P = 0.018), Child-Pugh score (χ(2) = 6.844, P = 0.022), and postoperative portal vein branch development (χ(2) = 6.738, P = 0.034) were statistically significantly different between the two groups. Logistic regression analysis showed that preoperative ALT level, total bilirubin level, and portal vein branch development after TIPS were correlated with the elevated total bilirubin in the early postoperative period. The polymorphism of the c.211G > A locus of the UGT1A1 gene correlation had elevated total bilirubin in the early postoperative period of TIPS. The risk of elevated total bilirubin was increased in the population carrying allele A (P = 0.001, OR = 4.049) in the early postoperative period. Allelic polymorphisms in the TATA box promoter region and enhancer c.-3279 T > G and c.686C > A had no statistically significant difference between the bilirubin-elevated group and the normal bilirubin group. Conclusion: The preoperative ALT level, total bilirubin level, and portal vein branch development are correlated with the elevated total bilirubin in early postoperative patients. The polymorphisms of the UGT1A1 gene and enhancer c.211G > A are correlated with the occurrence of elevated total bilirubin in the early postoperative period of TIPS. Allele A carrier may have a higher risk of elevated total bilirubin in the early postoperative period.
Female ; Humans ; Male ; Bilirubin ; Esophageal and Gastric Varices ; Gastrointestinal Hemorrhage/surgery* ; Portasystemic Shunt, Transjugular Intrahepatic ; Postoperative Period ; Retrospective Studies ; Treatment Outcome ; Adult ; Middle Aged ; Glucuronosyltransferase/genetics*

Non-alcoholic fatty liver disease (NAFLD) is a metabolic-related disorder induced by multiple factors and mainly characterized by excessive fat buildup in hepatocytes. With the consumption of a Western-style diet and obesity prevalence in recent years, the incidence of NAFLD has gradually increased, becoming an increasingly serious public health problem. Bilirubin is a heme metabolite and a potent antioxidant. Studies have demonstrated that bilirubin levels have an inverse correlation with the incidence rate of NAFLD; however, which form of bilirubin plays the main protective role is still controversial. It is considered that the main protective mechanisms for NAFLD are bilirubin antioxidant properties, insulin resistance reduction, and mitochondrial function. This article summarizes the correlation, protective mechanism, and possible clinical application of NAFLD and bilirubin.
Humans ; Non-alcoholic Fatty Liver Disease/metabolism* ; Bilirubin ; Antioxidants ; Obesity/complications* ; Hepatocytes/metabolism* ; Liver/metabolism*

The American Academy of Pediatrics updated the guidelines for the management of hyperbilirubinemia in the newborn infants with a gestational age of ≥35 weeks in September 2022. Based on the evidence over the past 18 years, the guidelines are updated from the aspects of the prevention, risk assessment, intervention, and follow-up of hyperbilirubinemia in the newborn infants with a gestational age of ≥35 weeks. This article gives an interpretation of the key points in the guidelines, so as to safely reduce the risk of bilirubin encephalopathy and unnecessary intervention.
Infant, Newborn ; Humans ; Infant ; United States ; Child ; Hyperbilirubinemia, Neonatal/therapy* ; Bilirubin ; Hyperbilirubinemia/therapy* ; Kernicterus/prevention & control* ; Risk Assessment ; Gestational Age

