Objective:To screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P＜0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Objective:To analyze the gender difference in behavioral and psychological symptoms of dementia (BPSD) of amnestic mild cognitive impairment (aMCI) and Alzheimer′s disease (AD).Methods:It was a cross-sectional study. The clinical data of 201 patients with aMCI and 146 patients with AD were continuously collected from the Chinese Imaging, Biomarkers and Lifestyle Study of Alzheimer′s Disease (CIBL) cohort between June 1, 2021 to February 1, 2023 in Beijing Tiantan Hospital, Capital Medical University. The BPSD subtypes were compared between different gender. The gender-different BPSD subtypes were divided into depression group (126 cases) and non-depression group (221 cases), anxiety group (140 cases) and non-anxiety group (207 cases), indifference group (131 cases) and non-indifference group (216 cases). The sociodemographic data (age, sex, education level, marital status), hypertension, diabetes, stroke, heart disease, hyperlipidemia, smoking history, drinking history, carrier status of apolipoprotein E epsilon4 allele (APOE ε4), and the scores of the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), Activity of Daily Living (ADL) were compared by using hypothesis testing. Multivariate logistic regression was used to analyze the gender differences of BPSD in aMCI and AD patients.Results:The incidence rates of depression and anxiety in female were both significantly higher than those in male (44.93% vs 23.57%, 44.93% vs 33.57%), and the incidence rate of apathy was significantly lower than that in male (32.37% vs 45.71%) (all P<0.05). The proportion of female and ADL scores in depression group were both significantly higher than those in non-depression group [73.81% vs 51.58%, 22.00 (20.00, 30.00) vs 20.00 (20.00, 26.00) points], and the proportion of smoking and drinking history and MoCA scores in depression group were all significantly lower than those in non-depression group [13.49% vs 25.79%, 19.84% vs 35.75%, 16.00 (10.00, 22.00) vs 19.00 (13.00, 24.00) points] (all P<0.05). The proportion of female and ADL scores in anxiety group were both significantly higher than those in non-anxiety group [66.43% vs 55.07%, 23.00 (20.00, 30.75) vs 20.00 (20.00, 25.00) points], and the MMSE and MoCA scores in anxiety group were both significantly lower than those in non-anxiety group [23.00 (16.00, 27.00) vs 24.00 (19.00, 28.00) points, 16.00 (10.00, 21.00) vs 20.00 (13.00, 13.00) points] (all P<0.05). The proportion of female and the MMSE and MoCA scores in apathy group were all significantly lower than those in non-apathy group [51.15% vs 64.81%, 19.00 (11.00, 25.00) vs 26.00 (22.00, 28.00) points, 14.00 (7.00, 19.00) vs 21.00 (15.25, 24.00) points], and the age, proportion of APOE ε4 carriers and ADL scores in apathy group were all significantly higher [67.0 (61.0, 76.0) vs 66.0 (60.0, 71.0) years, 42.74% vs 31.31%, 27.00 (22.00, 38.00) vs 20.00 (20.00, 22.00) points] (all P<0.05). Female ( OR=2.384, 95% CI: 1.274-4.459) and decrease in MoCA score ( OR=0.955, 95% CI: 0.914-0.998) were positively correlated with risk of depression. Female ( OR=1.704, 95% CI: 1.077-2.695) was positively correlated with risk of anxiety. Male ( OR=0.558, 95% CI: 0.333-0.936), decrease in MoCA scores ( OR=0.937, 95% CI: 0.894-0.983) and increase in ADL scores ( OR=1.070, 95% CI: 1.027-1.116) were positively correlated with risk of apathy (all P<0.05). Conclusions:There are significant gender differences in BPSD in aMCI and AD patients. Female is positively correlated with risk of depression and anxiety, while male is positively correlated with the occurrence of apathy. Clinical attention should be paid to hierarchical management of BPSD patients of different gender.

Objective To investigate the clinical phenotypes and genotypes of children with congenital fibrinogen disorder(CFD).Methods A retrospective analysis was conducted on the clinical data of 16 children with CFD.Polymerase chain reaction was used to amplify all exons and flanking sequences of the FGA,FGB,and FGG genes,and sequencing was performed to analyze mutation characteristics.Results Among the 16 children,there were 9 boys(56%)and 7 girls(44%),with a median age of 4 years at the time of attending the hospital.Among these children,9(56%)attended the hospital due to bleeding events,and 7(44%)were diagnosed based on preoperative examination.The children with bleeding events had a significantly lower fibrinogen activity than those without bleeding events(P<0.05).Genetic testing was conducted on 12 children and revealed a total of 12 mutations,among which there were 4 novel mutations,i.e.,c.80T>C and c.1368delC in the FGA gene and c.1007T>A and C.1053C>A in the FGG gene.There were 2 cases of congenital afibrinogenemia caused by null mutations of the FGA gene,with relatively severe bleeding symptoms.There were 7 cases of congenital dysfibrinogenemia mainly caused by heterozygous missense mutations of the FGG and FGA genes,and their clinical phenotypes ranged from asymptomatic phenotype to varying degrees of bleeding.Conclusions The clinical phenotypes of children with CFD are heterogeneous,and the severity of bleeding is associated with the level of fibrinogen activity,but there is a weak association between clinical phenotype and genotype.

