Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To compare the effects of different reference brain regions on the semi-quantitative SUV ratio (SUVR) of 18F-Florzolotau PET images of Alzheimer′s disease (AD). Methods:The 18F-Florzolotau PET images of 28 (13 males, 15 females, age (57.3±9.5) years) normal controls (NC), 19 patients (4 males, 15 females, age (73.3±7.3) years) with β-amyloid (Aβ)-positive mild cognitive impairment (MCI) and 40 patients (19 males, 21 females, age (61.9±9.1) years) with AD were collected from Huashan Hospital, Fudan University between November 2018 and July 2020. Six semi-quantitative reference brain regions were defined, including whole cerebellum (WC), cerebellar gray matter (GM), cerebellar white matter (WM), parametric estimation of reference signal intensity (PERSI), WC after partial volume correction (WC_pvc), cerebellar GM after partial volume correction (GM_pvc). SUVR was calculated for 14 ROIs, which included the whole brain defined by the automated anatomical labeling (AAL) template, fusiform, inferior temporal, lingual, middle temporal, occipital, parahippocampal, parietal, posterior cingulate, precuneus defined by the AAL template, and Meta ROI composed of the above brain regions, and braak_Ⅰ-Ⅱ, braak_Ⅲ-Ⅳ, braak_Ⅴ-Ⅵ defined by the Desikan Killiany template. AUC was used to evaluate the classification ability of SUVR, and the correlation between SUVR and clinical scale scores were assessed by Spearman rank correlation analysis. Results:The SUVRs of most brain regions showed a steady upward trend in the AD disease spectrum. In the classification task of NC and MCI, the overall performance of SUVR based on WC_pvc was relatively optimal (AUCs: 0.975-1.000). In the classification task of NC and AD, SUVRs of 10 ROIs based on the WC_pvc method showed the relatively best performance (AUCs: 0.976-1.000). The correlation between SUVR of fusiform based on cerebellar WM and mini-mental state examination (MMSE) score was the strongest ( rs=-0.72, P<0.001), and the SUVR of precuneus based on WC_pvc showed the strongest correlation with clinical dementia rating (CDR) score ( rs=0.78, P<0.001). Conclusion:The SUVR based on WC_pvc method performs well in classification and correlation tasks, and is recommended to be used in semi-quantification of 18F-Florzolotau PET images of AD.

This study aimed to investigate the therapeutic effects of Morinda officinalis iridoid glycosides (MOIG) on bone loss of rheumatoid arthritis (RA) rats, and the mechanism of osteoclast function and activity induced by lipopolysaccharide (LPS). RA rats were established by injecting bovin type II collagen. The Bio-ethic Committee of Zhejiang Chinese Medical University approved all experimental protocols associated with this study (IACUC-20180410-03). The collagen-induced arthritis (CIA) rats were administered drug by gavage for 8 weeks; the femoral trabecular micro-structure changes were observed in CIA rats by micro-CT; the LPS-induced osteoclasts model further observed the effect and mechanism of anti-inflammatory osteoporosis in vitro. The results indicated that MOIG could markedly increase bone mineral density (BMD) in CIA rats, improve trabecular micro-structure. In vitro studies demonstrated that MOIG could significantly inhibit osteoclastogensis and differentiation, suppress tartrate resistant acid phosphatase (TRAP) activity, F-actin ring formation, TNF receptor associated factor 6 (TRAF6) recruitment, and inhibitor of nuclear factor kappa-Bα (IκBα) degradation as well as p65 phosphorylation, thereby repressing nuclear factor kappa-B (NF-κB) signaling pathway activation. Subsequently, MOIG effectively inhibited osteoclast nuclear factor of activated T-cells c1 (NFATc1) and cellular oncogene Fos (c-Fos) expression, as well as bone resorption related protein activity including matrix metalloprotein 9 (MMP-9) and cathepsin K (CtsK). Meanwhile, MOIG also repressed the phosphorylation expression of Janus activating kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), thereby inhibiting JAK2/STAT3 signaling pathway activation. Moreover, further studies found that MOIG could suppress glycogen synthase kinase-3β (GSK-3β) activity, and GSK-3β gene silencing could markedly inhibit oetsoclast F-actin ring formation as well as the phosphorylation expression of p65 and STAT3. Of note, compared with GSK-3β gene silencing group, there was no significant difference in the group treated with both MOIG with GSK-3β gene silencing simultaneously. Thus, the results suggested that MOIG may inhibit NF-κB signaling pathway and JAK2/STAT3 signaling pathway activation via regulating GSK-3β, thereby alleviating bone destruction in RA.

