Objective To investigate the expression of matrix metalloproteinase 3 (MMP3) in a mouse silicosis model induced by SiO₂, and explore its role in pulmonary fibrosis. Methods Six male C57B/6 mice were randomly divided into control and silicosis groups (n=3). The silicosis model was established via intratracheal instillation of SiO₂ suspension (0.2 g/kg); the control group were intratracheally instilled with the same amount of normal saline. Human pulmonary fibroblasts (HPF-a) and mouse lung fibroblasts (MLg) were treated with 5 ng/ml of transforming growth factor-β₁ (TGF-β₁) to construct an ex vivo silicosis cell model. Masson trichrome and Sirius red staining were used to assess the effects of SiO₂ on pulmonary tissue and extracellular matrix (ECM) deposition. Single-cell transcriptomics was performed on mouse lung tissue, with bioinformatics analyses identifying ECM-associated cellular composition changes and key genes. The expression and distribution of these key genes were analyzed by spatial transcriptomics. Western blotting was employed to detect Vimentin and MMP3 protein levels in mouse lung tissue and fibroblasts. Immunofluorescence staining was used to localize MMP3 in lung ECM and TGF-‍β₁-treated fibroblasts and to evaluate its accumulation in the ECM. Results Masson's and Sirius red staining revealed fibrotic changes and significant ECM collagen deposition in mice of silicosis group. Single-cell and spatial transcriptomics identified fibroblast-associated alterations in ECM components, with MMP3 emerging as a key gene. MMP3 mRNA expression was significantly elevated in mouse lungs of silicosis group and was localized primarily to fibrotic lesions. Western blotting showed a significant increase in MMP3 protein levels in the lungs of silicosis group mice compared to control group (P<0.05). TGF-‍β₁ treatment led to a time-dependent increase in MMP3 protein levels in HPF-a cells (P<0.05). Immunofluorescence revealed elevated MMP3 expression in the ECM of mouse lungs in silicosis group (P<0.05). When TGF-‍β₁ treated MLg cells were seeded onto normal mouse lung ECM, MMP3 expression increased (P<0.05). Similarly, after decellularizing ECM seeded with MLg cells, MMP3 expression levels remained significantly elevated (P<0.01). Co-localization analysis showed enhanced Vimentin and MMP3 signals in and around silicotic nodules in mice of silicosis group (P<0.01). Conclusions In the mouse silicosis model, secretion of MMP3 from fibroblasts increased with TGF‑β₁ treatment, accumulating in the pulmonary ECM, exacerbating collagen deposition, and promoting fibrosis. MMP3 may serve as a potential therapeutic target for silicosis-induced pulmonary fibrosis.

