Objective To investigate the association between UGT1A1 inhibitors-induced liver injury(DILI)and UGT1A1 gene polymorphisms through a pharmacogenomics approach.Methods Information on relevant drugs that may induce liver injury,blood routine tests,and liver function tests was collected from hospitalized patients diagnosed with DILI between June 2022 and June 2024.Relevant databases were searched to categorize DILI-associated drugs into UGT1A1 enzyme inhibitors and those without interaction with UGT1A1.Sanger sequenc-ing or MassARRAY SNP typing technology was utilized to detect and genotype the UGT1A1 gene.Results A total of 219 patients with drug-induced liver injury(DILI)were enrolled,including 98 males,with a mean age of 46.32±14.95 years.A literature search of relevant databases revealed that 20 drugs(16.26%,20/123)associated with DILI had inhibitory effects on the UGT1A1 enzyme.The proportion of DILI cases related to UGT1A1 inhibitors was 60.73%(133/219).Compared to non-UGT1A1 inhibitor-related DILI group,the UGT1A1 inhibitor-related DILI group exhibited significantly higher levels of ALT,AST,ALP,and GGT(P<0.05),while no significant differences were observed in age,gender,TBIL,IBIL,WBC,Hb,PLT,injury type,or injury grade(P>0.05).The prevalence of UGT1A1 polymorphisms was significantly higher in the UGT1A1 inhibitor-related DILI group(68.42%)com-pared to the non-UGT1A1 inhibitor-related DILI group(51.16%),with an odds ratio(OR)of 2.068(95%CI:1.183 to 3.617;χ2=6.58,P=0.010).There was also a significant difference in the distribution of genotypes between the UGT1A1 inhibitor-related and non-UGT1A1 inhibitor-related DILI groups(χ2=9.60,P=0.022).Univariate logistic regression analysis indicated that ALT and UGT1A1*6 were associated with UGT1A1 inhibitor-related DILI,while multivariate analysis confirmed that UGT1A1*6 was independently associated with UGT1A1 inhibitor-related DILI[OR(95%CI)=3.143(1.398 to 7.067),P=0.006].Conclusion The UGT1A1*6 allele increases the susceptibility to drug-induced liver injury(DILI)associated with UGT1A1 inhibitory drugs.

Objective To investigate the association between UGT1A1 inhibitors-induced liver injury(DILI)and UGT1A1 gene polymorphisms through a pharmacogenomics approach.Methods Information on relevant drugs that may induce liver injury,blood routine tests,and liver function tests was collected from hospitalized patients diagnosed with DILI between June 2022 and June 2024.Relevant databases were searched to categorize DILI-associated drugs into UGT1A1 enzyme inhibitors and those without interaction with UGT1A1.Sanger sequenc-ing or MassARRAY SNP typing technology was utilized to detect and genotype the UGT1A1 gene.Results A total of 219 patients with drug-induced liver injury(DILI)were enrolled,including 98 males,with a mean age of 46.32±14.95 years.A literature search of relevant databases revealed that 20 drugs(16.26%,20/123)associated with DILI had inhibitory effects on the UGT1A1 enzyme.The proportion of DILI cases related to UGT1A1 inhibitors was 60.73%(133/219).Compared to non-UGT1A1 inhibitor-related DILI group,the UGT1A1 inhibitor-related DILI group exhibited significantly higher levels of ALT,AST,ALP,and GGT(P<0.05),while no significant differences were observed in age,gender,TBIL,IBIL,WBC,Hb,PLT,injury type,or injury grade(P>0.05).The prevalence of UGT1A1 polymorphisms was significantly higher in the UGT1A1 inhibitor-related DILI group(68.42%)com-pared to the non-UGT1A1 inhibitor-related DILI group(51.16%),with an odds ratio(OR)of 2.068(95%CI:1.183 to 3.617;χ2=6.58,P=0.010).There was also a significant difference in the distribution of genotypes between the UGT1A1 inhibitor-related and non-UGT1A1 inhibitor-related DILI groups(χ2=9.60,P=0.022).Univariate logistic regression analysis indicated that ALT and UGT1A1*6 were associated with UGT1A1 inhibitor-related DILI,while multivariate analysis confirmed that UGT1A1*6 was independently associated with UGT1A1 inhibitor-related DILI[OR(95%CI)=3.143(1.398 to 7.067),P=0.006].Conclusion The UGT1A1*6 allele increases the susceptibility to drug-induced liver injury(DILI)associated with UGT1A1 inhibitory drugs.

