Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding developed a strategy for platelet and plasma infusion management in critically ill children based on systematic reviews and consensus meetings of international multidisciplinary experts. One good practice statement and six expert consensus statements were proposed for plasma and platelet transfusions in critically ill children following severe trauma, traumatic brain injury, and/or intracranial hemorrhage. This article introduces the specific methods and basis for the formation of recommendations in this part of the guide.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Background/Aims: Regorafenib is recommended by guidelines and trials as a sequential second-line therapy following progression on first-line sorafenib or lenvatinib in hepatocellular carcinoma (HCC). However, efficacy is limited, highlighting the urgent need to screen suitable patients and develop sensitization strategies. Methods: Acquired sorafenib- or lenvatinib-resistant (SR or LR) HCC cell lines and organoids were established. Genome-wide CRISPR library screen was performed in SR or LR cell strains to identify synthetic lethal targets of regorafenib. RNA-seq and FITC-regorafenib efflux assay were used to elucidate ERBB3-driven downstream signaling. Preclinical mouse models of cell line- and patient-derived xenografts and clinical cohorts of HCC patients were employed to validate the efficacy of ERBB3-guided patient stratification. Results: Screening with CRISPR library, we showed that inhibition of ERBB3 was synthetic lethal with regorafenib in SR or LR cell strains and organoids. Mechanistically, SR or LR triggered feedback activation of ERBB3 signaling and mediated regorafenib efflux via ERBB3-HIF1A-ABCB1 cascade pathway, limiting sensitivity to regorafenib. Moreover, ERBB3-low tumors following SR or LR exhibited significant sensitivity to regorafenib, suggesting its potential as a predictive biomarker to screen optimal candidates for sequential therapy. Seribantumab, an ERBB3-targeting monoclonal antibody, inhibited ERBB3-HIF1A-ABCB1 cascade, and its combination with regorafenib exerted marked synergistic anti-tumor effects on ERBB3-high tumors resistant to sorafenib or lenvatinib both in vitro and in vivo. Conclusions This study revealed that ERBB3 was a key resistance factor driving limited efficacy to sequential regorafenib, but also an effective therapeutic target whose inhibition enhanced regorafenib sensitivity after SR or LR.

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 translate the Maternal Childbirth Fatigue Perception Questionnaire(MCFQ)into Chinese and examine its reliability and validity among women undergoing vaginal deliv-ery.Methods Following the Brislin translation model,the MCFQ was translated,back-translated,culturally adapted and pre-tested to develop a Chinese version.By using the convenience sampling method,574 parturients were selected for a questionnaire survey from January to April 2024,and the reliability and validity of the Chinese questionnaire were evaluated.Results The Chinese version of MCFQ consisted of 3 dimensions and 13 items,namely physical fatigue(7 items),perceived fatigue(3 items)and emotional fatigue(3 items).The item-level content validity index ranged from0.813 to 1.000,and the scale-level content validity index was 0.938.The overall Cronbach's α coefficient of the scale was 0.870,and the split-half reliability coefficient was 0.848.Confirmatory factor analysis demonstrated that the question naire had a good fit.Conclusion The Chinese version of MCFQ has good reliability and validity and can be used as an effective tool to assess the fatigue level of parturients during the delivery process.It is helpful for clinical medical staff to optimize the management of the la-bor process,improve the quality of delivery,and ensure the safety of mothers and infants.

Objective: To investigate the current status and influencing factors for cognitive frailty among the elderly in community, so as to provide the evidence for early identification and prevention of cognitive frailty among the elderly. Methods: Residents aged 60 years and above with local household registration from 11 counties (cities, districts) in Zhejiang Province from 2021 to 2023 were selected as study participants using a multistage random sampling method. Demographic information, lifestyle, and health status were collected through questionnaire surveys. Depressive symptoms were assessed using the Patient Health Questionnaire. Cognitive frailty was evaluated using the FRAIL Scale and the Mini-Mental State Examination. Factors affecting cognitive frailty among the elderly in community were identified using a multivariable logistic regression model. Results: A total of 16 613 individuals were surveyed, including 7 465 males (44.93%) and 9 148 females (55.07%). The average age was (70.97±7.29) years. A total of 784 individuals were detected with depressive symptoms, with a detection rate of 4.72%. A total of 724 individuals were detected with cognitive frailty, with a detection rate of 4.36%. Multivariable logistic regression analysis showed that females (OR=1.419, 95%CI: 1.179-1.708), aged ≥70 years (70-<80 years old, OR=1.869, 95%CI: 1.490-2.345; ≥80 years old, OR=5.017, 95%CI: 3.935-6.398), without a spouse (OR=1.495, 95%CI: 1.234-1.810), sedentary (OR=2.420, 95%CI: 1.829-3.202), chronic diseases (1 type, OR=1.456, 95%CI: 1.175-1.804; ≥2 types, OR=1.639, 95%CI: 1.314-2.045), and depressive symptoms (OR=4.191, 95%CI: 3.361-5.225) were associated with a higher risk of cognitive frailty among the elderly in community. Conversely, a lower risk of cognitive frailty was seen among the elderly in community who had primary school or above (primary school, OR=0.512, 95%CI: 0.389-0.676; junior high school or above, OR=0.464, 95%CI: 0.354-0.608), engaged in physical exercise (OR=0.396, 95%CI: 0.291-0.539), and were reported average or good self-rated health status (average, OR=0.641, 95%CI: 0.475-0.866; good, OR=0.150, 95%CI: 0.109-0.208). Conclusions The detection rate of cognitive frailty among the elderly in community is relatively low and is influenced by demographic factors such as gender, age, education level, as well as lifestyle like sedentary and physical exercise, and health status. It is recommended to reduce the risk of cognitive frailty among the elderly through multidimensional interventions, including health education, promotion of healthy lifestyles, and enhanced mental health support.