Objective To explore the effect of mangiferin (MF) on pyroptosis in an amyotrophic lateral sclerosis (ALS) cell model by regulating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway. Methods (1)Mouse NSC-34 cell lines transfected with hSOD1^WT and hSOD1^G93A plasmids were randomly divided into blank group, model group, MF (100 μmol/L) group, MF (200 μmol/L) group. MF was added into the culture plate for 24 hours. Cell viability was assessed using CCK-8 kit. Lactate dehydrogenase (LDH) release was measured using LDH cytotoxicity detection kit. Levels of inflammatory factors interleukin (IL)-1β and IL-18 in cell supernatant were determined by enzyme-linked immunosorbent assay (ELISA). The expression of Nrf2, HO-1, NADPH quinone oxidoreductase-1 (NQO-1), NOD-like receptor protein 3 (NLRP3), gasdermin D (GSDMD)-N and caspase-1 was detected by Western blotting. (2)Mouse hSOD1^G93A NSC-34 cells were randomly divided into model group, MF(200 μmol/L) group, Nrf2-siRNA group and Nrf2-siRNA+MF(200 μmol/L) group. The cells were transiently transfected with Nrf2-siRNA using Lipofectamine^TM 3000. Western blotting was used to detect the protein expression levels of Nrf2, HO-1, NQO-1, NLRP3, caspase-1 and GSDMD-N. Results (1) The results of the CCK-8 assay showed that after the hSOD1^G93A NSC-34 cells were treated with MF at concentrations of 300 μmol/L and below for 24 hours, the changes in cell viability were not significant (P>0.05). Compared with blank group, the release of LDH, the contents of IL-1β and IL-18 in the cell culture supernatant of model group were increased (P<0.001); the protein expression levels of Nrf2, HO-1, and NQO-1 were decreased (P<0.05 or P<0.01); the protein expression levels of NLRP3, caspase-1, and GSDMD-N were increased (P<0.05 or P<0.01 or P<0.001). Compared with model group, the release of LDH, the contents of IL-18 and IL-1β in the culture supernatant in MF(100 μmol/L) and MF(200 μmol/L) groups were decreased (P<0.001); the protein expression levels of NLRP3, caspase-1 and GSDMD-N were decreased (P<0.05 or P<0.001), and the expression levels of Nrf2, HO-1 and NQO-1 were increased (P<0.05 or P<0.01). (2) Compared with model group, the protein expession levels of Nrf2, NO-1 and NQO-1 were increased (P<0.05 or P<0.001) in MF(200 μmol/L) group, while the protein expression levels of NLRP3, caspase-1 and GSDMD-N were decreased (P<0.001); the protein expression levels of Nrf2 and HO-1 were decreased in Nrf2-siRNA group (P<0.01 or P<0.001), while the protein expression levels of NLRP3, caspase-1 and GSDMD-N were increased (P<0.001). Compared with Nrf2-siRNA group, the protein expression levels of Nrf2, HO-1 and NQO-1 in Nrf2-siRNA+MF(200 μmol/L) group were increased (P<0.01 or P<0.001), and the protein expression levels of NLRP3, caspase-1 and GSDMD-N were decreased (P<0.001). Conclusion MF can inhibit pyroptosis in the ALS cell model through Nrf2/HO-1 signaling pathway, playing a protective role.

In recent years, the incidence and mortality of heatstroke have been increasing annually alongside global warming, with a marked rise in cases exhibiting atypical symptoms. To address the increasingly complex challenges in heatstroke prevention and treatment, Heatstroke Prevention and Treatment Research Center of Chinese PLA, Expert Group of Heatstroke Prevention and Treatment of Chinese PLA, and Chinese PLA Professional Committee of Critical Care Medicine have jointly developed this guideline (2025 edition). Utilizing the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, Appraisal of Guidelines for Research and Evaluation (AGREE) criteria, and Reporting Items for Practice Guidelines in Healthcare (RIGHT) standards, and based on the 2015 draft "Expert Consensus on the Standardized Diagnosis and Treatment of Heatstroke" and the 2019 "Chinese Expert Consensus on the Diagnosis and Treatment of Heatstroke", this guideline has been crafted. This guideline provides 25 evidence-based recommendations to guide the prevention, treatment and research of heatstroke, which thoroughly covers 8 critical domains: clinical classification, pathophysiological mechanisms, clinical manifestations, diagnostic criteria, differential diagnosis, treatment protocols, rehabilitation and return to work, and prevention.

Non-steroidal anti-inflammatory drugs (NSAIDs), commonly utilized analgesics, are extensively employed for managing pain associated with musculoskeletal disorders or injuries. Recent clinical studies have demonstrated a heightened risk of bone stress injuries (BSI) in soldiers and athletes, particularly during high-intensity training, due to NSAID usage. Furthermore, the impact of NSAIDs on fracture healing is well-documented; however, the precise mechanism by which their use during training contributes to an increased incidence of stress bone injuries remains unclear. This article aims to summarize potential mechanisms through an extensive review of domestic and international literature in order to standardize the utilization and clinical management of NSAIDs, optimize pain management strategies, and prevent stress bone injuries or fractures in specific populations such as soldiers and elite athletes.

