Idiopathic pulmonary fibrosis （IPF） can be classified as pulmonary collateral disease，and its pathogenesis is mainly characterized by the loss of Qi meridian nourishment，the loss of Yin meridian nourishment，and the formation of blood stasis in the blood vessels. Qi Yin deficiency is the pathological basis that runs through IPF，and obstruction of meridians and collaterals is a key element in the development of the disease. The dysfunction of "spleen being in charge of the defensive function" is closely related to the formation of the pathological pattern of "lung deficiency and collateral stasis" in IPF. The term "spleen being in charge of the defensive function" originated from the Yellow Emperor's Inner Canon. If the spleen is healthy，the Qi will be filled with vitality. Positive energy is stored inside，evil cannot be dried up. Its concept is quite similar to the immune defense function in modern medicine. If the principle of "spleen being in charge of the defensive function" is lost，the key structure and function of the IPF alveolar epithelial barrier may be abnormal，and it can interact with various innate immune cells to promote inflammation and fibrosis processes. Therefore，this article explains the imbalance of immune homeostasis in IPF alveolar epithelium from two aspects：the barrier function of alveolar epithelial cells（AECs） and their interaction with innate immune cells. And based on the theory of "spleen being in charge of the defensive function"，using traditional Chinese medicine for strengthening the spleen and nourishing Qi to treat IPF from the perspective of the spleen. This not only strengthens the scientific connotation of "spleen being in charge of the defensive function" in the pathogenesis of IPF，but also provides new research directions and ideas for its future clinical prevention and treatment.

PURPOSE: To evaluate the diagnostic accuracy of the observational chart for traumatic limb swelling (OCTLS) for osteofascial compartment syndrome (OCS). METHODS: This was a descriptive-longitudinal study. Data of 316 patients who underwent surgical treatment for tibial fractures in our department from January 2015 to December 2023 were collected. Patients with Gustilo type II or higher open fractures, vascular injury, or bilateral fractures were excluded from the study. Two groups of double-blinded investigators independently assessed patients for the presence of OCS using 2 distinct diagnostic methods. Three senior orthopedic trauma surgeons evaluated patients with post-fracture calf swelling for OCS and the need for fasciotomy based on clinical signs and their extensive clinical experience. Subsequently, fasciotomy was performed according to their judgment, followed by postoperative examination of muscle and soft tissue conditions. Additionally, a follow-up evaluation was conducted to assess for complications such as ischemic muscle contracture. Another 3 trained researchers used OCTLS to grade swelling severity and determine the need for fasciotomy. The final diagnostic gold standard of OCS was determined by referring to whether there was escape of muscles at fasciotomy and/or color change in the muscles or muscle necrosis intraoperatively, and neurological abnormality or contracture at the last follow-up. The results of the 2 diagnostic methods were compared with the final diagnostic result. Kappa consistency test, paired χ² test (McNemar test), and receiver operating characteristic curve were used to evaluate the diagnostic efficacy of the 2 diagnostic methods. RESULTS: Of the 316 patients, 211 were finally included in the study, including 160 males and 51 females, with an average follow-up time of (14.5 ± 2.7) months. Among the 211 patients with tibial fracture-associated swelling, 42 were definitively diagnosed with OCS. Based on clinical symptoms and signs judgment, among the 65 fasciotomy patients, 38 were confirmed as correct, while among the 146 non-fasciotomy patients, 4 developed ischemic muscle contractures. Based on the OCTLS for assessment, fasciotomy was correctly recommended in 36 out of 43 cases, while 6 out of 168 non-fasciotomy patients developed OCS. Compared to the use of the gold standard, clinical signs judgment showed moderate consistency (McNemar's test p < 0.001, Kappa = 0.618, p < 0.001), whereas OCTLS demonstrated strong agreement (McNemar's test p = 1.000, Kappa = 0.808, p < 0.001). Receiver operating characteristic analysis revealed higher diagnostic accuracy for OCTLS (area under curve = 0.908, 95% CI: 0.843 - 0.972) compared to clinical signs judgment (area under curve = 0.872, 95% CI: 0.812 - 0.933). OCTLS achieved superior accuracy (93.8% vs. 85.3%, χ² = 8.221, p < 0.001) and a lower fasciotomy rate (20.4% vs. 30.8%, χ² = 6.023, p = 0.014). CONCLUSION Compared to clinical signs judgment, OCTLS significantly reduces unnecessary fasciotomy, improves diagnostic accuracy for OCS, and enables non-invasive, dynamic, and quantitative assessment, making it a valuable tool for clinical practice.
Humans ; Compartment Syndromes/etiology* ; Male ; Female ; Adult ; Tibial Fractures/surgery* ; Middle Aged ; Fasciotomy ; Edema/etiology* ; Longitudinal Studies ; Aged ; Young Adult