Eighteen compounds were isolated from the methanol extract of the fruits of Litsea cubeba by silica gel, ODS, Sephadex LH-20 column chromatography, semi-preparative RP-HPLC, chiral HPLC and recrystallization. Their structures were elucidated by spectroscopic analyses and by comparison with reported spectroscopic data and physicochemical properties, and the absolute configurations of the enantiomers were established by experimental and calculated electronic circular dichroism spectra. These compounds were identified as (+)-(R)-4-hydroxypiperitenone (1a), (-)-(S)-4-hydroxypiperitenone (1b), (3S,4S,6R)-3,6-dihydroxy-1-menthene (2), (4S,5R)-4-hydroxy-5-isopropyl-2-methylcyclohex-2-en-1-one (3), (R)-6-hydroxy-3-(2-hydroxypropan-2-yl)-6-methylcyclohex-2-enone (4), (4S,6R)-4-hydroxy-6-isopropyl-3-methylcyclohex-2-enone (5), (1R,3S,4R)-3-hydroxy isopulegol (6), subamone (7), (6S)-3,7-dimethyl-7-hydroxy-2(Z)-octen-6-olide (8), (6S)-6,7-dihydroxy-3,7-dimethyloct-2(Z)-enoate (9), holostylactone (10), sesamin (11), dimethylmatairesinol (12), p-hydroxybenzoylcarbinol (13), syringaldehyde (14), p-hydroxybenzaldehyde (15), 4-hydroxy-3-methoxybenzaldehyde (16), 5,4ʹ-dihydroxy-7-methoxyflavone (17). Among them, compounds 1a and 1b were a pair of new monoterpenoid enantiomers, 8 and 9 were new natural products, 2-7, 10, 11 and 17 were isolated from Litsea genus for the first time. The in vitro anti-inflammatory effects of compounds 1-17 were evaluated using lipopolysaccharide-stimulated RAW264.7 cells, the results showed that compound 14 exhibited significant anti-inflammatory activity with NO inhibitory rate of 66.27% at a concentration of 40 μmol·L^-1.

Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.

Purpose To explore the value of the new generation tau PET tracer 18F-Florzolotau in Alzheimer's disease(AD)at different stages.Materials and Methods Twenty-five MCI patients and sixty-one AD patients with positive β-amyloid status in Huashan Hospital,Fudan University from February 2020 to January 2022 were retrospectively enrolled with 18F-Florzolotau PET imaging and demographic and clinical data.The pre-processed PET images were analyzed by SPM two-sample t-test between MCI and AD groups,and the standardized uptake value ratios(SUVR)were extracted from the region of interest defined by SPM analysis(P＜0.001);scaled subprofile model/principal component analysis was used to construct the different tau related patterns(MCItauRP,ADtauRP)and calculate the corresponding expression values.The classification efficiency of SUVR and MCItauRP,ADtauRP expression values was evaluated by receiver operating characteristic curve.Results Compared with MCI patients,tau protein deposition of AD patients was increased mainly in the bilateral temporal,occipital lobe(P＜0.001),and the SUVR of these brain region in the AD group was higher than that in the MCI group(Z=-3.164,P＜0.00l);the expression values of MCItauRP and ADtauRP were significantly different between the AD group and MCI group(t=3.72,Z=-3.51;both P＜0.001),and these expression values of AD patients were higher than those in the MCI group;the accuracy of tauRP expression values and SUVR for the differentiation between the AD and MCI group were 61.63％,65.12％and 65.12％,respectively;the sensitivity was 88.00％,96.00％and 100.00％,respectively;the specificity was 50.82％,52.46％and 50.82％,respectively.Conclusion The new tau PET can identify and distinguish the differences in tau protein deposition between AD and MCI patients.However,the classification and diagnosis efficiency is not high.In the future,it is necessary to find a more ideal analysis method.

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 investigate the safety and efficacy of mitoxantrone liposome in the treatment of children with high-risk acute myeloid leukemia(AML).Methods:The children with high-risk AML who received the mitoxantrone liposome regimen at Wuhan Children's Hospital from January 2022 to February 2023 were collected as the observation group,and the children with high-risk AML who received idarubicin regimen were enrolled as controls,and their clinical data were analyzed.Time to bone marrow recovery,the complete remission rate of bone marrow cytology,the clearance rate of minimal residual disease,and treatment-related adverse reactions were compared between the two groups.Results:The patients treated with mitoxantrone liposome showed shorter time to recovery of leukocytes(17 vs 21 day),granulocytes(18 vs 24 day),platelets(17 vs 24 day),and hemoglobin(20 vs 26 day)compared with those treated with idarubicin,there were statistical differences(P＜0.05).The effective rate and MRD turning negative rate in the observation group were 90.9％and 72.7％,respectively,while those in the control group were 94.1％and 76.4％,with no statistical difference(P＞0.05).The overall response rate of the two groups of patients was similar.Conclusion:The efficacy of mitoxantrone liposome is not inferior to that of idarubicin in children with high-risk AML,but mitoxantrone liposome allows a significantly shorter duration of bone marrow suppression and the safety is better.

Objective:To summarize the clinical features of reversible posterior encephalopathy syndrome(PRES)after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in children.Methods:The clinical data of six children who developed PRES after undergoing allo-HSCT in the Department of Hematology of Wuhan Children's Hospital from June 2016 to December 2022 were retrospectively analyzed,and their clinical characteristics,imaging examination,laboratory examination,and treatment regression were summarized.Results:Among 281 children underwent allo-HSCT,6 cases(2.14％)developed PRES,with a median age of 5.1(1.5-9.7)years old.4 cases underwent related haploidentical donor transplantation,and 2 cases underwent sibling allografting and unrelated donor allografting donor transplantation,respectively.All six children had an acute onset of illness,with clinical manifestations of nausea and vomiting,seizures,psychiatric disorders,visual disturbances.The five cases elevated blood pressure.All children with PRES were treated with oral immunosuppressive drugs during seizures,and 3 cases were combined with different degrees of graft-versus-host disease.Most of the children showed effective improvement in clinical symptoms and imaging after adjusting/discontinuing suspected medications(cyclosporine,etc.)and symptomatic supportive treatments(oral antihypertensive,diazepam for antispasmodic,mannitol to lower cranial blood pressure),and one of them relapsed more than 8 months after the first seizure.Conclusion:PRES is rare after hematopoietic stem cell transplantation in children,and its onset may be related to hypertension,cytotoxic drugs,graft-versus-host disease,etc.Most of them can be recovered after active treatment,but not completely reversible,and the prognosis of those who combined with TMA is poor.