AIM:This study aims to investigate the effect of Agaricus blazei extract FA-2-b-β on ferroptosis of Burkitt lymphoma cells and its mechanism.METHODS:Burkitt lymphoma cell lines Raji and CA46 were treated with FA-2-b-β alone and in combination with ferrostatin-1,a ferroptosis inhibitor,or Stattic,a signal transducer and activator of transcription 3(STAT3)inhibitor.Cell viability was assessed using the CCK-8 method,and the half-maximal inhibitory concentration(IC50)of FA-2-b-β was calculated.Flow cytometry was used to detect apoptosis,cell cycle,mitochondrial membrane potential,and reactive oxygen species(ROS).Additionally,malondialdehyde(MDA)and glutathione(GSH)levels were measured using kits.The mRNA and protein expression levels of ferroptosis-related molecules were determined by RT-qPCR and Western blot.RESULTS:The extract FA-2-b-β at different concentrations significantly inhibited the proliferation of Raji and CA46 cells(P＜0.05),promoted their death,regulated cell arrest in G0/G1 phase,and decreased the mitochondrial membrane potential.(2)ROS and MDA levels were significantly increased with different concentrations of the extract FA-2-b-β(P＜0.05),while the GSH content was significantly decreased(P＜0.05).(3)The protein and mRNA levels of signal transducer and activator of transcription 3(STAT3),p-STAT3,and glutathione peroxidase 4(GPX4)were down-regulated at different concentrations of the extract FA-2-b-β.In addition,prostaglandin-endoperoxide synthase 2(PTSG2)and transferrin receptor protein 1(TfR1)protein and mRNA were up-regulated(P＜0.05),while the protein and mRNA levels of solute carrier family 7 member 11(SLC7A11)were not significantly changed.CONCLU-SION:The extract FA-2-b-β can induce ferroptosis in burkitt lymphoma,and the mechanism may be related to the inhibi-tion of STAT3/GPX4 signaling pathway.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

Objective:To evaluate the efficacy and safety of eculizumab in treating acute attacks of aquaporin-4 antibody(AQP4-IgG)positive neuromyelitis optica spectrum disorder(NMOSD).Methods:Six patients with AQP4-IgG-positive NMOSD treated with eculizumab at the Affiliated Hospital of Qingdao University from August 2023 to April 2024 were included.The patients' clinical characteristics, changes in scores of neurological function, pain and spasm before and after eculizumab treatment, and adverse drug reactions during the treatment period were described, and the data were subjected to Friedman test using SPSS 25.0.Results:The median score of expanded disability status scale in the six patients decreased from 3.25 before treatment to 1.25 after treatment, and the difference was statistically significant ( F=44.77, P<0.01).The functional status score showed noticeable improvement as early as week 1, demonstrating greater sensitivity to treatment response.Three patients experienced moderate to severe pain before treatment, with a mean pain score of 6, which reduced to 4.67 and 1.33 at week 2 and 6, respectively( F=29.17, P<0.05).Two patients reported spasms before treatment, with a mean score of 3.00, which decreased to 2.00, 1.50, and 1.00 at week 2, 3, and 6 after treatment, respectively( F=18.00, P>0.05).No serious adverse reactions were reported during the treatment. Conclusion:Eculizumab can effectively improve the neurological function and alleviate pain in patients with AQP4-IgG-positive NMOSD during acute attacks, and demonstrate good safety.

Objective:To evaluate the efficacy and safety of eculizumab in treating acute attacks of aquaporin-4 antibody(AQP4-IgG)positive neuromyelitis optica spectrum disorder(NMOSD).Methods:Six patients with AQP4-IgG-positive NMOSD treated with eculizumab at the Affiliated Hospital of Qingdao University from August 2023 to April 2024 were included.The patients' clinical characteristics, changes in scores of neurological function, pain and spasm before and after eculizumab treatment, and adverse drug reactions during the treatment period were described, and the data were subjected to Friedman test using SPSS 25.0.Results:The median score of expanded disability status scale in the six patients decreased from 3.25 before treatment to 1.25 after treatment, and the difference was statistically significant ( F=44.77, P<0.01).The functional status score showed noticeable improvement as early as week 1, demonstrating greater sensitivity to treatment response.Three patients experienced moderate to severe pain before treatment, with a mean pain score of 6, which reduced to 4.67 and 1.33 at week 2 and 6, respectively( F=29.17, P<0.05).Two patients reported spasms before treatment, with a mean score of 3.00, which decreased to 2.00, 1.50, and 1.00 at week 2, 3, and 6 after treatment, respectively( F=18.00, P>0.05).No serious adverse reactions were reported during the treatment. Conclusion:Eculizumab can effectively improve the neurological function and alleviate pain in patients with AQP4-IgG-positive NMOSD during acute attacks, and demonstrate good safety.