Objective To understand the change in distribution and antimicrobial resistance of bacteria isolated from blood specimens of Hunan Province,and provide for the initial diagnosis and treatment of clinical bloodstream infection(BSI).Methods Data reported from member units of Hunan Province Antimicrobial Resistance Survei-llance System from 2012 to 2021 were collected.Bacterial antimicrobial resistance surveillance method was imple-mented according to the technical scheme of China Antimicrobial Resistance Surveillance System(CARSS).Bacteria from blood specimens and bacterial antimicrobial susceptibility testing results were analyzed by WHONET 5.6 soft-ware and SPSS 27.0 software.Results A total of 207 054 bacterial strains were isolated from blood specimens from member units in Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021,including 107 135(51.7％)Gram-positive bacteria and 99 919(48.3％)Gram-negative bacteria.There was no change in the top 6 pathogenic bacteria from 2012 to 2021,with Escherichia coli(n=51 537,24.9％)ranking first,followed by Staphylococcus epidermidis(n=29 115,14.1％),Staphylococcus aureus(n=17 402,8.4％),Klebsiella pneu-moniae(17 325,8.4％),Pseudomonas aeruginosa(n=4 010,1.9％)and Acinetobacter baumannii(n=3 598,1.7％).The detection rate of methicillin-resistant Staphylococcus aureus(MRSA)decreased from 30.3％in 2015 to 20.7％in 2021,while the detection rate of methicillin-resistant coagulase-negative Staphylococcus(MRCNS)showed an upward trend year by year(57.9％-66.8％).No Staphylococcus was found to be resistant to vancomy-cin,linezolid,and teicoplanin.Among Gram-negative bacteria,constituent ratios of Escherichia coli and Klebsiella pneumoniae were 43.9％-53.9％and 14.2％-19.5％,respectively,both showing an upward trend(both P＜0.001).Constituent ratios of Pseudomonas aeruginosa and Acinetobacter baumannii were 3.6％-5.1％and 3.0％-4.5％,respectively,both showing a downward trend year by year(both P＜0.001).From 2012 to 2021,resistance rates of Escherichia coli to imipenem and ertapenem were 1.0％-2.0％and 0.6％-1.1％,respectively;presenting a downward trend(P＜0.001).The resistant rates of Klebsiella pneumoniae to meropenem and ertapenem were 7.4％-13.7％and 4.8％-6.4％,respectively,presenting a downward trend(both P＜0.001).The resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannii to carbapenem antibiotics were 7.1％-15.6％and 34.7％-45.7％,respectively.The trend of resistance to carbapenem antibiotics was relatively stable,but has de-creased compared with 2012-2016.The resistance rates of Escherichia coli to the third-generation cephalosporins from 2012 to 2021 were 41.0％-65.4％,showing a downward trend year by year.Conclusion The constituent ra-tio of Gram-negative bacillus from blood specimens in Hunan Province has been increasing year by year,while the detection rate of carbapenem-resistant Gram-negative bacillus remained relatively stable in the past 5 years,and the detection rate of coagulase-negative Staphylococcus has shown a downward trend.

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.

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug dis-covery.In the present study,we used a mass spectrometry(MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds.The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells.Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol,as well as the noncanonical targets of clinically approved tamoxifen,lovastatin,and their derivatives.Furthermore,the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints.This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

AIM To identify the chemical components of Longmu Qingxin Mixture by UPLC-Q-TOF-MS and study its material basis for the treatment of attention deficit hyperactivity disorder.METHODS The sample was detected by mass spectrometry in positive and negative ion mode on a Waters CORTECS? UPLC? T3 chromatographic column.The data were analyzed with Peakview 1.2 software and matched with the Natural Products HR-MS/MS Spectral Library 1.0 database,and the components were identified in combination with literature reports.The material basis of Longmu Qingxin Mixture for the treatment of attention deficit hyperactivity disorder was analysed according to the identified components.RESULTS Forty chemical components were identified,including 11 flavonoids,6 monoterpene glycosides,4 triterpene saponins,3 phenolic acids,6 alkaloids etc.,which mainly derived from Radix Astragali,Radix Paeoniae Alba,Radix Scutellariae,licorice root,Ramulus Uncariae cum,etc.,baicalein,formononetin,astragaloside Ⅳ and rhynchophylline may be the material basis for the therapeutic effect of Longmu Qingxin Mixture.CONCLUSION UPLC-Q-TOF-MS can quickly identify the chemical components of Longmu Qingxin Mixture.Flavonoids,triterpene saponins and alkaloids may be the material basis for Longmu Qingxin Mixture for the treatment of attention deficit hyperactivity disorder,which can provide the basis for its material basis research,quality standard establishment and pharmacological study of the dismantled formula.

