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.

ObjectiveTo investigate the therapeutic mechanism of Danhe granules in treating mixed hyperlipidemia based on network pharmacology， as well as animal and cell experiments. MethodsThe active compounds and targets of Danhe granules were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）. Related targets for mixed hyperlipidemia were obtained from the GeneCards database. The intersecting targets were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. A high-fat model was established in human hepatocellular carcinoma cells （HepG2） induced by palmitic acid （PA）， followed by intervention with Danhe granules to assess intracellular lipid accumulation and oxidative stress levels. A mixed hyperlipidemia rat model was also established and divided into low-， medium-， and high-dose Danhe granules groups （1.134， 2.268， and 4.536 g·kg^-1， respectively）， as well as a positive control group treated with pravastatin sodium （4.020 mg·kg^-1）. After eight weeks of intervention， serum lipid levels， inflammatory factors， oxidative stress indices， and the expression of key hepatic lipid metabolism-related proteins were determined. ResultsNetwork pharmacology identified 93 intersecting targets between Danhe granules and mixed hyperlipidemia， with peroxisome proliferator-activated receptor gamma （PPARG）， peroxisome proliferator-activated receptor alpha （PPARA）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， and IL-1B among the key nodes. The PPAR signaling pathway， AGE/RAGE signaling pathway， lipid metabolism， atherosclerosis and non-alcoholic fatty liver disease （NAFLD） were among the most significantly enriched pathways. Cellular experiments demonstrated that Danhe granules significantly reduced reactive oxygen species （ROS） and malondialdehyde （MDA） levels while increasing catalase （CAT） activity （P<0.05）， thereby alleviating intracellular lipid accumulation and triglyceride （TG） content in HepG2. In animal experiments， Danhe granules markedly decreased serum total cholesterol （TC）， TG， and low-density lipoprotein cholesterol （LDL-C） levels （P<0.05）， reduced hepatic MDA levels， and elevated superoxide dismutase （SOD） and CAT levels. Histological analysis showed alleviation of hepatic steatosis， upregulation of hepatic PPARA and lipoprotein lipase （LPL） expressions， and downregulation of sterol regulatory element-binding protein 1 （SREBP1） expression （P<0.05， P<0.01）. ConclusionDanhe granules improve lipid metabolism disorders in mixed hyperlipidemia by reducing MDA levels， enhancing SOD and CAT activities， scavenging excessive ROS， inhibiting oxidative stress， and mitigating liver injury. The underlying mechanism may involve the upregulation of PPARA and LPL and the suppression of SREBP1 expression.

ObjectiveTo investigate the therapeutic mechanism of Danhe granules in treating mixed hyperlipidemia based on network pharmacology， as well as animal and cell experiments. MethodsThe active compounds and targets of Danhe granules were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）. Related targets for mixed hyperlipidemia were obtained from the GeneCards database. The intersecting targets were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. A high-fat model was established in human hepatocellular carcinoma cells （HepG2） induced by palmitic acid （PA）， followed by intervention with Danhe granules to assess intracellular lipid accumulation and oxidative stress levels. A mixed hyperlipidemia rat model was also established and divided into low-， medium-， and high-dose Danhe granules groups （1.134， 2.268， and 4.536 g·kg^-1， respectively）， as well as a positive control group treated with pravastatin sodium （4.020 mg·kg^-1）. After eight weeks of intervention， serum lipid levels， inflammatory factors， oxidative stress indices， and the expression of key hepatic lipid metabolism-related proteins were determined. ResultsNetwork pharmacology identified 93 intersecting targets between Danhe granules and mixed hyperlipidemia， with peroxisome proliferator-activated receptor gamma （PPARG）， peroxisome proliferator-activated receptor alpha （PPARA）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， and IL-1B among the key nodes. The PPAR signaling pathway， AGE/RAGE signaling pathway， lipid metabolism， atherosclerosis and non-alcoholic fatty liver disease （NAFLD） were among the most significantly enriched pathways. Cellular experiments demonstrated that Danhe granules significantly reduced reactive oxygen species （ROS） and malondialdehyde （MDA） levels while increasing catalase （CAT） activity （P<0.05）， thereby alleviating intracellular lipid accumulation and triglyceride （TG） content in HepG2. In animal experiments， Danhe granules markedly decreased serum total cholesterol （TC）， TG， and low-density lipoprotein cholesterol （LDL-C） levels （P<0.05）， reduced hepatic MDA levels， and elevated superoxide dismutase （SOD） and CAT levels. Histological analysis showed alleviation of hepatic steatosis， upregulation of hepatic PPARA and lipoprotein lipase （LPL） expressions， and downregulation of sterol regulatory element-binding protein 1 （SREBP1） expression （P<0.05， P<0.01）. ConclusionDanhe granules improve lipid metabolism disorders in mixed hyperlipidemia by reducing MDA levels， enhancing SOD and CAT activities， scavenging excessive ROS， inhibiting oxidative stress， and mitigating liver injury. The underlying mechanism may involve the upregulation of PPARA and LPL and the suppression of SREBP1 expression.

