ObjectiveTo construct and evaluate a mouse model that simulates the pathological progression of immune checkpoint inhibitor-associated pneumonitis (CIP), in order to address the critical issue of the lack of standardized animal models in this research field. MethodsThirty-five SPF-grade 6-week-old male C57BL/6J mice were randomly assigned to a control group (n=5), a bleomycin (BLM) group (n=15), and a BLM+programmed death-1 (PD-1) monoclonal antibody (BLM+PD-1) group (n=15). Corresponding drugs were administered via intraperitoneal injection for intervention. The general condition, body weight changes, survival rate, and pulmonary histopathological alterations were systematically monitored. ResultsCompared with the BLM group, the BLM+PD-1 group exhibited significantly more severe pulmonary fibrosis, characterized by progressive body weight loss and more severe deterioration of general conditions. Histopathological examination showed that pulmonary inflammation was alleviated 4 weeks post-modeling in the BLM group. In contrast, pulmonary lesions continued to worsen in the BLM+PD-1 group, with no evidence of resolution of inflammation 28 days post-modeling. Quantitative immunohistochemical analysis revealed that the positive expression rate of interleukin-17A (IL-17A) in lung tissues reached 34.28% in the BLM+PD-1 group 14 days post-modeling, which was markedly higher than that in the BLM group (24.02%, P < 0.000 1). The positive expression rate of α-smooth muscle actin (α-SMA) was 12.40% in the BLM+PD-1 group 14 days post-modeling, nearly twice the level in the BLM group (5.87%). 28 days post-modeling, the positive expression rate of α-SMA remained at 7.72% in the BLM+PD-1 group, while it declined to 3.38% in the BLM group. ConclusionThe addition of a PD-1 inhibitor to bleomycin treatment accelerates the progression of pulmonary interstitial fibrosis and effectively recapitulates the pathological process of lung injury and fibrosis driven by aberrant immune activation during clinical immunotherapy. Accordingly, this study successfully establishes a dynamic CIP animal model recapitulating the progression from early inflammatory response to pulmonary fibrosis. This model addresses the critical shortage of animal models for this condition and offers an experimental platform for further mechanistic studies and the development of therapeutic strategies.

In this work,four salicylhydrazone compounds(L1?L4)were designed and synthesized by using vanillin derivatives as raw material.The structures were confirmed by nuclear magnetic resonance(NMR)and high-resolution mass spectrometry(HRMS).The optical experiments showed that probe L1 and probe L3 could be used as aluminium ion(Al3+)fluorescence probes.The fluorescence color of probe L1 solution changed from colorless to blue after adding Al3+,and the limit of detection was 25.1 nmol/L.Compared with probe L1,the fluorescence color of probe L3 solution changed from colorless to green after complexing with Al3+,and the limit of detection was 17.3 nmol/L.Probe L1 and probe L3 showed the advantages of fast response speed,high selectivity and good anti-interference.The mechanism of Al3+recognition was further demonstrated by HRMS and 1H NMR.Cell imaging experiments showed that probe L1 and L3 had low cytotoxicity and had great application potential in detection of Al3+in vivo.

Nichrome(NiCr)wire with strong mechanical properties,excellent flexibility,good corrosion resistance and high thermal stability was selected as a promising fiber substrate to replace the fragile fused-silica counterpart.The NiCr layered double hydroxide nanosheets(NiCr LDHs NSs)were in-situ grown on the NiCr fiber substrate.Then,the extraction performance of the NiCr@NiCr LDHs NSs fiber was evaluated using four kinds of chlorophenol(CPs)as model compounds combined with high performance liquid chromatography-ultraviolet detection(HPLC-UV).The results showed that the assembled fibers exhibited superior extraction selectivity and enhanced extraction efficiency for CPs in comparison to commercial PA,PDMS,and PDMS/DVB fibers.Under the optimized experimental conditions,the established method showed good linearity in the range of 0.2-200 μg/L,with coefficient of determination(R2)>0.9989.The limits of detection(LODs)and limits of quantification(LOQs)were 0.050-0.157 μg/L and 0.165-0.502 μg/L,respectively.Relative standard deviations(RSDs)for intra-day and inter-day analyses ranged from 2.85%to 4.05%and from 3.16%to 4.96%,respectively.The developed method with the constructed fiber was applied to preconcentration and detection of different types of CPs in real water samples,showing satisfactory recoveries ranging from 80.0%to 106.9%,with RSDs of 3.12%-7.81%.Moreover,the NiCr@NiCr LDHs NSs fiber could maintain good extraction performance even after 240 extraction-desorption cycles.

