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 study the effect of metformin sensitizing pancreatic cancer cells with radiotherapy, with a focus on elucidating the underlying mechanisms of radiotherapy resistance. In particular, the role of the PERK/P-eIF2/ATF4 signaling pathway in mediating these effects was preliminarily explored. Methods : Pancreatic cancer cell lines(PANC-1 and PANC-2) were categorized into control, radiotherapy, and drug treatment groups. Following the respective treatments, cell proliferation inhibition was assessed using the CCK-8 assay, colony formation assays, and cell death staining. Senescence was quantified by β-galactosidase(SA-β-Gal) staining. The expression of cell cycle regulators(P21, P16, γ-H2AX), apoptosis markers(Bax, Bcl-2, Cleaved caspase-3), and pathway-related proteins(PERK, P-eIF2, ATF4) was evaluated by Western blot and immunofluorescence. To further investigate the role of the PERK/P-eIF2/ATF4 axis in metformin-mediated modulation of pancreatic cancer cell senescence and radiosensitization, selective inhibitors(GSK2606414) and agonists(MK-28) of PERK were employed. Results : Radiotherapy markedly upregulated senescence-associated markers(P21, P16, γ-H2AX, and β-galactosidase activity) in pancreatic cancer cells. Senescent cells exhibited enhanced proliferative activity and increased tumor volume both in vitro and in vivo. Metformin mitigated radiotherapy-induced senescence by reducing the expression of senescence markers and significantly suppressing the clonogenic and proliferative capacity of treated cells. Mechanistically, radiotherapy activated the PERK signaling pathway, leading to increased expression of PERK, P-eIF2, and ATF4, thereby driving cellular senescence. Pharmacological inhibition of PERK reduced β-galactosidase activity, while PERK activation further promoted the expression of senescence-associated proteins—an effect that was reversed by metformin. Conclusion Metformin inhibits the activation of the PERK/P-eIF2/ATF4 signaling pathway in pancreatic cancer cells following radiotherapy, thereby delaying cellular senescence and reducing the associated radiotherapy resistance of senescent cells. This modulation contributes to the sensitization of pancreatic cancer cells to radiotherapy.

Objective:To explore the effects of diversified teaching combined with the affective-cognitive theory in neurology clerkship instruction.Methods:We enrolled 406 medical students on clerkship at the affiliated hospitals of Sun Yat-sen University from November 2023 to April 2024. They were randomly assigned by cluster to either observation group ( n=164) or control group ( n=242). The observation group received a diversified teaching model that selected context-appropriate teaching methods based on clinical scenarios, while using the affective-cognitive theory to optimize instructional pathways. The control group received traditional teaching. The effectiveness of teaching was evaluated through an objective structured clinical examination (OSCE; maximum score, 10 points) and a questionnaire survey. SPSS 22.0 was used to perform Mann-Whitney U test, chi-square test, and multiple linear regression analysis. NVivo 12.0 was employed to process open-ended questions. Results:In the OSCE, the observation group had a significantly higher mean score than the control group [9 (8, 10) points vs. 8 (7, 9) points, Z=-6.10, P<0.001]. The distribution difference across different score ranges between the two groups was also statistically significant ( Z=-5.94, P<0.001). Stratified analyses by sex and neurological theory test score demonstrated significantly higher mean scores in the observation group than in the control group ( P<0.001). The multiple linear regression analysis indicated an independent positive correlation between the novel teaching model and OSCE score ( P<0.001). The results of the questionnaires revealed that in the observation group, 98.57% reported that they were satisfied with the teaching model, and 90.72% reported that they accomplished the core teaching objectives; core competencies including knowledge and skills, communication and collaboration, and professionalism were improved; additionally, the participants of the observational group highly endorsed the practical content, the logical structure and richness of instruction, and the active classroom learning environment. Conclusions:The diversified teaching model integrated with the affective-cognitive theory significantly improves proficiency in core clinical skills across different groups of neurology clerks.