The endoplasmic reticulum is an important organelle responsible for the synthesis,folding and processing of proteins.When the endoplasmic reticulum protein folding ability is affect-ed,internal unfolded proteins or misfolded proteins accumulate in the endoplasmic reticulum accumulation,leading to endoplasmic reticulum structural dysfunction resulting in endoplasmic reticu-lum stress.Autophagy is the process by which cells selectively remove stress endoplasmic reticulum and error proteins.Under stress,the endoplasmic reticulum can maintain normal physiolog-ical functions through unfolded protein responses and autophagy.Postmenopausal osteoporosis is mainly due to an imbalance be-tween bone resorption by osteoclasts and bone formation by oste-oblasts.Endoplasmic reticulum stress and autophagy both modu-late bone cells status with consequences for bone homeostasis.This article provides a review of the progress of research on en-doplasmic reticulum stress and autophagy interaction in the path-ogenesis of postmenopausal osteoporosis.

Objective To explore the long-term efficacy of percutaneous pulmonary valve implantation(PPVI)and the durability of the domestic self-expanding Venus P valve.Methods A total of 8 patients with post-surgical right ventricular outflow tract(RVOT)dysfunction,who were admitted to hospital from October 2014 to July 2016 and deemed anatomically suitable for PPVI with self-expanding valve,were included prospectively.Clinical,imaging,procedural and follow-up data were analyzed.The survival rates,perioperative and long-term complication rates,long-term efficacy of PPVI,and long-term function of Venus P in 8 patients were evaluated.The immediate procedural results were evaluated by clinical implant success rate,which is defined as successful valve implantation with echocardiography-assessed pulmonary regurgitation＜moderate and peak trans-pulmonary pressure gradient＜40 mmHg.Results A total of 8 patients were included,with 7 females,aged 14 to 36 years.The initial diagnosis included post-surgical Tetralogy of Fallot(5 cases),post-surgical Trilogy of Fallot(1 case),post-surgical Quadricuspid pulmonary valve stenosis(1 case)and post-surgical Double-Outlet Right Ventricle(1 case).The indications of PPVI included RVOT-pulmonary obstruction and regurgitation(1 case)and isolated regurgitation(7 cases).Clinical implant success was achieved in all of the 8 patients with firmly fixed valve,and there were no such complications as valve detachment,displacement or stent fracture.All patients experienced significant symptom relief after the procedure.The right ventricular end-diastolic volume index(RVEDVi)measured by CMR 6 months after PPVI showed a significant decrease compared to preprocedural values[(89.99±13.85)ml/m2 vs.(144.93±11.28)ml/m2,P=0.001].Postoperative pulmonary regurgitation were significantly improved or disappeared in all patients,and there was no statistically significant difference in the average peak pressure gradient measured by echocardiogram between preoperative and the latest follow-up[(23.25±8.39)mmHg vs.(18.75±6.28)mmHg,P=0.210].Over an average follow-up period of(9.25±0.71)years,1 case of infective endocarditis occurred 5 years after PPVI.During the follow-up,no death,deterioration of heart failure,malignant arrhythmia or other serious complications were observed.All patients completed 8-year follow-up,and 3 completed 10-year follow-up.All patients were graded as NYHA functional class one at the latest follow-up.Conclusions PPVI using the domestically produced self-expanding Venus P is safe and feasible for the treatment of patients with post-surgical RVOT dysfunction and suitable anatomy.Our study confirms the long-term efficacy and durability of Venus P from multiple perspectives,and no severe stent fracture occurred without pre-stent implantation in the native RVOT.

