Background: Montelukast (MTK), a potent antagonist of cysteinyl leukotriene receptor 1, has shown therapeutic promise for the treatment of neuropsychiatric disorders. Delirium, a common complication in critically ill patients, lacks effective treatment. This study aims to explore the impact of pre-intensive care unit (ICU) MTK use on in-hospital delirium incidence and, subsequent, prognosis in critically ill patients. Methods: A retrospective cohort study (n = 6344) was conducted using the MIMIC-IV database. After propensity score matching, logistic/Cox regression, E-value sensitivity analysis, and causal mediation analysis were performed to assess associations between pre-ICU MTK exposure and delirium and prognosis in critically ill patients. Results: Pre-ICU MTK use was significantly associated with reduced in-hospital delirium (OR: 0.705; 95% CI 0.497–0.999; p = 0.049) and 90-day mortality (OR: 0.554; 95% CI 0.366–0.840; p = 0.005). The association was more significant in patients without myocardial infarction (OR: 0.856; 95% CI 0.383–0.896; p = 0.014) and could be increased by extending the duration of use. Causal mediation analysis showed that the reduction in delirium partially mediated the association between MTK and 90-day mortality (ACME: −0.053; 95% CI −0.0142 to 0.0002; p = 0.020). Conclusions: In critically ill patients, MTK has shown promising therapeutic benefits by reducing the incidence of delirium and 90-day mortality. This study highlights the potential of MTK, beyond its traditional use in respiratory disease, and may contribute to the development of novel therapeutic strategies for delirium.

Nivolumab (Opdivo®) is the first anti-PD-1 antibody approved in the world. LY01015 is a potential biosimilar of nivolumab. This phase I study aimed to establish the pharmacokinetic equivalence between LY01015 and the original investigational nivolumab (Opdivo®) in healthy Chinese male subjects. Additionally, safety and immunogenicity were assessed. A randomized, double-blind, parallel-controlled, phase I trial was conducted with 176 healthy male adults receiving a single intravenous infusion of LY01015 or nivolumab at 0.3 mg/kg. Pharmacokinetics, safety, and immunogenicity were evaluated over a 99-day period. The primary pharmacokinetics endpoint was AUC0–∞, and the secondary pharmacokinetic endpoints included AUC0–t and Cmax. Pharmacokinetic bioequivalence was confirmed using standard equivalence margins of 80.00–125.00 https://www.chictr.org.cn/ #ChiCTR2200064771).

In the current study, we assessed the relationship between mutations and the blood cell counts and early progression of patients with diffuse large-B cell lymphoma (DLBCL). A total of 109 patients with newly diagnosed DLBCL were included in this study. UBE2A mutation was only found in patients with bone marrow involvement. The mutations of ZNF608, SF3B1, DTX1, and NCOR2 were related to blood cell counts. NCOR2 mutations were only detected in patients of the noncomplete response group (PR + SD + PD). In addition, the mutations of ATM, BTG2, TBL1XR1, and TP53 were linked to lower PFS/OS rate, while SGK1, SCOS1, and NFKBIE were related to higher PFS/OS rate. Importantly, we identified that Ann Arbor stage (III-IV), B symptoms, absolute lymphocyte count (ALC) abnormity, and MTOR mutation were the four independent influencing factors of the 12-month progression of DLBCL patients. Overall, this study revealed that mutations were associated with the early progression of DLBCL.

BackgroundThe clinical manifestations of multiple myeloma (MM) and bone metastatic tumor are both systemic bone pain, which is difficult to distinguish from imaging manifestations, leading to misdiagnosis and missed diagnosis.Case summaryWe reported a man with a unique case whose tumors were MM with bone metastatic tumor of clear cell renal cell carcinoma (CCRCC). Computed tomography (CT) showed multifocal osteolytic bone destruction, while magnetic resonance imaging (MRI) showed multifocal bone marrow infiltration with soft tissue mass. Pathology and immunohistochemistry established the diagnosis of the coexistence of myeloma with bone metastatic tumor of CCRCC in the spine. Immunotherapy and systemic chemotherapy were adopted in the clinic, and vertebral decompression was performed after anemia was corrected. This case with MM and bone metastatic tumor of CCRCC received radiotherapy and immunotherapy and acquired satisfying outcome after 1 year of follow-up.ConclusionIt is difficult to differentiate MM and bone metastatic tumor on imaging, especially when there are bone lesions at the same time, which is an easily missed diagnosis and needs to be comprehensively evaluated in combination with functional procedures, clinical laboratory tests, and histopathology.

