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.

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.

OBJECTIVE: To explore the morphological characteristics of the postero-superior protuberance of the calcaneus and to explore its relationship with Haglund malformation. METHODS: Ankle lateral X-ray films of 391 hospitalized patients between May 2021 and June 2024 were retrospectively collected. The morphological parameters of the postero-superior protuberance of the calcaneus were measured, including the length of the base, the height of the base, and the tip angle of the postero-superior protuberance of the calcaneus, and the morphological types were classified according to the above parameters, including the peak type, the hill type, and the flat type. The related parameters of Haglund malformation were measured, including Fowler-Philipp angle (FPA), calcaneal pitch angle (CPA), parallel pitch line (PPL), Chauveaux-Liet angle (CLA), and X/Y ratio (total calcaneal length/length of greater tuberosity of calcaneus). The differences of the morphological parameters of the postero-superior protuberance of the calcaneus and the related indicators of Haglund deformity among the three types and between the males and the females were compared and analyzed, and the differences of the positive numbers of the related indicators of Haglund deformity among the three types were compared. RESULTS: According to the morphological parameters of the postero-superior protuberance of the calcaneus, there were 64 cases of peak type, 245 cases of hill type, and 82 cases of flat type. There was no significant difference in the length of the base of the postero-superior protuberance of the calcaneus, CPA, CLA, and X/Y ratio among the three types ( P>0.05). Among the three types, the peak type had the largest FPA and the flat type had the smallest ( P<0.05); the peak type had the smallest tip angle of the postero-superior protuberance of the calcaneus and the flat type had the largest ( P<0.05); the positive rate of PPL in the hill type was significantly higher than that in the peak type and flat type ( P<0.05); the height of the base of the postero-superior protuberance of the calcaneus in the flat type was the smallest ( P<0.05). FPA, CPA, CLA, PPL, and X/Y ratio were positive in 2, 42, 172, 142, and 77 patients, respectively. There was no significant difference in the number of positive Haglund deformity indicators among the three types ( P>0.05). There was no significant difference between male and female patients in the tip angle of the postero-superior protuberance of the calcaneus, FPA, the positive rate of PPL, and X/Y ratio ( P>0.05). The length and the height of the base of the postero-superior protuberance of the calcaneus, CPA, and CLA in male patients were significantly higher than those in female patients ( P<0.05). CONCLUSION The postero-superior protuberance of the calcaneus can be divided into three types: the peak type, the hill type, and the flat type. The peak type is more likely to suffer from Haglund deformity, and the males are more likely to suffer from Haglund deformity than the females.
Humans ; Calcaneus/anatomy & histology* ; Male ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Adolescent ; Young Adult ; Radiography ; Child ; Aged

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.

OBJECTIVE: To construct and validate a prognostic prediction model for children with sepsis using the Phoenix sepsis score (PSS). METHODS: A retrospective case series study was conducted to collect clinical data of children with sepsis admitted to the pediatric intensive care unit (PICU) of the Affiliated Hospital of Guizhou Medical University from January 2022 to April 2024. The data included general information, the worst values of laboratory indicators within the first 24 hours of PICU admission, PSS score, pediatric critical illness score (PCIS), and the survival status of the children within 30 days of admission. The statistically significant indicators in univariate Logistic regression analysis were included in multivariate Logistic regression analysis to screen the risk factors affecting the prognosis of children with sepsis and construct a nomogram model. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive performance of the model. The Bootstrap method was used to perform 1 000 repeated sampling internal verification and draw the calibration curve of the model. RESULTS: A total of 199 children with sepsis were included, of which 32 died and 167 survived 30 days after admission. In the univariate Logistic regression analysis, shock, white blood cell count (WBC), international normalized ratio (INR), lactic acid (Lac), PSS score, and PCIS score were identified as statistically significant predictors. These variables were then included in the multivariate Logistic regression analysis, which demonstrated that shock [odds ratio (OR) = 4.258, 95% confidence interval (95%CI) was 1.049-17.288], WBC (OR = 1.124, 95%CI was 1.052-1.210), and PSS score (OR = 1.977, 95%CI was 1.298-3.012) were independent risk factors for mortality in pediatric patients with sepsis (all P < 0.05). A nomogram model was constructed based on these three risk factors, with the model equation as follows: -4.809+1.449×shock+0.682×PSS score+0.117×WBC. The calibration curve results showed that the model's predictions were highly consistent with the actual observations. The ROC curve showed that when the Youden index of the prediction model was 0.792, the sensitivity and specificity were 90.6% and 88.6%, respectively, and the area under the curve (AUC) was 0.957 (95%CI was 0.930-0.984), which was higher than the AUC of shock, WBC, and PSS score alone (0.808, 0.667, 0.908, respectively). CONCLUSIONS Shock, WBC, and PSS score have demonstrated certain predictive value for mortality in children with sepsis. The nomogram model based on the above indicators has important clinical significance for evaluating the prognosis and guiding treatment of children with sepsis.
Humans ; Sepsis/diagnosis* ; Prognosis ; Retrospective Studies ; Logistic Models ; Intensive Care Units, Pediatric ; Nomograms ; Child ; ROC Curve ; Risk Factors ; Male ; Female ; Child, Preschool ; Infant

