ObjectiveTo investigate the antitumor effect and mechanism of Guiqi Yiyuan ointment on Lewis lung cancer mice based on the extracellular regulatory protein kinase （ERK） signaling pathway. MethodsA Lewis lung cancer mouse model was established. Except for the blank group， the model mice were randomly divided into the model group， Guiqi Yiyuan ointment low， medium， and high dose groups， and the extracellular ERK1/2 inhibitor group， with 10 mice per group. The Guiqi Yiyuan ointment was administered by gavage at doses of 1.75， 3.5， 7.0 g·kg^-1·d^-1 for the low， medium， and high dose groups， respectively. The ERK1/2 inhibitor group was given the ERK1/2 inhibitor LY3214996 （100 mg·kg^-1·d^-1） by gavage. The treatment was administered for 14 consecutive days， after which samples were collected. Tumor histopathological changes were observed using hematoxylin-eosin （HE） staining. Transmission electron microscopy was used to observe ultrastructural changes in tumor cells. Immunofluorescence was performed to measure the phosphorylation of ERK1/2 （p-ERK1/2） and the expression of programmed cell death ligand-1 （PD-L1） in tumor tissues. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of p-ERK1/2， PD-L1， the autophagy marker Beclin-1， the autophagic protein p62， and the microtubule-associated protein light chains LC3Ⅰ and LC3Ⅱ at both the protein and gene levels. ResultsCompared with the model group， the average tumor weight was significantly reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and markedly reduced in the high dose and inhibitor groups （P<0.01）. Tumor cells in all treatment groups became progressively irregular， with ruptured nuclei and expanded areas of cell disintegration and necrosis. The number of organellar ablations in tumor tissues increased， and the number of autophagic vesicles also increased in all groups. The mean fluorescence intensity of p-ERK1/2 and PD-L1 was reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and significantly reduced in the high dose and inhibitor groups （P<0.01）. The mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， while LC3Ⅰ/Ⅱ mRNA expression was elevated （P<0.05）. In the high dose and inhibitor groups， mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ mRNA expression was significantly increased （P<0.01）. Protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， and LC3Ⅰ/Ⅱ protein expression was elevated （P<0.05）. In the high dose and inhibitor groups， protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ protein expression was significantly elevated （P<0.01）. ConclusionGuiqi Yiyuan ointment may inhibit the activation of the ERK signaling pathway， downregulate the expression of p-ERK1/2， promote autophagic flux in tumor cells， and regulate the expression of PD-L1， thereby exerting an inhibitory effect on tumor growth in Lewis lung cancer mice.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.

Aim To explore the effect of targeted inhi-bition of co-signaling molecule B7-H3 on the growth,migration,and angiogenesis ability of human umbilical vein endothelial cells(HUVECs).Methods Small interference RNA was used to knock down HUVECs B7-H3 molecules.CCK-8 test was used to detect cell proliferation at 24 h,48 h and 72 h.Transwell test was then used to detect 24 h cell migration,and three-dimensional cell culture was used to observe cell angio-genesis.Results Compared with the negative control group(siRNA-Control),siRNA-720,siRNA-1707 and siRNA-1690 had different inhibitory effects on the expression of B7-H3.B7-H3 inhibition of siRNA-1690 was significantly higher than that of siRNA-720 and siRNA-1707,and siRNA-1690 sequence was chosen for follow-up experiment.The results of CCK-8 cell vi-ability assay showed that the proliferation ability of HU-VECs decreased by 24％,22％(P＞0.05,compared with 24 h)and 15％(P＜0.05,compared with 48 h)respectively at 24 h,48 h and 72 h after B7-H3 knockout.The migration ability of B7-H3 for 24 h was significantly lower than that of siRNA-Control group(P＜0.01).The results of three-dimensional cell cul-ture showed that the angiogenic ability of HUVECs de-creased significantly after si-B7-H3 knockdown of B7-H3 gene(P＜0.01).Conclusion Targeting B7-H3 inhibits the growth,migration,and angiogenesis of hu-man umbilical vein endothelial cells.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

This study was aimed at investigating the pathogenic and molecular characteristics of Klebsiella pneumoniae(KP)in fecal samples of diarrhea cases in a district of Beijing.Fecal samples from diarrhea cases in an outpatient department in a district of Beijing from 2018 to 2021 were collected,and used for isolation and culture of KP.The KP strains isolated strains were subjected to drug resistance phenotype testing and whole-genome sequencing.Multilocus sequence typing and whole-genome phyletic evolution analysis were performed on the sequencing results.The cases'epidemiological and clinical characteristics were analyzed.From 2018 to 2021,1 103 fecal samples were collected and detected.The total detection rate of KP was 10.43％(115/1 103),and the infection rate of KP mixed with other diarrhea-causing pathogens was 42.61％(49/115).The positivity rate was slightly high(12.47％,61/489)a-mong females and was highest in young adults 16-45 years of age.Small peaks were observed in January,April to May,and August to September.The gastrointestinal symptoms in cases were mainly nausea and watery stool,and the suspicious food was unknown.Ampicillin,tetracycline,and sulfafurazole were the top three antibiotics to which these 115 KP strains showed resistance,and 29 strains were resistant to multiple antibiotics.The strains were divided into 72 sequence types,among which ST23 was dominant.According to the phylogenetic tree,the strains were divided into four main branches,among which 14 ST23 strains had a very close genetic relationship with the highly virulent NTUH-K2044 reference strain.KP infection persisted in fecal samples from diarrhea cases in the district of Beijing.Women and young adults were particularly susceptible.The drug resistance of KP strains in this region was very serious,and the ST types were diverse.Moreover,the ST23 pathogenic strains were closely related to high virulence strains.

