Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

Objective To analyze the target,signal pathway and potential mechanism of Banxia Baizhu Tianma Decoction in the treatment of epilepsy based on network pharmacology,and to verify it by molecular docking technology and animal experiments.Methods The active ingredients and drug targets of Banxia Baizhu Tianma Decoction were screened by BATMAN and other databases.The targets of epilepsy-related diseases were obtained by GeneCards and other databases,and the intersection targets were taken.Constructing'drug-ingredient-target-disease'network and PPI network to screen the core targets.The core active ingredients were screened according to GO,KEGG functional enrichment analysis and'pathway-target-active ingredient'network.Molecular docking was used to verify the core targets and core active ingredients.In the animal experiment,the rat model of epilepsy was induced by lithium chloride-pilocarpine,and 40 Wistar rats were divided into normal control group,model control group,carbamazepine group and Banxia Baizhu Tianma Decoction group.The seizures were observed by behavior.Nissl staining was used to observe neuronal damage in hippocampus.Immunohistochemistry was used to detect the expression of BAX,BCL-2 and Caspase-3 protein.Results A total of 1072 targets of Banxia Baizhu Tianma Decoction were screened,1046 disease targets of epilepsy were screened,and 220 intersection targets of Banxia Baizhu Tianma Decoction in the treatment of epilepsy were screened.The core targets AKT1,ALB,ACTB,INS and TNF of PPI network were obtained.KEGG pathway mainly involves TNF signaling pathway,IL-17 signaling pathway,cAMP signaling pathway,pathways of neurodegeneration-multiple diseases,serotonergic synapse and Dopaminergic synapse.The core active ingredients with the highest correlation in the'pathway-target-active component'network were Betulin,Ephedrine,Ergotamine and Thymol.Results of molecular docking indicated that the core target had satisfactory affinity with those active ingredients.Animal experiments showed that Banxia Baizhu Tianma Decoction could effectively reduce epileptic seizures in rats,improve hippocampal neuronal damage in rats,significantly reduce the percentage of neuronal apoptosis,significantly down-regulate the expression of pro-apoptotic proteins BAX and Caspase-3,and up-regulate the expression of anti-apoptotic protein BCL-2.Conclusion Banxia Baizhu Tianma Decoction has the characteristics of multi-component,multi-target and multi-pathway in the treatment of epilepsy.Inhibiting neuronal apoptosis and reducing hippocampal neuronal damage may be one of the important mechanisms for its treatment of epilepsy.

This study was aimed at determining the genetic characteristics of Yersinia pestis in Subei County through differ-ential region(DFR),clustered regularly interspaced short palindromic repeats(CRISPR),and variable number tandem repeat(VNTR)analyses,to guide the tracing of plague outbreaks.The DNA of 89 Yersinia pestis strains isolated from various ani-mal in foci of Subei County from 1973 to 2017 was extracted.Primers for genotyping by DFR,CRISPR,and MLVA were used in PCR,and agarose electrophoresis was used to determine whether the amplified products were present.Genotypes were deter-mined through comparison against the DFR database of Yersinia pestis in China.The PCR products were sequenced and com-pared against the online CRISPR database for Yersinia pestis to determine the genotype.The number of VNTR repeats in each strain was calculated through capillary electrophoresis,and the minimum spanning tree was constructed with BioNumerics 7.6 according to the numbers of VNTR repeats from 89 Yersinia pestis strains in Subei County and 11 strains from a Marmota hi-malayana focus in Qinghai Province.The Yersinia pestis strains in Subei County were divided into six main genotypes by DFR:8,7,lb,5,32,and 44.The Yersinia pestis strains were divided into three gene clusters and three genotypes by CRISPR.Ca35'was the main gene cluster in Subei County;the genotype was 26';and the distribution was primarily in Dangchengwan Town,Yuerhong Township,and Shibaocheng Township.Ca7 and CaΔ5'comprised secondary gene clusters,with genotypes 22 and 24,and were distributed in Dangchengwan Town,Yuerhong Township,and Shibaocheng Township.The Yersinia pes-tis strains in Subei County were divided primarily into three clusters:the Dangchengwan Machang cluster,Yuerhong Township cluster and Dangchengwan Town cluster.Therefore,the Yersinia pestis strains in Subei County,divided into major and minor genotypes according to DFR,CRISPR and MLVA,showed different regional distribution characteristics,highly diverse geno-types,and complex population characteristics.These aspects are particularly important in tracing the sources of plague out-breaks.