Objective: To establish a nomogram prediction model for Alzheimer's disease (AD) among the elderly in community, so as to provide the evidence for early screening and prevention of AD. Methods: Based on the Zhejiang Healthy Aging Cohort Study, the elderly aged 60-90 years who completed the baseline survey were selected as the study subjects. Follow-up surveys were conducted from 2015 to 2016 and from 2019 to 2021. Sociodemographic characteristics, lifestyle factors, medical history, and waist circumference were collected through questionnaire surveys and physical examinations. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), and a diagnosis of AD was made based on the Alzheimer's Disease Assessment Scale-Cognitive Subscale and medical history. The participants were randomly divided into training and validation sets at 8∶2 ratio. LASSO regression was used to screen for predictive factors. Multivariable logistic regression model was used to analyze predictive factors and construct a nomogram. The model was analyzed and evaluated using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results: A total of 6 988 elderly were included at baseline, with a mean age of (68.19±6.63) years. There were 3 438 males (49.20%), and 3 550 females (50.80%). The median follow-up duration was 4.90 (interquartile range, 3.80) years, with 817 new cases of AD were identified, yielding an incidence of 11.69%. LASSO regression and multivariable logistic regression showed that age (OR=1.017, 95%CI: 1.005-1.030), gender (female, OR=1.820, 95%CI: 1.533-2.165), educational level (primary school, OR=0.813, 95%CI: 0.673-0.980), physical exercise (not active, OR=1.572, 95%CI: 1.260-1.980), dining companions (spouse and children, OR=0.771, 95%CI: 0.598-0.995), baseline MMSE score (OR=0.843, 95%CI: 0.821-0.866), and waist circumference (OR=0.981, 95%CI: 0.973-0.989) were risk predictors for AD among the elderly in community. The prediction model demonstrated an area under the ROC curve of 0.740 (95%CI: 0.698-0.783) in the validation set, with a sensitivity of 0.731 and a specificity of 0.667. DCA indicated that when the probability threshold was 0.060 to 0.325, the clinical net benefit was relatively high. Conclusion The AD risk prediction model constructed in this study has good discrimination and clinical practicability, can be used for early screening of AD among the elderly in the community.

Objective To evaluate the clinical efficacy and safety of vericiguat combined with the new"Quadruple Therapy"for treating heart failure with reduced ejection fraction(HFrEF)and to explore its impact on left ventricular reverse remodeling(LVRR)in patients with different baseline characteristics.Methods A total of 87 patients with chronic heart failure treated with vericiguat at the Department of Cardiology,Nanjing Drum Tower Hospital from June 2022 to March 2024,were consecutively enrolled as the observation group.These patients were matched at 1:1 by age,sex,and left ventricular ejection fraction(LVEF)with 87 patients who received the standard quadruple therapy without vericiguat as the control group.Propensity score matching was used to further balance confounding factors,resulting in 64 patients in each group for final analysis.Changes in echocardiographic parameters,liver and kidney function,electrolyte levels,and blood pressure were analyzed at baseline and during the 6-month follow-up to assess the efficacy and safety of vericiguat.The primary efficacy endpoint was the occurrence of LVRR.Subgroup analyses were conducted based on baseline characteristics such as age and sex.Interaction analysis was utilized to evaluate the heterogeneity of vericiguat's efficacy.Results After 6 months of treatment,the vericiguat group showed significant improvements in cardiac structure and function compared to the control group.The left ventricular end-diastolic diameter was significantly reduced[-0.43(-1.00,-0.10)mm vs.-0.22(-0.53,0.02)mm,P=0.002],and the LVEF was significantly increased[8.45％(1.40％,16.50％)vs.2.75％(0,11.00％),P=0.002].The percentage of patients in the vericiguat group who achieved LVRR was significantly larger than in the control group(46.4％vs.27.4％,P=0.011).Multivariate logistic regression revealed that the combination of vericiguat was an independent predictor of LVRR(Model 2:OR=2.54,95％CI:1.29～5.01,P=0.007).The reverse remodeling effect remained consistent across different subgroups and was not significantly influenced by specific baseline characteristics(Pinteraction>0.05).Vericiguat did not affect blood pressure,liver and kidney function,or electrolyte levels,achieving satisfactory safety,despite its significantly higher incidence of gastrointestinal reactions(16.1％vs.5.7％,P<0.001).Conclusion The addition of vericiguat to the quadruple therapy significantly improves cardiac function and promotes left ventricular reverse remodeling in HFrEF patients while maintaining a favorable safety profile.

