Psoriasis vulgaris is notoriously difficult to treat and prone to recurrence. Traditional Chinese medicine （TCM）， however， has shown considerable efficacy in mitigating or suppressing such recurrence. The underlying reason lies in the TCM concept of "latent pathogens"， which are prone to be reactivated by external pathogenic factors， thereby triggering relapse. At the early stage of recurrence， manifestations of "latent fire" often appear externally. If treatment is not thorough， the condition may shift into a state of "stalemate between healthy Qi and pathogenic factors"， in which the disease appears on the skin but is rooted in deeper pathological layers， remaining unresolved and accumulating internally. Over time， blood stasis arises from fire， and the fire further congeals due to stasis， leading ultimately to recurrent flare-ups. This aligns with the modern immunological concept of "immunological memory" mediated by tissue-resident memory T cells （T_RM） in the skin， which corroborates the TCM view of "latent fire inducing blood stasis". The interaction between T_RM and keratinocytes （KC） parallels the entanglement of latent fire and latent stasis， both of which are deeply entrenched and difficult to resolve. The core pathogenesis of recurrent psoriasis vulgaris lies in "latent fire causing blood stasis". The hallmark is the deep concealment and persistence of latent fire and stasis， which linger and await an opportunity to reemerge. Based on this understanding， Xijiao Dihuangtang is employed to cool the blood， resolve stasis， and eliminate latent pathogens， and treatment is tailored according to the disease stage through three-phase syndrome differentiation. In the progressive stage， both exterior and interior are treated， with emphasis on clearing latent fire. In the stationary stage， the focus shifts to dispelling latent stasis and simultaneously regulating the Zang-fu organs. In the regressive stage， efforts are made to prevent the retention of latent pathogens and to strengthen healthy Qi. Accordingly， drugs effective in dispersing wind and clearing heat， pungent-moistening and dredging the collaterals， and tonifying deficiency and moistening dryness are often employed to achieve optimal outcomes. The precise mechanisms by which Xijiao Dihuangtang treats recurrent psoriasis vulgaris remain to be fully elucidated. Current research suggests it may intervene in the recurrence process through inhibiting KC proliferation via the PI3K/Akt/mTOR signaling pathway and glycolysis， regulating the Th1/Th2 and Th17/Treg cell balances to restore immune homeostasis， suppressing inflammatory cytokine production to alleviate the inflammatory response， modulating angiogenesis-related factors， such as vascular endothelial growth factor A （VEGF-A） and matrix metalloproteinase-9 （MMP-9）， to control disease progression， and restructuring the gut microbiota to modulate systemic immunity and thereby influence the course of disease recurrence.

Objective To study the chemical constituents of Fallopia aubertii L.Henry Holub. Methods The chemical constituents of Fallopia aubertii L.Henry Holub. were separated and purified by online two-dimensional preparative liquid chromatography and identified by physical and chemical constants and spectral analysis. The inhibitory activities on xanthine oxidase were determined by ultraviolet spectrophotometry. Results Ten compounds were isolated from the extract of Fallopia aubertii L.Henry Holub, including isotachioside（1）, 3,4,5-trimethoxyphenyl-（6'-O-galloyl）-O-β-D-Glucopyranoside（2）, 1-hydroxy-,4,5-1-O-[6'-O-（4''-carboxy-1'',3'',5'trihydrotrimethoxyphenylxy）-phenyl]-β-D-glucopyranoside（3）, myricetrin（4）, myricetin（5）, rutin（6）, quercetin-3-O-β-D-galactoside（7）, quercetin-3-O-β-D-glucopyranoside（8）, lyciumideA（9）, and N-trans-Feruloyltyramine（10）. The inhibitory activity test results showed that the IC₅₀ of compound 5 was 15.92 μmol/L, and the IC₅₀ of compound 6 was 87.36 μmol/L. Conclusion Compounds 1,2,3,4 and 8 were isolated from Medicago polymorpha for the first time. Compounds 5 and 6 had xanthine oxidase inhibitory activity.

Aim To explore the mechanism of baicalin combined with heat stimulation in treating acute lym-phoblastic leukemia(ALL)based on network pharma-cology and in vitro experiments.Methods The CCK-8 assay was used to screen the suitable conditions for heat stimulation to interfere ALL cell lines Jurkat,CCRF-CEM,Hut-78 and a normal lymphocyte HMy2.CIR,and the effects of baicalin combined with heat stimulation on the proliferation of three ALL cell lines and a normal lymphocyte were tested.The key targets of baicalin combined with fever stimulation for the treatment of ALL were obtained based on network phar-macological analysis,and the potential mechanisms were predicted by gene ontology(GO)annotation and kyoto encyclopedia of genes and genomes(KEGG)en-richment.The expression levels of TNF-α,AKT1,TYMS and CASP3 mRNA in ALL cell lines Jurkat and CCRF-CEM were examined by RT-qPCR with baicalin alone and baicalin combined with heat stimulation.Results The optimal conditions for heat stimulation to intervene ALL cells were 41 ℃ for 24 h,and heat stimulation combined with baicalin synergistically inhibited the growth of ALL cell lines and effectively reduced the cy-totoxicity of baicalin.Based on the network pharmaco-logical analysis,55 intersecting targets of baicalin with ALL diseases and 77 intersecting targets of baicalin with fever were obtained.The results of GO annotation and KEGG enrichment suggested that baicalin com-bined with fever stimulation to intervene ALL might be associated with influencing intracellular reactive oxygen species metabolism,DNA transcription and apoptotic processes involved in cysteine enzymes.Apoptosis,TNF and IL-17 signaling pathways were the key pathways for baicalin combined with heat stimulation in treating ALL.Under heat stimulation at 41 ℃ using SDHA gene as housekeeping gene,in vitro experiments showed that baicalin significantly up-regulated the expression of TNF-α and CASP3,and down-regulated the expression of TYMS in ALL cells.Conclusions Based on net-work pharmacologic analyses and in vitro experiments,baicalin combined with heat stimulation can regulate TNF-α and CASP3 gene levels in ALL cells and de-stroy cellular structure to promote cell apoptosis,thus synergistically treating ALL.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

