Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

OBJECTIVES: To investigate the effects of Naoluo Xintong Decoction (NLXTD) on proliferation of rat brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation/reoxygenation (OGD/R) injury and role of the HIF-1α/VEGF pathway in mediating its effect. METHODS: Using a BMEC model of OGD/R, we tested the effects of 10% NLXTD-medicated rat serum, alone or in combination with 2ME2 or 10% NAKL, on cell proliferation, migration, tube-forming ability and permeability using CCK-8 assay, Transwell chamber assay, tube formation assay and permeability assay. Cellular expressions of VEGF and Notch were detected using ELISA and laser confocal immunofluorescence analysis, and the expressions of HIF-1α, VEGFR2, Notch1, ERK and P-ERK1/2 proteins were detected with Western blotting. RESULTS: OGD/R injury significantly decreased viability of BMECs. NLXTD treatment of the cells with OGD/R could significantly promoted cell proliferation, migration and tube formation ability, but these effects were strongly attenuated by application of 2ME2. NLXTD treatment also significantly increased the percentages of VEGF- and Notch-positive cells in the cell models and obviously enhanced the expression levels of HIF-1α, VEGFR2, Notch1 and P-ERK1/2. CONCLUSIONS NLXTD promotes proliferation, migration, and tube formation of rat BMECs after OGD/R injury possibly by activating the HIF-1α/VEGF signaling pathway.
Animals ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Rats ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects* ; Glucose ; Brain/blood supply* ; Cells, Cultured ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor Receptor-2/metabolism* ; Oxygen/metabolism* ; Cell Hypoxia

In the context of continuously deepening medical and health system reforms and comprehensively promoting the "Healthy China" strategy, Henan Provincial People's Hospital has established a regional collaborative and vertically integrated critical care service structure and network. This initiative aims to enhance information empowerment, strengthen regional collaboration, improve the insufficient primary medical services, and ensure timely and effective treatment for critically ill patients. By establishing a comprehensive dispatch service platform for regional collaborative critical care, building a "top-down" remote medical collaboration network, and forming a cross-regional specialty alliance for critical care, the hospital has improved the efficiency of medical services and enhanced regional capabilities for treating critically ill patients. Simultaneously, for critically serious patients and those with complex diseases at primary medical institutions, a one-stop consultation and referral service has been implemented. This service adopts a "three specialists" approach and a multidisciplinary consultation mechanism within the hospital, constructs a multi-dimensional critical care transfer mode integrating air, ground, and the internet, creates a regional collaborative rescue mode, and implements full-cycle treatment for critically serious patients. The comprehensive, flexible, and efficient service pathway for regional collaborative critical care established by this system ensures timely and safe treatment for critically ill patients, promotes the distribution of high-quality medical resources, and effectively addresses issues such as uneven distribution of high-quality medical resources and varying levels of critical care capabilities. It has facilitated the formation of a new tiered diagnosis and treatment order characterized by "first diagnosis at the primary level, two-way referral, separate treatment for acute and chronic diseases, and vertical integration". This approach has enhanced the diagnostic and comprehensive service capabilities of primary medical institutions. Currently, by strengthening information empowerment and sharing, creating a full-process critical care diagnosis and treatment model, providing medical assistance and cultivating primary-level critical care talent, and promoting appropriate technologies, the hospital has gradually overcome challenges such as barriers to information exchange and sharing between hospitals, overloaded critical care teams, high pressure on patient reception and transfer, and limited critical care capabilities at primary medical institutions. This article summarizes the construction and practical application of this regionally coordinated critical care system, aiming to provide a reference for the management of critical care treatment.
Humans ; China ; Critical Care/organization & administration* ; Delivery of Health Care/organization & administration*

