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 systematically compare mature experiences of comprehensive drug value assessment in typical countries/regions and to provide decision-making references for China to establish a scientific and standardized comprehensive drug value assessment system for medical-insured drugs. METHODS The literature analysis was used to systematically review drug value assessment frameworks in 11 representative countries/regions， namely the UK， Canada， Italy， Australia， Germany， France， South Korea， Japan， the United States， as well as Taiwan （China） and Hong Kong （China）. Comparisons were made across three dimensions： assessment entities， value dimension， and application of results. RESULTS &CONCLUSIONS In most countries/regions， independent technical assessment institutions have been established as part of the drug value evaluation system， with the involvement of multiple stakeholders （e.g.， the UK， Canada）. The mainstream drug value assessment frameworks have generally transcended the traditional core dimensions of safety， efficacy， and cost-effectiveness， exhibiting two major trends： the continuous expansion of assessment dimensions and stricter evidence requirements. Assessment outcomes are closely integrated with payment policies， ranging from providing technical advice for decision-making （e.g.， Italy， France） to directly determining reimbursement eligibility （e.g.， the UK， Germany）. The following recommendations are proposed for China： first， establish an evaluation mechanism featuring multi-stakeholder participation and separation of evaluation from decision-making. Second， develop a comprehensive evaluation framework integrating clinical， economic， patient， and societal value， emphasizing quantitative indicator exploration and real-world evidence application. Third， promote direct linkage between value-based tiering outcomes and medical insurance reimbursement decisions or access negotiations to balance patient benefits， fund sustainability， and industrial innovation.

BACKGROUND:Because of its anti-inflammatory and antioxidant activities,Apelin-13 plays an effective role in the treatment of common clinical diseases such as neuroinflammation,cardiovascular injury and pneumonia.However,there is no relevant basic research on whether Apelin-13 also has a good effect in the treatment of inflammatory bone loss. OBJECTIVE:To explore the therapeutic effect and mechanism of Apelin-13 on inflammatory bone loss,in order to find potential drugs for the treatment of inflammatory bone loss. METHODS:(1)In vitro experiment:RAW264.7 cells were divided into three groups:control group,lipopolysaccharide group and treatment group.The control group was only added with DMEM complete medium;lipopolysaccharide group was added with lipopolysaccharide(100 ng/mL)induced inflammation DMEM medium;and the treatment group was added with 10 nmol/L Apelin-13+lipopolysaccharide induced inflammation DMEM medium.Then,24 hours after lipopolysaccharide induced inflammation,western blot was used to detect the marker proteins inducible nitric oxide synthase and CD86 of M1 macrophages,and cell immunofluorescence was extracted to detect the expression of inducible nitric oxide synthase.Finally,the same amount of receptor activator of nuclear factor-κB ligand(RANKL;50 ng/ml)was added to the control group,lipopolysaccharide group and treatment group to induce osteoclasts.The results of osteoclast induction were evaluated by tartrate-resistant acid phosphatase staining and F-actin staining after 6 days of induction.(2)In vivo experiment:Eighteen male C57bl/6 mice were randomly divided into three groups:sham group,lipopolysaccharide group and treatment group.The sham group received intraperitoneal injection of 0.1 mL of PBS;the lipopolysaccharide group was injected with 0.1 mL of PBS diluent containing lipopolysaccharide(5 mg/kg);and the treatment group was injected with 0.1 mL of PBS diluent containing lipopolysaccharide(5 mg/kg)+Apelin-13(100 μg/kg).After 7 days of continuous intraperitoneal injection,the mice in each group were killed on the 8th day,and two femurs of each mouse were collected.Half of them were scanned by micro-CT and analyzed by bone mineral density,and the other half were stained by hematoxylin-eosin staining RESULTS AND CONCLUSION:(1)In vitro experiment:Western blot results showed that the expressions of inducible nitric oxide synthase and CD86 in the lipopolysaccharide group were significantly higher than those in the control group,and Apelin-13 could significantly inhibit the M1 polarization of macrophages induced by lipopolysaccharide.Cell immunofluorescence results also showed that the expression of inducible nitric oxide synthase in the treatment group was lower than that in the lipopolysaccharide group.Besides,tartrate-resistant acid phosphatase staining and F-actin staining results showed that Apelin-13 inhibited the abnormal activation and bone resorption of lipopolysaccharide induced osteoclasts.(2)In vivo experiment:The results of micro-CT showed that systemic inflammation led to significant bone loss in the distal femur,while Apelin-13 could significantly inhibit bone loss in vivo.Hematoxylin-eosin staining results also showed that Apelin-13 could effectively alleviate inflammation induced bone loss in the distal femur of mice.To conclude,Apelin-13 can alleviate bone loss induced by systemic inflammation by inhibiting M1 polarization of macrophages,inhibiting abnormal activation of osteoclasts and bone resorption.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

