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Early prognostic prediction is crucial for determining appropriate clinical interventions. Previous single-omics models had limitations, such as high contingency and overlooking complex physical conditions. In this paper, we introduced multi-omics graph knowledge representation to predict in-hospital outcomes for pneumonia patients. This method utilizes CT imaging and three non-imaging omics information, and explores a knowledge graph for modeling multi-omics relations to enhance the overall information representation. For imaging omics, a multichannel pyramidal recursive MLP and Longformer-based 3D deep learning module was developed to extract depth features in lung window, while radiomics features were simultaneously extracted in both lung and mediastinal windows. Non-imaging omics involved the adoption of laboratory, microbial, and clinical indices to complement the patient's physical condition. Following feature screening, the similarity fusion network and graph convolutional network (GCN) were employed to determine omics similarity and provide prognostic prediction. The results of comparative experiments and generalization validation demonstrat that the proposed multi-omics GCN-based prediction model has good robustness and outperformed previous single-type omics, classical machine learning, and previous deep learning methods. Thus, the proposed multi-omics graph knowledge representation model enhances early prognostic prediction performance in pneumonia, facilitating a comprehensive assessment of disease severity and timely intervention for high-risk patients.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb), results in significant morbidity and mortality worldwide. Host-directed therapy (HDT), including conventional drugs, is a promising anti-TB strategy that shows synergistic antibacterial effects when combined with anti-TB drugs. Here, the mycobactericidal effect of three anti-diabetic drugs was examined. Of these, only Troglitazone (Trog) enhanced the antimycobacterial effect in vitro and in vivo. This was due to Trog-mediated autophagy activation. Moreover, a knock-down experiment revealed that Trog activated autophagy and exhibited antimycobacterial activity through the LKB1-AMPK signaling pathway. Molecular docking and co-immunoprecipitation experiments demonstrated that Trog promoted LKB1 phosphorylation and activation by targeting STRADA. Finally, we found that Trog inhibited the intracellular survival of clinical isoniazid (INH)-resistant Mtb, and the combination of Trog and INH showed additive antibacterial effects against Mtb H37Rv. Taken together, anti-diabetic Trog may be repurposed as an HDT candidate and combined with first-line anti-TB drugs., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

To explore the influence of storage temperature and time on the stability of different concentrations of hepatitis C virus nucleic acid (HCV RNA) samples and to provide data reference for laboratory quality control. Serum samples of 10 patients with HCV RNA detection quantitation of 10 6 -10 8 IU/mL were collected. The samples of each patient were diluted into three concentrations: high, medium, and low. Then the samples of each concentration were divided into 21, which were divided into three groups according to the storage conditions of -20°C, 4°C, and 25°C, with seven samples in each group. The samples were selected from each group for quantitative detection of HCV RNA on day 0, day 1, day 3, day 5, day 7, day 14, and day 30. The results of each concentration and storage temperature sample remained stable within 5 days. Based on the mixed-effect linear model, the main effects of temperature, time, and concentration were statistically significant ( P < 0.01). There was an interaction effect between concentration and time ( P = 0.0448), and there was also an interaction effect between temperature and time ( P < 0.01). There was no interaction effect between concentration and temperature ( P = 0.11) or between concentration, temperature, and time ( P = 0.90). The results of serum samples with different concentrations of the HCV RNA remained stable within 5 days. The lower the initial concentration of HCV RNA serum sample, the worse the stability; the higher the storage temperature, the worse the stability. If conditions permit, the laboratory should store such samples at -20°C., Importance: Previously, there were few reports about the influence of different concentrations of sample nucleic acid on the stability of samples at various temperatures and times in various literatures. Therefore, it is necessary to analyze the influence of concentration factors on the stability of samples and test results at different storage times and temperatures. This study took the concentration of hepatitis C virus nucleic acid as the research object to further understand the stability of hepatitis C virus nucleic acid test samples under various storage conditions, to provide data reference for the treatment of hepatitis C virus nucleic acid and RNA test samples before clinical laboratory test, and provide guidance and help for the improvement of laboratory quality control., Competing Interests: The authors declare no conflict of interest.

Background: The respiratory microbiota plays a crucial role in the development of tuberculosis (TB). While existing research has underscored imbalances in the respiratory microbiota of adult patients with TB, information regarding the lower respiratory tract (LRT) microbiota in pediatric patients with TB remains scarce., Methods: We employed 16S rRNA gene sequencing technology to investigate the LRT microbial communities of 85 children of different ages with active TB of different severities, 33 children with infectious diseases other than TB, and 48 sex- and age-matched healthy children., Results: A marked imbalance in the respiratory microbiota was observed in children with TB, highlighted by reduced alpha diversity and a distinct microbial community structure. Comparative analysis indicated that patients with severe TB exhibited lower Neisseria levels than those with non-severe TB (1.01% vs. 3.93%, respectively; p = .02). Streptococcus and Gemella levels were lower in bacteriologically confirmed TB cases compared with clinically diagnosed cases, and higher in healthy children younger than 10 years old than in the older group. Spearman correlation analysis demonstrated significant associations between the microbiota of the LRT and cytokine concentrations in the sputum of children with TB (e.g., an inverse correlation between Veillonella and interleukin-17A)., Conclusions: TB induced significant dysbiosis in the LRT microbiota of children that was associated with disease severity and the immunological response in the respiratory tract. Our findings may offer a deeper understanding of the role of the respiratory microbiome in TB pathogenesis and progression., (© 2024 Wiley Periodicals LLC.)

Benzyl isothiocyanate (BITC) is a naturally active bacteriostatic substance and κ-carrageenan (KC) is a good film-forming substrate. In the present study, a nanoemulsion incorporating BITC was fabricated with a particle size of 224.1 nm and an encapsulation efficiency of 69.2 %. Subsequently, the acquired BITC nanoemulsion (BITC-NE) was incorporated into the KC-based film, and the light transmittance of the prepared composite films was lower than that of the pure KC film. Fourier transform infrared spectroscopy and scanning electron microscopy revealed that BITC-NE was compatible with the KC matrix. BITC-NE incorporation enhanced the tensile strength of the KC-based films by 33.7 %, decreased the elongation at break by 33.8 %, decreased the water vapor permeability by 60.1 %, increased the maximum thermal degradation temperature by 48.8 %, and decreased the oxygen permeability by 42 % (p < 0.05). Furthermore, the composite films showed enhanced antimicrobial activity against Staphylococcus aureus, Salmonella typhimurium, and Pseudomonas fluorescens. The developed KC-based composite films were applied to wrap raw beef, which significantly delayed the increase in total viable count, total volatile base nitrogen content, and thiobarbituric acid reactive substances, and prolonged the shelf-life of the raw beef by up to 10 days. These results indicated that the composite films prepared by incorporating BITC nanoemulsions into KC matrices have great antimicrobial application potential., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Severe pneumonia is a crucial issue in the development of acute kidney injury (AKI). This study evaluated the efficacy of early goal-directed renal replacement therapy (GDRRT) for the treatment of severe pneumonia-associated AKI., Methods: In this real-world retrospective cohort study, we recruited 180 patients with severe pneumonia who were hospitalized and received GDRRT in a third-class general hospital in East China between January 1, 2017, and December 31, 2021. Clinical data on baseline characteristics, biochemical indicators, and renal replacement therapy were collected. Patients were divided into Early and Late RRT groups according to fluid status, inflammation progression, and pulmonary radiology. We investigated in-hospital all-cause mortality (primary endpoint) and renal recovery (secondary endpoint) between the two groups., Results: Among the 154 recruited patients, 80 and 74 were in the early and late RRT groups, respectively. There were no significant differences in the demographic characteristics between the two groups. The duration of admission to RRT initiation was significantly shorter in Early RRT group [2.5(1.0, 8.7) d vs. 5.0(1.5,13.5) d, p  = 0.027]. At RRT initiation, the patients in the Early RRT group displayed a lower percentage of fluid overload, lower doses of vasoactive agents, higher CRP levels, and higher rates of radiographic progression than those in the Late RRT group. The all-cause in-hospital mortality was significantly lower in the Early RRT group than in Late group (52.5% vs. 86.5%, p  < 0.001). Patients in the Early RRT group displayed a significantly higher proportion of complete renal recovery at discharge (40.0% vs. 8.1%, p  < 0.001)., Conclusion: This study clarified that early GDRRT for the treatment of severe pneumonia-associated AKI based on fluid status and inflammation progression, was associated with reduced hospital mortality and better recovery of renal function. Our preliminary study suggests that early initiation of RRT may be an effective approach for severe pneumonia-associated AKI.