Objective:To analyze the effects of preoperative renin-angiotensin system inhibitor (RASi) use on postoperative renal function and short-term and long-term prognosis in patients undergoing coronary artery bypass grafting (CABG).Methods:A retrospective cohort analysis was conducted. Based on the registration study data of CABG patients at Fuwai Hospital, Chinese Academy of Medical Sciences, the clinical data of adult patients who underwent CABG from January 2013 to December 2022 were analyzed. Preoperative use of RASi (PreRASi) was defined as receiving RASi treatment within 48 hours before surgery. Postoperative acute kidney injury (AKI) was defined using the diagnostic criteria of Kidney Disease: Improving Global Outcomes (KDIGO). Demographic characteristics, past medical history, comorbidities, preoperative medication, preoperative laboratory test results, specific information on surgical procedures, and postoperative treatment related data were extracted. The primary endpoint was the incidence of postoperative AKI. Secondary endpoints included in-hospital all-cause mortality and all-cause mortality within the longest follow-up period. According to whether RASi was used before surgery, the patients were divided into PreRASi group and No-PreRASi group. The baseline data of the two groups were balanced by propensity score matching (PSM). Logistic regression model and Cox proportional hazards model were used to assess the correlation between PreRASi and postoperative AKI and clinical outcomes, and analyze the subgroups of hypertension and heart failure with preserved ejection fraction (HFpEF) in the cohort.Results:A total of 33?884 patients who underwent CABG were included, with a mean follow-up duration of (3.0±2.4) years and the longest follow-up duration up to 8.5 years. There were 9?128 cases (26.94%) in the PreRASi group and 24?756 cases (73.06%) in the No-PreRASi group. The incidence of postoperative AKI in the PreRASi group was 47.61% (4?346 cases), compared to 52.37% (12?964 cases) in the No-PreRASi group. Two groups were matched with 5?094 patients each. Compared to the No-PreRASi group, both before and after PSM, PreRASi was associated with a reduction of risk of postoperative AKI [before PSM: odds ratio ( OR) = 0.834, 95% confidence interval (95% CI) was 0.793-0.877, P < 0.001; after PSM: OR = 0.875, 95% CI was 0.808-0.948, P = 0.001]. Subgroup analysis of hypertensive and HFpEF patients showed that PreRASi was associated with a decreased risk of postoperative AKI before and after PSM. The in-hospital mortality for the PreRASi and No-PreRASi groups were 0.61% (56 cases) and 0.49% (121 cases), respectively. Analysis of the overall cohort and subgroups with hypertension and HFpEF showed no correlation between PreRASi and in-hospital mortality or longest follow-up mortality. Conclusion:The perioperative use of RASi can reduce the risk of postoperative AKI in patients undergoing CABG, has a certain renal protective effect, but is not associated with short-term or long-term death risk after surgery.

Objective To develop an expert consensus on subcutaneous injection nursing for allergic asthma in children,standardize nursing practice to reduce the occurrence of related adverse reactions.Methods The clinical guideline,expert consensus,systematic review,evidence summary and original research on subcutaneous injection of monoclonal antibody drug for children with allergic asthma were comprehensively searched in domestic and foreign databases.The time limit for retrieval was from the establishment of databases until August 2023.Combined with clinical practice experience,the first draft of the consensus was formed.From December 2023 to February 2024,27 experts were invited to conduct 2 rounds of expert letter consultation,revise and improve the contents of the first draft,and expert demonstration was conducted,and finally a consensus final draft was formed.Results The effective recovery rate of the 2 rounds of letter consultation questionnaires was 100％;the authority coefficient of experts was 0.88;the judging basis coefficient was 0.93;the familiarity coefficient was 0.83.In the 2 rounds of correspondence,the Kendall concordant coefficients of expert opinions were 0.241 and 0.252,respectively(P＜0.001 for both).The consensus includes 6 parts,including personnel management,environmental layout,indications and contraindications,subcutaneous injection operation norms,identification and treatment of adverse reactions,and health education.Conclusion The consensus is strongly scientific and practical,and can provide guidance for nursing practice of subcutaneous injection of monoclonal antibodies in children with allergic asthma.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the incidence and risk factors for acute kidney injury(AKI)in children with primary nephrotic syndrome(PNS),as well as the role of neutrophil gelatinase-associated lipocalin(NGAL)and kidney injury molecule-1(KIM-1)in the early identification of AKI in these children.Methods A prospective collection of clinical data from children hospitalized with PNS at the Children's Hospital of the Capital Institute of Pediatrics from January 2021 to October 2022 was conducted.The children were divided into two groups based on the presence of AKI:the AKI group(47 cases)and the non-AKI group(169 cases).The risk factors for AKI in children with PNS were identified by multivariate logistic regression analysis.Urinary KIM-1 and NGAL levels were compared between the AKI and non-AKI groups,as well as among the different stages of AKI.Results The incidence of AKI in children with PNS was 21.8%.Multivariate logistic regression analysis revealed that steroid-resistant nephrotic syndrome,gastrointestinal infections,and heavy proteinuria were independent risk factors for AKI in these children with PNS(P<0.05).Urinary KIM-1 and NGAL levels were higher in the AKI group compared to the non-AKI group(P<0.05),and the urinary NGAL and KIM-1 levels in the AKI stage 2 and stage 3 subgroups were higher than those in the AKI stage 1 subgroup(P<0.017).Conclusions KIM-1 and NGAL can serve as biomarkers for the early diagnosis of AKI in children with PNS.Identifying high-risk populations for AKI in children with PNS and strengthening the monitoring of related risk factors is of significant importance.

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.