Sophorae Flavescentis Radix is one of the commonly used traditional Chinese medicine in China, and a large amount of pharmaceutical residue generated during its processing and production is discarded as waste, which not only wastes resources but also pollutes the environment. Therefore, elucidating the chemical composition of the residue of Sophorae Flavescentis Radix and the differences between the residue and Sophorae Flavescentis Radix itself is of great significance for the comprehensive utilization of the residue. This study, based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) technology combined with multivariate statistical methods, provides a thorough characterization, identification, and differential analysis of the overall components of Sophorae Flavescentis Radix and its residue. Firstly, 61 compounds in Sophorae Flavescentis Radix were rapidly identified based on their precise molecular weight, fragment ions, and compound abundance, using a self-constructed compound database. Among them, 41 compounds were found in the residue, mainly alkaloids and flavonoids. Secondly, through principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA), 15 key compounds differentiating Sophorae Flavescentis Radix from its residue were identified. These included highly polar alkaloids, such as oxymatrine and oxysophocarpine, which showed significantly reduced content in the residue, and less polar flavonoids, such as kurarinone and kuraridin, which were more abundant in the residue. In summary, this paper clarifies the overall composition, structure, and content differences between Sophorae Flavescentis Radix and its residue, suggesting that the residue of Sophorae Flavescentis Radix can be used as a raw material for the extraction of its high-activity components, with promising potential for development and application in cosmetics and daily care. This research provides a scientific basis for the future comprehensive utilization of Sophorae Flavescentis Radix and its residue.
Drugs, Chinese Herbal/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Mass Spectrometry/methods* ; Sophora/chemistry* ; Flavonoids/chemistry* ; Alkaloids/chemistry*

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Background: Intradermal microdroplet injections of botulinum toxin type-A (BoNT/A) effectively ameliorate rosacea-related angiogenesis, but the mechanism remains unclear. Objective: To explore the anti-angiogenesis of BoNT/A in the rosacea-like mouse model and to measure the secretion of vascular endothelial growth factor (VEGF) by mast cells. Methods: A rosacea-like mouse model was induced by LL37 in both Mas-related G-proteincoupled receptor B2 conditional knockout (MrgprB2 −/− ) mice and wild-type (WT) mice, then treated with BoNT/A and/or Apatinib. The abundance of endothelial cells and mast cells in mouse skin was determined using dual immunofluorescence staining. The VEGF levels in supernatants and cell lysates of laboratory of allergic disease 2 (LAD2) mast cells were assessed using reverse transcription quantitative polymerase chain reaction, western blots, and enzyme-linked immunosorbent assay. The effect of conditioned medium (CM) collected from LAD2 on human umbilical vein endothelial cells (HUVECs) was determined using tube formation assays. The number of proliferative cells was confirmed using the 5-ethynyl-2’-deoxyuridine incorporation assays.The effect of BoNT/A on the internalization of Mas-related G-protein-coupled receptor X2 (MRGPRX2) was detected using flow cytometry and immunofluorescence staining. Results: LL37-induced rosacea-like skin manifestations were significantly alleviated in MrgprB2 −/− mice compared to WT controls. BoNT/A mitigated the LL37-induced secretion of VEGF by LAD2. The CM from BoNT/A-treated LAD2 inhibited HUVEC proliferation and tube formation. The LAD2 cells co-treated with LL37 and BoNT/A exhibited dramatically enhanced MRGPRX2 internalization. Conclusion BoNT/A enhances LL37-mediated MRGPRX2 internalization in mast cells, thereby reducing VEGF secretion and neovascularization and improving facial flushing symptom in rosacea.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective To observe the effect of Renshen(ginseng)-Yuzhu(fragrant solomonseal rhizome)on inflammatory factors and inflammasomes in depression rats,and to explore the antidepressant mechanism of Renshen-Yuzhu.Methods Fifty male SD rats were divided into the blank group,model group,fluoxetine group(2.1 mg/kg),Renshen-Yuzhu low-dose group(1.89 g/kg),and Renshen-Yuzhu high-dose group(5.67 g/kg),with ten rats in each group.Except for the blank group,the rats in the other groups were treated with chronic unpredictable mild stress to establish a depression rat model.On the second day after the end of modeling,the rats in each group were given the corresponding drugs once daily for 14 days.After modeling and dosing,body weight,forced swimming immobility time,and sucrose preference rate were measured.After dosing,hematoxylin-eosin staining was used to detect neuronal damage in the cerebral cortex,enzyme-linked immunosorbent assay was used to detect the contents of interleukin-4(IL-4),interleukin-23(IL-23),and interleukin-27(IL-27)in cortex,real-time PCR was used to detect the mRNA expression of interleukin-24(IL-24)in cortex,and the protein expressions of nucleotide-binding oligomerization domain-like receptor protein 1(NLRP1),absent in melanoma 2(AIM2),and nucleotide-binding oligomerization domain-like receptor protein 4(NLRC4)were detected by Western blotting.Results After dosing,compared with the blank group,the body weight of the model group decreased,the sucrose preference rate decreased,the swimming immobility time was prolonged,the neuronal tissue in cortex was destroyed,the content of IL-4 in cortex decreased,the contents of IL-23 and IL-27 in cortex increased,and the protein expressions of NLRP1,AIM2 and NLRC4 in cortex increased(P＜0.01).Compared with the model group,the body weight of rats in each administration group increased,the sucrose preference rate increased,the swimming immobility time was shortened,the damage of neuronal tissues in cortex improved,the content of IL-4 in cortex increased,the contents of IL-23 and IL-27 in cortex decreased,and the protein expressions of NLRP 1,AIM2 and NLRC4 in cortex decreased(P＜0.05).Conclusion Renshen-Yuzhu couplet medicines can improve the depressive-like behavior and exert antidepressant effect in chronic stress rats,and its mechanism may be related to the inhibition of NLRP 1,NLRC4,AIM2 inflammasome activation and its mediated inflammatory response in cortex,reducing pro-inflammatory cytokines,and increasing the level of antiinflammatory cytokines.

