Alzheimer' s disease (AD) is a progressive neurodegenerative disorder histologically characterized by the presence of senile plaques and neurofibrillary tangles (NFTs) found in and around pyramidal neurons in cortical tissue. Mounting evidence suggests regional increased iron load and dyshomeostasis have been associated with oxidative stress, oxidation of proteins and lipids, and cell death, and appears to be a risk factor for more rapid cognitive decline, thereby involved in multiple aspects of the pathophysiology of AD. Ferroptosis is a newly identified iron-dependent lipid peroxidation-driven cell death and emerging evidences have demonstrated the involvement of ferroptosis in the pathological process of AD. Notably, some novel compounds targeting ferroptosis can relieve AD-related pathological symptoms in AD cells and animal model and exhibit potential clinical benefits in AD patients. This review systematically summarizes the growing molecular and clinical evidence implicating ferroptosis in the pathogenesis of AD, and then reviews the application of ferroptosis inhibitors in mouse/cell models to provide valuable information for future treatment and prevention of AD.

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.

Objective:To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST)in the treatment of patients with acute myeloid leukemia(AML).Methods:Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed.The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor(GPBSC),followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission(CR).The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated.Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype,including KIR ligand mismatch,2DS1,haplotype,and HLA-Cw ligands on survival prognosis of patients.Results:Forty-two patients received MST induction therapy,and the CR rate was 57.1％after 1 course and 73.7％after 2 courses.Multivariate analysis showed that,medium and high doses of NK cells was significantly associated with improved disease-free survival(DFS)of patients(HR=0.27,P=0.005;HR=0.21,P=0.001),and high doses of NK cells was significantly associated with improved overall survival(OS)of patients(HR=0.15,P=0.000).Donor 2DS1 positive significantly increases OS of patients(HR=0.25,P=0.011).For high-risk patients under 60 years old,patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group(P=0.036);donor 2DS1 positive significantly prolonged OS of patients(P=0.009).Conclusion:NK cell dose,KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST,improve the survival of AML patients.

Objective:To investigate the effect of flow cytometric minimal residual disease(MRD)detection at different time points during AML chemotherapy on prognosis.Methods:130 adult primary AML patients diagnosed and standardized with chemotherapy from March 2018 to March 2022 were retrospectively analyzed,MRD was detected by flow cytometry,Kaplan-Meier curves was used for survival analysis and log-rank test was used for variance analysis,and univariate and multifactor influencing patient survival with COX proportional risk regression model analysis.Cumulative incidence rate(CIR)analysis with competing risk model and variance analysis using Fine-Gray.Results:There were 81 CR1,26 CR2,14 PR,and 9 NR patients in 130 patients.OS of the CR1 group was higher than that in the CR2,PR,and NR groups.OS of the CR2 group was higher than that in the PR group,but there was no statistically difference compared to the NR group.There was no statistically difference in OS between the PR and NR groups.107 patients in CR1 and CR2 were grouped according to MRD detected by flow cytometry,and after the first induction chemotherapy,for patients in the MRD-and MRD+groups,the 4-year expected RFS rates were 65.3％and 27.9％respectively,the 4-year expected OS rates were 58.7％and41.4％respectively,and the 4-year expected CIR were 34.7％and 69.7％respectively,with statistically significant differences between 2 groups(x2=6.639,P=0.010;x2=6.131,P=0.013 and x2=6.637,P=0.010).After the second chemotherapy,for patients in the MRD-and MRD+groups,the 4-year expected RFS rates were 50.8％and 37.9％respectively,the 4-year expected OS rates were 49.2％and 44.5％respectively,and the 4-year expected CIR were 49.2％and 59.5％respectively,with no statistically significant differences between 2 groups(x2=1.475,P=0.225;x2=2.432,P=0.119 and x2=1.416,P=0.234).During consolidation therapy,for patients in the MRD-and MRD+groups,the 4-year expected RFS rates were 51.9％and 29.6％respectively,the 4-year expected OS rates were 67.5％and 24.6％respectively,and the 4-year expected CIR were 48.1％and 70.4％respectively,with statistically significant differences between 2 groups(x2=20.982,P＜0.001;x2=17.794,P＜0.001 and x2=19.879,P＜0.001).For patients with MRD-at all three time points and positive at either time point,the 4-year expected RFS rates were 69.9％and 33.3％respectively,the 4-year expected OS rates were 59.1％and 44.7％respectively,and the 4-year expected CIR were 30.1％and 65.1％respectively,with statistically significant differences between 2 groups(x2=7.367,P=0.007;x2=6.042,P=0.014 and x2=7.662,P=0.006).Univariate analysis showed that karyotype at high risk of chromosome was an unfavorable factor affecting patients'RFS and OS,while 2 cycles of induction chemotherapy achieved CR,MRD-after the first induction chemotherapy and MRD-after the second induction chemotherapy was a protective factor affecting patients'RFS and OS.MRD-during consolidation therapy and MRD-at all three time points were all protective factors affecting patients'RFS,OS and CIR.Multivariate analysis showed that induction chemotherapy for 2 cycles achieved CR was a protective factor affecting patients'RFS and CIR,and MRD-during consolidation therapy was a protective factor affecting patients'RFS,OS and CIR.Conclusion:Early achievement of CR and MRD-in adult AML patients,especially MRD-during consolidation therapy,is a marker of good prognosis,and flow cytometry is the most commonly used method for MRD detection in AML 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.

