Immune checkpoints include a series of receptor-ligand pairs that play a key role in the proliferation, activation, and immune regulatory responses of immune cells. Although immune checkpoint inhibitors (ICIs), such as programmed death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have achieved good therapeutic effects in clinical practice, some patients still experience ineffective treatment and immune resistance. A large amount of evidence has shown that immune checkpoint proteins are related to cell metabolism during immune regulation. On the one hand, immune checkpoints connect to alter the metabolic reprogramming of tumor cells to compete for nutrients required by immune cells. On the other hand, immune checkpoints regulate the metabolic pathways of immune cells, such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) to affect the activation of immune cells. Based on a review of the literature, this article reviews the mechanisms by which PD-1, CTLA-4, T cell immunoreceptor with Ig and ITIM domains (TIGIT), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), cluster of differentiation 47 (CD47), and indoleamine 2,3-dioxygenase 1 (IDO1) regulate cell metabolic reprogramming, and looks forward to whether targeting the ligand-receptor pairs of immune checkpoints in a "dual regulation" manner and inhibiting metabolic pathways can effectively solve the problem of tumor immune resistance.
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Humans ; Neoplasms/genetics* ; Metabolic Networks and Pathways/immunology* ; Animals ; Immune Checkpoint Inhibitors/pharmacology*

OBJECTIVE To compare the effect on umbilical care of the neonates between the natural dying method and the traditional ethanol disinfection method so as to provide a better method of umbilical nursing for the neo-nates.METHODS A total of 212 healthy neonates who were given birth in the First Medical Center of Chinese PLA General Hospital from Aug.2024 to Nov.2024 were recruited as the research subjects and were randomly divided into the natural drying method with 103 cases and the traditional ethanol disinfection method with 109 cases ac-cording to the method of umbilical care.The time of umbilical cord separation,rate of umbilical bleeding and inci-dence of umbilical secretions were observed and compared between the two groups of neonates.RESULTS There were 16 neonates with the healing time of umbilical cord separation no more than 7 days under the treatment of natural drying method,with 5 cases more than the neonates under the treatment of traditional ethanol disinfection method.The average healing time of umbilical cord separation was 11.69 days under the natural drying method,1.43 days shorter than 13.12 days under the traditional ethanol disinfection method,and there was significant difference(P＜0.05).The rate of umbilical bleeding was 5.82％under the natural drying method,a reduction of 0.60％as compared with 6.42％under the traditional ethanol disinfection method;the incidence of umbilical se-cretions was 0.97％under the national drying method,a reduction of 1.78％as compared with 2.75％under the traditional ethanol disinfection method,but there were no significant differences.CONCLUSIONS As compared with the traditional ethanol disinfection method,the natural drying method can shorten the time of umbilical cord separation,reduce the risk of umbilical infection,and reduce the stress from the neonatal nursing.It is worthy to be promoted.

OBJECTIVE To compare the effect on umbilical care of the neonates between the natural dying method and the traditional ethanol disinfection method so as to provide a better method of umbilical nursing for the neo-nates.METHODS A total of 212 healthy neonates who were given birth in the First Medical Center of Chinese PLA General Hospital from Aug.2024 to Nov.2024 were recruited as the research subjects and were randomly divided into the natural drying method with 103 cases and the traditional ethanol disinfection method with 109 cases ac-cording to the method of umbilical care.The time of umbilical cord separation,rate of umbilical bleeding and inci-dence of umbilical secretions were observed and compared between the two groups of neonates.RESULTS There were 16 neonates with the healing time of umbilical cord separation no more than 7 days under the treatment of natural drying method,with 5 cases more than the neonates under the treatment of traditional ethanol disinfection method.The average healing time of umbilical cord separation was 11.69 days under the natural drying method,1.43 days shorter than 13.12 days under the traditional ethanol disinfection method,and there was significant difference(P＜0.05).The rate of umbilical bleeding was 5.82％under the natural drying method,a reduction of 0.60％as compared with 6.42％under the traditional ethanol disinfection method;the incidence of umbilical se-cretions was 0.97％under the national drying method,a reduction of 1.78％as compared with 2.75％under the traditional ethanol disinfection method,but there were no significant differences.CONCLUSIONS As compared with the traditional ethanol disinfection method,the natural drying method can shorten the time of umbilical cord separation,reduce the risk of umbilical infection,and reduce the stress from the neonatal nursing.It is worthy to be promoted.

ObJective·To evaluate the dentofacial phenotype in non-syndromic tooth agenesis(NSTA)patients with paired box gene 9(PAX9)mutation.Methods·Patients with NSTA who visited the Department of Second Dental Center of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,between January 2016 and December 2023 received whole-exome sequencing to screen PAX9 mutation.The location and number of missing teeth were evaluated by oral pantomography,and dentofacial deformities were evaluated by X-ray cephalometrics.Results·Seven patients with PAX9 mutation were included in the study,including 3 males(42.9％)and 4 females(57.1％).The patients were 7-31 years old at first visit,with a mean age of(19.7±8.0)years old.All the 7 patients were PAX9 heterozygotes,of which 4 were missense and 3 were frameshift.The average number of missing teeth was 15.9±2.9.The number of missing teeth in maxilla(9.6±2.6)was slightly higher than that in mandible(6.3±2.4)(P=0.030).Maxillary second molar(100.0％),maxillary canine(85.7％)and mandibular second premolar(85.7％)were the three most common missing teeth,while mandibular lateral incisor(14.3％)and mandibular canine(14.3％)were the two least missing teeth.Patients with frameshift mutation had more missing teeth(18.3±2.1)than those with missense mutation(14.0±1.8)(P=0.032).X-ray cephalometrics analysis results showed that the angle sella-nasion-subspinale(SNA),angle nasion-subspinale-subspinale-porion(NA-Apo)and sella-nasion(S-N)in adult patients with PAX9 mutation were significantly lower than the normal reference values,suggesting a shorter anterior cranial base and maxillary length.The frankfort horizontal plane-nasion-porion(FH-NPo)was higher than the reference value,and the Y-axis was lower than the reference value,indicating a more prognathic mandible.The angle subspinale-nasion-supramental(ANB)was lower than the reference value,indicating a skeletal angle Ⅲ malocclusion.The angle upper central incisor-nasion-subspinale(angle U1-NA)was higher than the reference value,indicating a lip inclination of maxillary central incisor.The angle lower central incisor-mandibular plane(IMPA)and lower central incisor-nasion-supramental(L1-NB)were lower than the reference values,indicating a retroclination of the mandibular central incisor,and crossbite in the maxillary and mandibular anterior teeth.Conclusion·The dentofacial phenotype of PAX9-mutated patients with NSTA is reported comprehensively.It is helpful to improve the understanding of the role of PAX9 in human maxillofacial development.