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Objective To investigate the relationship and predictive value of blood urea nitrogen(BUN)levels with the risk of in-hospital mortality in patients with septic shock.Methods Clinical data of 328 patients diagnosed with septic shock from January 1,2018 to September 30,2023 in Shenzhen Second People's Hospital were retrospectively collected.The primary outcome indicator was in-hospital death in patients with septic shock.Simple logistic regression analyses was used to explore the correlation between BUN and in-hospital death in patients with septic shock;multiple logistic regression analyses model was used to explore the quantitative relationship between BUN and in-hospital death in septic shock,sensitivity analyses was utilized to test the stability of the results.Results Simple logistic regression analyses suggested that BUN was a risk factor for in-hospital mortality in patients with septic shock.Multiple logistic regression analyses showed a positive correlation between BUN and in-hospital mortality in patients with septic shock:the risk of in-hospital mortality in patients with septic shock was increased by 3.3%for every 1 mmol/L increase in BUN(OR=1.033,P<0.01);after adjusting for different vari-ables,the risk of in-hospital death increased by 2.9%(OR=1.029,P<0.05)and 3.2%(OR=1.032,P<0.05)for each 1 mmol/L increase in BUN,respectively.Sensitivity analyses further confirmed the stability of the results(OR=1.04,P<0.05).Conclusion There is a positive correlation between BUN levels and in-hospital death in patients with septic shock,and it has a predictive value for the risk of in-hospital death in patients with septic shock.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Objective:To analyze the association between waist circumference (WC) and ischemic stroke (IS).Methods:The data for the present study were from the prospective cohort study of China Kadoorie Biobank in Qingdao. Using baseline information and IS events of the participants, the Cox proportional hazard regression model and restricted cubic spline (RCS) were used to analyze the association between WC and IS.Results:A total of 33 355 participants were included in the study, with 302 008.88 person-years of follow-up. A total of 1 093 new cases of IS were observed. Multivariate Cox proportional hazard regression model analysis showed that compared to the respondents with normal WC (male <85.0 cm, female <80.0 cm), respondents with excessive WC (male ≥85.0 cm, female ≥80.0 cm) had a 78% higher risk of IS incidence [hazard ratio( HR)=1.78, 95% CI: 1.51-2.10], and the risk increased by 72% ( HR=1.72, 95% CI: 1.40-2.12) and 83% ( HR=1.83, 95% CI: 1.40-2.39) in men and women. According to the RCS, the increase in WC and the risk of IS showed an "S" trend of nonlinear dose-response relationship. Conclusions:The risk of IS would increase with the WC. Keeping a normal WC is important for preventing IS.