Objective:To explore the effects of diversified teaching combined with the affective-cognitive theory in neurology clerkship instruction.Methods:We enrolled 406 medical students on clerkship at the affiliated hospitals of Sun Yat-sen University from November 2023 to April 2024. They were randomly assigned by cluster to either observation group ( n=164) or control group ( n=242). The observation group received a diversified teaching model that selected context-appropriate teaching methods based on clinical scenarios, while using the affective-cognitive theory to optimize instructional pathways. The control group received traditional teaching. The effectiveness of teaching was evaluated through an objective structured clinical examination (OSCE; maximum score, 10 points) and a questionnaire survey. SPSS 22.0 was used to perform Mann-Whitney U test, chi-square test, and multiple linear regression analysis. NVivo 12.0 was employed to process open-ended questions. Results:In the OSCE, the observation group had a significantly higher mean score than the control group [9 (8, 10) points vs. 8 (7, 9) points, Z=-6.10, P<0.001]. The distribution difference across different score ranges between the two groups was also statistically significant ( Z=-5.94, P<0.001). Stratified analyses by sex and neurological theory test score demonstrated significantly higher mean scores in the observation group than in the control group ( P<0.001). The multiple linear regression analysis indicated an independent positive correlation between the novel teaching model and OSCE score ( P<0.001). The results of the questionnaires revealed that in the observation group, 98.57% reported that they were satisfied with the teaching model, and 90.72% reported that they accomplished the core teaching objectives; core competencies including knowledge and skills, communication and collaboration, and professionalism were improved; additionally, the participants of the observational group highly endorsed the practical content, the logical structure and richness of instruction, and the active classroom learning environment. Conclusions:The diversified teaching model integrated with the affective-cognitive theory significantly improves proficiency in core clinical skills across different groups of neurology clerks.

BACKGROUND:Kidney deficiency is the main pathogenesis of osteoporosis.To study the relationship between the two major syndrome types of kidney deficiency,Kidney-Yang deficiency and Kidney-Yin deficiency,is beneficial for the development of clinical diagnosis and treatments based on the combination of disease and syndrome. OBJECTIVE:To evaluate the biomechanical differences of the rat femurs with Kidney-Yang deficiency and Kidney-Yin deficiency caused by Yougui pills,and to demonstrate the scientific efficacy of medication based on the combination of disease and syndrome in osteoporosis from a biomechanical perspective. METHODS:The bilateral ovaries of 60 female Sprague-Dawley rats were surgically removed to establish an ovariectomized osteoporosis model.At 10 weeks after modeling,all the rats were randomly divided into a Kidney-Yang deficiency group(n=30)and a Kidney-Yin deficiency group(n=30).Rats with Kidney-Yang deficiency were given gluteal intramuscular injection of hydrocortisone,while rats with Kidney-Yin deficiency were orally administered with thyroid tablet suspension,once a day,for 14 consecutive days.After successful modeling,20 rats in each group were given a suspension of Yougui pills by gavage once a day for 12 consecutive weeks and the remaining 10 rats were used as the control group without intervention.After gavage,the microstructural parameters of the bone were measured using Micro-CT scanning.Three-point bending,finite element simulation,femoral head compression,and surface indentation distribution experiments of the femurs were performed on a mechanical testing machine. RESULTS AND CONCLUSION:Micro-CT revealed that the femoral bone density,bone volume fraction,bone surface density,trabecular number,and trabecular separation were improved in the Kidney-Yin deficiency+Yougui pills group compared with the Kidney-Yin deficiency group(P＜0.05);the femoral bone volume fraction,bone surface density,trabecular number,and trabecular thickness were improved in the Kidney-Yang deficiency+Yougui pills group compared with the Kidney-Yang deficiency group(P＜0.05).The three-point bending experiment showed that the femur elastic modulus,maximum bending strength and bending fracture strength were decreased(P＜0.05)and toughness was increased(P＜0.05)in the Kidney-Yang deficiency+Yougui pills group compared with the Kidney-Yang deficiency group.Finite element simulation showed that Yougui pills could significantly improve the bending resistance of the femurs in the Kidney-Yang deficiency group,but had no significant effect on the Kidney-Yin deficiency group.The femoral head compression experiments showed that Yougui pills could enhance the ability of the femoral head to resist deformation in the Kidney-Yang deficiency group,but there was no significant difference in the effect of Yougui pills on the surface properties of the femoral head in the Kidney-Yin deficiency group and the Kidney-Yang deficiency group.To conclude,Yougui pills can significantly enhance the biomechanical properties of the osteoporotic bones with Kidney-Yang deficiency,but have no significant effect on the osteoporotic bone with Kidney-Yin deficiency.