Mitochondria are sensitive organelles that sense intrinsic and extrinsic stressors and maintain cellular physiological functions through the dynamic homeostasis of mitochondrial fusion and fission. Numerous pathological processes are associated with mitochondrial fusion and fission disorders. However, the molecular mechanism by which stress induces cardiac pathophysiological changes through destabilising mitochondrial fusion and fission is unclear. Therefore, this study aimed to investigate whether the endoplasmic reticulum stress signalling pathway initiated by the turbulence of mitochondrial fusion and fission under stressful circumstances is involved in cardiomyocyte damage. Based on the successful establishment of the classical stress rat model of restraint plus ice water swimming, we measured the content of serum lactate dehydrogenase. We used haematoxylin-eosin staining, special histochemical staining, RT-qPCR and western blotting to clarify the cardiac pathology, ultrastructural changes and expression patterns of mitochondrial fusion and fission marker proteins and endoplasmic reticulum stress signalling pathway proteins. The results indicated that mitochondrial fusion and fission markers and proteins of the endoplasmic reticulum stress JNK signalling pathway showed significant abnormal dynamic changes with the prolongation of stress, and stabilisation of mitochondrial fusion and fission using Mdivi-1 could effectively improve these abnormal expressions and ameliorate cardiomyocyte injury. These findings suggest that stress could contribute to pathological cardiac injury, closely linked to the endoplasmic reticulum stress JNK signalling pathway induced by mitochondrial fusion and fission turbulence.

The dorsomedial hypothalamus nucleus (DMH) is an important component of the autonomic nervous system and plays a critical role in regulating the sympathetic outputs of the heart. Stress alters the neuronal activity of the DMH, affecting sympathetic outputs and triggering heart rate variability. However, the specific molecular mechanisms behind stress leading to abnormal DMH neuronal activity have still not been fully elucidated. Therefore, in the present study, we successfully constructed a stressed rat model and used it to investigate the potential molecular mechanisms by which IL-6 regulates GABAA receptors in the DMH through activation of the JAK/STAT pathway and thus affects heart rate variability in rats. By detecting the c-Fos expression of neurons in the DMH and electrocardiogram (ECG) changes in rats, we clarified the relationship between abnormal DMH neuronal activity and heart rate variability in stressed rats. Then, using ELISA, immunohistochemical staining, Western blotting, RT-qPCR, and RNAscope, we further explored the correlation between the IL-6/JAK/STAT signaling pathway and GABAA receptors. The data showed that an increase in IL-6 induced by stress inhibited GABAA receptors in DMH neurons by activating the JAK/STAT signaling pathway, while specific inhibition of the JAK/STAT signaling pathway using AG490 obviously reduced DMH neuronal activity and improved heart rate variability in rats. These findings suggest that IL-6 regulates the expression of GABAA receptors via the activation of the JAK/STAT pathway in the DMH, which may be an important cause of heart rate variability in stressed rats.