Graves' ophthalmopathy (GO) is a specific autoimmune disease occurring in orbital tissues and is closely related to hyperthyroidism caused by Graves' disease (GD). Its disabling and disfiguring features significantly impact the quality of life of patients. The exact mechanism of GO still remains to be fully elucidated. In recent years, gene sequencing and medical microbiology studies have shown that changes in the gut microbiota may play a role in the development and progression of GO, with gut dysbiosis altering immune system regulatory signals and causing immune damage to organs. Clarifying the correlation between gut microbiota and GO helps to understand the disease's pathogenic mechanism and provides a theoretical basis for the diagnosis and treatment of GO. This review summarizes the impact of gut microbiota dysbiosis in the pathogenesis of GO and promising therapeutic approaches, including research progress in aspects such as gut microbiota experiments, case studies, pathogenesis, and treatment strategies.

Objective To investigate the clinical characteristics and management strategies of spinal infarction (SCI) combined with hypoxic-ischemic encephalopathy (HIE). Methods We report a case of SCI induced by cardiopulmonary arrest in a patient admitted to the General Hospital of Southern Theater Command in June 2021. A review of the relevant literature published in PubMed and CNKI from January 2014 to March 2024, was conducted to summarize the etiology, features, and treatment approaches for SCI. Results The patient presented with clinical features of quadriplegia accompanied by paresthesia, lumbar and cervical pain with paresthesia, dysphagia, dysphonia, and urinary and fecal incontinence. Spinal MRI revealed abnormal signals in the anterior and lateral columns at the C₂-T₁ spinal level, with no enhancement observed in contrast-enhanced scan. The patient was diagnosed as SCI combined with HIE, and was treated with antiplatelet therapy and rehabilitation. Literature review revealed that SCI is a rare central nervous system disease with multiple causes, often related to aortic surgery or pathology, presenting with segmental sensory disturbances among other clinical manifestations. MRI plays a significant role in its diagnosis, and there is currently no specific effective treatment available. Conclusions SCI has a sudden onset and is often insidious, frequently accompanying other diseases, leading to a high risk of misdiagnosis. In this case, SCI was considered to be caused by low blood pressure and vertebral artery tenuity. Clinical manifestations include paraplegia at the lesion level along with back/neck pain or limb paresthesia. Diagnosis primarily relies on MRI imaging while treatment involves secondary stroke prevention measures, rehabilitation training, complication prevention strategies as well as hyperbaric oxygen therapy.

Gastrointestinal stromal tumor (GIST) is the most prevalent mesenchymal tumor of the gastrointestinal tract, with imatinib serving as the first-line drug for metastatic GIST due to its good clinical efficacy. However, the majority of patients exhibit tumor progression within several years of drug therapy, primarily due to the high rate of drug resistance, which significantly impedes drug therapeutic outcome and patient prognosis. Traditional approaches to counteract resistance, including dosage increase and subsequent line therapy yielded suboptimal results. As a research hotspot, intestinal flora has been proven to be closely related to drug resistance of various tumors. In recent years, it has been observed that specific intestinal flora could serve as biomarkers for early GIST patient screening or as potential drug targets, and modulating the intestinal flora through interventions may delay or even reverse the progression of imatinib secondary drug resistance in GIST. This review delineates the drug resistance of GIST, correlations between intestinal flora and drug resistance of tumors, as well as the relationship between intestinal flora and drug resistance of GIST, aiming to provide novel perspectives and methodologies for clinical application.

Spinal cord injury (SCI) is a structural and functional disruption of the spinal cord caused by various factors, leading to neurological dysfunction. As a common central nervous system disorder in clinical practice, SCI poses significant risks to human life and health. Its pathological mechanism is exceedingly complex, involving multiple pathological processes. Given the irreversibility of primary injury, targeting secondary injury has gradually become the main direction for the clinical treatment of SCI in recent years. Recent studies have highlighted the crucial role of blood-spinal cord barrier damage and microvascular dysfunction in the progression of secondary injury following SCI. Therefore, investigating the pathological mechanisms of microcirculation and exploring targeted therapies could provide valuable insights for clinical SCI treatment. This paper aims to provide an objective review of the role of microcirculation in SCI, identify the critical regulators of microvascular function, and summarize strategies for treating SCI by targeting microcirculation. The findings of this study may offer novel references for the clinical management of SCI.