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

Objective To investigate risk factors for the occurrence of an outbreak of surgical site infection(SSI)in the orthopedic department of a hospital.Methods Patients with SSI in the orthopedic department of a hospital in June-July 2017 were investigated,and the high-risk factors for infection were analyzed through case-control study.Specimens were taken from patients,health care workers(HCWs),environment and surgical devices for microbial detection.The homology between patients'and environmental isolates was analyze by pulsed-field gel electrophore-sis(PFGE).Results Staphylococcus aureus(S.aureus)were isolated from nasal secretion of four HCWs,including one doctor(D1)who was also isolated S.aureus from his forehead and hands.PFGE analysis found that S.aureus isolated from incision secretion of 2 patients were homologous to S.aureus isolated from the nasal cavity,forehead,and hands of doctor D1.Several targeted comprehensive infection control measures were implemented,including suspending sterile manipulation(such as surgery and dressing changes)of doctor D1;decolonization for all HCWs(including doctor D1)who carried S.aureus,requiring doctor D1 regularly trim nasal hair;strengthening the edu-cation and supervision of sterile manipulation and hand hygiene;implementing centralized isolation for SSI patients,et al.After timely implementation of the above comprehensive intervention measures,this SSI outbreak was effec-tively controlled in a short period of time.Conclusion Colonization of S.aureus in surgeons may lead to SSI in pa-tients,regular active screening and decolonization of surgeons involved in specific surgeries can be considered,and if necessary,nasal colonized people with dense nasal hair are required to regularly trim their nasal hair to reduce the occurrence of SSI.

Aim To investigate the effects of rutae-carpine(RUT)on lung inflammation in septic mice and the underlying mechanisms.Methods The sepsis mouse model was generated by intraperitoneal injection of lipopolysaccharide(LPS)at 5 mg·kg-1.The mice were randomly divided into the Control group,Model group,Low-dose,Medium-dose,High-dose RUT(5,10,20 mg·kg-1)treatment group and dexamethasone(DEX,2 mg·kg-1),with 10 mice in each group.The mice were intraperitoneally injected with RUT 30 min before LPS injection.HE staining was used to observe the morphology of lung tissues,and activity of my-eloperoxidase was determined to assess the neutrophil infiltration.Wet/dry weight ratio and Evan's blue ex-travasation of lung tissues were examined to assess lung edema.Survival analysis was performed to determine the in vivo protective effects of RUT.ELISA and quan-titative RT-PCR analysis were employed to determine the contents and gene expression of pro-inflammatory mediators,including tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β),IL-6,and IL-18 in lung tis-sues.Western blot was used to detect the protein levels of p38 MAPK,NF-κB,Caspase-1,NOD-like receptor family pyrin domain containing 3(NLRP3)and IL-18.Results RUT at 10-20 mg·kg-1 could dose-de-pendently inhibit leukocyte infiltration,reduce pro-in-flammatory mediator production,vascular permeability and wet/dry weight ratio in lungs,similar to the effects induced by DEX.The mice treated with RUT exhibited increased survival,down-regulated expressions of p-p38 MAPK,p-NF-κB,Caspase-1,NLRP3,and IL-18 pro-teins in lungs,with decreased IL-18 mRNA level.Conclusions RUT exhibits protective effects on sep-sis-induced lung injury,manifested by reduced inflam-mation and edema,potentially via inhibition of p38 MAPK signaling pathway and inflammasome formation.

