This study aimed to investigate the effects of the peptide secreted protein isthmin-1 (ISM1) on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells. ISM1 expression in NSCLC was detected by immunohistochemistry (IHC). ISM1 was overexpressed in lung cancer cell lines by transient transfection of ISM1 plasmids, or establishing ISM1 overexpression stable cell lines, or by treating cells with recombined ISM1 (rISM1). CCK-8 was used to examine cell growth. The intracellular signal transduction pathways regulated by rISM1 were analyzed by transcriptome sequencing, and verified by qRT-PCR and Western blot. The levels of intracellular ROS and apoptosis were further detected using the kit. The results showed that the expression of ISM1 was decreased in human NSCLC tissue samples compared to normal lung tissue samples. Overexpression of ISM1 or rISM1 treatment significantly suppressed the growth of lung cancer cells. RNA sequencing revealed that rISM1 mainly regulated the FoxO signaling pathway. rISM1 treatment decreased the expression of FoxO3 and FoxO1, increased reactive oxygen species (ROS) production, and induced cell apoptosis. These results suggest that ISM1 can inhibit the growth of NSCLC by regulating the FoxO signaling pathway. These findings provide new strategies for cancer therapy.

OBJECTIVE To systematically identify the dilemmas in value assessment of antitumor combination therapies， and to provide evidence for health insurance coverage， drug pricing， and clinical decision-making. METHODS The concept of “surplus value space” was introduced to cons truct a value assessment framework， under which the dilemmas in three assessment scenarios were analyzed. Optimization recommendations were proposed by drawing on international research addressing similar challenges. RESULTS & CONCLUSIONS The core dilemma of value assessment for antitumor combination therapies lies in insufficient surplus value space. When the cost of the backbone therapy exceeds its corresponding health value， the add-on drug encounters a “free but uneconomical”problem. Existing international value assessment methods have limitations such as flawed evaluation frameworks， difficulty in operationalizing the quality-adjusted life year allocation framework， and frequent occurrence of the “free but uneconomical”problem， rendering them inadequate for the complex scenarios of antitumor combination therapies. To address these dilemmas， strategies such as adjusting payment thresholds， exploring discounted pricing， conducting multi-product linkage negotiations， and delaying insurance access are recommended to improve the rationality and feasibility of value assessment for antitumor combination therapies.

To analyze the prevalence, drug resistance and whole genome characteristics of Mycoplasma pneumoniae (MP) in respiratory throat swab samples of hospitalized children with pneumonia in Suzhou City from 2023 to 2024. Throat swab samples of hospitalized children aged 0-14 years old with pneumonia in Suzhou were collected from September 2023 to September 2024. Real-time fluorenscence quantitative PCR technology was used to detect MP nucleic acid. The results showed that the positive rate of MP in 3 235 samples was 22.44% (726/3 235), with a rate of 55.00% in week 47 of 2023. The positive rate of MP increased with age ( χ2=45.842, P<0.001). The study selected MP nucleic acid test positive samples from week 20 (5.13-5.19) to week 23 (6.3-6.9) of 2024 for isolation, culture and resistance phenotype detection. About 31 MP strains were successfully isolated and cultured, all of which were resistant to macrolides. The next-generation sequencing technology and nanopore sequencing technology were used for genome sequencing. All 31 strains carried the A2063G mutation, with the main prevalent genotype being the P1-1, and the main mlST type being the ST3. Despite the overall genomic similarity between strains being over 99%, there were significant differences between the P1-1 and P1-2 strains in the P1 gene region. In summary, from 2023 to 2024, the main MP type prevalent in Suzhou City is the P1-1 genotype. All isolated MP strains carry an A2063G resistance site mutation and are resistant to macrolides, requiring continuous monitoring and further research.