Objective:To observe any effect of bilateral high-frequency repetitive transcranial magnetic stimulation (rTMS) of the cerebellum on the swallowing of stroke survivors with dysphagia.Methods:Thirty-eight patients with post-stroke dysphagia were randomly divided into a cerebellar stimulation group of 20 and a sham group of 18. In addition to drug therapy and physical rehabilitation training, the cerebellar stimulation group received 500 pulses of rTMS of the cerebellum daily at 10Hz and 120% of the resting movement threshold lasting 1s at 9s intervals. The sham stimulation group was treated with sham rTMS (with the angle between the stimulation coil and the scalp at 90°). Twenty minutes later, both groups were given 30 minutes of routine swallowing training daily by the same speech therapist. The treatment was administered 5 times a week for 3 weeks. Before the treatment and afterward, both groups′ swallowing was evaluated y videofluoroscopic swallowing study (VFSS), using a functional dysphagia scale (FDS) and using the Rosenbek penetration aspiration scale (PAS). Oral transport time, swallowing response time, pharyngeal transport time, laryngeal vestibular closure time and upper esophageal sphincter opening duration were recorded, and the changes in swallowing function and swallowing time parameters before and after the treatment were compared between the two groups.Results:Before the stimulation there were no significant differences between the two groups. Afterward, the average PAS and FDS scores of both groups had improved significantly, but with significantly greater improvement in the cerebellar stimulation group than in the sham group. Average oral transit time and swallow response time had shortened significantly, but with significantly shorter time, on average, in the cerebellar stimulation group.Conclusion:Bilateral high-frequency rTMS of the cerebellum can improve the swallowing of persons with dysphagia, and shorten their oral transit time and swallow response time.

Humans ; Fibrosarcoma/surgery* ; Sarcoma ; Temporal Bone ; Soft Tissue Neoplasms/surgery*

Humans ; COVID-19/genetics* ; SARS-CoV-2/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; CRISPR-Cas Systems/genetics* ; RNA, Viral/genetics*

AIM: To investigate the effectiveness of panretinal photocoagulation(PRP)combined with intravitreal conbercept(IVC)for patients with different stages of proliferative diabetic retinopathy(PDR).METHODS: Retrospective study. The medical records for 100 patients(100 eyes)with PDR treated with PRP combined with IVC from January 2018 to June 2020 were reviewed, including 34 eyes with early PDR(group A), 43 with high-risk PDR(group B), and 23 with fibrovascular PDR(group C). The baseline information, best corrected visual acuity(BCVA), central macular thickness(CMT), the rate of vitrectomy and retinal detachment of the patients in the three groups at 1, 3, 6mo and the last follow-up after combination treatment were observed.RESULTS: The patients were followed up for 14.60±11.64mo(6-52mo), with a mean age of 54.22 ±9.32 years. We found 15 eyes(15.0%)who underwent vitrectomy after the combination treatment. The vitrectomy rates of the three groups were 2.9% in group A, 13.9% in group B, and 34.7% in group C. We found no instances of retinal detachment after the treatments. Most patients demonstrated improved BCVA and CMT values with the treatments.CONCLUSION: PRP combined with IVC is safe and effective in patients with different PDR stages.