Rice (Oryza sativa L.), as a thermophilic crop, is highly susceptible to cold stress during its growth process. Chilling injury at the plumule stage and seedling stage often affects the morphological development and leads to yield reduction of rice. The exploration and utilization of cold tolerance genes are among the most direct and effective approaches to address cold stress in rice. To identify quantitative trait loci (QTLs) associated with cold tolerance at plumule and seedling stages, in this study, we measured the seedling rates and survived seedling rates of the indica rice cultivar 'HZ', the japonica cultivar 'Nekken2', and their 120 recombinant inbred lines (RILs) under cold stress. A previously constructed high-density genetic linkage map was used for the mapping of the QTLs conferring cold tolerance at the plumule and seedling stages. A total of 4 QTLs for plumule-stage cold tolerance and 9 QTLs for seedling-stage cold tolerance were detected, with the maximum limit of detection reaching 5.20. Notably, a genetically overlapping QTL for both plumule and seedling stages was identified on chromosome 8, spanning a physical interval of 24 432 953-25 295 129 bp. Candidate genes within the detected QTL intervals were screened, and quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to analyze the gene expression during the plumule and seedling stages. The results revealed that LOC_Os03g06570, LOC_Os03g07100, LOC_Os06g08280, LOC_Os08g38440, LOC_Os08g39100, and LOC_Os08g39540 exhibited significantly differential expression between the parental lines. These genes were either significantly downregulated or upregulated under cold stress. Among them, the first three gene (LOC_Os03g06570, LOC_Os03g07100, and LOC_Os06g08280) were hypothesized to be key candidates regulating the cold tolerance of rice seedlings, while the latter three genes (LOC_Os08g38440, LOC_Os08g39100, and LOC_Os08g39540) were identified as comprehensive regulators of cold tolerance during both plumule and seedling stages. These findings lay a foundation for the fine mapping and cloning of cold tolerance genes at the plumule and seedling stages, providing valuable insights for breeding cold-tolerant rice varieties.
Quantitative Trait Loci/genetics* ; Oryza/growth & development* ; Seedlings/growth & development* ; Cold Temperature ; Chromosome Mapping ; Gene Expression Regulation, Plant

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.

Aim To study the diastolic effect and mechanism of farrerol on isolated pulmonary arteries of C57BL/6J mice.Methods After anesthesia,mouse lung tissue was quickly removed and placed into the 4 ℃ K-H buffer,pulmonary arteries were isolated under the microscope and cut into 2 mm long vascular rings for spare use.(1)The effect of farrerol on the resting tension of isolated mouse pulmonary arteries:in the resting state,the active mouse pul-monary artery rings were treated with different concentrations of farrerol(10-6,3×10-6,10-5,3×10-5 and 10-4 mol/L).(2)Farrerol relaxed mouse pulmonary artery experiment:pulmonary arteries were contracted using phenylephrine(PE,1 μmol/L)or KCl(60 mmol/L),and when the contraction reached the platform,different concentrations of farrerol(10-6,3×10-6,10-5,3×10-5 and 10-4 mol/L)was added.(3)Farrerol inhibited pulmonary artery contraction experi-ment:under conditions with or without the addition of farrerol,pulmonary arteries were contracted using different concen-trations of PE(10-9,3×10-9,10-8,3 × 10-8,10-7,3×10-7 and 10-6 mol/L)or KCl(20,30,40,60,80 and 120 mmol/L),and the pulmonary artery muscle tension was recorded.(4)Calcium free and recalcification experiments:under conditions with or without the addition of farrerol,the changes of isolated mouse pulmonary artery tension were meas-ured in the state of calcium free or recalcification { 2.5 mmol/L[Ca2+]ex }.(5)The relationship between farrerol in-duced relaxation of isolated mouse pulmonary arteries and potassium ion channels:firstly,60 mmol/L KCl solution was used to contract the mouse pulmonary arteries until the platform.Then,3 mmol/L aminopyridine(4-AP),2 mmol/L tet-raethylammonium(TEA),30 μmol/L BaCl2,and 10 μmol/L glibenclamide(Gli)were added and treated for 15 min.Subsequently,the pulmonary arteries were relaxed using a concentration gradient of farrerol.Results Farrerol had no significant effect on the mouse pulmonary arteries in the resting state,but had a concentration-dependent relaxing effect on the mouse pulmonary arteries pre-contracted with PE and KCl.While the pretreatment of 3×10-5 mol/L farrerol could sig-nificantly reduce the maximum contraction of mouse pulmonary arteries induced by PE and KCl(P＜0.01),as well as sig-nificantly reduce the contraction of mouse pulmonary arteries induced by KCl under calcium free or recalcification conditions(P＜0.01).Addition of the voltage-dependent potassium ion channel blocker 4-AP significantly reduced the maximum diastolic rate of mouse pulmonary arteries induced by farrerol(P＜0.01),while addition of the high conductivity calcium activated potassium ion channel blocker TEA,inward rectifying potassium ion channel blocker BaCl2,or ATP sensitive po-tassium ion channel blocker Gli had no significant effect on the vasodilation effect of farrerol(P＞0.05).Conclusion Farrerol has a relaxing effect on isolated mouse pulmonary arteries,and its mechanism may be related to open voltage-de-pendent potassium ion channels.