To report a case of nonbullous neutrophilic lupus erythematosus. A 57-year-old male patient presented with recurrent erythematous pruritic papules and plaques on the trunk and extremities for over 10 years. Skin examination revealed scattered urticaria-like papules and plaques on the trunk and limbs, with thin scales on the edge of some lesions. Laboratory tests showed positive antinuclear antibodies at a titer of 1∶320 (granular type), anti-Sj?gren syndrome A (SSA) antibodies (++), anti-SSB antibodies (+++), anti-Ro-52 antibodies (+++), and anti-neutrophil cytoplasmic antibodies at a level of 369.09 RU/ml (reference range: 0 - 20 RU/ml). Histopathological analysis of the skin lesions on the back revealed epidermal hyperkeratosis in a basket-like shape, liquefaction degeneration of basal cells, infiltration of numerous neutrophils in the superficial dermis with karyorrhexis, perivascular infiltration of lymphocytes in the superficial and middle dermis, and extensive extracellular mucin deposition throughout the dermis. Finally, the patient was diagnosed with nonbullous neutrophilic lupus erythematosus.

OBJECTIVE: To explore the mechanism underlying the inhibitory effect of quercetin against testicular oxidative damage induced by a mixture of 3 commonly used phthalates (MPEs) in rats. METHODS: Forty male Sprague-Dawley rats were randomly divided into control group, MPEs exposure group, and MPEs with low-, median- and high-dose quercetin treatment groups. For MPEs exposure, the rats were subjected to intragastric administration of MPEs at the daily dose of 900 mg/kg for 30 consecutive days; Quercetin treatments were administered in the same manner at the daily dose of 10, 30, and 90 mg/kg. After the treatments, serum levels of testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), and testicular malondialdeyhde (MDA), catalase (CAT) and superoxide dismutase (SOD) were detected, and testicular pathologies of the rats were observed with HE staining. The expressions of nuclear factor-E2-related factor 2 (Nrf2), Kelch-like ECH2 associated protein 1 (Keap1) and heme oxygenase 1 (HO-1) in the testis were detected using immunofluorescence assay and Western blotting. RESULTS: Compared with the control group, the rats with MPEs exposure showed significant reductions of the anogenital distance, weight of the testis and epididymis, and the coefficients of the testis and epididymis with lowered serum testosterone, LH and FSH levels (P < 0.05). Testicular histological examination revealed atrophy of the seminiferous tubules, spermatogenic arrest, and hyperplasia of the Leydig cells in MPEs-exposed rats. MPEs exposure also caused significant increments of testicular Nrf2, MDA, SOD, CAT and HO-1 expressions and lowered testicular Keap1 expression (P < 0.05). Treatment with quercetin at the median and high doses significantly ameliorated the pathological changes induced by MPEs exposure (P < 0.05). CONCLUSION Quercetin treatment inhibits MPEs-induced oxidative testicular damage in rats possibly by direct scavenging of free radicals to lower testicular oxidative stress and restore the regulation of the Nrf2 signaling pathway.
Rats ; Male ; Animals ; Testis ; Quercetin/pharmacology* ; Rats, Sprague-Dawley ; NF-E2-Related Factor 2/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Oxidative Stress ; Testosterone/pharmacology* ; Superoxide Dismutase/metabolism* ; Follicle Stimulating Hormone ; Luteinizing Hormone