This study aimed to provide data for the clinical features of invasive pneumococcal disease (IPD) and the molecular characteristics of Streptococcus pneumoniae isolates from paediatric patients in China. We conducted a multi-centre prospective study for IPD in 19 hospitals across China from January 2019 to December 2021. Data of demographic characteristics, risk factors for IPD, death, and disability was collected and analysed. Serotypes, antibiotic susceptibility, and multi-locus sequence typing (MLST) of pneumococcal isolates were also detected. A total of 478 IPD cases and 355 pneumococcal isolates were enrolled. Among the patients, 260 were male, and the median age was 35 months (interquartile range, 12-46 months). Septicaemia (37.7%), meningitis (32.4%), and pneumonia (27.8%) were common disease types, and 46 (9.6%) patients died from IPD. Thirty-four serotypes were detected, 19F (24.2%), 14 (17.7%), 23F (14.9%), 6B (10.4%) and 19A (9.6%) were common serotypes. Pneumococcal isolates were highly resistant to macrolides (98.3%), tetracycline (94.1%), and trimethoprim/sulfamethoxazole (70.7%). Non-sensitive rates of penicillin were 6.2% and 83.3% in non-meningitis and meningitis isolates. 19F-ST271, 19A-ST320 and 14-ST876 showed high resistance to antibiotics. This multi-centre study reports the clinical features of IPD and demonstrates serotype distribution and antibiotic resistance of pneumococcal isolates in Chinese children. There exists the potential to reduce IPD by improved uptake of pneumococcal vaccination, and continued surveillance is warranted.

Background: To investigate the clinical relevance of cytokine levels in assessment of the severity of mycoplasma pneumoniae pneumonia (MPP) in children., Methods: A retrospective study was conducted on 150 pediatric cases of MPP admitted to a local hospital in China from November 1, 2022 to October 31, 2023. These MPP cases were divided into mild (n=100) and severe (n=50) groups according to the severity of the disease. Cytokine levels, including Interferon-γ (IFN-γ), Tumor Necrosis Factor-α (TNF-α), C-reactive protein (CRP), Interleukin-6 (IL-6), Interleukin-2 (IL-2), and D-Dimer (D-D), were compared between the two groups. The diagnostic efficacy of each cytokine in assessing the severity of MPP was analyzed through Receiver Operating Characteristic (ROC) curves, and correlation between cytokine levels and disease severity was assessed using Pearson's correlation coefficient., Results: The IL-2 level was significantly lower, while TNF-α, IL-6, and IFN-γ levels were significantly higher in the severe group compared to the mild group (all P<0.05). TNF-α, IFN-γ, IL-2, IL-6, CRP, and D-D were identified as factors influencing the severity of MPP (all P<0.05). The ROC curve analysis showed that the areas under the curve (AUCs) of TNF-α, IL-2, IL-6, IFN-γ, CRP, and D-D were 0.864, 0.692, 0.874, 0.949, 0.814, and 0.691, respectively (all P<0.001), indicating their diagnostic value in assessing the severity of MPP. There exists a positive correlation between IL-2 and the percentage of normal lung density on Computed Tomography (CT) scan (P<0.05), while TNF-α, IL-6, IFN-γ, CRP, and D-D showed negative correlations with the percentage of normal lung density (P<0.05)., Conclusion: Cytokines such as TNF-α, IL-2, IL-6, IFN-γ, CRP, and D-D are aberrantly expressed in children with MPP and are associated with the severity of the disease. These cytokines have high diagnostic value and can serve as reference indicators for clinical, especially prognostic assessment of the severity of (pediatric) MPP., Competing Interests: None., (AJTR Copyright © 2024.)

BACKGROUND Foreign body aspiration (FBA) is a common and serious problem in childhood that requires early recognition and treatment. Common complications include asphyxia, hemorrhage, infection, and pneumothorax. In severe cases of foreign body obstruction, death can result from asphyxia. We report an interesting case in which a forgotten cotton ball was inhaled into the lungs. CASE REPORT A 5-year-old boy presented to the local hospital with coughing for 6 days and fever for 4 days, without any information of foreign body aspiration upon admission. Laboratory findings indicated an elevated white blood cell; therefore, cefprozil was given as anti-infective treatment. However, the child's condition did not improve. A computed tomography scan showed left pulmonary atelectasis. Considering that the child's condition was serious, he was referred to our hospital for diagnosis and treatment. After referral, auscultation revealed decreased breath sounds over the left lung. After multidisciplinary discussion, combined with the results of auxiliary examination, the possibility of a foreign body was considered. He underwent rigid bronchoscopy, which confirmed a yellow-white foreign body in the left main bronchus that was later verified as a cotton ball. The operation was very successful. Eventually, his condition improved and he was discharged, without additional complications. CONCLUSIONS For children with unclear history of foreign body aspiration, bronchoscopy is recommended if there is recurrent pulmonary infection, low auscultation breath sounds, or abnormal imaging. The choice of surgical method depends on the location and type of foreign body and the experience of the surgeon, which is also very important.

Objective: To evaluate the effects of ganciclovir combined with recombinant human interferon on clinical efficacy and immune function of children with infectious mononucleosis(IM)., Methods: This was a retrospective study. Children (n=120) with IM hospitalized in Beijing Children's Hospital Affiliated to Capital Medical University Baoding Hospital from January 2020 to January 2022 were selected and randomly divided into study group and control group((n=60). Patients in the control group were treated with ganciclovir by intravenous infusion, and patients in the study group were given ganciclovir+recombinant human interferon-α1b. The time for eliminating clinical symptoms, the levels of inflammatory cytokines, immune function condition and T-lymphocyte subsets between the two groups were compared and analyzed., Results: After treatment, the time for body temperature returned to normal, time for recovery from cervical lymphadenopathy, time for recovery from hepatosplenomegaly and time for disappearance of angina and oral mucosal congestion in the study group were significantly shorter than those in the control group(p= 0.00); after treatment, the levels of TNF-a and IL-6 in the study group were significantly lower than those in the control group; the indexes of CD3 + and CD8 + in the study group were significantly lower than those in the control group; after treatment, the levels of CD4 + and CD4 + /CD8 + in the study group were significantly higher than those in the control group., Conclusion: Ranciclovir combined with recombinant human interferon-α1b, rapid improvements of clinical symptoms, significantly decreased inflammatory cytokines, improved T-lymphocyte function and no significant increase in adverse drug reactions were found in children with IM., Competing Interests: Conflicts of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Objective: This study aimed to summarise the clinical features and management strategies concerning auditory canal duplication anomalies in children with congenital first branchial cleft anomalies (CFBCAs), and to provide guidance for precise treatment., Methods: We retrospectively analysed 84 children with CFBCAs who had complete data, diagnosed between December 2018 and February 2024., Results: All the lesions identified were located around the external auditory canal or near the mandibular angle, manifested as pinhead-sized perforations in 10 cases, painless masses in 18 cases, recurrent swelling and pain with purulent discharge in 52 cases, and otorrhea in 4 cases. Otoscopy examinations revealed external auditory canal swelling in seven children, fistulas within the auditory canal in four children, and a myringa web in three children. Fifty-six children had a preoperative history of infection. Using Work's classification system, Work I and II in 70 (87.5%) and 14 (12.5%) children, respectively. Intraoperatively, 80 (95.2%) children had auditory canal duplication anomalies at the base of the lesion, closely associated with the cartilage of the inferior wall of external auditory canal(EAC), We then classified auditory canal duplication anomalies into three types: Type A (duplication anomalies of epithelial tissue structure between the skin of the EAC and the cartilage of the inferior wall, n = 16 children), Type B (duplication anomalies of the epithelial and/or skin tissue structure, sharing a wall with the cartilage of the inferior wall, n = 40), and Type C (duplication anomalies of the skin and cartilage tissue structure, connected to the cartilage of the inferior wall of EAC, n = 24). Sixty-eight children had lesions superficial to the facial nerve, 12 had lesions deep to the facial nerve, and four had lesions between branches. There were two cases of transient postoperative facial paralysis, three cases of CFBCA recurrence, and two cases of transient auditory canal stenosis., Conclusion: Auditory canal duplication anomalies are an important feature of first branchial cleft anomalies in children. Precise staging and accurate identification of the base of the lesion facilitate complete removal, thereby increasing the cure rate., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Otitis media with effusion (OME) is a prevalent and costly disease, especially in children. This article analyzed the expression patterns and clinical significance of T helper-1 (Th1)/Th2 cytokines in the peripheral blood of children with OME and allergic rhinitis (AR)., Methods: Subjects were assigned to the OME + AR group and the Control group (children with OME), with their clinical baseline data documented. The correlations between Th1/Th2 cytokines and between the total nasal symptom score (TNSS) and Th1/Th2 cytokines were analyzed. The risk factors and the predictive value of Th1/Th2 cytokines for OME + AR were analyzed using logistics multivariate regression analysis and receiver operating characteristic curve., Results: Significant differences were observed in tympanic pressure/speech frequency/air conduction valve/TNSS score/immunoglobulin E (IgE) level between both groups. The OME + AR children exhibited evidently elevated interleukin-2 (IL-2)/tumor necrosis factor-α (TNF-α)/IL-4/IL-10/IL-6 levels and no significant difference in interferon-γ (IFN-γ) level. Th1/Th2 cytokines were remarkably positively-correlated with the TNSS score. IL-2/TNF-α/IL-4/IL-6 were risk factors for OME with AR. The area under the curves (AUCs) of IL-6/IL-2/IL-4/TNF-α levels in predicting the occurrence of OME + AR were 0.805/0.806/0.775/0.781, with sensitivities of 75.76 %/89.39 %/72.21 %/72.73 % and specificities of 74.29 %/61.34 %/72.86 %/70.00 %, and the cut-off values were 239.600/20.300/29.880/34.800 (pg/mL). The AUC of their combination in predicting OME + AR was 0.955 (93.94 % sensitivity, 85.71 % specificity)., Conclusion: Th1/Th2 cytokine levels were imbalanced and obviously positively-correlated with the TNSS score in OME + AR children. IL-2, TNF-α, IL-4, and IL-6 levels had auxiliary predictive value in the occurrence of OME + AR., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Leukemia, the most common malignant tumor in childhood, can be categorized into acute leukemia and chronic leukemia. However, the role of FUNDC1 in childhood leukemia (CL) remains unknown. This study aims to investigate the effects of FUNDC1 on patients with CL and its underlying mechanism both in vivo and in vitro . The mRNA expression levels of FUNDC1 were found to be up-regulated in serum samples from CL patients as well as in leukemia cell lines. Furthermore, it was observed that the mRNA expression of FUNDC1 was lower in stage I-II CL patients compared to stage III-IV patients. The up-regulation of FUNDC1 was found to promote leukemia metastasis. Additionally, it was discovered that FUNDC1 up-regulation reduces ferroptosis by inhibiting mitochondrial damage. In a leukemia model, FUNDC1 up-regulation induces the expression of FBXL2. Moreover, FUNDC1 up-regulation reduces FBXL2 ubiquitination, thus maintaining FBXL2 protein expression in leukemia. By inducing FBXL2, FUNDC1 reduces ferroptosis in leukemia through the inhibition of mitochondrial damage. The stability of FUNDC1 is controlled by METTL3 methylation. Overall, this study sheds light on the role of FUNDC1 in CL and provides insights into its underlying mechanisms., Competing Interests: Conflict of interest: The authors state that there are no financial, personal, or professional conflicts of interests that may hinder this work., (© 2024 the author(s), published by De Gruyter.)

