Objective To investigate application value of three-dimensional light sheet microscopy imaging for evaluating intraplaque neovascularization in arterial plaques and the efficacy of intervention, and to assess the effect of melatonin (MLT) on neovascularization by these means. Methods Thirty-six ApoE^-/- model mice were randomly divided into three groups (n=12): vehicle group, MLT group, and MLT+GW9662 intervention group (MLT+GW). The mice were treated with vehicle, MLT alone, or MLT combined with peroxisome proliferator activated receptor‑γ (PPARγ) inhibitor GW9662, respectively. The carotid arteries of the models were three-dimensionally imaged using a light sheet microscopy, and the length, volume and other indicators of neovascularization were quantitatively analyzed using Imaris software. Subsequently, CD31 immunohistochemical staining was performed for verification. Results The light sheet microscopy preliminarily achieved the three-dimensional visualization of intraplaque neovascularization, and its structure was observed to be three-dimensionally reticular and scattered. The results of Imaris quantitative analysis showed that, compared with vehicle group, the total intraplaque neovas cularization length in the MLT group was shortened [(15.79±12.90) mm vs. (33.42±11.16) mm, P<0.05], the total volume was reduced [(1.34±1.47)×10^-3 mm³ vs. (13.44±7.35)×10^-3 mm³, P<0.05], and the volume ratio was decreased (0.44%±0.47% vs. 3.76%±1.74%, P<0.05). The above indicators in MLT+GW group were significantly increased compared with those in MLT group [total length: (35.31±4.69) mm, total volume: (8.87±3.46)×10^-3 mm³, volume ratio: 2.89%±0.38%; P<0.05]. The CD31 immunohistochemical staining also supported the above findings (P<0.05). Conclusions Based on the light sheet microscopy imaging technology, the three-dimensional visualization and quantitative analysis of intraplaque neovascularization were preliminarily realized. It was found that MLT could reduce the overall burden of intraplaque neovascularization, and PPARγ might be involved in its regulatory process.

Objective To investigate the effect of total paeony glycoside (TPG) on airway remodeling in bronchial asthma mice and its underlying mechanisms. Methods Forty-eight BALB/c mice were randomly divided into control group, model group, ovalbumin+budesonide group (OVA+BUD group), and OVA+TPG group, with 12 mice in each group. Except the control group, mice in other groups were sensitized by intraperitoneal injection of 10% OVA aluminum hydroxide suspension, and then stimulated by atomized inhalation of 1% OVA to establish mouse asthma model. One hour before each inhalation of OVA, mice in OVA+BUD group were atomized with 2 ml BUD suspension, and mice in OVA+TPG group were given 5 g/kg TPG by intragastric administration. Lung tissues and bronchoalveolar lavage fluid (BALF) of mice from each group were collected, and the pathological morphology of the lung tissues was detected by hematoxylin-eosin (HE) and periodic acid schiff (PAS) staining. Inflammatory cell counts [white blood cell (WBC), neutrophil (NEU), eosinophils (EOS), and leukomonocyte (LYM)] in BALF were detected by Wright-giemsa staining. The contents of inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 in BALF were determined by ELISA. Airway remodeling proteins [fibronectin, α-smooth muscle actin (α-SMA), collagen Ⅰ] and NOD-like receptor protein 3 (NLRP3) inflammasome-related proteins [NLRP3, cleaved caspase-1, apoptosis-associated speck-like protein (ASC)] levels were detected by Western blotting. Human bronchial smooth muscle cells (HBSMCs) were divided into control group (normal culture), transforming growth factor (TGF)-β₁ group (culture medium containing 10 ng/ml TGF-β₁), and TGF-β₁+TPG group (culture medium containing 10 ng/ml TGF-β₁ and 50 µg/ml TPG). Cell proliferation was detected by CCK-8 method, and Western blotting was used to detect the expression of airway remodeling proteins and NLRP3 inflammasome-related proteins. Results Compared with control group, model group exhibited increased infiltration of inflammatory cell in lung tissues, mucosal epithelium hyperplasia, narrowed bronchial lumen narrowed, tube wall thickened, increased cup cells and mucus secretion, and an elevated pathological score of lung injury (P<0.05); the number of inflammatory cells (WBC, NEU, EOS, and LYM) and the levels of inflammatory factors (TNF-α, IL-1β, and IL-6) in BALF were increased (P<0.05), and the expressions of fibronectin, α-SMA, collagen Ⅰ, NLRP3, cleaved caspase-1 and ASC were elevated (P<0.05). Compared with model group, BUD or TPG treatment effectively reduced asthma symptoms, improved lung histopathology injury, inhibited bronchial wall thickening, significantly reduced the number of inflammatory cells (WBC, NEU, EOS, and LYM) and the content of inflammatory factors (TNF-α, IL-1β, and IL-6) in BALF, and inhibited expression of fibronectin, α-SMA, collagen Ⅰ, NLRP3, cleaved caspase-1 and ASC (P<0.05). Compared with control group, the proliferation rate of HBSMCs was increased, and the protein expression levels of fibronectin, α-SMA, collagen Ⅰ, NLRP3, cleaved caspase-1 and ASC were increased in TGF-β₁ group (P<0.05). Compared with TGF-β₁ group, TPG treatment decreased cell proliferation and inhibited the protein expression of fibronectin, α-SMA, collagen Ⅰ, NLRP3, cleaved caspase-1 and ASC (P<0.05). Conclusion TPG may alleviate airway remodeling and asthma symptoms by decreasing the expression of airway remodeling-related proteins, inhibiting NLRP3 inflammasome activation, and reducing the inflammatory response.