OBJECTIVE: To explore the clinical effect of Li-Dan-He-Ji in the treatment of infantile cholestatic hepatic fibrosis. METHODS: Patients who met the diagnostic criteria of infantile cholestatic hepatic fibrosis in the department of integrated traditional Chinese and Western medicine and the department of gastroenterology of Wuhan Children's Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January to December 2021 were included in the study by prospective randomized controlled trial. They were divided into the conventional treatment group and Li-Dan-He-Ji group according to the random number table. The patients in the conventional treatment group were given conventional treatment according to the guidelines. In the Li-Dan-He-Ji group, the self-made Chinese medicinal compound Li-Dan-He-Ji (prescription: Herba Artemisiae Scopariae, Fructus Forsythiae, Radix et Rhizoma Rhei preparata, Radix Polygoni Multiflori Preparata, Radix Paeoniae Rubra, Ramulus Cinnamomi, Fructus Aurantii, Rhizoma Atractylodis Macrocephalae, Fructus Schisandrae Chinensis, Carapax Trionycis, and Radix Glycyrrhizae) was given on the basis of the routine treatment, by oral, enema or nasal feeding, 60 mL each day, divided into 2 or 3 times, for 28 days. Outpatient follow-up was maintained for 4 weeks. Before and after treatment, serum liver fibrosis 4 items [type IV collagen (IV-C), hyaluronidase (HA), type III procollagen (PC III), laminin (LN)], liver function and cholestasis-related markers [total bilirubin (TBil), direct bilirubin (DBil), total bile acid (TBA), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST)], oxidative stress markers [superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH)], liver stiffness measurement (LSM) detected by transient elastography (TE), aspartate aminotransferase-to-platelet ratio index (APRI), and liver and spleen retraction time were recorded in the two groups. RESULTS: During the observation period, a total of 40 cases of cholestatic hepatic fibrosis were treated, including 21 cases in the conventional treatment group and 19 cases in the Li-Dan-He-Ji group. Before treatment, the differences in serum liver fibrosis 4 items, serum liver function and cholestasis-related markers, oxidative stress indexes, LSM and APRI of the two groups were not statistically significant. After treatment, the liver fibrosis 4 items, liver function and cholestasis-related markers, LSM, and APRI were all significantly decreased in both groups, and the indexes in the Li-Dan-He-Ji group were significantly lower than those in the conventional treatment group [HA (ng/L): 165.81±21.57 vs. 203.87±25.88, PC III (μg/L): 69.86±9.32 vs. 81.82±7.39, IV-C (μg/L): 204.14±38.97 vs. 239.08±24.93, LN (μg/L): 162.40±17.39 vs. 190.86±15.97, TBil (μmol/L): 37.58±27.63 vs. 53.06±45.09, DBil (μmol/L): 20.55±19.34 vs. 30.08±27.39, ALP (U/L): 436.50±217.58 vs. 469.60±291.69, γ-GGT (U/L): 66.78±35.84 vs. 87.00±32.82, ALT (U/L): 64.75±50.53 vs. 75.20±50.19, AST (U/L): 77.25±54.23 vs. 96.80±59.77, TBA (μmol/L): 74.35±44.44 vs. 85.45±39.50, LSM (kPa): 5.24±0.39 vs. 7.53±3.16, APRI: 0.52±0.39 vs. 0.98±0.29, all P < 0.05]. After treatment, MDA in the two groups were significantly lower than those before treatment, and SOD and GSH were significantly higher than those before treatment. The level of SOD in the Li-Dan-He-Ji group was significantly higher than that in the conventional treatment group (kU/L: 64.56±6.69 vs. 51.58±5.98, P < 0.05). In addition, the liver retraction time (day: 20.13±10.97 vs. 24.33±13.46) and spleen retraction time (day: 25.93±13.01 vs. 29.14±14.52) in the Li-Dan-He-Ji group were significantly shorter than those in the conventional treatment group (both P < 0.05). CONCLUSIONS The use of Li-Dan-He-Ji in the treatment of cholestatic hepatic fibrosis can effectively improve the indicators of cholestasis, hepatic fibrosis, oxidative stress and clinical symptoms in children.
Child ; Humans ; Prospective Studies ; Cholestasis/pathology* ; Liver ; Liver Cirrhosis/drug therapy* ; Bilirubin/pharmacology* ; Oxidative Stress ; Aspartate Aminotransferases/metabolism* ; Superoxide Dismutase/metabolism*