【Objective】 To elucidate the possible role of arginine and histidine in the pathogenesis of schizophrenia by exploring the serum levels of semi-essential amino acids (arginine and histidine) in patients with schizophrenia and their correlation with psychiatric symptoms. 【Methods】 We selected 72 inpatients with schizophrenia admitted to The First Affiliated Hospital of Xi’an Jiaotong University from March 2021 to October 2022 and 72 healthy volunteers enrolled in Yanta Community during the same period as the research subjects. Serum arginine and histidine levels were measured in patients with schizophrenia and healthy controls using serum liquid chromatography-mass spectrometry (LC-MS). We used the Positive and Negative Symptom Scale (PANSS) to evaluate the mental symptoms of patients with schizophrenia and analyzed the correlation of serum arginine and histidine levels with disease course, frequency of onset, and PANSS score. 【Results】 The levels of serum arginine (P<0.001) and histidine (P=0.011) in the schizophrenia group were significantly lower than those in the control group. The levels of serum arginine and histidine were significantly negatively correlated with the frequency of onset (rs=-0.410, rs=-0.262), total score of PANSS (rs=-0.298, rs=-0.256), positive factors (rs=-0.299, rs=-0.234) and cognitive impairment factors (rs=-0.251, rs=-0.296). In addition, serum arginine levels had significantly negative correlation with anxiety and depression factors (rs=-0.269, P<0.05). 【Conclusion】 The serum levels of arginine and histidine in patients with schizophrenia are significantly lower than those in healthy individuals, and are negatively correlated with overall mental symptoms, severity of positive symptoms and cognitive impairment. The severity of anxiety and depression symptoms is negatively correlated with arginine levels. The detection of serum arginine and histidine can provide reference for the diagnosis and assessment of the severity of schizophrenia in the future.

Objective To observe the effects of different doses of Kiwi fruit essence on fibroblast growth factor 2(FGF2)and extracellular regulatory protein kinase 1/2(ERK1/2)in lung tissue of rats with pulmonary fibrosis.Methods SD rats were divided into blank control group(0.9％NaCl),model group(0.9％NaCl),positive control group(5 mg·kg-1 prednesone acetate),experimental group-L,-M,-H(60,120,180 mg·kg-1 Kiwi fruit essence),except the blank control group was injected with 0.9％NaCl at one time.The other groups were injected 5 mg·kg-1 bleomycin A5 into the trachea to construct the rat pulmonary fibrosis model.The expressions of FGF2 and ERK1/2 proteins and mRNA were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction.Results The relative expression levels of FGF2 protein in blank control group,model group,positive control group and experimental group-L,-M,-H groups on the day 28 were 0.07±0.01,0.63±0.15,0.14±0.02,0.16±0.01,0.26±0.02 and 0.44±0.03,respectively;the relative expression levels of ERK1/2 protein on day 28 were 0.06±0.00,0.41±0.05,0.09±0.00,0.10±0.00,0.14±0.02,0.21±0.02,respectively;the relative expression levels of FGF2 mRNA on day 28 were 0.98±0.05,9.32±1.03,2.21±0.32,2.87±0.44,5.32±0.21,6.37±0.66,respectively;the relative expression levels of ERK1/2 mRNA on day 28 were 1.00±0.01,9.22±0.85,1.93±0.63,2.36±0.54,5.34±0.44 and 6.85±1.09,respectively.The above indexes in the model group were significantly different from those in the blank control group(all P＜0.05).The above indexes in the positive control group and the experimental-L,-M,-H groups were significantly different from those in the model group(all P＜0.05).Conclusion Kiwi essence may inhibit pulmonary fibrosis by regulating the expression of FGF2 and ERK1/2.

Cohort study of children and adolescents health is an ideal method to explore health-related problems from childhood to adulthood, to which more attention has been paid. This paper summarizes the progress in cohort study of children and adolescents health conducted both at home and abroad by introducing the study design, main contents. Emphasizing the international exchange and cohort integration, continuously expanding cohort research field, and using multi-source data for high-quality follow-up have become the trend of cohort study of children and adolescents health.