BACKGROUND:Percutaneous retrograde screws and minimally invasive percutaneous plates are extensively used in the treatment of unilateral pubic ramus fractures.However,the above internal fixations have the disadvantages of mistakenly penetrating the hip joint and damaging the medial pelvic trophoblastic artery.A new type of retrograde superior pubic ramus intramedullary nail offers advantages,such as fewer radiographic exposures and shorter surgery times,but the validation of the biomechanical properties of the three endoprostheses is lacking.OBJECTIVE:To compare the biomechanical differences post-treatment of upper and lower pubic ramus fractures using percutaneous retrograde screws,minimally invasive percutaneous plates,and retrograde superior pubic ramus intramedullary nail under various conditions through finite element analysis.METHODS:Pelvic CT data were collected from one volunteer and imported into Mimics 20,Geomagic Wrap 2021,and SolidWorks 2019 to create geometric models of three types of internal fixation for treating unilateral pubic ramus fractures:hollow screw group,plate group,and intramedullary nail group.Each model was imported into Ansys 2022 software,where it was set up in vertical,book-opening,and shear conditions for preprocessing and calculation to compare and analyze the mechanical stability of the implants.RESULTS AND CONCLUSION:(1)In vertical conditions,the biomechanical stability of the hollow screw treatment for unilateral pubic fractures was superior to that of the steel plate and intramedullary nail,with the smallest peak stress in the implant,which was four times lower compared to the other two groups.(2)In book-opening conditions,the steel plate treatment for unilateral pubic fractures showed better biomechanical stability,particularly in reducing stress at the fracture ends of the upper pubic branch,with stress values five times higher in the other two groups.(3)In shear conditions,the intramedullary nail treatment for unilateral pubic fractures exhibited good biomechanical stability,maintaining the best pelvic displacement,with a 25％greater displacement observed in the other two groups.(4)These findings reveal the biomechanical differences of different implants:the peak stress of implants is the smallest under vertical working conditions with percutaneous retrograde screws.Minimally invasive percutaneous plates reduce the stress at the broken end of superior pubic branch under open-book working condition.Retrograde superior pubic ramus intramedullary nail of superior pubic branch maintains pelvic displacement under shear working condition.The surgeon can combine the biomechanical differences of the implants with the actual situation of pubic injury in clinical practice to make the best implant treatment.

Objective To explore the clinical characteristics as well as molecular epidemiological features of resis-tance genes and virulence genes of carbapenem-resistant Klebsiella pneumoniae(CRKP)infection in a region,and provide scientific basis for the prevention,treatment,and epidemiological study of CRKP.Methods 60 non-repeti-tive CRKP strains isolated clinically from Puyang Oilfield General Hospital from November 2023 to September 2024 were analyzed retrospectively.Antimicrobial susceptibility testing was performed using VITEK 2 Compact automa-tic microbial analyzer,K-B disk diffusion method,and micro-broth dilution method.Mucus phenotype of bacterial strains was identified by string test.Carbapenemase was detected by carbapenemase inhibitor enhancement assay.Molecular features,such as multi-locus sequence typing(MLST),capsule serotypes,resistance genes,virulence genes,plasmid replication types of strains,as well as the genetic and evolutionary relationships of strains were de-termined by whole genome sequencing and bioinformatics analysis.Results CRKP strains were mainly isolated from elderly male hospitalized patients.Specimens were mostly from sputum(71.67％),mainly distributed in depart-ment of respiratory medicine(30.00％).All strains were highly resistant to multiple commonly used antimicrobial agents,only with high susceptibility rates to cefotaxime/avibactam,tigecycline,and polymyxin B(＞60.00％).Two CRKP strains were positive for string test.95.00％of the strains produced class A serine carbapenemase.All strains carried fluoroquinolone,phosphomycin,β-lactam,and aminoglycoside resistance genes;enterobactin,Esche-richia coli common pilus(ECP),and outer membrane protein-related virulence genes;as well as plasmids from the IncF plasmid family.Carbapenemase gene was mainly blaKPC-2(95.00％),and the major capsule serotype was KL19(43.33％).In MLST,ST11(51.67％)was the dominant clone group,and ST11-KL62(n=12)was the dominant subtype.Conclusion CRKP in this hospital is highly resistant to multiple commonly used antimicrobial agents,and its mechanism of resistance to carbapenems is mainly related to the presence of blaKPC-2 resistance gene.All strains have coexisting multiple resistance genes and virulence genes,and show a phenomenon of multi-clone transmission.ST11 is the dominant clone group,and ST11-KL62 is the main prevalent subclone type.