AIM:To investigate the role of Ywhab in the growth of mouse B-cell lymphoma,and to explore the potential underlying mechanisms.METHODS:The correlation between Ywhab and human diffuse large B-cell lymphoma(DLBCL)was investigated by bioinformatics analysis.Infection with retroviral vector was performed to establish stable mouse B-cell lymphoma 38B9 cell line with overexpression of Ywhab gene,which was verified by RT-qPCR and Western blot.The impact of Ywhab overexpression on 38B9 cell growth both in vitro and in vivo was detected by cell counting,CCK-8 assay,and subcutaneous tumor loading experiments.The expression of apoptosis-related proteins was detected by RT-qPCR and Western blot.Co-immunoprecipitation combined with mass spectrometry(CoIP-MS)was employed to search for proteins specifically binding to Ywhab gene product 14-3-3β,which was confirmed by Western blot and molecu-lar docking analysis.RESULTS:The Ywhab gene exhibited low expression in DLBCL,which was correlated with poor clinical prognosis of DLBCL patients.Compared with normal mouse bone marrow B cells,Ywhab expression was low in 38B9 cells.Overexpression of Ywhab induced apoptosis of 38B9 cells both in vitro and in vivo,promoted the expression of pro-apoptotic proteins Puma,Noxa and Bax at both mRNA and protein levels,and inhibited the mRNA and protein expres-sion of anti-apoptotic protein Bcl2(P＜0.05).The 14-3-3β protein specifically bound to Hsp90aa1 and reduced Hsp90aa1 protein levels,thereby suppressing the growth of 38B9 cells.CONCLUSION:Ywhab promotes the apoptosis of B-cell lymphoma cells by binding to Hsp90aa1 and thereby inhibiting the function of Hsp90aa1.

Objective:To evaluate the effect of hydrogen on lipopolysaccharide (LPS) and nigericin-induced pyroptosis in macrophages and the role of long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1).Methods:Human monocyte-derived macrophages THP-1 cells were cultured in vitro and divided into 4 groups ( n=25 each) using a random number table method: control group (group C), LPS and nigericin group (group LN), hydrogen-rich medium+ LPS and nigericin group (group H+ LN), and lentiviral transfection+ hydrogen-rich medium+ LPS-nigericin group (group LV+ H+ LN). THP-1 cells were cultured in the common culture medium for 24 h in group C. LPS at a final concentration of 100 ng/ml and nigericin 10 μmol/L were added to the culture medium, and the cells were incubated for 24 h in group LN. In group H+ LN, the culture medium was replaced with 0.6 mmol/L hydrogen-rich medium, then LPS at a final concentration of 100 ng/ml and nigericin 10 μmol/L were immediately added, and the cells were incubated for 24 h. In group LV+ H+ LN, THP-1 cells over-expressing NEAT1 stably after being transfected with lentivirus were used, then LPS at a final concentration of 100 ng/ml and nigericin 10 μmol/L were immediately added, and the cells were incubated for 24 h. Cell viability was detected by CCK-8 assay. Lactic dehydrogenase (LDH) release was assessed by colorimetric method. The amount of LDH released was measured by colorimetry. The concentrations of interleukin-1beta (IL-1β) and IL-18 in culture medium were measured by enzyme-linked immunosorbent assay. The pyroptotic rate was detected by flow cytometry. The expression of nucleotide-binding oligomerization domain-like receptor-containing pyrin domain 3 (NLRP3), apoptosis-associated speck-like protein (ASC), caspase-1 and gasdermin D (GSDMD) was detected by Western blot. The expression of NEAT1 gene was determined by quantitative real-time polymerase chain reaction. Results:Compared with group C, the cell viability was significantly decreased, the amount of LDH released, concentrations of IL-1β and IL-18, and pyroptotic rate were increased, and the expression of NEAT1 gene, NLRP3, ASC, caspase-1 and GSDMD was up-regulated in group LN ( P<0.05). Compared with group LN, the cell viability was significantly increased, the amount of LDH released, concentrations of IL-1β and IL-18, and pyroptotic rate were decreased, and the expression of NEAT1 gene, NLRP3, ASC, caspase-1 and GSDMD was down-regulated in group H+ LN ( P<0.05). Compared with group H+ LN, the cell viability was significantly decreased, the amount of LDH released, concentrations of IL-1β and IL-18, and pyroptotic rate were increased, and the expression of NEAT1 gene, NLRP3, ASC, caspase-1 and GSDMD was up-regulated in group LV+ H+ LN ( P<0.05). Conclusions:Hydrogen can ameliorate LPS and nigericin-induced pyroptosis in macrophages, and the mechanism may be associated with down-regulating the expression of lncRNA NEAT1.

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.