OBJECTIVE A clinical comprehensive evaluation of five biologic targeted drugs for the treatment of severe eosinophilic asthma （SEA） was conducted to provide objective evidence for the rational selection of these medications in medical institutions. METHODS Using the evaluation methods from the Chinese Medical Institution Drug Evaluation and Selection Rapid Guide （ Third Edition ）， the effectiveness， safety， pharmaceutical characteristics， cost-effectiveness， and other attributes of five biologics targeting SEA （omalizumab， mepolizumab， benralizumab， dupilumab， and tezepelumab） already marketed in China were quantitatively scored across five dimensions， and their recommendation levels were categorized based on the scores. RESULTS The comprehensive scoring results showed that mepolizumab scored 81.29， making it a highly recommended variety； benralizumab scored 78.05， dupilumab scored 77.84 and omalizumab scored 70.14，all of which are recommended varieties； tezepelumab scored 67.77， considered weakly recommended variety. CONCLUSIONS Mepolizumab shows excellent performance in eosinophil clearance， good accessibility， and is more cost-effective than the others， making it more selective in SEA treatment； omalizumab has more advantages in the treatment of SEA patients with elevated immunoglobulin E levels； dupilumab can be used as the preferred treatment for SEA patients with chronic obstructive pulmonary disease.

OBJECTIVE A clinical comprehensive evaluation of five biologic targeted drugs for the treatment of severe eosinophilic asthma （SEA） was conducted to provide objective evidence for the rational selection of these medications in medical institutions. METHODS Using the evaluation methods from the Chinese Medical Institution Drug Evaluation and Selection Rapid Guide （ Third Edition ）， the effectiveness， safety， pharmaceutical characteristics， cost-effectiveness， and other attributes of five biologics targeting SEA （omalizumab， mepolizumab， benralizumab， dupilumab， and tezepelumab） already marketed in China were quantitatively scored across five dimensions， and their recommendation levels were categorized based on the scores. RESULTS The comprehensive scoring results showed that mepolizumab scored 81.29， making it a highly recommended variety； benralizumab scored 78.05， dupilumab scored 77.84 and omalizumab scored 70.14，all of which are recommended varieties； tezepelumab scored 67.77， considered weakly recommended variety. CONCLUSIONS Mepolizumab shows excellent performance in eosinophil clearance， good accessibility， and is more cost-effective than the others， making it more selective in SEA treatment； omalizumab has more advantages in the treatment of SEA patients with elevated immunoglobulin E levels； dupilumab can be used as the preferred treatment for SEA patients with chronic obstructive pulmonary disease.

At present,the diagnostic criteria for acute severe autoimmune hepatitis(AS-AIH)include acute onset,consistency with the diagnostic criteria for autoimmune hepatitis(AIH),presence of jaundice,and international normalized ratio≥1.5 at the time of diagnosis,without evidence of hepatic encephalopathy or previous liver disease.As a special subtype of AIH,AS-AIH is characterized by acute onset and rapid disease progression,and thus early diagnosis is of vital importance.Glucocorticoid therapy should be given as early as possible after diagnosis to prevent the progression to acute liver failure and reduce the risk of liver transplantation.Management of AS-AIH patients is challenging,since patients often lack typical clinical features and histological manifestations of AIH at the time of diagnosis,and early assessment of glucocorticoid response and a treatment regimen with proper doses are important for improving the prognosis of patients.

At present,the diagnostic criteria for acute severe autoimmune hepatitis(AS-AIH)include acute onset,consistency with the diagnostic criteria for autoimmune hepatitis(AIH),presence of jaundice,and international normalized ratio≥1.5 at the time of diagnosis,without evidence of hepatic encephalopathy or previous liver disease.As a special subtype of AIH,AS-AIH is characterized by acute onset and rapid disease progression,and thus early diagnosis is of vital importance.Glucocorticoid therapy should be given as early as possible after diagnosis to prevent the progression to acute liver failure and reduce the risk of liver transplantation.Management of AS-AIH patients is challenging,since patients often lack typical clinical features and histological manifestations of AIH at the time of diagnosis,and early assessment of glucocorticoid response and a treatment regimen with proper doses are important for improving the prognosis of patients.

Neonatal sepsis is a global health problem that seriously affects the body health and life safety of newborns. It has a higher incidence in preterm infants,especially for early-onset sepsis (EOS) within 72 hours of birth. The diagnosis of neonatal EOS requires a series of examinations,and early and accurate diagnosis can improve clinical outcomes and reduce antibiotic overuse in a timely manner. At present,the commonly used biomarkers and traditional blood culture methods for EOS diagnosis have certain shortcomings,so it is urgent to find new molecular diagnostic methods. This article summarizes and compares the early and novel diagnostic methods of neonatal EOS,in order to provide a reference for clinical practice.