Background and Aims: The use of corticosteroids in chronic drug-induced liver injury (DILI) is an important issue. Our previous randomized controlled trial showed that patients with chronic DILI benefited from a 48-week steroid stepwise reduction (SSR) regimen. However, it remains unclear whether a shorter course of therapy can achieve similar efficacy. In this study, we aimed to assess whether a 36-week SSR can achieve efficacy similar to that of 48-week SSR., Methods: A randomized open-label trial was performed. Eligible patients were randomly assigned to the 36- or 48-week (1:1) SSR group. Liver biopsies were performed at baseline and at the end of treatment. The primary outcome was the proportion of patients with relapse rate (RR). The secondary outcomes were improvement in liver histology and safety., Results: Of the 90 participants enrolled, 84 (87.5%) completed the trial, and 62 patients (68.9%) were women. Hepatocellular damage was observed in 53.4% of the cohort. The RR was 7.1% in the 36-week SSR group but 4.8% in the 48-week SSR group, as determined by per-protocol set analysis (p = 1.000). Significant histological improvements in histological activity (93.1% vs. 92.9%, p = 1.000) and fibrosis (41.4% vs. 46.4%, p = .701) were observed in both the groups. Biochemical normalization time did not differ between the two groups. No severe adverse events were observed., Conclusions: Both the 36- and 48-week SSR regimens demonstrated similar biochemical response and histological improvements with good safety, supporting 36-week SSR as a preferable therapeutic choice (ClinicalTrials.gov, NCT03266146)., (© 2024 The Authors. Liver International published by John Wiley & Sons Ltd.)

The speciation of heavy metals in soil is an important factor determining their bioavailability and toxicity, and it is crucial for the scientific assessment of ecological risks posed by heavy metals in soils of typical carbonate areas with high geological background in southwest China. In order to investigate the distribution of speciation of heavy metals in soils of carbonate rock with high geological background, we selected a typical carbonate rock distribution area in Guizhou Province and used the second national soil survey plots as sampling units. A total of 309 topsoil samples were collected from farmland. The improved Tessier seven-step sequential extraction method was used to analyze the seven chemical forms of heavy metals:water-soluble (F1); exchangeable (F2); carbonate-bound (F3); weakly organic-bound (F4); iron-manganese oxide-bound (F5); strongly organic-bound (F6); and residual (F7) forms of arsenic (As), cadmium (Cd), copper (Cu), mercury (Hg), nickel (Ni), lead (Pb), and zinc (Zn). The study found that the residual forms of heavy metals As, Cu, Hg, Ni, Pb, and Zn in the soil accounted for more than 50%, the effective components (F1-F3) accounted for less than 5%, and the potential biological effective components (F4-F6) were less than 45%, indicating low reactivity and low ecological risk. The effective and potentially bioavailable components of Cd accounted for 55.49% and 29.37%, respectively, which were much higher than those of other heavy metals. The ecological risk based on the speciation of heavy metals in the soil was much lower than that based on the total content of heavy metals. The stepwise regression equations could effectively establish the relationship between the bioavailable and potentially bioavailable fractions of Cd, Cu, and Pb and their influencing factors. Total heavy metal contents and pH value were important factors influencing the speciation of heavy metals in soils of carbonate rock with high geological background areas. The enrichment of heavy metal elements in the residual fraction was influenced by long-term zinc smelting activities and the weathering of carbonate rocks into soil. Soil organic matter (OM) and oxide content had a relatively small influence on the speciation of heavy metals in the soil.

Mesosulfuron-methyl, an inhibitor of acetolactate synthase (ALS), has been extensively used in wheats. However, it can damage wheat ( Triticum aestivum ) and even lead to crop death. Herbicide safeners selectively shield crops from such damage without compromising weed control. To mitigate the phytotoxicity of mesosulfuron-methyl in crops, several purine derivatives were developed based on active substructure splicing. The synthesized title compounds underwent thorough characterization using infrared spectroscopy, 1 H nuclear magnetic resonance ( 1 H NMR), 13 C nuclear magnetic resonance ( 13 C NMR), and high-resolution mass spectrometry. We evaluated chlorophyll and glutathione contents as well as various enzyme activities to evaluate the safer activity of these compounds. Compounds III-3 and III-7 exhibited superior activity compared with the safener mefenpyr-diethyl. Molecular structure analysis, along with predictions of absorption, distribution, metabolism, excretion, and toxicity, indicated that compound III-7 shared pharmacokinetic traits with the commercial safener mefenpyr-diethyl. Molecular docking simulations revealed that compound III-7 competitively bound to the ALS active site with mesosulfuron-methyl, elucidating the protective mechanism of the safeners. Overall, this study highlights purine derivatives as potential candidates for novel safener development.

Purpose: Conceptualizing adolescent NSSI and emotional symptoms as a system of causal elements could provide valuable insights into the development of non-suicidal self-injury (NSSI) in adolescent. This study aimed to explore the intricate relationship between NSSI, depressive symptoms, and anxious symptoms in adolescents, identifying key symptoms to establish a theoretical foundation for targeted and effective interventions addressing NSSI behaviors in this population., Methods: A total of 412 adolescents with NSSI behaviors were selected from outpatients. Generalized anxious disorder scale (GAD-7) and patient health questionnaire (PHQ-9) were employed to measure anxious symptoms and depressive symptoms, respectively. The adolescent non-suicidal self-injury assessment questionnaire (ANSSIAQ) was used to evaluate NSSI of adolescent. Using network analysis, the NSSI、depressive symptoms and anxious symptoms network were constructed to identify the most central symptoms and the bridge symptoms within the networks., Results: The findings revealed that the NSSI functional nodes "coping with sadness and disappointment" and "relieving stress or anxious" exhibited the strongest correlation, with a regularized partial correlation coefficient was 0.401. The symptoms "having a desire to harm oneself and unable to stop" and the node "depressive symptoms" had the highest strength centrality in the network, and their strength centrality indices were 1.267 and 1.263, respectively. The bridge nodes were "having a desire to harm oneself and unable to stop" and "expressing one's despair and hopelessness", with expected impact indices of 0.389 and 0.396, respectively., Conclusion: In adolescents, the network revealed a closer connection between NSSI and depressive symptoms. "The desire to not stop hurting oneself" is not only broadly connected to other nodes but also could activate other nodes to maintain NSSI behavior. In light of these findings, precise targets for pharmacological treatment, psychotherapy, physical therapy, etc., are identified for adolescents with NSSI. Targeting this specific aspect in interventions may contribute to preventing and reducing NSSI behavior in adolescents., (© 2024. The Author(s).)

Background: Little attention has been paid to the pathophysiological changes in the natural history of chronic obstructive pulmonary disease (COPD). The destructions of the small airways were visualized on thoracic micro-computed tomography scan. We investigated whether small airway inflammation (SAI) was the risk for the development of COPD., Methods: A total of 1062 patients were enrolled and analyzed in the study. The partitioned airway inflammation was determined by exhaled nitric oxide (NO) of FnNO, FeNO 50 , FeNO 200 , and calculated CaNO dual . Both FeNO 200 and CaNO dual were compared to detect the promising predictor for peripheral airway/alveolar inflammation in COPD. The correlation between exhaled NO and white cell classification was evaluated to determine the inflammation type during the development of COPD., Results: Exhaled NO levels (FnNO, FeNO 50 , FeNO 200 , and CaNO dual ) were the highest in the COPD group compared with all other groups. Furthermore, compared with controls, exhaled NO levels (FeNO 50 , FeNO 200 , and CaNO dual ) were also significantly higher in the emphysema, chronic bronchitis, and smoking groups. FeNO 200 was found to be a promising predictor for peripheral airway/alveolar inflammation (area under the curve [AUC] of the receiver operating characteristic [ROC] curve, area under the curve [AUC] = 0.841) compared with CaNO dual (AUC ROC = 0.707) in COPD. FeNO 200 was the main risk factor (adjusted odds ratio, 2.191; 95% CI, 1.797-2.671; p = 0.002) for the development of COPD. The blood eosinophil and basophil levels were correlated with FeNO 50 and FeNO 200 ., Conclusion: The complete airway inflammations were shown in COPD, whereas SAI was the main risk factor for the development of COPD, which might relate to eosinophil and basophil levels., (© 2024. The Author(s).)