Objective To analyze the target,signal pathway and potential mechanism of Banxia Baizhu Tianma Decoction in the treatment of epilepsy based on network pharmacology,and to verify it by molecular docking technology and animal experiments.Methods The active ingredients and drug targets of Banxia Baizhu Tianma Decoction were screened by BATMAN and other databases.The targets of epilepsy-related diseases were obtained by GeneCards and other databases,and the intersection targets were taken.Constructing'drug-ingredient-target-disease'network and PPI network to screen the core targets.The core active ingredients were screened according to GO,KEGG functional enrichment analysis and'pathway-target-active ingredient'network.Molecular docking was used to verify the core targets and core active ingredients.In the animal experiment,the rat model of epilepsy was induced by lithium chloride-pilocarpine,and 40 Wistar rats were divided into normal control group,model control group,carbamazepine group and Banxia Baizhu Tianma Decoction group.The seizures were observed by behavior.Nissl staining was used to observe neuronal damage in hippocampus.Immunohistochemistry was used to detect the expression of BAX,BCL-2 and Caspase-3 protein.Results A total of 1072 targets of Banxia Baizhu Tianma Decoction were screened,1046 disease targets of epilepsy were screened,and 220 intersection targets of Banxia Baizhu Tianma Decoction in the treatment of epilepsy were screened.The core targets AKT1,ALB,ACTB,INS and TNF of PPI network were obtained.KEGG pathway mainly involves TNF signaling pathway,IL-17 signaling pathway,cAMP signaling pathway,pathways of neurodegeneration-multiple diseases,serotonergic synapse and Dopaminergic synapse.The core active ingredients with the highest correlation in the'pathway-target-active component'network were Betulin,Ephedrine,Ergotamine and Thymol.Results of molecular docking indicated that the core target had satisfactory affinity with those active ingredients.Animal experiments showed that Banxia Baizhu Tianma Decoction could effectively reduce epileptic seizures in rats,improve hippocampal neuronal damage in rats,significantly reduce the percentage of neuronal apoptosis,significantly down-regulate the expression of pro-apoptotic proteins BAX and Caspase-3,and up-regulate the expression of anti-apoptotic protein BCL-2.Conclusion Banxia Baizhu Tianma Decoction has the characteristics of multi-component,multi-target and multi-pathway in the treatment of epilepsy.Inhibiting neuronal apoptosis and reducing hippocampal neuronal damage may be one of the important mechanisms for its treatment of epilepsy.

Mastitis is one of the common and prevalent diseases in dairy cows,and the natural prod-uct daidzein is a kind of natural flavonoids with a wide range of pharmacological and anti-inflam-matory effects.However,the effect of daidzein on mastitis in dairy cows has not been reported.Therefore,in this study,we explored the effects of daidzein on LPS-induced inflammatory response and tight junction damage in dairy mammary epithelial cells Firstly,we pretreated the MAC-T cell line using different concentrations of daidzein,and it was clarified that daidzein below 200 μmol/L had no effect on the cell activity.Next,we examined the production of pro-inflammatory mediators in LPS-stimulated MAC-T cell lines using qRT-PCR,and clarified that daidzein could reduce the production of pro-inflammatory mediators in a concentration-dependent manner.Subsequently,af-ter the expression of Occludin,Claudin3 and ZO-1 was detected by immunofluorescence and West-ern Blot,it was clear that daidzein could alleviate MAC-T cell intercellular tight junction injury.Fi-nally,it was demonstrated that daidzein significantly inhibited LPS-induced activation of the NF-κB signaling pathway within MAC-T using network pharmacological analysis and Western Blot.The above results suggest that daidzein can inhibit LPS-induced inflammatory response and tight junc-tion damage in mammary epithelial cells of cows by suppressing the activation of NF-κB signaling pathway.The present study provides a theoretical basis for the alleviation of mastitis by natural products and further expands the pharmacological effects of daidzein.

Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30％and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P＜0.001],the degree of stenosis was significantly reduced[(13.24±6.60)％vs.(65.18±10.59)％,P＜0.001].Procedural success was achieved in 100％of cases,and device success was 98.8％.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P＜0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P＜0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P＜0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P＜0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.