Objective:To explore the distribution variation of ultrasound-detected inflammatory lesions with clinical signs in patients with psoriatic arthritis (PsA).Methods:This was based on the Peking University First Hospital Psoriatic Arthritis (PKUPsA) cohort. Patients enrolled from January 2019 to June 2024 were inchuded, patients with complete data of physical examination and ultrasonographic evaluations of 62 joints in the hand and foot. The ultrasound-detected inflammatory lesions including synovitis, tenosynovitis, enthesitis, and soft tissue inflammation were compared with joint tenderness/swelling. The χ2 test was employed to analyze differences between groups. Results:A total of 7 440 joints in 120 PsA patients were included. Overall, the proportion of joints with clinical signs (tenderness or swelling) was higher than those with ultrasound-detected inflammatory lesions [9.14%(680/7 440) vs. 7.93%(590/7 440), χ2=1 245.928, P<0.001], with more tenderness joints than swelling joints [7.72%(574/7 440) vs. 6.14%(457/7 440), χ2=3 264.45, P<0.001]. Clinical signs were primarily observed in hand proximal interphalangeal (PIP), distal interphalangeal (DIP), wrist and ankle joints, mostly in DIP2 joints [19.58%(47/240)]. Ultrasound-detected inflammatory lesions were predominantly found in metatarsophalangeal (MTP), wrist, and ankle joints, mostly in MTP2 joints (18.75%, 45/240). Clinical signs were more prevalent than ultrasound-detected inflammatory lesions in hand PIP1-3, PIP5, DIP2, and DIP5 joints ( P<0.05), whereas more frequent ultrasound-detected inflammatory lesions than clinical tenderness/swelling were in MTP1-4 joints ( P<0.05). Among ultrasound-detected inflammatory lesions, synovitis in MTP2 joints (18.75%, 45/240), tenosynovitis in ankle joints (10.00%, 24/240), enthesitis in hand DIP2 joints (8.75%, 21/240), and soft tissue inflammation in MTP4 joints (2.50%, 6/240) most commonly observed. Dactylitis was more frequently observed in toes than in fingers, with the fourth toe most commonly affected(16.67%, 40/240). Ultrasound-detected inflammatory lesions were observed in 72.37%(55/240) of fingers/toes with clinical dactylitis, mainly presenting as synovitis, tenosynovitis, or combinations of these. Conclusion:PsA exhibits significant heterogeneity in the inflammatory lesions across different joints and lesion types. The discrepancies between clinical findings and ultrasonic inflammatory changes highlight the limitations of physical examination in fully capturing the pathological features of PsA. As a critical tool for PsA evaluation, ultrasonography offers distinct advantages in detecting subclinical inflammation and differentiating inflammatory from non-inflammatory lesions.

Rodent models play a crucial role in research on human periodontal diseases,providing key evidence for investigation into the pathological mechanisms of periodontal bone defects.Relevant research in the field involves gene expression,inflammatory regulation mechanisms,host-microbial interactions,as well as disease resolution and healing processes.Research methodology in the field falls under 2 categories-periodontal inflammation models and surgical defect models.The former simulates periodontal defects by inducing periodontal diseases,while the latter constructs clinically simulated periodontal defects through surgical removal of periodontal tissue.However,the currently available animal models of periodontitis face challenges in simultaneously capturing the disease complexity,tracking dynamic repair processes,and meeting translational needs.Herein,we reviewed and summarized the methods and characteristics of periodontal disease modeling in recent years.We proposed the establishment of a multimodal assessment framework integrating technologies such as spatial transcriptomics,single-cell sequencing,and in vivo fluorescence imaging,which may serve as a critical pathway for overcoming existing research challenges.

Objective:To establish an ion chromatography-integrated amperometric detection method for iodide in water.Methods:After the water sample was filtered through a filter membrane, the AS 11-HC anion chromatography column of ion chromatography method was used to separate iodide ions under the conditions of 70 mmol/L sodium hydroxide solution as the eluent, injection volume of 100 μl, column temperature of 30 ℃, and flow rate of 1.0 ml/min. The results were determined by silver working electrode integral amperometric detection method. Under the optimized experimental conditions, methodological evaluations such as method calibration curves, detection limits, quantification limits, precision, and accuracy were conducted.Results:Iodide followed a square correction curve within the concentration range of 0 - 100 μg/L, with a correlation coefficient ( r) > 0.999 9. The detection limit of the method was 0.30 μg/L, and the quantification limit was 1.00 μg/L. The determination results of the national standard substances GBW09113f and GBW09114f for iodine composition analysis in water were within the reference range [(8.4 ± 1.2), (55 ± 6) μg/L]. The recovery rates of low, medium, and high concentration spiked samples with low background values ranged from 91.7% to 97.2%, and the relative standard deviation ranged from 0.40% to 1.60%. Conclusion:This method has the characteristics of simple water sample pretreatment, high sensitivity, and good accuracy, which can meet the determination of trace iodides in bulk water samples for iodine deficiency disorders monitoring.