Purpose: Plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of fibrinolytic systems. The effect of PAI-1 on inflammatory response is still inconsistent. Our study was conducted to investigate its effects on inflammation to clarify the role of PAI-1 in acute lung injury (ALI) induced by lipopolysaccharide (LPS)., Material and Methods: ALI models were established in wild-type (WT) and PAI-1 knockout (KO) mice by LPS intervention for 48 ​h. Lung histopathology, wet-dry ratio, total cell count and TNF-α concentration in bronchoalveolar lavage fluid (BALF), and inflammation related proteins were detected. Flow cytometry was used to sort neutrophils, macrophages, regulatory T cells (Treg) and T helper cell 17 (Th17). RNA sequencing was performed to find differentially expressed genes. Masson staining and immunohistochemistry were used to analyze pulmonary fiber deposition and proliferation., Results: Compared with ALI (WT) group, the wet-dry ratio, the total number of BALF cells, the concentration of TNF-α in BALF, and the expression of pp65 in the lung tissue was increased in ALI (PAI-1 KO) group, with increased proportion of neutrophils, decreased proportion of macrophages and decreased proportion of Treg/Th17 in the lung tissue. Collagen fiber deposition and PCNA expression were lighter in ALI (PAI-1 KO) group than ALI (WT) group. PPI analysis showed that PAI-1 was closely related to TNF, IL-6, IL-1β, Smad2/3 and mainly concentrated in the complement and coagulation system, TNF-α and IL-17 signaling pathways., Conclusions: PAI-1 KO could aggravate ALI induced by LPS at 48 ​h. PAI-1 may be an important target to improve the prognosis of ALI., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To explore the correlation of iron deficiency (ID) indexes with eradication and recurrence of Helicobacter pylori (Hp) infection in children., Methods: This is a clinical comparative study. One hundred and twenty-six children who were first diagnosed as Hp infection in Baoding Children's Hospital (Hp infection group); and the control group included 200 children without Helicobacter Pylori infection (negative stool Hp antigen test and/or 13C-urea breath test) in local region at the same time from January 2020 to January 2022. Enrolled children were subjected to routine blood test, serum ferritin (SF), serum iron (SI) and total iron binding capacity (TIBC) detection. Meanwhile, children with Hp infection were given triple therapy for eradication and followed up for one year., Results: The levels of SI, SF and Hb in non-eradication group were lower than those in eradication group (P<0.05); while TIBC level in the former group was higher than that in the latter group (P<0.05). Furthermore, SF level in the recurrence group was lower than that in the non-recurrence group (P<0.05). While there was no significant difference in Hb, SI and TIBC levels between the recurrence group and the non-recurrence group (P>0.05)., Conclusion: Low level of SF may be a risk factor for difficulty in eradication and recurrence after eradication in children with Hp infection. Meanwhile, low levels of Hb and SI are influential factors for difficulty in eradication in children with Hp infection., Competing Interests: Declaration of conflicting interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Objective: To explore the diagnosis and treatment experience of complex respiratory foreign bodies in children. Methods: The clinical data of 1 243 cases of respiratory foreign bodies in children were retrospectively analyzed, among which 10 cases（0.8%） were complicated respiratory foreign bodies. Results: Among the 10 cases of complex respiratory foreign bodies, 2 cases were removed by open thoracotomy, 1 case was removed by tracheotomy, 1 case was removed by lobectomy, 1 case was removed by fiberoptic bronchoscopy because of difficult airway caused by the accompanying congenital pulmonary artery sling, and the pulmonary artery sling correction was synchronized with the fiberoptic bronchoscopic removal, 3 cases were removed by fiberoptic bronchoscopic holmium laser and/or freezing method to make the foreign body deformed and fragmented and then taken out by the sound gate, and 2 cases were removed because of the In 3 cases, the foreign bodies were deformed and fragmented by fiberoptic bronchoscopy, and in 2 cases, the foreign bodies were removed through the vocal folds because of their special characteristics. Two cases were intubated and sent to ICU after surgery because of obvious vocal edema and difficulty in deoxygenation, two cases were transferred to ICU after cardiac or thoracic surgery, and the rest of them returned to ordinary wards after surgery, and all 10 cases recovered well after surgery. Conclusion: Respiratory foreign body combined with airway stenosis, when the foreign body type, shape, embedded location of special foreign body, foreign body is too large, need to rationally choose the method of foreign body removal. If necessary, a combination of methods can be used to ensure that the airway obstruction is quickly relieved with the best program., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: Using the published survival statistics from cancer registration or population-based studies, we aimed to describe the global pattern and trend of lung cancer survival., Methods: By searching SinoMed, PubMed, Web of Science, EMBASE, and SEER, all survival analyses from cancer registration or population-based studies of lung cancer were collected by the end of November 2022. The survival rates were extracted by sex, period, and country. The observed, relative, and net survival rates of lung cancer were applied to describe the pattern and time changes from the late 1990s to the early 21st century., Results: Age-standardized 5-year relative/net survival rate of lung cancer was typically low, with 10%-20% for most regions. The highest age-standardized relative/net survival rate was observed in Japan (32.9%, 2010-2014), and the lowest was in India (3.7%, 2010-2014). In most countries, the five-year age-standardized relative/net survival rates of lung cancer were higher in females and younger people. The patients with adenocarcinoma had a better prognosis than other groups. In China, the highest 5-year overall relative/net survival rates were 27.90% and 31.62% in men and women in Jiangyin (2012-2013)., Conclusion: Over the past decades, the prognosis of lung cancer has gradually improved, but significant variations were also observed globally. Worldwide, a better prognosis of lung cancer can be observed in females and younger patients. It is essential to compare and evaluate the histological or stage-specific survival rates of lung cancer between different regions in the future., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Aflatoxin B1 (AFB1) is highly toxic and challenging to remove, posing significant risks to both human health and economic development. Therefore, there is an urgent need to develop rapid, simple, and sensitive detection technologies. In this study, we introduce a naked-eye and colorimetric method based on multiple isothermal amplifications coupled with CRISPR-Cas14a and investigate its biosensing properties. This technique utilizes composite nanoprobes (MAPs) comprising magnetic nanoparticles and gold nanoparticles. AFB1 is efficiently identified through an aptamer competition process facilitated by magnetic nanoparticles , which triggers multiple isothermal amplification. This converts trace amounts of the toxin into a large quantity of DNA signal. Upon specific activation of the CRISPR-Cas14a complex, the MAPs are cleaved, resulting in significant changes in both color and colorimetric signal. The method demonstrates acceptable sensitivity, with a detection limit of 31.90 pg mL -1 and a wide detection range from 0.05 to 10 ng mL -1 . Furthermore, the assay exhibits satisfactory specificity and high accuracy when it is applied to practical samples. Our approach offers a universal sensing platform with potential applications in food safety, environmental monitoring, and clinical diagnostics.