Objective: To compare the effect of different endocrine therapy drugs on liver function in patients with early breast cancer. Methods: A retrospective cohort study was conducted to include 4 318 patients with early breast cancer who received adjuvant endocrine therapy in Department of Breast Surgery, Peking Union Medical College Hospital from January 1, 2013 to December 31, 2021. All the patients were female, aged (51.2±11.3) years (range: 20 to 87 years), including 1 182 patients in the anastrozole group, 592 patients in the letrozole group, 332 patients in the exemestane group, and 2 212 patients in the toremifene group. The mixed effect model was used to analyze and compare the liver function levels of patients at baseline, 6, 12, 18, 24, 36, 48, 60 months of medication, and 1 year after drug withdrawal among the three aromatase inhibitors (anastrozole, letrozole, exemestane) and toremifene. Results: ALT and AST of the 4 groups were significantly higher than the baseline level at 6 months (all P<0.01), and there were no significant differences in total bilirubin, direct bilirubin and AST levels among all groups one year after drug withdrawal (P: 0.538, 0.718, 0.061, respectively). There was no significant difference in the effect of all groups on AST levels (F=2.474, P=0.061), and in the effect of three aromatase inhibitors (anastrozole, letrozole, and exemestane) on ALT levels (anastrozole vs. letrozole, P=0.182; anastrozole vs. exemestane, P=0.535; letrozole vs. exemestane, P=0.862). Anastrozole and letrozole had significantly higher effects on ALT levels than toremifene (P<0.01, P=0.009). The proportion of abnormal liver function in each group increased significantly at 6 months compared with baseline, and then the proportion showed a decreasing trend over time. Conclusions: Three aromatase inhibitors (anastrozole, letrozole, and exemestane) and toremifene can significantly increase the level of ALT and AST in patients with breast cancer, and the levels can gradually recover to the baseline after 1 year of drug withdrawal. The effect of non-steroidal aromatase inhibitors (anastrozole, letrozole) on ALT levels is greater than toremifene.
Female ; Humans ; Anastrozole ; Aromatase Inhibitors/therapeutic use* ; Bilirubin ; Breast Neoplasms/drug therapy* ; Letrozole ; Liver ; Retrospective Studies ; Toremifene ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over

Objective: To observe the characteristics of the evolution of liver indexes in patients with relapsed/refractory multiple myeloma (RRMM) treated with CAR-T-cells based on BCMA. Methods: Retrospective analysis was performed of patients with RRMM who received an infusion of anti-BCMA CAR-T-cells and anti-BCMA combined with anti-CD19 CAR-T-cells at our center between June 1, 2019, and February 28, 2023. Clinical data were collected to observe the characteristics of changes in liver indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) in patients, and its relationship with cytokine-release syndrome (CRS) . Results: Ninety-two patients were included in the analysis, including 41 patients (44.6%) in the group receiving a single infusion of anti-BCMA CAR-T-cells, and 51 patients (55.4%) in the group receiving an infusion of anti-BCMA combined with anti-CD19 CAR-T-cells. After infusing CAR-T-cells, 31 patients (33.7%) experienced changes in liver indexes at or above grade 2, which included 20 patients (21.7%) with changes in one index, five patients (5.4%) with changes in two indexes, and six patients (6.5%) with changes in three or more indexes. The median time of peak values of ALT and AST were d17 and d14, respectively, and the median duration of exceeding grade 2 was 5.0 and 3.5 days, respectively. The median time of peak values of TBIL and DBIL was on d19 and d21, respectively, and the median duration of exceeding grade 2 was 4.0 days, respectively. The median time of onset of CRS was d8, and the peak time of fever was d9. The ALT, AST, and TBIL of patients with CRS were higher than those of patients without CRS (P=0.011, 0.002, and 0.015, respectively). CRS is an independent factor that affects ALT and TBIL levels (OR=19.668, 95% CI 18.959-20.173, P=0.001). The evolution of liver indexes can be reversed through anti-CRS and liver-protection treatments, and no patient died of liver injury. Conclusions: In BCMA-based CAR-T-cell therapy for RRMM, CRS is an important factor causing the evolution of liver indexes. The evolution of liver indexes after CAR-T-cell infusion is transient and reversible after treatment.
Humans ; Antigens, CD19 ; B-Cell Maturation Antigen/therapeutic use* ; Bilirubin ; Immunotherapy, Adoptive ; Liver ; Multiple Myeloma/drug therapy* ; Retrospective Studies ; T-Lymphocytes

Hereditary bilirubin metabolic disorder is an important cause for jaundice. For its diverse types and similar clinical manifestations, it has been difficult to make a clear etiological diagnosis. The application of next generation sequencing in recent years has delineated the more and more genetic etiologies for jaundice. This article has reviewed the clinical manifestations and genetic etiology of bilirubin metabolic disorder jaundice, with an aim to enhance the understanding of such diseases and facilitate their clinical diagnosis and treatment, which will provide a reference for genetic counseling and/or prenatal diagnosis for the affected individuals and families.
Female ; Pregnancy ; Humans ; Metabolic Diseases/genetics* ; Jaundice/genetics* ; Bilirubin ; Genetic Counseling ; Phenotype