Objective To investigate the improvement effects of homogeneous fecal microbiota transplantation (FMT) on chemotherapy-induced diarrhea (CID) in mice. Methods Fifteen C57BL/6N mice were divided into control group, CID model group and CID+FMT group according to the random number distribution and remainder grouping method, with 5 mice per group. Control group received no intervention, and their feces were used to prepare fecal bacteria suspension. CID model group was injected intraperitoneally with fluorouracil (65 mg/kg) for 5 consecutive days to construct the CID mouse model, followed by gavage with 0.1 ml of saline on alternate days. CID+FMT group was given 0.1 ml fecal bacteria suspension gavage on alternate days for one week, followed by intraperitoneal injection of fluorouracil (65 mg/kg) for 5 consecutive days to construct the CID mouse model, with the experiment ending on the 14th day. During the experiment, the mice's food intake and body weight were recorded. At the end of the experiment, the mice were euthanized with deep carbon dioxide anesthesia, and the mice colonic specimens from cecum to anus were collected for hematoxylin and eosin (HE) staining and histopathological examination. Fecal samples were collected for 16S rRNA gene sequencing. Shannon index, Simpson index and Chao1 algorithm were used to analyze the α-diversity species of the intestinal flora in each group of mice. Similarity analysis (Anosim) was used to perform non-parametric on the inter-group differences of intestinal flora among the mice. Linear discriminate analysis size effect (LEfSe) and nonmetric multidimensional scaling (NMDS) were employed to analyze the intestinal dominant flora and the similarity classification relationships in each group of mice. Results The colonic specimen's length from cecum to anus in CID model group was significantly shorter than that in control group (P<0.05), while there was no significant difference between CID+FMT group and CID model group (P>0.05). The weight of mice in CID model group decreased by 42.04%, while control group mice gained 10.24%, with a significant difference between the two groups (P<0.05). The weight of mice in CID+FMT group decreased by 8.12%, which was significantly improved compared to CID model group (P<0.05). HE staining results revealed the intestinal mucosal structure in CID model group was severely damaged, with atrophy and deformation, accompanied by inflammatory cell infiltration, and the pathological score was higher than that of control group (P<0.05). Compared with CID model group, the intestinal mucosal integrity and crypt cells in the CID+FMT group were improved, with less damage, and the pathological score was lower than that of CID model group, but the difference was not statistically significant (P>0.05). The α-diversity analysis showed that there were significant differences in the Shannon, Simpson and Chao1 indices among the three groups (P<0.05). ANOSIM and NMDS analysis revealed that the intestinal flora in CID+FMT group was closer to the normal intestinal flora compared to CID model group. LEfSe analysis showed that the intestinal flora in CID model group was enriched in famliy_Bacteroidaceae, and the intestinal flora in CID+FMT group was similar to that of control group, with an enrichenment of familiy_Enterobacteriaceae. Conclusion Homogeneous FMT can improve the abundance of intestinal flora in CID mice, making it more similar to normal intestinal flora, thereby protecting intestinal mucosa, reducing damage and alleviating the severity of CID.

Systemic lupus erythematosus (SLE) is a chronic diffuse connective tissue disease characterized by abnormal activation of the immune system, which attacks the body's tissues. It has a complex course and its pathological basis is vasculitis. In recent years, research on the relationship between SLE and the gut microbiota has increased significantly, but how to regulate the gut microbiota for the treatment of SLE remains unclear. Studies have found that the intestinal microbiota of SLE patients differs from that of healthy people in terms of Firmicutes, Bacteroidetes, Actinomycetes, and Proteobacteria, etc., and this has been verified in animal experiments. In this review, the changes of intestinal microbiota in SLE patients and their association with the pathogenesis and progression of the disease are systematically reviewed, aiming to provide new insights into the treatment of SLE.