Aim To study the diastolic effect and mechanism of farrerol on isolated pulmonary arteries of C57BL/6J mice.Methods After anesthesia,mouse lung tissue was quickly removed and placed into the 4 ℃ K-H buffer,pulmonary arteries were isolated under the microscope and cut into 2 mm long vascular rings for spare use.(1)The effect of farrerol on the resting tension of isolated mouse pulmonary arteries:in the resting state,the active mouse pul-monary artery rings were treated with different concentrations of farrerol(10-6,3×10-6,10-5,3×10-5 and 10-4 mol/L).(2)Farrerol relaxed mouse pulmonary artery experiment:pulmonary arteries were contracted using phenylephrine(PE,1 μmol/L)or KCl(60 mmol/L),and when the contraction reached the platform,different concentrations of farrerol(10-6,3×10-6,10-5,3×10-5 and 10-4 mol/L)was added.(3)Farrerol inhibited pulmonary artery contraction experi-ment:under conditions with or without the addition of farrerol,pulmonary arteries were contracted using different concen-trations of PE(10-9,3×10-9,10-8,3 × 10-8,10-7,3×10-7 and 10-6 mol/L)or KCl(20,30,40,60,80 and 120 mmol/L),and the pulmonary artery muscle tension was recorded.(4)Calcium free and recalcification experiments:under conditions with or without the addition of farrerol,the changes of isolated mouse pulmonary artery tension were meas-ured in the state of calcium free or recalcification { 2.5 mmol/L[Ca2+]ex }.(5)The relationship between farrerol in-duced relaxation of isolated mouse pulmonary arteries and potassium ion channels:firstly,60 mmol/L KCl solution was used to contract the mouse pulmonary arteries until the platform.Then,3 mmol/L aminopyridine(4-AP),2 mmol/L tet-raethylammonium(TEA),30 μmol/L BaCl2,and 10 μmol/L glibenclamide(Gli)were added and treated for 15 min.Subsequently,the pulmonary arteries were relaxed using a concentration gradient of farrerol.Results Farrerol had no significant effect on the mouse pulmonary arteries in the resting state,but had a concentration-dependent relaxing effect on the mouse pulmonary arteries pre-contracted with PE and KCl.While the pretreatment of 3×10-5 mol/L farrerol could sig-nificantly reduce the maximum contraction of mouse pulmonary arteries induced by PE and KCl(P＜0.01),as well as sig-nificantly reduce the contraction of mouse pulmonary arteries induced by KCl under calcium free or recalcification conditions(P＜0.01).Addition of the voltage-dependent potassium ion channel blocker 4-AP significantly reduced the maximum diastolic rate of mouse pulmonary arteries induced by farrerol(P＜0.01),while addition of the high conductivity calcium activated potassium ion channel blocker TEA,inward rectifying potassium ion channel blocker BaCl2,or ATP sensitive po-tassium ion channel blocker Gli had no significant effect on the vasodilation effect of farrerol(P＞0.05).Conclusion Farrerol has a relaxing effect on isolated mouse pulmonary arteries,and its mechanism may be related to open voltage-de-pendent potassium ion channels.