This study was aimed at developing an in vitro fluorescent substrate assay for the activity of leucyl aminopeptid-ase(LAP)from Echinococcus multilocularis and comparing it with the chemical chromogenic substrate enzyme activity assay.Through the establishment of reaction conditions for the fluorescent substrate-based in vitro enzyme activity assay,we com-pared the differences between the fluorescent substrate L-Leucine-7-amido-4-methylocoumarin(Leu-AMC)and the chemical chromogenic substrate L-Leucine-4-nitroanilide(Leu-pNA)through molecular docking,inhibition rates,and precision measures.Molecular docking revealed that the fluorescent substrate Leu-AMC had higher affinity for the protein than the chemical chromogenic substrate Leu-pNA.Through analysis of the effects of varying reaction conditions on fluorescence intensi-ty,we optimized the fluorescent substrate enzyme activity assay to demonstrate favorable performance at a reaction temperature of 37℃,a pH of 9.0,a protein concentration of 800 nmol/L,and a reaction duration of 60 minutes.Leu-AMC exhibited significant and distinct responses at a 5 μmol/L substrate concentration,under varying substrate conditions.The fluo-rescent substrate assay demonstrated more significant intergroup differences than the chemical chromogenic substrate assay when various inhibitors were added.This study established a fluorescence-based enzyme activity assay for leucyl aminopeptidase from Echinococcus multilocularis by using Leu-AMC as the substrate;this method demonstrated a more significant intergroup difference and sensitivity than the chemical chromogenic substrate assay.

Traumatic brain injury(TBI)is a serious condition characterized by high rates of mortality and disability.Deaths caused by severe TBI usually occur within the first few hours after the injury.Timely and effective management of TBI during pre-hospital and emergency treatment phases is crucial for improving patients'prognosis.To address this issue,the Emergency Physicians Branch of the Chinese Medical Doctor Association,the Emergency Medicine Professional Committee of the People's Liberation Army,the Beijing Emergency Medicine Society,and the Chinese Emergency Medicine Specialist Association have jointly selected national experts in emergency medicine and neurosurgery to formulate the"Chinese Expert Consensus on the Pre-hospital and Emergency Diagnosis and Treatment of Adult Traumatic Brain Injury".This consensus consists of two parts focusing on pre-hospital and emergency diagnosis and treatment of TBI,with 24 recommendations put forward to guide relevant clinical practices in pre-hospital and emergency management.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Temporomandibular joint osteoarthritis(TMJOA)is a chronic degenerative disorder.Although current clinical interven-tions can effectively mitigate disease progression,they remain limited in fully reversing formed pathological structural alterations.Mesenchymal stem cell-derived exosomes(MSC-Exos),which mimic the primary therapeutic functions of mesenchymal stem cells,exhibit advantages such as excellent biocompatibility,low immunogenicity,and absence of cytotoxicity.In TMJOA,MSC-Exos exert therapeutic effects by modulating chondrocytes,immune cells,and the cartilage matrix.However,the clinical application of MSC-Exos still faces certain limitations.Enhancing their therapeutic efficacy has become a central research focus in this field.This review summarizes existing therapeutic strategies for TMJOA and explores the potential applications of MSC-Exos in TMJOA management,aiming to provide insights for future research.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Objective To analyze the association between lifestyle and the risk of type 2 diabetes(T2D)among adult residents.Methods The data was sourced from the Shanghai Suburban Adult Cohort and Biobank.A total of 42 096 adult residents who had not developed T2D were recruited from four districts of Shanghai(Songjiang,Jiading,Minhang,and Xuhui)between 2016 and 2019.The follow-up ended on Feb 28,2023.A structured questionnaire was used to collect information on six lifestyle-related items,including smoking,alcohol consumption,BMI,waist circumference(WC),physical activity,and diet.The unhealthy lifestyle scores(UHLS)were calculated by counting the number of all the unhealthy lifestyle items,with a range of 0-6.New-onset T2D events diagnosed by physicians were obtained through the medical information system.Cox proportional hazards regression model and restricted cubic spline model were utilized to evaluate the association between unhealthy lifestyles and the risk of T2D incidence.Results About 28.1%of the participants led 4-6 unhealthy lifestyles.A total of 1 752 new T2D cases were identified during 218 513.4 person-years of follow-up.Analysis of single unhealthy lifestyle showed that abnormal WC(HR=1.5,95%CI:1.4-1.7)and abnormal BMI(HR=1.3,95%CI:1.2-1.5)were associated with an increased risk of T2D.Compared with individuals with a UHLS of 0-1,those with a UHLS of 3 and 4-6 had 30%(95%CI:1.1-1.6)and 50%(95%CI:1.2-1.8)higher risks of T2D,respectively.Each additional unhealthy lifestyle was associated with a 10%increase in T2D incidence risk(HR=1.1,95%CI:1.1-1.2).Conclusion The risk of T2D in adult residents increases with the cumulative number of unhealthy lifestyles.Adult residents with abnormal WC or BMI,or have three or more unhealthy lifestyles accumulated,will increase the risk of new-onset T2D.