Objective To investigate the conformational states of ADAMTS13 under different pH conditions.Methods Atomic force microscopy(AFM)was applied to pull ADAMTS13 molecules with two distinct pulling systems:the Biotin-Streptavidin system and the 6×His-Anti-His antibody system.The rupture forces and molecular contour lengths were analyzed.Results Under pH 7.4 condition,when ADAMTS13 was pulled by Biotin-Streptavidin system,the mean molecular contour length was(30.93±1.56)nm,exhibiting a bimodal frequency distribution with peak positions at(22.12±0.01)and(49.57±0.05)nm.When ADAMTS13 was pulled using 6×Hist-anti-His antibody system,the mean molecular contour length was(32.77±0.72)nm,also showing a bimodal distribution,with a peak position at(25.73±0.16)and(43.84±0.63)nm,respectively.Under pH 6.0 condition,when ADAMTS13 was pulled by Biotin-Streptavidin system,the mean molecular contour length increased to(47.07±1.6)nm,and the frequency distribution shifted to trimodal,with peak positions at(22±1.25),(55.09±2.62)and(76.69±3.06)nm.The conformation of ADAMTS13 was more extended at pH 6.0 compared with that at pH 7.4.Conclusions ADAMTS13 exists in'closed'and intermediate conformational states at physiological pH 7.4.However,at pH 6.0,ADAMTS13 can adopt'closed',intermediate,and'open'conformational states.This study contributes to a further understanding of the role of ADAMTS13 in normal physiology and thrombotic thrombocytopenic purpura,providing insights for the development of novel recombination ADAMTS13 drugs.

OBJECTIVE To establish a preparation method for Phellodendrine-11-O-β-D-glucuronide(M1),a metabolite of Phellodendrine(PHE),and to evaluate its regulatory effects on glycolipid metabolism disorder in insulin-resistant HepG2(IR-HepG2)cells.METHODS The preparation,extraction,separation,purification and identification of M1 were completed by in vitro incuba-tion of intestinal microsomes combined with liquid phase,mass spectrometry and NMR.With Metformin as positive control,IR-HepG2 cells were treated with low(25 μmol·L-1),medium(50 μmol·L-1)and high(100 μmol·L-1)doses of M1 for 24 h.Glucose con-sumption,glucose uptake,triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDL-C)were quantified.The binding ability of M1 to the key targets INSR,IRS1,PI3K and AKT2 in the IRS1/PI3K/AKT pathway was explored through molecular docking technology.The effects of M1 on the mRNA and protein expression of these key targets in the IRS1/PI3K/AKT pathway were detected by qPCR and Western blot,respectively.RESULTS The purified product was confirmed by NMR as Phellodendrine-11-O-β-D-glucuronide(95%purity).Compared to the model group,all M1 do-ses significantly enhanced glucose consumption(P<0.01,P<0.001)and uptake(P<0.001)in IR-HepG2 cells,outperforming PHE(P<0.001).At medium and high doses,it could significantly reduce the content of TG and TC in cells(P<0.001),and its improve-ment effect at the TG level was better than that of PHE(P<0.01);while all concentrations decreased LDL-C(P<0.001)and in-creased HDL-C(P<0.01,P<0.001).Molecular docking revealed strong binding interactions between M1 and INSR,IRS1,PI3K,and AKT2.Compared with the model group,M1 administration group increased the expression of INSR,IRS1,PI3K,AKT2,and GLUT2 mRNA to varying degrees,downregulated the protein expression of p-IRS1/IRS1(P<0.001),and upregulated the protein ex-pression of PI3K,p-AKT/AKT,and p-GSK3β/GSK3β.CONCLUSION The established protocol enables high purity M1 prepara-tion.M1 alleviates IR by regulating IRS1/PI3K/AKT signaling pathway to improve the disorder of glycolipid metabolism.