Circular RNA(circRNA),as a kind of non-coding RNA,regulates a variety of biological functions.To explore the effect of circRNA on PEDV replication in the host porcine intestinal epi-thelial cells,this study screened and analyzed the differentially expressed circRNAs by bioinforma-tic software in African Green Monkey renal cells(Vero-E6 cells)infected by porcine epidemic di-arrhea virus(PEDV),the differentially expressed circRNA ssc_circ_PIK3C2A was identified and the secondary structure was analyzed.PCR was used to identify the ssc_circ_PIK3C2A circRNA structure,the model of PEDV-infected IPEC-J2 cells was constructed,the TCID50 test was used to validate the viral titer of PEDV.The expression of circ_PIK3C2A was detected by qRT-PCR in IPEC-J2 infected by PEDV.circ_PIK3C2A qRT-PCR was performed to detect the expression of N gene of PEDV when ssc_circ_PIK3C2A was over-expressed in IPEC-J2 cells.The results showed that ssc_circ_PIK3C2 A is a porcine circular RNA with a typical circular structure,the virus titer of PEDV reached 10-6/mL after PEDV infected IPEC-J2 cells for 48 h,the expression of circ_PIK3C2A increased extremely(P＜0.01)at 6 h after PEDV-infection,with the extension of infec-tion time,its expression gradually decreased,and the expression was the lowest at 24 h,but there was no time-dependent trend.The expression of PEDV N gene decreased significantly when ssc_circ_PIK3C2A was over-expressed in IPEC-J2 cells.In conclusion,when PEDV infects IPEC-J2 cells,the expression of porcine circ_PIK3C2A decreases,and replication of PEDV increases signifi-cantly in IPEC-J2 cells.our result provides a basis for further study of the mechanism of circular RNA on PEDV replication and its physiological activities in host cells in the future.

Objective To conduct preoperative simulations of three different osteotomy line design schemes under centric occlusion based on two distinct material assignment methods,evaluate biomechanical properties of the models,and explore which osteotomy line design schemes are more suitable for different types of mandibles.Methods Three types of mandibles were selected,and CT images were obtained for three-dimensional(3D)reconstruction.Material assignment was completed using the cortical/cancellous bone assignment method and the gray value assignment method.Osteotomy was simulated according to the three osteotomy line design schemes,followed by finite element analysis.Results In all simulation results of the mandibles,the maximum stress was 81.10 MPa,the maximum strain was 0.035 52,and the maximum displacement was 432.4 μm.The stress distributions obtained by the cortical/cancellous bone assignment method showed a larger stress distribution range than that that by the gray value assignment methods,but the maximum stress,strain,and displacement were generally lower.For the outflare type and common type mandibles,Scheme 1 showed lower maximum stress,strain,and displacement under both material assignment methods,but no clearly suitable scheme was found for the retracted type.Conclusions The outflare type and common type mandibles are more suitable for adopting the osteotomy line design scheme of Scheme 1.For the retracted type,other mandibular angle osteotomy plastic surgery methods may be considered to ensure better biomechanical characteristics.Whether choosing the osteotomy line design scheme or the modeling material assignment method,it is necessary to make the final decision based on the specific analysis objective and resource conditions.

