Objective To establish an oxidative stress mouse model of atopic dermatitis (AD) by applying 2,4-dinitrofluorobenzene (DNFB) to the back and post-auricular skin of KM mice, and to evaluate the regulatory role of the RAGE-NLRP3 axis (receptor for advanced glycation end products-NOD-like receptor family, pyrin domain containing 3 axis) in AD-related oxidative stress, thereby providing a potential therapeutic target for AD treatment. Methods Twenty SPF-grade female KM mice were randomly divided into a control group (Control group) and an experimental group (DNFB group), with 10 mice in each group. Mice in the Control group were treated with an acetone-olive oil vehicle (acetone: olive oil = 3:1) on their back and post-auricular skin. Mice in the DNFB group were treated with 0.5% DNFB (prepared by adding 0.5 g DNFB per 100 mL of acetone-olive oil vehicle) on the same areas, once daily for 14 consecutive days. The severity of skin lesions was scored on days 2, 4, 6, 9, 12, and 14 of treatment. On day 14, scratching behavior and ear thickness were evaluated. Ear swelling was evaluated on the final day by measuring bilateral ear thickness three times with a vernier caliper; the three measurements were averaged. HE staining was used to observe morphological and structural changes of cells in the back skin tissues. The mRNA and protein expression levels of RAGE (receptor for advanced glycation end products) in skin tissues were detected by quantitative real-time PCR, Western blot, and immunohistochemical staining. The mRNA expression levels of oxidative stress-related molecules, including NLRP3 (NOD-like receptor family, pyrin domain containing 3), caspase-1 (cysteine-dependent aspartate-specific protease 1), and IL-1β (Interleukin-1β), were detected by quantitative real-time PCR. Results On day 14, the back skin lesion scores of the Control group and DNFB group were (0.20±0.42) and (9.93±1.30) (P<0.000 1), respectively. Scratching behavior scores were (5.00±2.05) and (49.26±8.49) episodes, respectively (P<0.000 1), and ear thicknesses were (213.00±11.87) μm and (765.93±140.47) μm (P<0.000 1), respectively. The DNFB group exhibited marked skin dryness, desquamation, and thickening. HE staining results showed that skin inflammation was obvious in the DNFB group, consistent with the pathological features of AD. Quantitative real-time PCR and Western blot results showed that compared with the Control group, the mRNA expression level of RAGE in skin tissues of the DNFB group was significantly increased (P<0.05), and the protein expression level of RAGE was also significantly increased (P<0.01). Immunohistochemical staining results showed that compared with the Control group, skin tissue sections of the DNFB group exhibited thickened stratum corneum and fibrotic proliferation of fibroblasts in the interstitium under microscopic observation, with a significant increase in RAGE protein expression in the skin tissues (P<0.01). Quantitative real-time PCR results showed that the mRNA expression levels of NLRP3, caspase-1, and IL-1β in skin tissues of the DNFB group were all significantly increased (P<0.01). Conclusion The AD mouse oxidative stress model has been successfully established by topical DNFB application. RAGE may promote the development of AD by regulating the NLRP3 inflammasome and IL-1β release, forming an oxidative-inflammatory cascade, suggesting that it could be a potential therapeutic target for AD.