Background and Objective: Terahertz (THz) imaging has wide applications in biomedical research due to its properties, such as non-ionizing, non-invasive and distinctive spectral fingerprints. Over the past 6 years, the application of THz imaging in tumor tissue has made encouraging progress. However, due to the strong absorption of THz by water, the large size, high cost, and low sensitivity of THz devices, it is still difficult to be widely used in clinical practice. This paper provides ideas for researchers and promotes the development of THz imaging in clinical research., Methods: The literature search was conducted in the Web of Science and PubMed databases using the keywords "Terahertz imaging", "Breast", "Brain", "Skin" and "Cancer". A total of 94 English language articles from 1 January, 2017 to 30 December, 2022 were reviewed., Key Content and Findings: In this review, we briefly introduced the recent advances in THz near-field imaging, single-pixel imaging and real-time imaging, the applications of THz imaging for detecting breast, brain and skin tissues in the last 6 years were reviewed, and the advantages and existing challenges were identified. It is necessary to combine machine learning and metamaterials to develop real-time THz devices with small size, low cost and high sensitivity that can be widely used in clinical practice. More powerful THz detectors can be developed by combining graphene, designing structures and other methods to improve the sensitivity of the devices and obtain more accurate information. Establishing a THz database is one of the important methods to improve the repeatability and accuracy of imaging results., Conclusions: THz technology is an effective method for tumor imaging. We believe that with the joint efforts of researchers and clinicians, accurate, real-time, and safe THz imaging will be widely applied in clinical practice in the future., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-526/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Purpose: To investigate the anatomical relationships between the structures adjacent to the cartilaginous portion of the ear canal in children with Work type I congenital branchial cleft anomalies (CFBCAs) and to develop new classifications and surgical strategies., Methods: Retrospective analysis was performed on 50 children with Work type I CFBCAs admitted between December 2018 and December 2022., Results: Among the 50 children, total parotidectomy was performed on 49 sides. In 44 cases (88%), the main body of the lesion was closely associated with the cartilage of the inferior ear canal wall. Among these cases, the lesions in 40 cases occurred within the space enclosed by the dorsal inferior wall cartilage, mastoid process, and parotid gland, while in the remaining four cases, the lesions were located between the anterior inferior wall cartilage and parotid gland. Based on the preoperative imaging observations, clinical manifestations, and intraoperative findings, the cases were classified into 6 subtypes (a to f) including 21 cases (42%) of Type Ia (inferior wall of EAC), 7 cases (14%) of Type Ib (bottom wall of EAC), 12 cases (24%) of Type Ic (posterior-inferior wall of EAC), 4 cases (8%) of Type Id (anterior-inferior wall of EAC), 4 cases (8%) of Type Ie (anterior ear wall of EAC), and 2 cases (4%) of Type If (isolated from parotid)., Conclusion: Surgical intervention is the only treatment for first branchial cleft anomalies and a comprehensive understanding of the classifications will help with the precise localisation and excision of the lesions., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate the clinical significance of the inferior wall cartilage of the auditory meatus in surgical treatment of congenital first branchial cleft anomalies (CFBCAs) in children., Methods: Twenty children diagnosed with CFBCAs who underwent surgery between December 2018 and June 2022 at our hospital were retrospectively analyzed and classified according to their Work lesion type. The guiding significance of the inferior wall cartilage in the surgical treatment of CFBCAs was summarized by investigating the adjacent relationships of the surgical lesions with the external auditory canal and facial nerve., Results: Of the 20 patients, 16 were classified as Work type I and 4 as Work type II. The lesions were adjacent to the inferior wall cartilage of the auditory meatus in all children. Work type I lesions were located in the upper lateral aspect and were not adjacent to the facial nerve. Work type II lesions were located in the inferior-medial region of the facial nerve. The lesions were completely resected in all children. One patient experienced recurrence 3 months postoperatively because of a residual endochondral fistula. No patients developed facial paralysis or other complications., Conclusions: The inferior wall cartilage of the auditory meatus may help to the identify the initial lesion of the CFBCAs and can be regarded as a guiding anatomical structure. These lesions can be completely resected. For resection of Work type II first branchial cleft lesions, the surgical incision can be narrower, and can be precisely positioned with the assistance of endoscope., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background and Aims: The microbial spectrum and antimicrobial resistance patterns change over time and vary across regions in patients with spontaneous bacterial peritonitis (SBP). There is an urgent need to clarify the factors associated with in-hospital mortality in these patients., Methods: In this study, 377 patients with SBP and 794 patients with bacterascites were analyzed for the microbial spectrum, antimicrobial resistance profiles, and laboratory findings., Results: The most common pathogens were Escherichia coli (96, 25.5%), Staphylococcus epidermidis (55, 14.6%), and Enterococcus faecium (42, 11.1%). Multidrug-resistant (MDR) bacteria comprised 49.7% of gram-positive bacteria (GPB) and 48.8% of gram-negative bacteria (GNB). The most sensitive antibiotics were amikacin (91.5%), meropenem (89.8%) and piperacillin/tazobactam (87.6%). Extensively drug-resistant (XDR) (OR=51.457, p < 0.001), neutrophil count (OR=1.088, p < 0.001), and the model for end-stage liver disease (MELD) score (OR=1.124, p < 0.001) were independent predictive factors of in-hospital mortality in patients with SBP., Conclusion: MDR represented nearly half of the bacteria isolated from patients with SBP, of which the high prevalence of extended-spectrum β-lactamase-producing and Carbapenem-resistant bacteria is concerning. The presence of XDR, higher MELD score, and neutrophil count were independent predictive factors associated with higher in-hospital mortality in patients with SBP, indicating that intensive care should be provided to these patients., Competing Interests: Conflict of Interest The authors declare that there are no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: Tracheobronchial foreign body aspiration (TFBA) is a major cause of accidental death in children. Lower respiratory tract infection (LRTI) may be caused by TFBA, but there are few reports about LRTI associated with TFBA. This study collected TFBA cases in our hospital to analyze LRTI and determine its risk factors., Methods: A total of 194 children who underwent tracheobronchial foreign body (TFB) extraction in The Children's Hospital of Zhejiang University School of Medicine from June 2019 to April 2020 were enrolled. CT chest is routinely used in the workup of suspected airway FB at our institution to evaluate for patients, a FB was already highly suspected. The retention time was defined as from the time of TFB inhalation or presentation (if there was no history of TFBA) to the time of TFB removal. General characteristics including weight, clinical symptoms, operative records, cervicothoracic CT, retention time, type of TFB and postoperative hospitalization time were collected. Chi-square tests, rank sum tests and multivariate logistic regression analyses were performed., Results: The incidence of LRTI was 46.6%, 68.6%, and 68.6% when the retention time was within 24 hours, between 24 hours and up to 1 week and more than 1 week, respectively. Postoperative hospitalization time of LRTI group was significantly longer than that of non-LRTI group. Findings for cervicothoracic CT as pneumonia, emphysema, atelectasis meant more serious clinical manifestations and the retention time was longer in the LRTI group than in the non-LRTI group. There was a positive correlation between the retention time of a TFB and LRTI in multivariate logistic regression analysis., Conclusions: The incidence of LRTI caused by TFBA is high. LRTI is association with longer postoperative hospitalization time. The TFB retention time is an independent risk factor for LRTI. If a patient presents with significant LRTI symptoms, a course of steroids and antibiotics maybe a safer approach rather than proceeding immediately with bronchoscopic removal.

Background: Percutaneous transhepatic gallbladder drainage (PTGBD) is a relatively less invasive alternative treatment to cholecystostomy. However, the influence of the difficulty of delayed laparoscopic cholecystectomy (DLC) after PTGBD on clinical outcomes remains unknown. This study aimed to evaluate the clinical effects of DLC following PTGBD., Methods: The clinical data of 113 patients diagnosed with moderate (grade II) acute cholecystitis according to the 2018 Tokyo Guidelines in the acute phase and who underwent DLC in our hospital from January 2018 to February 2022 were retrospectively collected and separated into two groups according to whether they received PTGBD treatment in the acute stage. The PTGBD group comprised 27 cases, and the no-PTGBD group included 86 cases. The TG18 difficulty score was used to evaluate every surgical procedure in the cases by reviewing the surgical videos. The clinical baseline characteristics and post-treatment outcomes were also evaluated., Results: Both groups showed significant differences in length of postoperative stay, blood loss, operation time, and difficulty score. The PTGBD group showed a significantly longer postoperative stay and operation time, more blood loss, and a much higher difficulty score than the no-PTGBD group. Conversion rates did not differ. The morbidity rate in the PTGBD group was statistically higher., Conclusions: PTGBD is an efficient way to relieve the symptoms of acute cholecystitis. However, it may increase the difficulty and complications of DLC., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The primary objective of this study was to evaluate the predictive and prognostic value of serum lipids in recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients received anti-PD-1 therapy., Materials and Methods: Patients treated with anti-PD-1 therapy (monotherapy or combined with chemotherapy) from two clinical trials (CAPTAIN and CAPTAIN-1st study) were included. Serum lipids were measured at baseline and after two cycles of treatment. We examined the impact of both baseline and post-treatment lipid levels on objective response rate (ORR), progression-free survival (PFS), and duration of response (DOR)., Results: Of 106 patients, 89 patients (84%) were male. The patients' median age was 49 years. An early elevated (after two cycles of treatment) cholesterol (CHO), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I (ApoA-I), and apolipoprotein B (ApoB) were significantly associated with better ORR. Moreover, early elevated CHO, LDL-C, and ApoA-I were also positively correlated with DOR and PFS. Further multivariate analysis showed that only early change in ApoA-I could independently predict PFS (HR, 2.27; 95% CI, 1.11-4.61; p = 0.034). The median PFS for patients with early elevated and reduced ApoA-I was 11.43 and 1.89 months, respectively. However, baseline lipids levels do not play a significant role in the prognosis and prediction of patients with anti-PD-1 treatment., Conclusion: Collectively, an early elevation in ApoA-I was correlated with better outcomes for anti-PD-1 therapy in patients with R/M NPC, suggesting that clinicians should consider the early alteration of ApoA-I as a useful marker in treating R/M NPC patients with anti-PD-1., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is characterized by diffuse alveolar injury primarily caused by an excessive inflammatory response. Regrettably, the lack of effective pharmacotherapy currently available contributes to the high mortality rate in patients with this condition. Xuebijing (XBJ), a traditional Chinese medicine recognized for its potent anti-inflammatory properties, exhibits promise as a potential therapeutic agent for ALI/ARDS. This study aimed to explore the preventive effects of XBJ on ALI and its underlying mechanism. To this end, we established an LPS-induced ALI model and treated ALI mice with XBJ. Our results demonstrated that pre-treatment with XBJ significantly alleviated lung inflammation and increased the survival rate of ALI mice by 37.5%. Moreover, XBJ substantially suppressed the production of TNF-α, IL-6, and IL-1β in the lung tissue. Subsequently, we performed a network pharmacology analysis and identified identified 109 potential target genes of XBJ that were mainly involved in multiple signaling pathways related to programmed cell death and anti-inflammatory responses. Furthermore, we found that XBJ exerted its inhibitory effect on gasdermin-E-mediated pyroptosis of lung cells by suppressing TNF-α production. Therefore, this study not only establishes the preventive efficacy of XBJ in ALI but also reveals its role in protecting alveolar epithelial cells against gasdermin-E-mediated pyroptosis by reducing TNF-α release., (Copyright © 2023 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Tuberculosis (TB) is a major public health problem, with nearly 10 million new cases and millions of deaths each year. Around 10% of these cases are in children, but only a fraction receive proper diagnosis and treatment. The spread of drug-resistant (DR) strain of TB has made it difficult to control, with only 60% of patients responding to treatment. Multi-drug resistant TB (MDR-TB) is often undiagnosed in children due to lack of awareness or under-diagnosis, and the target for children's DR-TB treatment has only been met in 15% of goals. New medications such as bedaquiline and delamanid have been approved for treating DR-TB. However, due to age and weight differences, adults and children require different dosages. The availability of child-friendly formulations is limited by a lack of clinical data in children. This paper reviews the development history of these drugs, their mechanism of action, efficacy, safety potential problems and current use in treating DR-TB in children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Zhou, Zhuang, Li, Bi and Mi.)