In the past few years, there has seen an increase in the detection rate of early upper gastric cancer. Early upper gastric cancer is of good prognosis. How to further enhance the postoperative quality of life of patients has increasingly become an issue of concern. This has naturally given rise to function-preserving proximal gastrectomy. However, due to its damage to the original structure of cardia and its vicinity, proximal gastrectomy is prone to postoperative reflux. To prevent postoperative reflux, various ways of digestive tract reconstruction have emerged one after another, but the optimal way thereof remains controversial. Therefore, reducing postoperative reflux through an appropriate way of digestive tract reconstruction has been taken as a focus of proximal gastrectomy. Esophagogastric anastomosis with seromuscular flap technique, as a way of digestive tract reconstruction, builds an "artificial cardia" on the basis of guarantee of normal entry of food into the digestive tract, and functions against postoperative reflux. For its good anti-reflux effect, eso-phagogastric anastomosis with seromuscular flap technique has gradually become a research focus. On top of the latest research progress at home and abroad and relevant evidence-based medicine, the authors provide on the principles, key points, improvement, postoperative status, and applica-tion of esophagogastric anastomosis with seromuscular flap technique in laparoscopic proximal gastrectomy.

Isochrysis galbana is considered an ideal bait for functional foods and nutraceuticals of humans because of its high fucoxanthin(Fx)content.However,multi-omics analysis of the regula-tory networks for Fx biosynthesis in I.galbana has not been reported.In this study,we report a high-quality genome assembly of I.galbana LG007,which has a genome size of 92.73 Mb,with a contig N50 of 6.99 Mb and 14,900 protein-coding genes.Phylogenetic analysis confirmed the monophyly of Haptophyta,with I.galbana sister to Emiliania huxleyi and Chrysochromulina tobinii.Evolutionary analysis revealed an estimated divergence time between I.galbana and E.huxleyi of～133 million years ago.Gene family analysis indicated that lipid metabolism-related genes exhibited significant expansion,including IgPLMT,IgOAR1,and IgDEGS1.Metabolome analysis showed that the content of carotenoids in I.galbana cultured under green light for 7 days was higher than that under white light,and β-carotene was the main carotenoid,accounting for 79.09％of the total carotenoids.Comprehensive multi-omics analysis revealed that the content of β-carotene,antheraxanthin,zeaxanthin,and Fx was increased by green light induction,which was significantly correlated with the expression of IgMYB98,IgZDS,IgPDS,IgLHCX2,IgZEP,IgLCYb,and IgNSY.These findings contribute to the understanding of Fx biosynthesis and its regulation,pro-viding a valuable reference for food and pharmaceutical applications.

In recent years, the detection rate of early gastric cancer in China has increased. Early gastric cancer has a good prognosis, and how to further improve the postoperative quality of life for patients has become an increasingly concerned problem in the treatment of early gastric cancer. Therefore, function preserving gastrectomy has emerged. Function preserving gastrectomy aims to reduce the resection scope and preserve part of the gastric function on the premise of radical tumor resection. As a representative of function preserving gastrectomy, pylorus-preserving gastrec-tomy is suitable for early gastric cancer in middle segment. Compared with distal gastrectomy, laparoscopic pylorus-preserving gastrectomy not only has the advantage of less trauma, but also can reduce the incidence of postoperative dumping syndrome, bile reflux gastritis and gallstones, and improve postoperative nutritional status. However, the practice of pylorus-preserving gastrectomy is still in controversial. Based on the new Japanese guidelines for the treatment of gastric cancer, and combined with the latest domestic and foreign research trends and relevant evidence-based medicine basis, the authors review the definition and indications, safety, advantages, technical points, digestive tract reconstruction methods, postoperative complications and other aspects of laparoscopic pylorus-preserving gastrectomy.