Objective:This study aimed to investigate the role of bone morphogenetic protein 2 (BMP2)/Smad8 signaling pathway in T-2 toxin-induced apoptosis of rat articular chondrocytes.Methods:Primary chondrocytes from SD rats were cultured in vitro and exposed to varying concentrations of T-2 toxin (0.00, 0.32, 1.60, 8.00 ng/ml). The changes in chondrocytes survival rate were determined by CCK8, and the apoptosis changes of chondrocytes were determined by TUNEL assay kit. Using a group design, chondrocytes were cultured in complete culture media and culture media containing T-2 toxin (1.60 ng/ml), BMP2 cytokine (500 ng/ml), or T-2 toxin (1.60 ng/ml) + BMP2 cytokine (500 ng/ml), referred to as the control group, T-2 toxin group, BMP2 group, and T-2 toxin + BMP2 group, respectively. The survival rate and apoptosis changes of chondrocytes in each group were determined. The expression levels of Caspase-3, BMP2, BMP receptor Ⅱ (BMP-R Ⅱ), and Smad1/4/5/8 were determined by quantitative real-time PCR. Results:Compared with the 0.00 ng/ml of T-2 toxin group [(100.00 ± 0.00)%, (4.33 ± 0.32)%], the chondrocyte survival rates [(85.77 ± 2.96)%, (72.79 ± 2.31)%, (48.87 ± 1.83)%] of the 0.32, 1.60, and 8.00 ng/ml of T-2 toxin groups were significantly lower ( P < 0.05), and the apoptosis rates [(5.43 ± 0.32)%, (6.17 ± 0.15)%, (5.07 ± 0.13)%] were significantly higher ( P < 0.05). Compared with the control group, the T-2 toxin group had a lower survival rate and a higher apoptosis rate of chondrocytes ( P < 0.05). Compared with the T-2 toxin group, the T-2 toxin + BMP2 group had a higher survival rate and lower apoptosis rate of chondrocytes ( P < 0.05). Compared with the control group, the T-2 toxin group showed higher expression level of Caspase-3 mRNA in chondrocytes, while the expression levels of BMP2, BMP-R Ⅱ, and Smad1/4/8 mRNA were lower ( P < 0.05). Compared with the T-2 toxin group, the expression level of Caspase-3 mRNA was lower in the T-2 toxin + BMP2 group, while the expression levels of BMP2 and Smad8 mRNA were higher ( P < 0.05). Conclusion:BMP2 may partially block the apoptosis of chondrocytes caused by T-2 toxin by regulating the BMP2/Smad8 signaling pathway.

This paper summarizes the academic thought and clinical experience of Professor Gu Ning in diagnosing and treating hy-peruricemia(HUA)based on the Waterway Theory.He proposes that the waterway is a pathway regulated by the Sanjiao and multiple organs,responsible for body fluid metabolism,and that turbid fluids produced after metabolism must be excreted through this pathway.Based on the Water Theory,Professor Gu Ning proposes that the pathogenesis of HUA involves dysfunction of the organs and impaired waterway due to external exposure to the six exogenous pathogens or internal injuries from the seven emotions.The key patho-logical mechanism lies in the accumulation of dampness-turbidity,which subsequently gives rise to various syndrome patterns.Profes-sor Gu Ning developed a therapeutic strategy of eliminating dampness and reducing turbidity for HUA based on the Waterway Theory.By combining and modifying two classical prescriptions,Simiao San and Wuling San,he formulated the Huashi Jiangzhuo For-mula,offering a novel diagnostic and therapeutic approach as well as a theoretical foundation for the treatment of HUA.

Influenza is a major public health problem worldwide,resulting in millions of hospitalizations each year.In addi-tion to vaccination and antiviral drugs against influenza,monoclonal antibody therapy is a promising treatment method because of its cross-reactivity and targeting.Widely reactive monoclonal antibodies can bind and neutralize multiple subtypes of influenza A virus,and also show good protective effect on infected mice,showing high potential in the prevention and treatment of influenza.In this review,we briefly review the recent research progress of broad-spectrum monoclonal antibodies targeting HA and NA,two important surface glycoproteins of influenza A virus.