To analyze the prevalence, drug resistance and whole genome characteristics of Mycoplasma pneumoniae (MP) in respiratory throat swab samples of hospitalized children with pneumonia in Suzhou City from 2023 to 2024. Throat swab samples of hospitalized children aged 0-14 years old with pneumonia in Suzhou were collected from September 2023 to September 2024. Real-time fluorenscence quantitative PCR technology was used to detect MP nucleic acid. The results showed that the positive rate of MP in 3 235 samples was 22.44% (726/3 235), with a rate of 55.00% in week 47 of 2023. The positive rate of MP increased with age ( χ2=45.842, P<0.001). The study selected MP nucleic acid test positive samples from week 20 (5.13-5.19) to week 23 (6.3-6.9) of 2024 for isolation, culture and resistance phenotype detection. About 31 MP strains were successfully isolated and cultured, all of which were resistant to macrolides. The next-generation sequencing technology and nanopore sequencing technology were used for genome sequencing. All 31 strains carried the A2063G mutation, with the main prevalent genotype being the P1-1, and the main mlST type being the ST3. Despite the overall genomic similarity between strains being over 99%, there were significant differences between the P1-1 and P1-2 strains in the P1 gene region. In summary, from 2023 to 2024, the main MP type prevalent in Suzhou City is the P1-1 genotype. All isolated MP strains carry an A2063G resistance site mutation and are resistant to macrolides, requiring continuous monitoring and further research.

Objective:To establish an ion chromatography-integrated amperometric detection method for iodide in water.Methods:After the water sample was filtered through a filter membrane, the AS 11-HC anion chromatography column of ion chromatography method was used to separate iodide ions under the conditions of 70 mmol/L sodium hydroxide solution as the eluent, injection volume of 100 μl, column temperature of 30 ℃, and flow rate of 1.0 ml/min. The results were determined by silver working electrode integral amperometric detection method. Under the optimized experimental conditions, methodological evaluations such as method calibration curves, detection limits, quantification limits, precision, and accuracy were conducted.Results:Iodide followed a square correction curve within the concentration range of 0 - 100 μg/L, with a correlation coefficient ( r) > 0.999 9. The detection limit of the method was 0.30 μg/L, and the quantification limit was 1.00 μg/L. The determination results of the national standard substances GBW09113f and GBW09114f for iodine composition analysis in water were within the reference range [(8.4 ± 1.2), (55 ± 6) μg/L]. The recovery rates of low, medium, and high concentration spiked samples with low background values ranged from 91.7% to 97.2%, and the relative standard deviation ranged from 0.40% to 1.60%. Conclusion:This method has the characteristics of simple water sample pretreatment, high sensitivity, and good accuracy, which can meet the determination of trace iodides in bulk water samples for iodine deficiency disorders monitoring.

