To guide transfusion practice in critically ill children who often need plasma and platelet transfusions, the Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB) developed Recommendations and Expert Consensus for Plasma and Platelet Transfusion Practice in Critically Ill Children. This guideline addresses 53 recommendations related to plasma and platelet transfusion in critically ill children with 8 kinds of diseases, laboratory testing, selection/treatment of plasma and platelet components, and research priorities. This paper introduces the specific methods and results of the recommendation formation of the guideline.

Objective To study the in vitro expression of three phenylalanine hydroxylase(PAH)mutants(p.R243Q,p.R241C,and p.Y356X)and determine their pathogenicity.Methods Bioinformatics techniques were used to predict the impact of PAH mutants on the structure and function of PAH protein.Corresponding mutant plasmids of PAH were constructed and expressed in HEK293T cells.Quantitative reverse transcription polymerase chain reaction was used to measure the mRNA expression levels of the three PAH mutants,and their protein levels were assessed using Western blot and enzyme-linked immunosorbent assay.Results Bioinformatics analysis predicted that all three mutants were pathogenic.The mRNA expression levels of the p.R243Q and p.R241C mutants in HEK293T cells were similar to the mRNA expression level of the wild-type control(P>0.05),while the mRNA expression level of the p.Y356X mutant significantly decreased(P<0.05).The PAH protein expression levels of all three mutants were significantly reduced compared to the wild-type control(P<0.05).The extracellular concentration of PAH protein was reduced in the p.R241C and p.Y356X mutants compared to the wild-type control(P<0.05),while there was no significant difference between the p.R243Q mutant and the wild type control(P>0.05).Conclusions p.R243Q,p.R241C and p.Y356X mutants lead to reduced expression levels of PAH protein in eukaryotic cells,with p.R241C and p.Y356X mutants also affecting the function of PAH protein.These three PAH mutants are to be pathogenic.[Chinese Journal of Contemporary Pediatrics,2024,26(2):188-193]

Objective:To explore the real work experience and needs of nursing assistants of elderly patients with disability and mental disorders, and provide reference for relevant institutions to develop a reasonable support system and promote their physical and mental health.Methods:From October to November 2022, purposive sampling was used to select nursing assistants of elderly patients with disability and mental disorders from the Affiliated Brain Hospital of Guangzhou Medical University as the research subject. The phenomenological method was used to conduct in-depth interviews, recordings, and transcripts of 12 nursing assistants. The Colaizzi analysis program was used to analyze, organize, refine, and summarize.Results:A total of five themes were extracted, including multiple emotional experiences, lack of rest and relaxation, insufficient professional identity and external support, lack of care knowledge and skills, heavy workload and poor treatment.Conclusions:Accompanying management institutions and hospitals need to strengthen their attention to nursing assistants, reduce their physical and mental burden, attach importance to skill training, increase welfare benefits, enhance professional identity, and improve the quality of care.

Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD. However, the exact mechanism of Aβ clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aβ. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro. Moreover, enhancing blood monocyte Aβ phagocytosis by improving energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.
Animals ; Mice ; Alzheimer Disease ; Amyloid beta-Peptides ; Monocytes ; Cognition ; Energy Metabolism ; Phagocytosis

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.
Mice ; Animals ; Alzheimer Disease/pathology* ; Receptor, Nerve Growth Factor ; Amyloid beta-Peptides ; Autoantibodies ; Mice, Transgenic

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Deficits in the clearance of amyloid β protein (Aβ) by the peripheral system play a critical role in the pathogenesis of sporadic Alzheimer's disease (AD). Impaired uptake of Aβ by dysfunctional monocytes is deemed to be one of the major mechanisms underlying deficient peripheral Aβ clearance in AD. In the current study, flow cytometry and biochemical and behavioral techniques were applied to investigate the effects of polysaccharide krestin (PSK) on AD-related pathology in vitro and in vivo. We found that PSK, widely used in therapy for various cancers, has the potential to enhance Aβ uptake and intracellular processing by human monocytes in vitro. After administration of PSK by intraperitoneal injection, APP/PS1 mice performed better in behavioral tests, along with reduced Aβ deposition, neuroinflammation, neuronal loss, and tau hyperphosphorylation. These results suggest that PSK holds promise as a preventive agent for AD by strengthening the Aβ clearance by blood monocytes and alleviating AD-like pathology.
Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Animals ; Cognition ; Disease Models, Animal ; Mice ; Mice, Transgenic ; Monocytes/pathology* ; Polysaccharides/therapeutic use* ; Proteoglycans