Objective:To investigate the value of MRI DWI-based radiomics models for evaluating the treatment response in osteosarcoma after neoadjuvant chemoherapy.Methods:A retrospective analysis was conducted on the medical records and imaging data of 41 patients with osteosarcoma (26 males and 15 females; aged (22.0±11.0) years, range of 11–49 years) who underwent MRI examinations before and after receiving neoadjuvant chemotherapy, and confirmed by postoperative histopathological examinations at the Third Hospital of Hebei Medical University from June 2015 to November 2017. In accordance with the postoperative histopathological examination results, patients with a tumor tissue necrosis rate of ≥90% were included in the good-efficacy group, and those with a necrosis rate of <90% were included in the poor-efficacy group. The apparent diffusion coefficient (ADC, denoted as ADC0, ADC1, and ADC2) were measured in all patients before neoadjuvant chemotherapy, within 5 days after the end of the first stage of chemotherapy, and after the completion of the entire chemotherapy. The differences in ADC were compared between the two groups. The region of interest of the lesion was manually delineated on DWI (b=1 000 s/mm 2) and ADC images after the end of the first stage of chemotherapy, and the radiomics features were extracted. Data were divided into training set and validation set by using random grouping at 6∶4. The SMOTE algorithm was used to expand the data on the training set. The variance threshold, SelectKBest, and least absolute shrinkage and selection operator (LASSO) algorithm were used to screen the radiomics features. A radiomics model was constructed using a logistic regression classifier. Independent sample t-test or Wilcoxon rank sum test was used to compare the two groups. Receiver operating characteristic (ROC) curves were used to evaluate the predictive efficacy of traditional imaging (ADC) and radiomics models on the efficacy of neoadjuvant chemotherapy for osteosarcoma. Results:A total of 10 and 31 cases were included in the good-efficacy and poor-efficacy groups, respectively. No statistically significant difference was found in the ADC0 value between the two groups ((0.95±0.05)×10 -3 mm 2/s vs. (1.05±0.05)×10 -3 mm 2/s, t=1.14, P>0.05)). The values of ADC1 and ADC2 in the good-efficacy group were higher than those in the poor-efficacy group, with statistical significance ((1.44±0.10)×10 -3 mm 2/s vs. (1.10±0.06)×10 -3 mm 2/s, t=-2.92, P<0.05; 1.68 (1.55, 1.85)×10 -3 mm 2/s vs. (1.33±0.06)×10 -3 mm 2/s, Z=-2.61, P<0.01). ROC curve analysis showed that when ADC1 ≥1.34×10 -3 mm 2/s, the sensitivity for evaluating the efficacy of neoadjuvant chemotherapy in osteosarcoma was 80%, the specificity was 81%, and the area under the curve (AUC) was 0.797 (95% CI: 0.629-0.965). When ADC2 ≥1.51×10 -3 mm 2/s, the sensitivity for evaluating the efficacy of neoadjuvant chemotherapy in osteosarcoma was 90%, the specificity was 71%, and the AUC was 0.777 (95% CI: 0.588–0.967). A total of 1 409 radiomics features were extracted from the DWI and ADC images after the end of the first stage of chemotherapy. They were randomly divided into training set and validation set at a ratio of 6∶4 (24 (good efficacy: 6, poor efficacy: 18)∶17 (good efficacy: 4, poor efficacy: 13)). The training set data were expanded to 70 (good efficacy: 20, poor efficacy: 50). After the radiomics features were screened, five optimal radiomics features were ultimately obtained, including InterquartileRange, Skewness, Uniformity, Median, and Maximum. Logistic regression classifier was used to construct a radiomics model. The ROC curves showed that in the training set, the AUC of the model for predicting the efficacy of neoadjuvant chemotherapy in osteosarcoma was 0.881 (95% CI: 0.811-0.942), with sensitivity of 90% and specificity of 74%. Meanwhile, in the validation set, the AUC was 0.769 (95% CI: 0.515–0.933), with sensitivity of 75% and specificity of 69%. Conclusion:The radiomics model based on MRI DWI outperforms the traditional imaging (ADC) in evaluating the efficacy of neoadjuvant chemotherapy for osteosarcoma, showing great potential in clinical applications.

Formaldehyde is a colourless irritating gas at room temperature, which, therefore, is usually stored in liquid form. This compound is often used as an antiseptic, disinfectant and fumigant in biology and medicine. Formaldehyde, as a potential carcinogen confirmed by the World Health Organization (WHO), is seriously harmful to human systems, such as the respiratory system, immune system and reproductive system. This article reports a case of a 50-year-old woman who died after accidentally drinking 25% formaldehyde solution in a transparent plastic bottle. Anatomical examination revealed fixed tissue morphology of the stomach and adjacent organs. The toxicity test results showed that the concentrations of formaldehyde in the blood and gastric tissue were 36.56 mg/kg and 274.48 mg/kg, respectively, which was consistent with death from formaldehyde poisoning. Due to the particular smell of formaldehyde, poisoning by accidentally drinking formaldehyde solution is rare. Of late, the mechanism of death from formaldehyde poisoning is that it rapidly causes coagulation of tissue cell protein, which may lose its normal function. Based on the pathological characteristics of the case, we put forward a new viewpoint on the mechanism of death from formaldehyde poisoning in which formaldehyde causes rapid fixation of blood in the tissue, thus leading to acute circulatory disturbance.