Background: and Purpose In patients with large vessel occlusion (LVO), intravenous thrombolysis (IVT) frequently alters thrombus location; however, the clinical impact of this phenomenon remains unclear. We aimed to compare post-IVT thrombus dynamics between tenecteplase and alteplase and to evaluate the association between thrombus dynamics and 3-month outcomes. Methods: This retrospective study analyzed prospectively collected, multicenter data from consecutive patients with LVO who underwent bridging therapy between January 2022 and December 2024. Thrombus dynamics were classified as resolution, migration, or stability. Analyses incorporated propensity score matching with weighting to balance baseline characteristics. Results: Of the 806 initially included patients, 746 were included after matching (373 treated with tenecteplase and 373 treated with alteplase). The incidence of thrombus migration was significantly higher in the tenecteplase group than in the alteplase group (19.3% vs. 11.3%; odds ratio [OR]: 1.92; 95% confidence interval [CI] 1.27–2.91). The advantage of tenecteplase over alteplase was restricted to patients with an IVT-to-puncture time of <60 minutes (18.6% vs. 6.2%; p=0.001) and was no longer significant when the interval ≥60 minutes (19.7% vs. 15.0%; p=0.204; pinteraction=0.043). Additionally, thrombus migration was associated with a better functional outcome (OR: 1.62; 95% CI 1.04–2.53). Finally, tenecteplase was associated with improved functional independence compared with alteplase (OR: 1.43; 95% CI 1.04–1.95). Conclusions Tenecteplase demonstrated superior efficacy in inducing thrombus migration compared with alteplase, particularly within 60 minutes of IVT administration. Thrombus migration independently predicted improved functional independence. These findings support the preferential use of tenecteplase for bridging therapy in patients with LVO.

Prolonged disorders of consciousness(pDoC)are complex and prolonged conditions that severely impact patient prognosis and remain a clinical treatment challenge.In recent years,neural regulation-based awakening therapies have been widely applied in the assessment and treatment of pDoC patients.Repetitive transcranial magnetic stimulation(rTMS)technology can regulate neural activity and improve patients'consciousness states,demonstrating positive awakening effects for pDoC patients.However,the optimal stimulation parameters and awakening mechanisms of rTMS remain unclear.This article reviews the pathological mechanisms of pDoC,clinical applications of rTMS at different targeting sites and stimulation frequencies,and focuses on exploring how rTMS promotes consciousness recovery through neural mechanisms such as altering neural pathways,reshaping brain networks,promoting synaptic plasticity and neurotransmitter release,regulating neurotrophic factor expression,and modulating cerebral hemodynamics.Based on artificial intelligence,the article also prospects the future clinical research applications of rTMS.

Objective:To evaluate the technical feasibility and perioperative safety of pyeloplasty assis-ted by the CarinaTM modular laparoscopic surgical robotic system in patients with ureteropelvic junction obstruction(UPJO).Methods:From November to December 2024,five consecutive patients diagnosed with UPJO underwent robot-assisted pyeloplasty using the CarinaTM modular laparoscopic surgical system at Peking University First Hospital.Data on patient demographics,intraoperative parameters(including docking time,console time,and estimated blood loss),perioperative outcomes,follow-up results,and surgeons' subjective evaluations of system performance were prospectively collected.Descriptive statistics were used;continuous variables were presented as median(range),and categorical variables as frequen-cy and percentage.Results:The cohort included four females and one male.All the patients successfully completed the robotic procedure without conversion to open or conventional laparoscopic surgery.The me-dian age was 32 years(24-37 years),and the median body mass index was 21.6 kg/m2(15.8-27.3 kg/m2).The median docking time was 8 min(3-12 min),and the median console time was 91 min(71-125 min).Intraoperative blood loss was uniformly 20 mL.The median postoperative drainage du-ration was 3 d(0-4 d),and the median length of hospital stay was 4 d(4-9 d).No Clavien-Dindo grade Ⅲ or higher complications occurred.All the patients had their double-J stents removed at 2 months postoperatively,and pain in the ipsilateral flank,reported preoperatively by all the five patients,was al-leviated.The subjective surgical success rate was 100％.Surgeons reported stable system performance throughout all the procedures,with no instances of mechanical arm interference or visual drift affecting surgical fluency.Conclusion:Preliminary findings indicate that pyeloplasty using the domestically deve-loped CarinaTM modular laparoscopic robotic system is technically feasible and perioperatively safe for the treatment of UPJO.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Objective:To observe any effect of combining interactive scalp acupuncture with constraint-induced movement therapy (CIMT) in treating the upper extremity motor function of children with spastic hemiplegic cerebral palsy.Methods:Fifty-seven children with spastic hemiplegic cerebral palsy were randomly divided into a control group of 28 and an observation group of 29. The control group was given conventional rehabilitation and routine CIMT, while the observation group was additionally provided with interactive scalp acupuncture. In the observation group the CIMT lasted for 30 minutes while the needles were retained. Then, after the needles were removed, the family administered simple rehabilitation training for 2.5 hours guided by a rehabilitation therapist. The treatments were administered 5 days per week for 3 weeks as a session, and the whole treatment consisted of 3 sessions. Before, as well as 1 month and 3 months after the treatment, upper extremity motor function in both groups was evaluated using the Melbourne assessment scale 2 (MA2) and the fine motor Peabody developmental motor scales. Muscle tone in the children′s elbow flexors was assessed using the modified Ashworth scale (MAS).Results:After both 1 and 3 months of treatment, the average MA2 scores of both groups were significantly better than those before treatment, with those of the observation group significantly superior to the control group′s averages. After both 1 and 3 months, both groups′ visual-motor integration scores, grasping ability scores and total scores had improved significantly, with those of the observation group significantly better than in the control group, on average. The MAS scores of both groups were also significantly better than before the treatment, but with no significant differences between the two groups at either time point.Conclusions:Interactive scalp acupuncture combined with constraint-induced movement therapy can significantly improve the upper extremity motor functioning and fine motor ability of children with spastic hemiplegic cerebral palsy.