Off-label drug use in psychiatry has long been prevelent, with common clinical practices lacking standardized guidance and associated risks warranting close attention. To address the practical needs of frontline clinicians, the Mental Health Branch of the China National Narcotic Drugs Association, in collaboration with multiple institutions, has launched a project to formulate the Guidelines on Off-label Use of Common Psychiatric Medications in China ("Guideline"). The Guidelines focuses on evaluating evidence and formulating recommendations regarding off-label use scenarios of common psychiatric medications, including indications, dosage, administration, and specific populations. It employs standard methodological frameworks, notably the GRADE-ADOLOPMENT approach (Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision frameworks for adoption, adaptation, and de?novo development of recommendations), to ensure both scientific rigor and practical applicability. This proposal systematically outlines the background, objectives, processes, organizational structure, and methodologies of the Guideline, aiming to provide psychiatrists with practical and evidence-based prescribing recommendations.

Off-label drug use in psychiatry has long been prevelent, with common clinical practices lacking standardized guidance and associated risks warranting close attention. To address the practical needs of frontline clinicians, the Mental Health Branch of the China National Narcotic Drugs Association, in collaboration with multiple institutions, has launched a project to formulate the Guidelines on Off-label Use of Common Psychiatric Medications in China ("Guideline"). The Guidelines focuses on evaluating evidence and formulating recommendations regarding off-label use scenarios of common psychiatric medications, including indications, dosage, administration, and specific populations. It employs standard methodological frameworks, notably the GRADE-ADOLOPMENT approach (Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision frameworks for adoption, adaptation, and de?novo development of recommendations), to ensure both scientific rigor and practical applicability. This proposal systematically outlines the background, objectives, processes, organizational structure, and methodologies of the Guideline, aiming to provide psychiatrists with practical and evidence-based prescribing recommendations.

Antibody-drug conjugates(ADCs), as an emerging therapy for cancer treatment, have made significant progress in the past few decades. However, due to the heterogeneity of ADCs, they still face various issues and challenges in clinical therapy. Therefore, site-specific conjugation techniques have become a crucial area of research in ADCs, and in recent years, this field has witnessed numerous breakthrough advancements, empowering ADCs with enhanced performance. The review provides a comprehensive overview of the frontiers in site-specific conjugation technologies for ADCs. Categorized into seven major classes including lysine-based, cysteine-based, low-abundance amino acid-based and glycosylation site-based conjugation techniques, ribosomal incorporation of unnatural and noncanonical amino acids and enzyme-mediated conjugation techniques, it meticulously describes 21 classical and emerging techniques such as the THIOMAB technology and linchpin-directed modification, in order to offer valuable insights for the development of next-generation ADCs.

Objective:To analyze the distribution characteristics of UGT1A1 mutant genes (including enhancers, promoters, and exons 1-5) and further explore the correlation between UGT1A1 genotype and clinical phenotypes in patients with inherited hyperunconjugated bilirubinemia.Methods:Patients diagnosed with hereditary hyperunconjugated bilirubinemia at Nanjing Second Hospital from June 2015 to December 2022 were retrospectively analyzed. The UGT1A1 gene was examined using Sanger sequencing in all patients. Complete blood count, liver function, and abdominal imaging examinations were performed. Comparison of categorical variable data using χ2 testor Fisher percision tests. Comparison of continaous veriable data with normal distribution using t-test. Results:112 cases (male:female ratio 81:31, aged 9-70 years) had inherited hyperunconjugated bilirubinemia, with a total of 14 mutation sites identified, of which seven were confirmed mutations, and the frequency ranged from high to low: (TA)n accounted for 50%, c.211G>A (p.G71R) accounted for 49.10%, 1456T>G (p.Y486D) accounted for 16.96%, c.686C>A (p.R229W) accounted for 12.5%, 1091C>T (p.P364L) accounted for 8.04%, and c- 3279T>G accounted for 0.982%. Simultaneously, all patients had one to four mutations, of which only one mutation was the most common (55.36%), followed by two mutations (37.5%), and rare three and four mutations (5.36% and 1.78%). There was no statistical significance in total bilirubin (TBil) levels among the four groups ( F=0.652, P=0.583). One mutation was most common in (TA)n and c.211G>A (p.G71R), among which TA6/TA7 ( n=10) and TA7/TA7 ( n=14) mutations were statistically significant in TBil ( t=2.143, P=0.043). The c.211G>A (p.G71R) heterozygous ( n=9) and isolated ( n=15) mutation had no statistical significance in TBil ( t=0.382, P=0.706). The GS group accounted for 75%, the intermediate group accounted for 16.9%, and the CNS-Ⅱ group accounted for 8%. TBil was statistically significant among the three groups ( F=270.992, P<0.001). There was no statistically significant difference ( χ2=3.317, P=0.19) between mutation 1 (44 cases, 14 cases, and 4 cases, respectively) and mutations ≥ 2 (40 cases, 5 cases, and 5 cases, respectively) in the GS group, intermediate group, and CNS-II group. Conclusion:The number of UGT1A1 gene mutation sites may have no synergistic effect on TBil levels in patients with inherited hyperunconjugated bilirubinemia. TA7/TA7 mutations are not uncommon, and TBil levels are relatively high.