Objective:To identify the bacteria isolated from sepsis patients in a tertiary hospital in Shanghai and analyze their antimicrobial resistance features.Methods:This study included 439 patients with clinically diagnosed sepsis who underwent microbiological culture in a tertiary hospital in Shanghai from July 2021 to October 2024. Results of microbiological culture and antimicrobial susceptibility testing were retrospectively collected and analyzed. Differences between groups were analyzed using Chi-square test and Fisher′s exact test. Results:The positive rate of microbiological culture was 49.0% (215/439). The positive rate of blood culture was 24.1% (93/386) and 100 strains were isolated from the samples, including 57 Gram-negative bacteria (57.0%). The predominant isolates in blood samples were Escherichia coli, Klebsiella pneumoniae, and coagulase-negative staphylococci. The positive rate of bacterial culture from bronchoalveolar lavage fluid samples was 84.1% (37/44), with Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa being the predominant strains. The positive rate of bacterial culture from urine samples was 35.6% (127/357), with Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecium being the most common. Escherichia coli, Klebsiella pneumoniae, Enterococcus faecium, coagulase-negative staphylococci, Pseudomonas aeruginosa, and Acinetobacter baumannii exhibited high resistance rates to fluoroquinolones [46.8% (29/62)-97.0% (32/33)]. The resistance rates of Acinetobacter baumannii to most commonly used antibiotics were >80.0%. The resistance rates of Escherichia coli and Klebsiella pneumoniae to the third-generation cephalosporins ranged from 41.8% (28/67) to 66.0% (31/47). Carbapenem resistance was observed in 38.1% (24/63)-40.3% (25/62) of Klebsiella pneumoniae isolates, and most of the isolates from bronchoalveolar lavage fluid samples showed a higher resistance rate than those from blood or urine samples ( P<0.05). Conclusions:The positive rate of bacterial culture is nearly 50% in this study, with Gram-negative bacteria being the most common. Six major pathogenic bacteria exhibit high resistance rates to fluoroquinolones. Klebsiella pneumoniae isolates have high resistance rates to the third-generation cephalosporins and carbapenems, with significant differences in the resistance rate between isolates from different samples, and it should be cautious to choose the third-generation cephalosporins and carbapenems in clinical practice.

Aim To explore the influence of demethy-lase fat mass and obesity-related genes(FTO)on the abnormal contractile function of diabetic coronary smooth muscle.Methods Smooth muscle specific FTO knockout mice(FTOSMKO)were prepared by Cre-loxP recombinant technology.They were divided into four groups:control(WT)group,diabetes model group(DM),FTO knockout group(FTOSMKO),and FTOSMKO diabetic group(FTOSMKO-DM),with 15 mice in each group.Diabetic mice were prepared by intraperitoneal injection of streptozotocin(STZ);the remaining mice were injected with an equal amount of citric acid-sodi-um citrate buffer.The effects of 5-HTon the contractile response of coronary artery smooth muscle in the four groups of mice were observed by the technique of small-vessel ring tensiometry.Western blot and Dot blot were used to detect the changes of FTO protein and N6-methyladenine(m6A)methylation modification levels in mouse vascular tissues.Results Compared with the WT group,the DM group had significantly higher blood glucose(P＜0.01)and lower body weight(P＜0.05);the level of FTO protein in aorta of DM group increased(P＜0.01),and the level of m6A methylation modification decreased(P＜0.01).The 5-HT-induced contractile response significantly de-creased in the DM group compared with the WT group(P＜0.01),whereas the contractile response signifi-cantly increased in the FTOSMKO-DM group compared with the DM group(P＜0.01);the non-L-type calci-um channel-mediated vascular smooth muscle contrac-tile response was enhanced in the FTOSMKO-DM group,among which,the contractions induced by 1,4,5-triphosphate inositol receptor(IP3R)and caffeine-ac-tivated ranine receptor(RyR)mediated by sarcoplas-mic reticulum calcium release both significantly in-creased(P＜0.05).Conclusions Specific knock-down of smooth muscle FTO improves coronary artery responsiveness to the vasoconstrictor 5-HT in diabetic mice,which may be related to abnormalities in the FTO-mediated 5-HT receptor signaling pathway.