Breast cancer is the leading cancer in women. Around 20-30% breast cancer patients undergo invasion or metastasis after radical surgical resection and eventually die. Number of breast cancer patients show poor sensitivity toward treatments despite the advances in chemotherapy, endocrine therapy, and molecular targeted treatments. Therapeutic resistance and tumor recurrence or metastasis develop with the ongoing treatments. Conducive treatment strategies are thus required. Chimeric antigen receptor (CAR)-modified T-cell therapy has progressed as a part of tumor immunotherapy. However, CAR-T treatment has not been effective in solid tumors because of tumor microenvironment complexity, inhibitory effects of extracellular matrix, and lacking ideal tumor antigens. Herein, the prospects of CAR-T cell therapy for metastatic breast cancer are discussed, and the targets for CAR-T therapy in breast cancer (HER-2, C-MET, MSLN, CEA, MUC1, ROR1, EGFR) at clinical level are reviewed. Moreover, solutions are proposed for the challenges of breast cancer CAR-T therapy regarding off-target effects, heterogeneous antigen expression by tumor cells and immunosuppressive tumor microenvironment. Ideas for improving the therapeutics of CAR-T cell therapy in metastatic breast cancer are suggested., Competing Interests: Declaration of Conflict Interest The author claims that there is no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Appraisal of cancer survival is essential for cancer control, but studies related to gynecological cancer are scarce. Using cancer registration data, we conducted an in-depth survival analysis of cervical, uterine corpus, and ovarian cancers in an urban district of Shanghai during 2002-2013., Materials and Methods: The follow-up data of gynecological cancer from the Changning District of Shanghai, China, were used to estimate the 1-5-year observed survival rate (OSR) and relative survival rate (RSR) by time periods and age groups during 2002-2013. Age-standardized relative survival rates estimated by the international cancer survival standards were calculated during 2002-2013 to describe the prognosis of cervical, uterine corpus, and ovarian cancers among women in the district., Results: In total, 1307 gynecological cancer cases were included in the survival analysis in the district during 2002-2013. Among gynecological cancers, the 5-year OSRs and RSRs of uterine corpus cancer were highest (5-year OSR 84.40%, 5-year RSR 87.67%), followed by those of cervical cancer (5-year OSR 73.58%, 5-year RSR 75.91%), and those of ovarian cancer (5-year OSR 53.89%, 5-year RSR 55.90%). After age adjustment, the 5-year relative survival rates of three gynecological cancers were 71.23%, 80.11%, and 43.27%, respectively., Conclusion: The 5-year relative survival rate did not show a systematic temporal trend in cervical cancer, uterine cancer, or ovarian cancer. The prognosis in elderly patients was not optimistic, and this needs a more advanced strategy for early diagnosis and treatment. The age structure of gynecological cancer patients in the district tended to be younger than the standardized age, which implies that more attention to the guidance and health education for the younger generation is needed., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The Parkland Grading Scale (PGS) is an intraoperative grading scale to stratify gallbladder disease severity during laparoscopic cholecystectomy (LC). We evaluated the usefulness of the PGS in predicting the difficulty levels of LC procedures using a novel approach., Methods: A total of 261 patients diagnosed with cholelithiasis and cholecystitis who underwent LC were assessed. The PGS and the surgical difficulty grading system were used to evaluate surgical procedures by reviewing the operation videos. Clinical baseline characteristics and post-treatment outcomes were also recorded. Differences between the five PGS grades in terms of surgical difficulty scores were analyzed using the Jonckheere-Terpstra test. The relationship between PGS grades and surgical difficulty scores was assessed using Spearman's Rank correlation. Finally, the linear trends between morbidity scores and PGS grades were evaluated using the Mantel-Haenszel test., Results: There was a significant difference in the surgical difficulty scores for the five PGS grades (p < 0.001). In pairwise comparison, each grade (1-5) was significantly different from the others (p < 0.05) in terms of surgical difficulty, except Grade 2 vs. 3 (p = 0.07) and Grade 3 vs. 4 (p = 0.08). There was a significant correlation between PGS grades and surgical difficulty scores (r s = 0.681, p < 0.001). There was also a significant linear association between morbidity and PGS grades (p < 0.001). Spearman's R value was 0.176 (p = 0.004)., Conclusion: The PGS can accurately assess the surgical difficulty level of LC. The precision and conciseness of the PGS make it suitable for use in future research., (© 2023. The Author(s).)

Background: Mycoplasma pneumoniae (MP) is a commonly occurring pathogen causing community-acquired pneumonia (CAP) in children. The global prevalence of macrolide-resistant MP (MRMP) infection, especially in Asian regions, is increasing rapidly. However, the prevalence of MRMP and its clinical significance during the COVID-19 pandemic is not clear., Methods: This study enrolled children with molecularly confirmed macrolide-susceptible MP (MSMP) and MRMP CAP from Beijing Children's Hospital Baoding Hospital, Capital Medical University between August 2021 and July 2022. The clinical characteristics, laboratory findings, chest imaging presentations, and strain genotypes were compared between patients with MSMP and MRMP CAP., Results: A total of 520 hospitalized children with MP-CAP were enrolled in the study, with a macrolide resistance rate of 92.7%. Patients with MRMP infection exhibited more severe clinical manifestations (such as dyspnea and pleural effusion) and had a longer hospital stay than the MSMP group. Furthermore, abnormal blood test results (including increased LDH and D-dimer) were more common in the MRMP group (P<0.05). Multilocus variable-number tandem-repeat analysis (MLVA) was performed on 304 samples based on four loci (Mpn13-16), and M3562 and M4572 were the major types, accounting for 74.0% and 16.8% of the strains, respectively. The macrolide resistance rate of M3562 strains was up to 95.1%., Conclusion: The prevalence of MRMP strains in hospitalized CAP patients was extremely high in the Baoding area, and patients infected with MRMP strains exhibited more severe clinical features and increased LDH and D-dimer. M3562 was the predominant resistant clone., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jiang, Sun, Wang, Qi, Tang, Wang, Han, Shi, Bi, Jiao and Shen.)

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor outcome and lacks of approved targeted therapy. Overexpression of epidermal growth factor receptor (EGFR) is found in more than 50% TNBC and is suggested as a driving force in progression of TNBC; however, targeting EGFR using antibodies to prevent its dimerization and activation shows no significant benefits for TNBC patients. Here we report that EGFR monomer may activate signal transducer activator of transcription-3 (STAT3) in the absence of transmembrane protein TMEM25, whose expression is frequently decreased in human TNBC. Deficiency of TMEM25 allows EGFR monomer to phosphorylate STAT3 independent of ligand binding, and thus enhances basal STAT3 activation to promote TNBC progression in female mice. Moreover, supplying TMEM25 by adeno-associated virus strongly suppresses STAT3 activation and TNBC progression. Hence, our study reveals a role of monomeric-EGFR/STAT3 signaling pathway in TNBC progression and points out a potential targeted therapy for TNBC., (© 2023. The Author(s).)

The microwave-assisted rock breaking technology has been proven to be feasible, and has received considerable attention in the field of civil and mining engineering. A copper foil was used to wrap basalt to simulate rock excavation of practical application scenario in this paper. To this end, a multi-mode cavity with an operating frequency of 2.45 GHz was used to conduct microwave irradiation experiments on basalts with different irradiation times and different power. The thermal properties, AE characteristics, and damage evolution process of basalt were studied. The results show that the high heat generated by microwave leads to the development of cracks in the upper part of basalt. The higher the power level, the higher the degree of crack propagation in the sample, the lower the basalt strength, and the more active the AE activity. The fluctuation rule of the b value indicates that the basalt is dominated by small-scale microfractures before failure. High power levels or long irradiation time lead to more microwave-induced cracks participating in the failure process during loading. Compared with unheated basalt, microwave-heating basalt detects the characteristics of the precursor of failure in advance. The AE source location and the nephogram of the maximum principal stress of microwave-treated basalt reflected that the fracture path begins in the upper part of the rock. In addition, the combination of high power level and short irradiation time can achieve the purpose of energy saving., (© 2023. The Author(s).)