BACKGROUND:Pauwels type Ⅲ femoral neck fractures may be subjected to more shear and bending forces,and may be prone to complications such as internal fixation failure,bone nonunion,or femoral head necrosis. There is no consensus on the optimal selection of internal fixation devices.OBJECTIVE:To compare the biomechanical properties of four types of internal fixation methods for Pauwels type Ⅲ femoral neck fracture by finite element analysisMETHODS:Femur CT data of a healthy young volunteer were imported into Mimics software to construct a three-dimensional model of normal femur. Pauwels type Ⅲ femoral neck fracture was simulated based on 70° fracture line. Four types of fracture internal fixation models were optimized and constructed using Geomagic and UG software:conventional inverted triangle hollow screw,femoral neck fixation system,femoral neck fixation system plus anterior or posterior hollow screw treatment. Finally,Ansys software was used to analyze the stress distribution,peak stress,and peak displacement of proximal femur fracture block in four types of different internal fixation models. The displacement distribution and peak displacement of internal fixation device and femoral neckfracture were observed.RESULTS AND CONCLUSION:(1) The peak stress of proximal fracture fragments in the four groups was concentrated near the fracture line. The peak stress in the femoral neck fixation system group was the largest,and that in the conventional inverted triangle hollow screw group was the smallest. (2) The peak displacement of fracture fragments was located at the top of the femoral head. The peak displacement of the conventional inverted triangle hollow screw group was the largest,and that in the femoral neck fixation system+hollow screw (posterior) group was the smallest. (3) The peak displacement of the internal fixation model was located at the top of the model. The peak displacement was maximum in the conventional inverted triangle hollow screw group and minimum in the femoral neck fixation system+hollow screw (posterior) group. (4) The displacement of the fracture surface in the femoral neck fixation system+hollow screw (posterior) group was at the upper part of the fracture end. The peak displacement was the largest in the conventional inverted triangle hollow screw group and the smallest in the femoral neck fixation system+hollow screw (posterior) group. (5) It is indicated that compared with the other three internal fixation methods,femoral neck fixation system+hollow screw (posterior) group showed good biomechanical stability. When Pauwels type Ⅲ femoral neck fracture occurs in a young person,from the point of view of finite element analysis,it may be a more favorable choice to treat the Pauwels type Ⅲ femoral neck fracture.

Objective To evaluate the impact of Jixiong Jiedu decoction on the efficacy of diabetic kidney disease in mice and its influence on intestinal flora and trimethylamine oxide(TMAO)levels.Methods Twelve 7-week-old male db/db mice were randomly assigned to the model group or Jixiong Jiedu decoction group(6 mice per group),while 6 male db/m mice were designated as the control group.Following 8 weeks of continuous gavage,we monitored the body weight and blood glucose levels of the mice at weeks 0,4,and 8.Additionally,we assessed urinary microalbumin,kidney injury molecule-1(KIM-1),creatinine(Scr),and urea nitrogen(BUN)levels in urine.Renal pathology was evaluated using HE and PAS staining.Furthermore,fecal samples underwent 16s RNA sequencing,and the serum TMAO levels were determined.Results Compared with the control group,the blood glucose,body weight,8-hour urinary microalbumin,KIM-1 and Scr in the model group were significantly increased,and the renal pathology showed that glomerular segmental mesangial matrix increased,glomerular volume hypertrophy and renal tubular epithelial cell swelling.The abundance of Lactobacillaceae and Lactobacillus in the model group was significantly increased(P<0.01).The abundance of Lachnospiraceae,Helicobacter and Oscillospira decreased significantly(P<0.01),the abundance of each bacterial group changed,and the serum TMAO content increased significantly.Compared with the model group,the 8h urinary microalbumin,KIM-1(P<0.01)and Scr(P<0.05)in the Jixiong Jiedu decoction group were significantly decreased,and there was no significant difference in BUN(P>0.05),and the renal pathological damage was significantly improved.The abundance of Lactobacillaceae and Lactobacillus in intestinal flora decreased significantly(P<0.01),while the abundance of Lachnospiraceae and Oscillospira increased significantly(P<0.01,P<0.05).The structure of gut microbiota,the abundance of dominant and non-dominant bacteria were positively adjusted,and the serum TMAO content was significantly decreased(P<0.01).Conclusion Jixiong Jiedu decoction effectively ameliorates intestinal flora disorders in db/db mice and regulates serum TMAO levels,thereby exerting a nephroprotective effect.