A 59-year-old male patient with sigmoid colon cancer and liver metastasis received the treatments of cetuximab combined with FOLFIRI regimen (irinotecan, calcium folinate, and fluorouracil). His serum creatinine (Scr) was 82 μmol/L, and estimated glomerular filtration rate (eGFR) was 96 ml/(min·1.73 m 2) before the treatment. On the 11th day after finishing the 4th cycle of treatments, the patient developed nausea and vomiting. Laboratory tests showed Scr 221 μmol/L, eGFR 29 ml/(min·1.73 m 2), serum albumin 29.0 g/L, urinary protein (+++), and 24 hour urine protein quantified 8.88 g. He was diagnosed as having nephrotic syndrome complicated with acute kidney injury, which was considered to be related to cetuximab. The drug was stopped and symptomatic treatments such as anti-inflammatory, anticoagulation and kidney protection were given. After 14 days, laboratory tests showed no proteinuria, Scr 156 μmol/L, and eGFR 44 ml/(min·1.73 m 2). Prednisone acetate tablet 50 mg were orally administered once daily. Fifty-nine days later, his Scr was 142 μmol/L, and eGFR was 49 ml/(min·1.73 m 2). Chemotherapy was suspended and cetuximab was discontinued permanently.

Purpose The study aimed to analyze the relationship between MET gene variants and clinicopathologi-cal features in patients with non-small cell lung cancer(NSCLC).Methods Next-generation sequencing technology was used to detect MET gene variants in NSCLC specimens.The association between MET gene variant status and clini-copathological features was then analyzed.Results Among 1 633 cases of NSCLC,the overall MET mutation rate was 4.53％(74/1 633).Variants were mainly observed in male patients,never-smokers,those older than 60 years,ade-nocarcinoma histology,and patients with TNM stage Ⅲ+Ⅳ disease(P＜0.05).MET gene variant status showed no significant assocication with patient age,sex,smoking history,or pathological subtype(P＞0.05),but was statistical-ly correlated with clinical stage and presence of distant metastasis(P＜0.05).The two major variant types were MET exon 14 skipping and MET amplification,which together accounted for 71.62％of all variants.In addition,MET am-plification was positively correlated with EGFR(P=0.003,rs=0.340)and TP53 mutations(P=0.002,rs=0.362),but showed no correlation with KRAS or ALK gene mutations.In contrast,MET exon 14 skipping was nega-tively correlated with EGFR gene mutations(P＜0.001,rs=-0.409),and showed no significant correlation with KRAS,ALK,or TP53 mutations.Conclusion Different types of MET gene variants(amplification,exon 14 skip-ping,fusion,and others)are significantly associated with clinical advanced clinical stage and distant metastasis in NSCLC,but are independent of patient age,sex,smoking history,and pathological subtype.MET amplification fre-quently co-occur with EGFR and TP53 co-mutations.

Objective:To identify the bacteria isolated from sepsis patients in a tertiary hospital in Shanghai and analyze their antimicrobial resistance features.Methods:This study included 439 patients with clinically diagnosed sepsis who underwent microbiological culture in a tertiary hospital in Shanghai from July 2021 to October 2024. Results of microbiological culture and antimicrobial susceptibility testing were retrospectively collected and analyzed. Differences between groups were analyzed using Chi-square test and Fisher′s exact test. Results:The positive rate of microbiological culture was 49.0% (215/439). The positive rate of blood culture was 24.1% (93/386) and 100 strains were isolated from the samples, including 57 Gram-negative bacteria (57.0%). The predominant isolates in blood samples were Escherichia coli, Klebsiella pneumoniae, and coagulase-negative staphylococci. The positive rate of bacterial culture from bronchoalveolar lavage fluid samples was 84.1% (37/44), with Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa being the predominant strains. The positive rate of bacterial culture from urine samples was 35.6% (127/357), with Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecium being the most common. Escherichia coli, Klebsiella pneumoniae, Enterococcus faecium, coagulase-negative staphylococci, Pseudomonas aeruginosa, and Acinetobacter baumannii exhibited high resistance rates to fluoroquinolones [46.8% (29/62)-97.0% (32/33)]. The resistance rates of Acinetobacter baumannii to most commonly used antibiotics were >80.0%. The resistance rates of Escherichia coli and Klebsiella pneumoniae to the third-generation cephalosporins ranged from 41.8% (28/67) to 66.0% (31/47). Carbapenem resistance was observed in 38.1% (24/63)-40.3% (25/62) of Klebsiella pneumoniae isolates, and most of the isolates from bronchoalveolar lavage fluid samples showed a higher resistance rate than those from blood or urine samples ( P<0.05). Conclusions:The positive rate of bacterial culture is nearly 50% in this study, with Gram-negative bacteria being the most common. Six major pathogenic bacteria exhibit high resistance rates to fluoroquinolones. Klebsiella pneumoniae isolates have high resistance rates to the third-generation cephalosporins and carbapenems, with significant differences in the resistance rate between isolates from different samples, and it should be cautious to choose the third-generation cephalosporins and carbapenems in clinical practice.