Background: 1,2,3,4,6-Penta-O-galloyl-β-D-glucose (β-PGG) is a polyphenol ellagic compound with a variety of pharmacological effects and has an inhibitory effect on lots of cancers., Objective: To explore the antitumor effects and mechanism of 1,2,3,4,6-Penta-O-galloyl-β-D-glucose on human hepatocellular carcinoma HepG2 cells., Design: A network pharmacology method was first used to predict the possible inhibition of hepatocellular carcinoma growth by 1,2,3,4,6-Penta-O-galloyl-β-D-glucose (β-PGG) through the p53 signaling pathway. Next, the Cell Counting Kit (CCK-8) assay was performed to evaluate changes in the survival rate of human hepatocellular carcinoma HepG2 cells treated with different concentrations of the drug; flow cytometry was used to detect changes in cell cycle, apoptosis, mitochondrial membrane potential (MMP) and intracellular Ca2+ concentration; real-time fluorescence quantification and immunoblotting showed that the expression of P53 genes and proteins associated with the p53 signaling pathway was significantly increased by β-PGG treatment., Reasult: It was found that β-PGG significantly inhibited survival of HepG2 cells, promoted apoptosis, decreased MMP and intracellular Ca2+ concentration, upregulated P53 gene and protein expression, increased CASP3 expression, and induced apoptosis in HepG2 cells., Conclusion: This study has shown that network pharmacology can accurately predict the target of β-PGG's anti-hepatocellular carcinoma action. Moreover, it was evident that β-PGG can induce apoptosis in HepG2 cells by activating the p53 signaling pathway to achieve its anti-hepatocellular carcinoma effect in vitro ., (© 2023 Yu-han Jiang et al.)

Finding novel and effective suppression of hepatic glucagon response antidiabetic compounds is urgently required for the development of new drugs against diabetes. Fungi are well known for their ability to produce new bioactive secondary metabolites. In this study, four new prenylated indole-terpenoids ( 1-4 ), named encindolenes I-L, as well as a known analogue ( 5 ), were isolated from the fungus Penicillium sp. HFF16from the rhizosphere soil of Cynanchum bungei Decne. The structures of the compounds were elucidated by spectroscopic data and ECD analysis. In the antidiabetic activity assay, compounds 1-5 could inhibit glucagon-induced hepatic glucose output with EC 50 values of 67.23, 102.1, 49.46, 25.20, and 35.96 μM, respectively, and decrease the intracellular cAMP contents in primary hepatocytes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Kong, Xiao, Li, Zhang, Lv, Liu, Kong, Bi, Lu, Kong, Hao, Zhou and Pan.)

Background: Soluble Amyloid-beta (Aβ) oligomers are thought to play a key role in the pathogenesis of Alzheimer's disease (AD), which is the most common age-associated neurodegenerative diseases with obvious neuropathological changes and functional decline in both cortical and subcortical regions. Melatonin is ubiquitously distributed and multifunctioning indoleamine. Accumulating studies support that melatonin is potential therapeutic molecule for AD through modulating a broad variety of signaling pathways. In recent years, Notch1 signaling pathway is been known involved in dynamic changes in the cellular architecture and function of adult brain, as well as associated with the pathophysiology of AD and other neurodegenerative disorders., Methods and Results: In this study, we performed real-time polymerase chain reaction, immunohistochemistry and western blotting analyses using the cerebral cortical tissues of Aβ 1-42 oligomers-induced AD rats with or without melatonin treatment. Our results showed that soluble Aβ 1-42 oligomers decreased the expression of the main components of Notch1 signaling pathway, Notch1, NICD and Hes1 in the cerebral cortex, and melatonin could restore the level of Notch1, NICD and Hes1., Conclusion: This observation suggests that targeting of Notch1 signaling might be a promising therapeutic approach for AD and other age-associated neurodegenerative diseases, and melatonin might serve as a potential therapeutic agent for AD and other age-associated neurodegenerative diseases., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Diabetes is frequently accompanied by cognitive impairment with insidious onset, and progressive cognitive and behavioral changes. β-1, 3-galactosyltransferase 2 (B3galt2) contributes to glycosylation, showing a clue for neuronal apoptosis, proliferation and differentiation. However, the role of B3galt2 in diabetic cognitive dysfunction (DCD) has not been investigated. In the present study, we aimed to explore the role of B3galt2 in DCD. Additionally, the potential therapeutic effects of salidroside on DCD was also explored. Diabetic C57BL/6J mice showed cognitive dysfunction together with down-regulated B3galt2. Overexpression of B3galt2 reversed the cognitive decline of diabetic C57BL/6J. Moreover, cognitive impairment was aggravated in B3galt2 +/- diabetic mice compared with C57BL/6J diabetic mice. Immunohistochemistry fluorescence indicated that B3galt2 and F3/Contactin were co-localized in the hippocampal regions. Importantly, the expression of F3/Contactin can be regulated by the manipulation of B3galt2, overexpression of which assuaged hippocampal neuronal damage, protected the synapsin, and reduced neuronal apoptosis in diabetic mice. Interestingly, SAL alleviated DCD and reversed the expression of B3galt2 in diabetic C57BL/6J mice. These findings indicate that inhibition of B3galt2/F3/Contactin pathway contributes to DCD, and participates in SAL reversed DCD., (Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Adjuvant Xuebijing therapy exhibited a protective effect on severe community-acquired pneumonia (SCAP) in previous studies. Blood inflammatory biomarkers related to the disease subtype and severity of SCAP might be associated with the effects of Xuebijing on clinical outcomes of SCAP., Purpose: To investigate whether neutrophils or lymphocytes are a useful biomarker of the therapeutic effect of Xuebijing on mortality and inflammation damage index., Study Design: A post hoc analysis of a randomized, placebo-controlled and double-blinded clinical trial of Xuebijing in patients with SCAP (Clinical Trial Registration: ChiCTR-TRC-13003534)., Methods: We compared 28-day mortality (primary outcome) and four clinical scores (secondary outcome), including pneumonia severity index (PSI) score, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE II) score, and systemic inflammatory response syndrome (SIRS) score, according to the baseline strata of neutrophil count and lymphocyte count., Results: A total of 675 patients were included in the analyses, of which 334 received Xuebijing and 341 received the placebo. Xuebijing was more effective in SCAP patients with higher lymphocyte counts and lower neutrophil counts. In the lymphocyte-dominated inflammation (LDI) subgroup, defined as neutrophil count <13 × 10 9 cells/l and lymphocyte count ≥0.65 × 10 9 cells/l, Xuebijing reduced 28-day mortality by 15% while mortality of the neutrophil-dominated inflammation (NDI) subgroup decreased by 4.7% (p = 0.050). There was also greater improvement in the PSI, SOFA, APACHE II, and SIRS scores following Xuebijing treatment in the LDI subgroup compared with the NDI subgroup., Conclusions: Xuebijing treatment shows stronger protective effects in SCAP patients with higher lymphocyte and lower neutrophil counts. Our findings may facilitate the selection of the most appropriate treatments for individual patients with SCAP, including who will receive Xuebijing injections., Competing Interests: Conflict of interest statement NULL of the pharmaceutical companies has given any commercial sources for this study. And the authors declare that there are no known conflicts of interest associated with this publication and we have no financial and personal relationships with other people or organizations that can inappropriately influence our work “The prediction of lymphocyte count and neutrophil count on the efficacy of Xuebijing adjuvant treatment for severe community-acquired pneumonia: a post-hoc analysis of a randomized controlled trial”., (Copyright © 2022. Published by Elsevier GmbH.)

DNA molecular machines are widely used in the fields of biosensors and biological detection. Among them, DNA walkers have attracted much attention due to their simple design and controllability. Herein, we attempt to develop a DNA walker triggered exponential amplification method and explore its application. The AuNP probes in the DNA walker are constructed by a freezing technology, instead of the time-consuming and complex synthesis process of the traditional method. Meanwhile, after the "recognition-cleavage-relative motion" cycle of this DNA walker reaction, the exponential amplification reaction is initiated, and leads to the fluorescence recovery of the molecular beacon. Taking ricin as a target, this new method shows a limit of detection of 2.25 pM by selecting aptamers with strong binding affinity, and exhibits a wide detection range, satisfactory specificity, and excellent stability in practical application. Therefore, our method provides a universal sensing platform and has great prospects in the fields of biosensors, food safety detection, and clinical diagnostics.