Natural products (NPs) have historically been a fundamental source for drug discovery. Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents, and corresponding targets. In the present study, an innovative natural product virtual screening-interaction-phenotype (NP-VIP) strategy that integrates virtual screening, chemical proteomics, and metabolomics to identify and validate the bioactive targets of NPs. This approach reduces false positive results and enhances the efficiency of target identification. Salvia miltiorrhiza (SM), a herb with recognized therapeutic potential against ischemic stroke (IS), was used to illustrate the workflow. Utilizing virtual screening, chemical proteomics, and metabolomics, potential therapeutic targets for SM in the IS treatment were identified, totaling 29, 100, and 78, respectively. Further analysis via the NP-VIP strategy highlighted five high-confidence targets, including poly [ADP-ribose] polymerase 1 (PARP1), signal transducer and activator of transcription 3 (STAT3), amyloid precursor protein (APP), glutamate-ammonia ligase (GLUL), and glutamate decarboxylase 67 (GAD67). These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM. The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research, proposing a comprehensive approach that could be adapted for broader pharmacological explorations.

Objective To explore the expression significance of serum Kisspeptin and luteinizing hormone(LH)in girls with central precocious puberty(CPP).Methods A total of 98 CPP girls were included as the study group,and 91 healthy girls during the same period were used as the control group.Under the condition of no intervention,CPP girls were followed up for 6 months and assigned into the fast progressive CPP(RP-CPP)group(n=46)and the slowly progressive CPP(SP-CPP)group(n=52)based on their developmental status during the follow-up period.ELISA was applied to detect serum Kisspeptin level.Chemiluminescence method was applied to detect serum LH and follicle stimulating hormone(FSH)levels.The correlation of serum Kisspeptin,LH baseline(B-LH)and growth development and imaging indicators was analyzed.Receiver operating characteristic curve(ROC)was applied to analyze the value of serum Kisspeptin and LH in predicting RP-CPP.Results Compared with the control group,body mass index(BMI),serum levels of Kisspeptin,B-LH,and FSH baseline(B-FSH)were significantly higher in the study group(P＜0.05).Compared with the SP-CPP group,BMI,bone age index(BAI),serum Kisspepti and B-LH levels were higher in the RP-CPP group,and ovarian volume was larger(P＜0.05).Correlation analysis showed that serum Kisspeptin level was positively correlated with BMI,BAI,ovarian and uterine volume of CPP girls(P＜0.05),and serum B-LH level was positively correlated with ovarian and uterine volume of CPP girls(r=0.218,0.381,0.300,P＜0.05).ROC curve showed that the sensitivity and specificity of Kisspeptin combined with B-LH in predicting RP-CPP were 95.65%and 82.69%,respectively.Conclusion Serum Kisspeptin and B-LH levels are higher in CPP girls,and the combined of the two has a high predictive value for RP-CPP,which can provide a certain reference for clinical diagnosis and treatment.