Objective To investigate the protective effect and mechanism of paeoniflorigenone(PFG),a natural active com-ponent in Xiongshao Capsule,against oxidized low-density lipoprotein(ox-LDL)induced vascular endothelial cell injury.Methods Network pharmacology and molecular docking were employed to identify hub targets and key active components of Xiongshao Capsulefor treating atherosclerosis.Human umbilicalvein endothelial cells(HUVECs)were divided into control,ox-LDL(100 μg/mL),PFG low-dose(20 μmol/L),and PFG high-dose(80 μmol/L)groups.Thecytotoxicity of PFG(10-160 μmol/L)and ox-LDL(5-200 μg/mL)was evaluated using the cell counting kit-8(CCK-8)assay.The effects of PFG(10,20,40,80 μmol/L)on ox-LDL-induced HUVEC viability after 24 hours of intervention were detected.Apoptosis was measured by flow cytome-try.The release of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)were quantified by enzyme-linked immunosorbent assay(ELISA).The mRNA expression levels of hub genes(EGFR,PIK3CA,SRC)were assessed by re-verse transcription quantitative PCR(qRT-PCR).Results Network pharmacology and molecular docking analysis demonstrated that PFG was a key active component of Xiongshao Capsule for treating atherosclerosis,stably binding to hub targets(EGFR,PIK3CA,and SRC)with binding affinities＜-7.0 kcal/mol.In vitro experiments revealed that compared to the control group,PFG-treated HUVECs showed no significant change in viability,while the ox-LDL group exhibited significantly reduced cell vi-ability,increased apoptosis levels,elevated concentrations of pro-inflammatory cytokines(TNF-α,IL-6,IL-1β),and upregulated mRNA expression of hub targets(EGFR,PIK3CA,SRC)(all P＜0.05).Compared to the ox-LDL group,PFG intervention sig-nificantly increased cell viability and decreased apoptosis levels,pro-inflammatory cytokine concentrations,and mRNA expres-sion of hub targets(all P＜0.05)in a dose-dependent manner.Conclusion This study demonstrates that PFG,the pivotal active ingredient of Xiongshao Capsule,may attenuate ox-LDL-induced vascular endothelial cell injury through the EGFR/PIK3CA/SRC regulatory axis.

Emerging evidence suggests that dysbiosis of the gut microbiota is associated with the pathogenesis of Parkinson's disease (PD), a prevalent neurodegenerative disorder. The microbiota-gut-brain axis plays a crucial role in the development and progression of PD, and numerous studies have demonstrated the potential therapeutic benefits of modulations in the intestinal microbiota. This review provides insights into the characterization of the gut microbiota in patients with PD and highlights associations with clinical symptoms and underlying mechanisms. The discussion underscores the increased influence of the gut microbiota in the pathogenesis of PD. While the relationship is not fully elucidated, existing research demonstrates a strong correlation between changes in the composition of gut microbiota and disease development, and further investigation is warranted to explain the specific underlying mechanisms.
Humans ; Parkinson Disease/microbiology* ; Gastrointestinal Microbiome/physiology* ; Dysbiosis/microbiology*

Objective To investigate the effects of Naoluo Xintong Decoction(NLXTD)on proliferation of rat brain microvascular endothelial cells(BMECs)after oxygen-glucose deprivation/reoxygenation(OGD/R)injury and role of the HIF-1α/VEGF pathway in mediating its effect.Methods Using a BMEC model of OGD/R,we tested the effects of 10%NLXTD-medicated rat serum,alone or in combination with 2ME2 or 10%NAKL,on cell proliferation,migration,tube-forming ability and permeability using CCK-8 assay,Transwell chamber assay,tube formation assay and permeability assay.Cellular expressions of VEGF and Notch were detected using ELISA and laser confocal immunofluorescence analysis,and the expressions of HIF-1α,VEGFR2,Notch1,ERK and P-ERK1/2 proteins were detected with Western blotting.Results OGD/R injury significantly decreased viability of BMECs.NLXTD treatment of the cells with OGD/R could significantly promoted cell proliferation,migration and tube formation ability,but these effects were strongly attenuated by application of 2ME2.NLXTD treatment also significantly increased the percentages of VEGF-and Notch-positive cells in the cell models and obviously enhanced the expression levels of HIF-1α,VEGFR2,Notch1 and P-ERK1/2.Conclusion NLXTD promotes proliferation,migration,and tube formation of rat BMECs after OGD/R injury possibly by activating the HIF-1α/VEGF signaling pathway.

The number of patients with reduced blood volume due to haemorrhage, fractures, severe infections, extensive burns and tumours is increasing, and traditional blood products are no longer able to meet the increasing clinical demand. Therefore, plasma substitutes have become particularly important in fluid resuscitation, especially artificial colloidal solutions, which have a sustained volume expansion time and a good volume expansion effect, and can significantly improve the circulatory status of patients. This article aims to review the classification of artificial colloidal plasma substitutes and their research progress in clinical practice, in order provide a more rigorous, professional and standardized reference for medicine.