The neurovascular unit (NVU) is the smallest structural unit that maintains the integrity of the blood-brain barrier (BBB), regulates cerebral physiological activities, and maintains the homeostasis of the brain's internal environment. It has become a hot topic in the study of brain physiology and pathological changes. NVU plays a crucial role in age-dependent central nervous system diseases such as cerebral white matter lesions, cognitive impairment, and cerebrovascular disease. Its dysfunction can lead to destruction of BBB integrity, with subsequent protein leakage, immune-inflammatory responses, and alterations in cerebral hemodynamics, all of which can trigger seizures or progression of neurodegenerative disorders. Conversely, seizures can also accelerate NVU dysfunction and promote brain aging. The review summarizes the role of dysfunctional constituent cells of the NVU in the pathogenesis of age-dependent epilepsy and the research progress in related molecular pathways, aiming to provide new perspectives for epilepsy treatment research.

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 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.

Objective To analyze the epidemiological distribution, microbiological characteristics, drug-resistance status, and risk factors for mortality in adult intensive care unit (ICU) patients with Klebsiella pneumoniae infection. Methods This multi-center prospective cohort study included ICU patients with suspected infection from 67 hospitals across 16 Chinese provinces/municipalities between July 1, 2021 and December 31, 2022. Clinical data and microbiological results were collected, and patients were divided into survival and non-survival groups according to their survival status and drug-resistance situation. Risk factors for mortality and drug resistance in ICU patients with Klebsiella pneumonia infection were determined through univariate and multivariate logistic regression analyses. Results A total of 2964 ICU-infected patients were enrolled, with 12 175 microbial specimens submitted for testing. Among these, 487 specimens tested positive for Klebsiella pneumoniae. Ultimately, 314 patients with Klebsiella pneumoniae infection were identified, primarily from lung infections, with a drug-resistance rate of 78.3%. The in-hospital mortality rate of ICU patients infected with Klebsiella pneumoniae was 19.8%. Univariate and multivariate logistic regression analyses revealed that older age (P=0.027), high drug-resistance rate (P=0.028), and low clinical-effectiveness rate (P<0.001) were independent risk factors for mortality in ICU patients infected with Klebsiella pneumoniae. Drug-resistance analysis showed that, compared with non-resistant cases, ICU patients with drug-resistant Klebsiella pneumoniae infection had lower pathogen-clearance rates (P=0.003), clinical-effectiveness rates (P=0.004), and antibiotic-effectiveness rates (P<0.010), and higher mortality rates (P=0.006). Patients with Klebsiella pneumoniae abdominal infection (P=0.003) and urinary tract infection (P=0.007) had higher drug-resistance incidences. There were no statistically significant differences in clinical-effectiveness rate, Klebsiella pneumoniae clearance, drug-resistance incidence, mortality rate, or hospital-stay length between patients with lung infection and those with non-lung infection of Klebsiella pneumoniae (P>0.05). Compared with patients with non-bloodstream infection, patients with bloodstream infection of Klebsiella pneumoniae had lower clinical-effectiveness rates (P=0.027) and higher mortality rates (P=0.021). Conclusions Older age, high drug-resistance rate, and low clinical-effectiveness rate are independent risk factors for mortality in ICU patients infected with Klebsiella pneumoniae. ICU patients with bloodstream infection of Klebsiella pneumoniae may have lower clinical-effectiveness rates and higher mortality rates. ICU patients with abdominal and urinary tract infections caused by Klebsiella pneumoniae are more likely to develop drug resistance.

Heatstroke, especially in high-temperature and high-humidity environments, is a life-threatening acute heat-injury disease that seriously endangers human health. Timely and effective on-site treatment is crucial for patients' survival and prognosis. Early recognition, rapid assessment, and on-site cooling are the core of pre-hospital treatment of heatstroke. Currently, there is a lack of standardized application procedures for pre-hospital emergency care of heatstroke. Therefore, the "Expert Consensus on Pre-hospital Emergency Management of Heatstroke (2024 edition)" was initiated by the Expert Group on Heatstroke Prevention of the People's Liberation Army and developed in collaboration with experts from local pre-hospital emergency care, emergency departments, and intensive care units. This consensus focuses on heatstroke prevention, on-site and ambulance-based treatment, and early emergency room interventions, and puts forward 10 evidence-based recommendations, aiming to provide a reference for scientific and standardized pre-hospital emergency care of heatstroke.

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.

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 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.