Objective: Glycosyltransferases contribute to the biosynthesis of glycoproteins, proteoglycans and glycolipids and play essential roles in various processes in the brain, such as learning and memory, brain development, neuronal survival and neurodegeneration. β-1,3-galactosyltransferase 2 (B3galt2) belongs to the β-1,3-galactosyltransferase gene family and is highly expressed in the brain. Recent studies have indicated that B3galt2 plays a vital role in ischemic stroke through several signaling pathways in a mouse model. However, the function of B3galt2 in the brain remains poorly understood., Methods: The genotypes of mice were determined by PCR. To verify B3galt2 expression in an adult mouse brain, X-gal staining was performed in 6-month-old B3galt2 heterozygous (B3galt2+/-) mice. Using adult B3galt2 homozygous (B3galt2-/-), heterozygous and wild-type (WT) littermates, spatial learning and memory were determined by the Morris Water Maze test, and neurotoxicity and synaptic plasticity were examined by immunofluorescence., Results: B3galt2 was highly expressed in the adult mouse hippocampus and cortex, especially in the hippocampal dentate gyrus. Compared to that of WT mice, the spatial learning ability of adult B3galt2-/- mice was impaired. B3galt2 mutations also caused neuronal loss and synaptic dysfunction in the hippocampus and somatosensory cortex, and these changes were more obvious in B3galt2-/- mice than in B3galt2+/- mice., Conclusions: The findings indicate that B3galt2 plays an important role in cognitive function, neuronal maintenance and synaptic plasticity in the adult mouse brain. This study suggests that genetic and/or pharmacological manipulation of glycosyltransferases may be a novel strategy for elucidating the mechanism of and managing various brain disorders., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The large-conductance calcium-activated potassium (BK) channel is a critical regulator and potential therapeutic target of vascular tone and architecture, and abnormal expression or dysfunction of this channel is linked to many vascular diseases. Vascular remodelling is the early pathological basis of severe vascular diseases. Delaying the progression of vascular remodelling can reduce cardiovascular events, but the pathogenesis remains unclear. To clarify the role of BK channels in vascular remodelling, we use rats with BK channel α subunit knockout (BK α ‒/‒ ). The results show that BK α ‒/‒ rats have smaller inner and outer diameters, thickened aortic walls, increased fibrosis, and disordered elastic fibers of the aortas compared with WT rats. When the expression and function of BK α are inhibited in human umbilical arterial smooth muscle cells (HUASMCs), the expressions of matrix metalloproteinase 2 (MMP2), MMP9, and interleukin-6 are enhanced, while the expressions of smooth muscle cell contractile phenotype proteins are reduced. RNA sequencing, bioinformatics analysis and qPCR verification show that C1q/tumor necrosis factor-related protein 7 ( CTRP7 ) is the downstream target gene. Furthermore, except for that of MMPs, a similar pattern of IL-6, smooth muscle cell contractile phenotype proteins expression trend is observed after CTRP7 knockdown. Moreover, knockdown of both BK α and CTRP7 in HUASMCs activates PI3K/Akt signaling. Additionally, CTRP7 is expressed in vascular smooth muscle cells (VSMCs), and BK α deficiency activates the PI3K/Akt pathway by reducing CTRP7 level. Therefore, we first show that BK channel deficiency leads to vascular remodelling. The BK channel and CTRP7 may serve as potential targets for the treatment of cardiovascular diseases.

The communication between myogenic cells and their surrounding connective tissues is indispensable for muscle morphogenesis. During late embryonic development in mice, myogenic progenitors migrate to discrete sites to form individual muscles. The detailed mechanism of this process remains unclear. Using mouse levator veli palatini (LVP) development as a model, we systematically investigated how a distinct connective tissue subpopulation, perimysial fibroblasts, communicates with myogenic cells to regulate mouse pharyngeal myogenesis. Using single-cell RNAseq data analysis, we identified that TGF-β signaling is a key regulator for the perimysial fibroblasts. Loss of TGF-β signaling in the neural crest-derived palatal mesenchyme leads to defects in perimysial fibroblasts and muscle malformation in the soft palate in Osr2 Cre ;Tgfbr1 fl/fl mice. In particular, Creb5, a transcription factor expressed in the perimysial fibroblasts, cooperates with TGF-β signaling to activate expression of Fgf18 . Moreover, Fgf18 supports pharyngeal muscle development in vivo and exogenous Fgf18 can partially rescue myogenic cell numbers in Osr2 Cre ;Tgfbr1 fl/fl samples, illustrating that TGF-β-regulated Fgf18 signaling is required for LVP development. Collectively, our findings reveal the mechanism by which TGF-β signaling achieves its functional specificity in defining the perimysial-to-myogenic signals for pharyngeal myogenesis., Competing Interests: JF, XH, YY, CC, EJ, TG, SP, MR, BZ, JB, JJ, MZ, JX, TH, YC No competing interests declared, (© 2022, Feng et al.)

Mycobacterium tuberculosis (Mtb), the pathogenic agent of tuberculosis, remains a primary inducement of morbidity and mortality globally. Mtb have evolved mechanisms to recognize diverse signals, such as acidic pH within phagolysosomes and therefore to reprogram multiple physiological and metabolic processes to adapt to intracellular survival. Moreover, lysine malonylation has been suggested to participate in regulation of enzymes in carbon metabolism. However, lysine malonylation in Mtb and its association with acidic pH associated metabolism adaptation remain unknown. Here, we systematically characterized the comparative malonylome of Mtb H37Rv grown in normal (7H9-Tyloxapol (Ty)-7.4) and acidic (7H9-Ty-4.5) medium mimicking lysosome pH. In total, 2467 lysine malonylation sites within 1026 proteins were identified, which related to diverse biological processes, particularly accumulated in metabolic process. 1090 lysine malonylation sites from 562 proteins were quantified, among which 391 lysine malonylation sites in 273 protein were down-regulated while 40 lysine malonylation sites from 36 proteins were up-regulated in acidic medium, indicating that malonylation may participate in acidic pH associated metabolism. Accordingly, the enzyme activity of GlcB was reduced under acidic stress corresponding to decreased malonylation of GlcB compared with that of normal condition and this was further demonstrated by site-specific mutations. We further found that Mtb-CobB, a sirtuin-like deacetylase and desuccinylase, involved in demalonylase activity. Together, the Mtb malonylome not only indicates the critical role of malonylation in metabolism regulation, but may provide new insights of malonylation on metabolism adaptation to acidic micro-environment in vivo., Competing Interests: Conflicts of interest None., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Objective: Obesity has increased across the globe in recent years and is considered an established risk factor for many diseases. The main objective was to investigate the early assessment value of Body Mass Index (BMI) in the prediction of severity in acute biliary pancreatitis (ABP) and by using BMI to evaluate the severity of ABP., Methods: The retrospective analysis was designed to assess the relationship between Body Mass Index and the severity of acute pancreatitis in Beijing Jishuitan Hospital from January 2019 to December 2021. The SPSS 24.0 software was used for statistical analysis, Logistic Regression, and ROC curve for the factors affecting the severity of acute biliary pancreatitis., Results: A total of 259 ABP patients were analyzed in our study. The BMI was significantly correlated with the Ranson scoring and MCTSI scoring ( p = 0.000, 0.000). The difference in BMI in different severity of ABP patients was statistically significant ( p = 0.000). The Logistic Regression analyses confirmed that BMI was an independent risk factor for the severity of ABP ( p = 0.035). Combined detection of BMI, WBC, serum calcium, and SAMY in prognosis of the severity of acute pancreatitis positive rate is higher than single positive rate., Conclusion: The BMI gradually increased with the severity of acute pancreatitis and was an independent risk factor for the condition. Combined detection of BMI and medical tests can effectively improve acute pancreatitis patients' clinical diagnostic accuracy and early treatment, and help to reduce complications., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Background: Pneumonia, caused by infection or other factors, seriously endangers the health of children. Meropenem is an effective broad-spectrum antibiotic using in the treatment of infectious diseases. In the therapy of pneumonia, meropenem is mostly employed for the treatment of moderate to severe pneumonia. Previously, we established a population pharmacokinetics (PPK) model for meropenem in pediatric severe infection and simulated the control rate of the time during which the free plasma concentration of meropenem exceeds the minimum inhibitory concentration (MIC) is 70% of the dosing interval (70% fT > MIC). Therefore, we plan to conduct a multicenter randomized controlled trial (RCT) to compare the efficacy and safety between conventional regimen and model regimen for meropenem in pediatric severe pneumonia. Methods: One hundred patients (aged 3 months to 15 years) will be recruited in this RCT. They will be assigned randomly (at a 1:1 ratio) to a conventional treatment group (20 mg/kg, q8h, with 0.5-1 h infusion) and a model treatment group (20 mg/kg, q8 h, with 4 h infusion). The primary outcome will be 70% fT > MIC. Secondary outcomes will be the prevalence of meropenem therapy failure, duration of antibiotic therapy, changes in levels of inflammatory indicators, changes in imaging examination results, and prevalence of adverse events. Ethical approval of our clinical trial has been granted by the ethics committee of Beijing Children's Hospital ([2022]-E-133-Y). This trial has been registered in the Chinese Clinical Trial Registry (ChiCTR2200061207). Discussion: Based on our previous PPK data, we have designed this RCT. It is hoped that it will promote rational use of antibacterial drugs in children suffering from severe pneumonia. Clinical Trial Registration : http://www.chictr.org.cn identifier, ChiCTR2200061207., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tian, Dong, Jiang, Tang, Wang, Wu, You, Bi, Qian, Qi and Shen.)