Humans ; Aortic Valve/surgery* ; Retrospective Studies ; Transcatheter Aortic Valve Replacement ; Sex Factors ; Heart Valve Prosthesis Implantation ; Treatment Outcome ; China ; Aortic Valve Stenosis/surgery* ; Risk Factors ; Risk Assessment

Humans ; Retrospective Studies ; Transcatheter Aortic Valve Replacement/adverse effects* ; Risk Assessment ; China ; Prognosis ; Aortic Valve Stenosis/surgery* ; Treatment Outcome ; Risk Factors ; Aortic Valve

Objective:To study the efficacy and safety of EndoClot polysaccharide hemostatic system (EndoClot PHS) for heparinized arterial hemorrhage of upper digestive tract (Forrest Ⅰa) in animal model.Methods:Twelve experimental pigs were randomly divided into the test group ( n=6) and the control group ( n=6) by simple random grouping method. Gastric arterial hemorrhage models were established. Endoclot PHS and Hemospray were used to spray on the wound to stop bleeding in the test group and the control group respectively. The time of effective hemostasis, the amount of hemostatic particles used, and the blockage of the powder feeding tube and its replacement were compared between the two groups. The survival and complications of experimental pigs were observed after the operation. In 10 days after the operation, the experimental pigs were euthanized for pathological dissection. Results:Spurting or pulsatile bleeding was achieved in all experimental pigs. There were significant differences in the time of effective hemostasis (8.75±0.84 min VS 9.83±0.62 min, t=-2.53, P=0.030) and the amount of hemostatic particles used to achieve effective hemostasis (6.71±0.39 g VS 14.10±1.62 g, t=-10.86, P<0.001) between the test group and the control group. There was no significant difference in the occurence of clogging or the replacement of powder feeding pipes between the two groups (0.64±0.02 times VS 0.67±0.04 times, t=-1.64, P=0.131). In addition, the gas source of the test group was stable, and the visual field under the endoscope was clear. Neither the test group nor the control group had gastric lesions, perforation, or embolism. The blood glucose, blood routine, and liver and kidney functions were normal, and no thrombosis or embolism of the main organs occurred in either group. Conclusion:EndoClot PHS is safe and effective for heparinized upper gastrointestinal arterial hemorrhage (Forrest Ⅰa) in animal models.

Objective:To study the clinical characteristics and classification of gastric neuroendocrine neoplasm(NEN) and prognostic factors of mixed adenoneuroendocrine carcinoma (MANEC) and gastric neuroendocrine carcinoma(NEC).Methods:A total of 148 gastric NENs were divided into type Ⅰ, type Ⅱ and type Ⅲ based on the classification of European Neuroendocrine Tumor Society (ENETS). Kaplan-Meier test and Cox regression model were used in univariate and multivariate survival analysis in 108 cases with pathological G3 gastric NEN.Results:In this study, the percentages of type Ⅰ, type Ⅱ and type Ⅲ were 25.0%(37), 3.4%(5) and 71.6%(106) respectively. Among type Ⅰ patients, 28(75.7%) lesions were located in gastric fundus or body, 29(78.4%) had bumps. Lymph node involvement was found in 4 (10.8%) patients. Twenty-six (70.3%) patients received endoscopic treatment and 11 (29.7%) with surgery. All 5 type Ⅱ patients presented lesions in gastric fundus or body, including 4 with ulcers, who were all treated by endoscope. Three type Ⅱ patients had gastrinoma, and 2 combined with multiple endocrine neoplasmⅠ. In type Ⅲ patients, 56(52.8%) showed ulcerative lesions. The majority of patients (102, 96.2%) had a single lesion, 94(88.7%) with lymph node or other organ metastasis. In this study, no deaths were reported in gastric NEN with a pathological grade of G1 or G2. The mortality rate was 38.9%(42/108) in patients with G3 NEN. Survival analysis suggested that age, metastasis of tumor were associated with poor prognosis ( P=0.041, 0.025). Conclusions:Patients with gastric NEN have heterogenous clinical presentations according to gender, age, endoscopic features, infiltration and metastasis, and pathological grade. Aging and metastasis are negative prognostic factors of G3 gastric NEN.