OBJECTIVE: This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease (NAFLD) in children with obesity. METHODS: We conducted a two-step case-control study. Ninety-three participants were subjected to whole-exome sequencing (exploratory set). Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing (validation set). RESULTS: In the exploratory set, 14 genes from the NAFLD-associated pathways were identified. In the validation set, after adjusting for sex, age, and body mass index, ECI2 rs2326408 (dominant model: OR = 1.33, 95% CI: 1.02-1.72; additive model: OR = 1.22, 95% CI: 1.01-1.47), C6orf201 rs659305 (dominant model: OR = 1.30, 95% CI: 1.01-1.69; additive model: OR = 1.21, 95% CI: 1.00-1.45), CALML5 rs10904516 (pre-ad dominant model: OR = 1.36, 95% CI: 1.01-1.83; adjusted dominant model: OR = 1.40, 95% CI: 1.03-1.91; and pre-ad additive model: OR = 1.26, 95% CI: 1.04-1.66) polymorphisms were significantly associated with NAFLD in children with obesity ( P < 0.05). Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516, COX11 rs17209882, and SCD5 rs3733228 was optional ( P < 0.05), demonstrating a negative interaction between the three genes. CONCLUSION In the Chinese population, the CALML5 rs10904516, C6orf201 rs659305, and ECI2 rs2326408 variants could be genetic markers for NAFLD susceptibility.
Humans ; Non-alcoholic Fatty Liver Disease/genetics* ; Child ; Male ; Female ; Genetic Predisposition to Disease ; Case-Control Studies ; Exome Sequencing ; Adolescent ; Polymorphism, Single Nucleotide ; Obesity/complications* ; Pediatric Obesity/complications* ; China

Research on immune checkpoints such as programmed death protein-1(PD-1)and cytotoxic T lymphocyte antigen-4(CTLA-4)has provided new directions for tumor treatment.V-domain immunoglobulin suppressor of T-cell activation(VISTA)is an emerging immune checkpoint within the B7 family.Functioning as both a ligand and a receptor,VISTA is an inhibitory immune checkpoint molecule expressed in tumor cells,myeloid cells and T lymphocytes.It plays a crucial role in regulating autoimmunity,inflammatory response and tumor immunity.The non-redundant interactions between VISTA and other immune checkpoints,such as PD-1,may offer new therapeutic strategies and serve as a new target for overcoming immunotherapy resistance.This review summarizes the recent research progress on VISTA in hematological tumors,aiming to provide new insights into its application in the treatment of these malignancies.

Neonatal sepsis is a global health problem that seriously affects the body health and life safety of newborns. It has a higher incidence in preterm infants,especially for early-onset sepsis (EOS) within 72 hours of birth. The diagnosis of neonatal EOS requires a series of examinations,and early and accurate diagnosis can improve clinical outcomes and reduce antibiotic overuse in a timely manner. At present,the commonly used biomarkers and traditional blood culture methods for EOS diagnosis have certain shortcomings,so it is urgent to find new molecular diagnostic methods. This article summarizes and compares the early and novel diagnostic methods of neonatal EOS,in order to provide a reference for clinical practice.

Objective:To explore and analyze the clinical features of patients with immunoglobulin (Ig)G4-related hepatobiliary-pancreatic disease and the independent factors affecting the prognosis of IgG4-related sclerosing cholangitis (IgG4-SC).Methods:The clinical data of 179 adult cases diagnosed with IgG4-related hepato-pancreato-biliary disease in the Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2011 to December 2022 were retrospectively analyzed. Patients were divided into three groups: isolated IgG4-SC, IgG4-SC/type 1 autoimmune pancreatitis(type 1 AIP), and isolated AIP according to the clinical manifestations. Demographic characteristics, baseline biochemical immunological indexes, and imaging manifestations were analyzed. The treatment response rate and survival rate were compared. The COX proportional hazards model was used to analyze the independent factors related to prognosis.Results:The mean age of diagnosis of patients with IgG4-related hepatobiliary-pancreatic disease was 60.3±12.0 years. Males accounted for 74.9%, and the median follow-up time was 38 months. The 1-year clinical response rate of patients with isolated IgG4-SC was lower than that of IgG4-SC/AIP (67.9% vs. 91.7%, P=0.019), and the primary endpoint-free 5-year survival rate was significantly reduced (64.9% vs. 95.9%, P<0.001). COX regression analysis showed that having cirrhosis before treatment ( HR=6.708, P=0.004) and poor response after half a year of treatment ( HR=11.488, P=0.002) were independent risk factors associated with the occurrence of adverse events in hepatobiliary diseases among patients with IgG4-SC. Conclusions:The clinical response rate and survival rate of patients with isolated IgG4-SC are lower than those of patients with IgG4-SC/AIP. Patients with IgG4-SC who do not respond well at six months of treatment and who have progressed to cirrhosis before treatment are at significantly increased risk of adverse events.