Objective:To explore the distribution variation of ultrasound-detected inflammatory lesions with clinical signs in patients with psoriatic arthritis (PsA).Methods:This was based on the Peking University First Hospital Psoriatic Arthritis (PKUPsA) cohort. Patients enrolled from January 2019 to June 2024 were inchuded, patients with complete data of physical examination and ultrasonographic evaluations of 62 joints in the hand and foot. The ultrasound-detected inflammatory lesions including synovitis, tenosynovitis, enthesitis, and soft tissue inflammation were compared with joint tenderness/swelling. The χ2 test was employed to analyze differences between groups. Results:A total of 7 440 joints in 120 PsA patients were included. Overall, the proportion of joints with clinical signs (tenderness or swelling) was higher than those with ultrasound-detected inflammatory lesions [9.14%(680/7 440) vs. 7.93%(590/7 440), χ2=1 245.928, P<0.001], with more tenderness joints than swelling joints [7.72%(574/7 440) vs. 6.14%(457/7 440), χ2=3 264.45, P<0.001]. Clinical signs were primarily observed in hand proximal interphalangeal (PIP), distal interphalangeal (DIP), wrist and ankle joints, mostly in DIP2 joints [19.58%(47/240)]. Ultrasound-detected inflammatory lesions were predominantly found in metatarsophalangeal (MTP), wrist, and ankle joints, mostly in MTP2 joints (18.75%, 45/240). Clinical signs were more prevalent than ultrasound-detected inflammatory lesions in hand PIP1-3, PIP5, DIP2, and DIP5 joints ( P<0.05), whereas more frequent ultrasound-detected inflammatory lesions than clinical tenderness/swelling were in MTP1-4 joints ( P<0.05). Among ultrasound-detected inflammatory lesions, synovitis in MTP2 joints (18.75%, 45/240), tenosynovitis in ankle joints (10.00%, 24/240), enthesitis in hand DIP2 joints (8.75%, 21/240), and soft tissue inflammation in MTP4 joints (2.50%, 6/240) most commonly observed. Dactylitis was more frequently observed in toes than in fingers, with the fourth toe most commonly affected(16.67%, 40/240). Ultrasound-detected inflammatory lesions were observed in 72.37%(55/240) of fingers/toes with clinical dactylitis, mainly presenting as synovitis, tenosynovitis, or combinations of these. Conclusion:PsA exhibits significant heterogeneity in the inflammatory lesions across different joints and lesion types. The discrepancies between clinical findings and ultrasonic inflammatory changes highlight the limitations of physical examination in fully capturing the pathological features of PsA. As a critical tool for PsA evaluation, ultrasonography offers distinct advantages in detecting subclinical inflammation and differentiating inflammatory from non-inflammatory lesions.

Objective To study the effect of high mobility group box B1(HMGB1)gene knockout on alleviating a-cute lung injury and inhibiting toll-like receptor 4(TLR4)/nuclear factor-KB(NF-κB)pathway of sepsis mice.Methods Wild-type(WT)mice were divided into WT-Sham group and WT-model group,and HMGB1 knockout(KO)mice were divided into KO-sham group and KO-model group.Sepsis ALI model was established by cecal ligation and perforation in WT-model group and KO-model group.Sham operation was performed in WT-Sham group and KO-Sham group.24 h after modeling,the partial pressure of arterial oxygen(PaO2)was detected,oxy-genation index(OI)was calculated,pathological changes of lung tissue were detected and lung injury score was calculated,the concentrations of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β),interleukin-6(IL-6),reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD),in serum and lung tissues and the expression of HMGB1,TLR4 and nuclear NF-κB in lung tissues were detected.Results The PaO2,OI and the concentration of SOD in serum and lung tissue of WT-model group were lower than those of WT-Sham group,the lung injury scores,the concentrations of TNF-α,IL-1 β,IL-6,ROS and MDA in serum and lung tissue,and the expression levels of HMGB1,TLR4 and nuclear NF-κB in lung tissue were higher than those in WT-Sham group(P＜0.05).HMGB1 was not expressed in lung tissue of KO-model group,and the concentrations of PaO2,OI and the concentration of SOD in serum and lung tissue of KO-model group were higher than those of WT-model group,the lung injury scores,the concentrations of TNF-α,IL-1β,IL-6,ROS and MDA in serum and lung tissue,and the expression levels of TLR4 and nuclear NF-κB in lung tissue were lower than those of the WT-model group(P＜0.05).Conclusion HMGB1 gene knockout alleviates acute lung injury of sepsis mice,the re-lated molecular mechanism may be the inhibition of TLR4/NF-κB pathway mediated inflammation and oxidative stress.