AIM:This study aims to investigate the effect of Agaricus blazei extract FA-2-b-β on ferroptosis of Burkitt lymphoma cells and its mechanism.METHODS:Burkitt lymphoma cell lines Raji and CA46 were treated with FA-2-b-β alone and in combination with ferrostatin-1,a ferroptosis inhibitor,or Stattic,a signal transducer and activator of transcription 3(STAT3)inhibitor.Cell viability was assessed using the CCK-8 method,and the half-maximal inhibitory concentration(IC50)of FA-2-b-β was calculated.Flow cytometry was used to detect apoptosis,cell cycle,mitochondrial membrane potential,and reactive oxygen species(ROS).Additionally,malondialdehyde(MDA)and glutathione(GSH)levels were measured using kits.The mRNA and protein expression levels of ferroptosis-related molecules were determined by RT-qPCR and Western blot.RESULTS:The extract FA-2-b-β at different concentrations significantly inhibited the proliferation of Raji and CA46 cells(P＜0.05),promoted their death,regulated cell arrest in G0/G1 phase,and decreased the mitochondrial membrane potential.(2)ROS and MDA levels were significantly increased with different concentrations of the extract FA-2-b-β(P＜0.05),while the GSH content was significantly decreased(P＜0.05).(3)The protein and mRNA levels of signal transducer and activator of transcription 3(STAT3),p-STAT3,and glutathione peroxidase 4(GPX4)were down-regulated at different concentrations of the extract FA-2-b-β.In addition,prostaglandin-endoperoxide synthase 2(PTSG2)and transferrin receptor protein 1(TfR1)protein and mRNA were up-regulated(P＜0.05),while the protein and mRNA levels of solute carrier family 7 member 11(SLC7A11)were not significantly changed.CONCLU-SION:The extract FA-2-b-β can induce ferroptosis in burkitt lymphoma,and the mechanism may be related to the inhibi-tion of STAT3/GPX4 signaling pathway.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

Objective:To observe the genetic variation of SH2B3 in patients with myeloid neoplasms.Methods:The results of targeted DNA sequencing associated with myeloid neoplasms in the Department of Hematology,Xuanwu Hospital,Capital Medical University from November 2017 to November 2022 were retrospectively analyzed,and the patients with SH2B3 gene mutations were identified.The demographic and clinical data of these patients were collected,and characteristics of SH2B3 gene mutation,co-mutated genes and their correlations with diseases were analyzed.Results:The sequencing results were obtained from 1 005 patients,in which 19 patients were detected with SH2B3 gene mutation,including 18 missense mutations(94.74％),1 nonsense mutation(5.26％),and 10 patients with co-mutated genes(52.63％).Variant allele frequency(VAF)ranged from 0.03 to 0.66.The highest frequency mutation was p.Ile568Thr(5/19,26.32％),with an average VAF of 0.49,involving 1 case of MDS/MPN-RS(with SF3B1 mutation),1 case of MDS-U(with SF3B1 mutation),1 case of aplastic anemia with PNH clone(with PIGA and KMT2A mutations),2 cases of MDS-MLD(1 case with SETBP1 mutation).The other mutations included p.Ala567Thr in 2 cases(10.53％),p.Arg566Trp,p.Glu533Lys,p.Met437Arg,p.Arg425Cys,p.Glu314Lys,p.Arg308*,p.Gln294Glu,p.Arg282Gln,p.Arg175Gln,p.Gly86Cys,p.His55Asn and p.Gln54Pro in 1 case each.Conclusion:A wide distribution of genetic mutation sites and low recurrence of SH2B3 is observed in myeloid neoplasms,among of them,p.Ile568Thr mutation is detected with a higher incidence and often coexists with characteristic mutations of other diseases.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.