Berberine (BBR) is the main pharmacological active ingredient of Coptidis, which has hypoglycemic effect, but its clinical application is limited due to its poor oral bioavailability. Polyphenols, derived from cinnamon, are beneficial for type 2 diabetes mellitus (T2DM). The combination of both may have an additive effect. The aim of this study was to investigate the hypoglycemic effect and mechanism of combined medication in diabetic rats. The modeling rats were randomly divided into 5 groups (berberine group, cinnamon group, combined group, metformin group, diabetic control group) and normal control group. The animal experiments were approved by the Animal Ethics Committee (approval number: HMUIRB2022003). The subjects were given orally, and the control group was given equal volume solvent and body weight was measured weekly. Thirty days after administration, oral glucose tolerance test and insulin sensitivity test were performed, and fasting blood glucose (FBG), glycated serum protein (GSP), and serum insulin (INS) levels were detected; high-throughput sequencing technology was used to detect intestinal microbiota structure; real-time quantitative PCR (RT-qPCR) and Western blot were used to detect G protein-coupled receptor 5 (TGR5) and glucagon-like peptide-1 (GLP-1) expression levels. The results showed that, compared with the diabetic control group, the levels of FBG (P < 0.01) and GSP (P < 0.01) in the combined group were lower, and the insulin resistance was improved, which was better than that in the berberine group. Combined treatment increased the relative abundance of Bacteroides, Prevotella and Lactobacillus, reversed the decrease in Lactobacillus in the berberine alone induction group, and the combination of the two could promote the expression of TGR5 and GLP-1. In summary, the combined application of cinnamon and berberine can regulate glucose metabolism better than the application of berberine alone. Berberine combined with cinnamon can improve the function of pancreatic islet β cells in diabetes mellitus type 2 rats by changing the intestinal microbiota, increasing the expression of TGR5 and GLP-1 proteins, and thereby better regulating glucose metabolism.

A 41-year-old male was presented with rapidly progression memory impairment for 2 months and episodic limb shaking for 2 weeks as the main manifestations.Physical examination showed verbal disadvantage with decreased memory,attention,comprehension,and orientation.Serum vitamin B12 levels decreased,serum anti gastric parietal cell antibodies and anti-intrinsic factor antibodies were positive.Blood analysis showed macrocytic anemia,neuropsychological scale showed functional impairment in multiple cognitive domains,electrophysiological examination showed peripheral nerve damage,cerebrospinal fluid and imaging examination showed no abnormalities.The patient was diagnosed as having vitamin B12 deficiency dementia,vitamin B12 deficiency related involuntary movement and pernicious anemia.Supplementing with B vitamins and folic acid significantly improved cognitive impairment and eliminated symptoms of limb shaking.The purpose of this case report is to enhance the understanding of clinical doctors about dementia and involunting movement caused by vitamin B12 deficiency,in order to diagnose and treat it early.

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 establish a highly sensitive and quantitative detection method for ABL1 kinase region mutations,provide strong support for the early diagnosis and treatment of chronic myeloid leukemia(CML).Methods:Sampele from 35 CML patients who were initially tested negative for ABL1 kinase region mutations by Sanger sequencing were collected.The ABL1 kinase region mutation was detected by the fluorescence quantitative detection kit of Shanghai Yuanqi Biopharmaceutical Technology Co.,Ltd.The mutation rate was analyzed byΔΔCt value method.The relative mutation rate of the final ABL1 kinase region was determined by dividing the mutation rate by the expression level of the fusion gene.Results:Among the 35 CML patients initially tested negative for ABL1 mutations by the Sanger sequencing method,7 cases of T315I mutation,2 cases of T315A mutation,2 cases of Y253H mutation,and 1 cases of E255K mutation after detection of the new method.The relative mutation rates range from 0.1％to 19.42％,which could not be detected by Sanger sequencing method.Subsequently,this method was used to detect the ABL1 mutation in 126 CML patients,and the positive rate exceeded that of the Sanger sequencing method.The BCR-ABL1 gene expression significantly reduced or negative after adjusting treatment strategy based on the mutation situation.Conclusion:Compared with Sanger sequencing,fluorescence quantitative PCR has higher sensitivity and can screen for low-frequency ABL1 kinase mutations in the early stage.Moreover,it can also perform relative quantitative analysis,so the method has good clinical application prospects for detecting ABL1 mutation.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]