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.

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.

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

Objective:To investigate the clinical efficacy of laparoscopic-assisted inters-phincteric resection (ISR) with different surgical approaches for low rectal cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 90 patients with low rectal cancer who were admitted to the Second Affiliated Hospital of Fujian Medical University from January 2016 to December 2020 were collected. There were 58 males and 32 females, aged (60±9)years. Of 90 patients, 60 cases underwent laparoscopic assisted ISR with transpelvic approach, 30 cases underwent laparoscopic assisted ISR with transabdominal and transanal mixed approach. Observation indicators: (1) clinicopathological characteristics of patients with transpelvic approach and mixed approach; (2) intraoperative and postoperative conditions of patients with transpelvic approach and mixed approach; (3) postoperative complications of patients with transpelvic approach and mixed approach; (4) follow-up. Follow-up was conducted by telephone interview and outpatient examination once every 3 months within postoperative 3 years, once every six months in the postoperative 3 to 5 years and once a year after postoperative 5 years to detect tumor recurrence and metastasis, and survival of patients.Follow-up was up to March 2021 or patient death. Measurement data with normal distribution were represented as Mean± SD, and the t test was used for comparison between groups. Measurement data with skewed distribution were expressed as M(range), and comparison between groups was conducted using the non-parametric Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was performed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed by the non-parametric rank sum test. Kaplan-Meier method was used to draw survival curves and calculate survival rates, and survival analysis was performed by the Log-Rank test. Results:(1) Clinicopathological characteristics of patients with transpelvic approach and mixed approach. The sex (males, females), distance from the distal margin of tumor to anal margin were 34, 26, (4.5±0.5)cm for patients with transpelvic approach, versus 24, 6, (3.5±0.5)cm for patients with mixed approach, respectively, showing significant differences between them ( χ2=4.75, t=8.35, P<0.05). (2) Intraoperative and postoperative conditions of patients with transpelvic approach and mixed approach. The operation time, volume of intraoperative blood loss, distance from the postoperative anastomosis to anal margin were (187±9)minutes, 50(range, 20?200)mL, (3.4±0.7)cm for patients with transpelvic approach, versus (256±12)minuets, 100(range, 20?200)mL, (2.6±0.7)cm for patients with mixed approach, showing significant differences between them ( t=?26.99, Z=?2.48, t=4.67, P<0.05). None of the 90 patients had a positive distal margin. The stoma reversal rates of patients with transpelvic and mixed approach were 93.3%(56/60) and 90.0%(27/30), respectively. Of the 60 patients with transpelvic approach, 3 cases had no stoma reversal due to anastomotic complications, and 1 case was not yet to the reversal time. Of the 30 patients with mixed approach, 2 cases had no stoma reversal due to anastomotic complications, and 1 case was not yet to the reversal time. The 1-, 3-month Wexner scores after stoma reversal were 15(range, 12?17), 12(range, 10?14) for patients with transpelvic approach, versus 16(range, 14?18), 14(range, 12?16) for patients with mixed approach, showing significant differences between them ( Z=?4.97, ?5.49, P<0.05). The 6-month Wexner score after stoma reversal was 10(range, 9?12) for patients with transpelvic approach, versus 11(range, 8?12) for patients with mixed approach, showing no significant difference between them ( Z=?1.59, P>0.05). (3) Postoperative complications of patients with transpelvic approach and mixed approach. The complications occurred to 16 patients with transpelvic approach and 9 patients with mixed approach, respectively, showing no significant difference between them ( χ2=0.11, P>0.05). Cases with postoperative anastomotic fistula, cases with anastomotic bleeding, cases with anastomotic stenosis, cases with intestinal obstruction, cases with incision infection, cases with urinary retention, cases with pelvic infection, cases with pulmonary infection, cases with incisional hernia, cases with chylous fistula, cases with abdominal and pelvic abscess were 5, 2, 1, 7, 0, 1, 5, 3, 1, 1, 1 for patients with transpelvic approach, versus 6, 3, 2, 2, 2, 1, 2, 3, 1, 1, 1 for patients with mixed approach, showing no significant difference between them ( P>0.05). The same patient could have multiple postoperative complications. (4) Follow-up. All the 90 patients were followed up for 27(range, 6?62)months. The follow-up time of 60 patients with transpelvic approach was 27(range, 8?62)months. The follow-up time of 30 patients with mixed approach was 28(range, 6?53)months. Of the 60 patients with transpelvic approach, 3 cases had local recurrence, 4 cases had liver metastasis, 3 cases had lung metastasis, and all of them survived with tumor. Of the 30 patients with mixed approach, 1 case had local recurrence, 2 cases had liver metastasis, 1 case had lung metastasis, and all of them survived with tumor. There was no death. The 3-year disease-free survival rates of patients with transpelvic approach and mixed approach were 84.7% and 87.9%, respectively, showing no significant difference between them ( χ2=0.39, P>0.05). Conclusions:Lapa-roscopic assisted ISR via transpelvic approach or mixed approach for low rectal cancer are safe and feasible. Compared with transanal mixed approach, the transpelvic approach of laparoscopic-assisted ISR has shorter operation time, less volume of intraoperative blood loss and longer distance from the postoperative anastomosis to anal margin.

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.