AIM: To observe the changes of the morphology and structure of macula, blood flow density of macula and optic disc, as well as retinal nerve fiber layer thickness by optical coherence tomography(OCT)and optical coherence tomography angiography(OCTA)in patients with rhegmatogenous retinal detachment(RRD)under went sclera buckling(SB). METHODS: As a cross-sectional case-controlled study, 25 patients(25 eyes)were diagnosed with RRD in the department of ophthalmology, Ganzhou People's Hospital from July 2014 to March 2021. The differences in the vascular density(VD)of superficial vessel cluster(SVC), the VD of deep vessel cluster(DVC)of macula, the SVC-VD of optic disc, retinal nerve fiber layer(RNFL), central macular thickness(CMT), subfoveal choroidal thickness(SFCT)and outer structure of macula between the affected eyes and healthy eyes at the last post-operative follow-up were compared, and the correlation indicators affecting best corrected visual acuity(BCVA, LogMAR)of the affected eyes at the last follow-up were analyzed. RESULTS: There were no statistically significant in SVC-VD and DVC-VD of macula, SVC-VD of optic disc, RNFL, CMT, SFCT between the affected eyes and healthy eyes at the last post-operative follow-up(all P>0.05); At the last follow-up visit, the comparison of macular outer structure on OCT between the affected eyes and the healthy eyes showed that the light band integrity of the external limiting membrane(ELM), myoid zone(MZ), ellipsoid zone(EZ)and outer segment of photoreceptor(OS)had no statistically significant difference(all P>0.05), while the light band integrity of interdigitation zone(IZ)had significant difference(P=0.014); The difference of BCVA(LogMAR)between the affected eyes and the healthy eyes at the last follow-up was statistically significant(P=0.002). There was significant correlation between BCVA(LogMAR)of affected eyes at the last post-operative follow-up and the presence or absence of macular involvement, the correlated with SVC-VD of optic disc, the integrity of the light bands of ELM, MZ, EZ, OS and IZ on the outer structure of macula, it was positively correlated with the presence or absence of macular involvement(rs=0.401, P=0.047)and it was negatively correlated with SVC-VD of optic disc, the integrity of the light bands of ELM, MZ, EZ, OS and IZ on the outer structure of macula(all P<0.05).CONCLUSION: The OCT and OCTA can be used to observe fundus changes after SB surgery for RRD to obtain long-term follow-up information related to vision prognosis, and visual prognosis depends on the recovery of retinal outer structure, and the integrity of IZ structure is more important for visual recovery; The SVC-VD of optic disc is correlated with visual prognosis, and whether it was correlated with intraocular pressure require further observation and verification with postoperative continuous data.

ObjectiveTo explore the relationship between marital status and the prevalence of mild cognitive impairment （MCI） and dementia in the community dwelling old adults， so as to provide sociological data basis for the prevention and control of cognitive impairment. MethodsPeople aged 65 and above in urban and rural areas of Hubei Province were selected by cluster random sampling， and face-to-face interviews were conducted in community health service centers to complete general investigation and neuropsychological evaluation， as well as clinical physical examination and laboratory examination. The diagnostic expert panels， including two neuroscientists and two neuropsychologists with specialized knowledge of dementia， diagnosed MCI and dementia according to Petersen's MCI standard and Chinese Diagnostic guidelines for dementia and Cognitive impairment. Multivariate Logistic regression was used to analyze the correlation between marital status and MCI and dementia in different age groups. ResultsDuring 2018~2020， 8 221 people completed the full neurocognitive assessment and clinical physical examination， with an average age of （71.96±5.895） years， and 1 953 people， accounting for 23.75% of the total number， were without spouses. The crude prevalence of MCI and dementia in HMACS were 25.98%， 95%CI （24.99%， 26.98%） and 7.24%， 95%CI （6.68%，7.80%）， respectively in total participants. After standardization for age and sex using data from the 2010 population census in Hubei Province， the prevalence of MCI and dementia were 26.28% and 6.98%.The prevalence of MCI and dementia in non-spouse ［28.07%， 95%CI （26.08%， 30.06%）；12.45%， 95%CI （10.99%， 13.91%）］ was significantly higher than that in spouse ［22.85%， 95%CI（21.81%， 23.89%； 5.62%， 95%CI （5.05%， 6.19%）］. Multivariable logistic regression model showed that the rates of MCI and dementia for married men aged 65~69 ［P=0.028， OR=0.639，95%CI（0.429， 0.952）］ and above 80 years ［P=0.004，OR=0.460， 95%CI （0.269， 0.785）］ were significantly lower than those of widowed men. However， there was no statistical difference between the presence or absence of spouses and the prevalence of MCI and dementia in older women. ConclusionsThe prevalence of MCI and dementia is higher in older adults without spouses. Especially for men aged 65~69 and 80 and above， having spouses is important to protect cognitive function.