ObjectiveTo investigate the mechanism by which modified Shengjiangsan （MSJS） improves diabetic kidney disease （DKD） by activating mitochondrial autophagy. MethodsSixty SPF-grade male Sprague-Dawley rats aged 7-8 weeks were selected. A DKD model was established using a high-sugar， high-fat diet combined with intraperitoneal injection of streptozotocin （STZ）. After successful modeling， the rats were randomly divided into six groups： a normal control group， a model group， low-， medium-， and high-dose MSJS groups （7.7， 15.4， 30.8 g·kg^-1， respectively）， and an irbesartan group （0.384 g·kg^-1）. Each group received either normal saline or the corresponding drug by gavage once daily for 28 consecutive days. Blood glucose， body weight， and kidney weight were recorded. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected using an automatic blood analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to determine urinary microalbumin （mALB）， and serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）. Histopathological changes in renal tissues were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy （TEM）. The expression levels of mitochondrial autophagy-related proteins in renal tissues were analyzed by Western blot. Immunofluorescence co-localization was employed to detect the co-expression of microtubule-associated protein 1 light chain 3 beta （LC3B） and cytochrome c oxidase subunit Ⅳ （COX Ⅳ）. ResultsCompared with the normal control group， the model group exhibited significant increases in renal index， blood glucose， and 24-hour urinary microalbumin （24 h mALB） （P<0.05， P<0.01）. The levels of serum SCr and BUN were significantly elevated （P<0.01）， and the serum levels of TNF-α， IL-1β， and IL-6 were markedly upregulated （P<0.01）. Histopathological examination revealed glomerular hypertrophy， mesangial expansion and increased deposition， podocyte foot process flattening and fusion， a decreased number of autophagosomes accompanied by mitochondrial swelling， vacuolar degeneration of renal tubular epithelial cells， and inflammatory cell infiltration in the renal interstitium. The expression levels of autophagy-related proteins LC3B， PTEN-induced putative kinase 1 （PINK1）， and E3 ubiquitin-protein ligase （Parkin） were significantly decreased （P<0.05， P<0.01）， while expression of the selective autophagy adaptor protein p62 was significantly increased （P<0.01）. Immunofluorescence signal intensity and LC3B-COX Ⅳ co-expression were both diminished. Compared with the model group， the MSJS treatment groups and the irbesartan group showed significant reductions in renal index， blood glucose， and 24 h mALB （P<0.05， P<0.01）. The serum SCr and BUN levels decreased significantly （P<0.05） and TNF-α， IL-1β， and IL-6 levels were significantly downregulated （P<0.05， P<0.01）. Histopathological damage was alleviated， including reduced glomerular hypertrophy， decreased mesangial deposition， and attenuated podocyte foot process fusion. The number of autophagosomes increased， and mitochondrial swelling was improved. The expression levels of LC3B， PINK1， and Parkin in renal tissues were significantly upregulated， whereas p62 expression was significantly downregulated （P<0.05， P<0.01） in MSJS groups. Immunofluorescence signal intensity was enhanced， and LC3B-COX Ⅳ co-expression was increased. ConclusionMSJS alleviates the inflammatory response in DKD rats and exerts renal protective effects by regulating the PINK1/Parkin signaling pathway and activating mitochondrial autophagy.

ObjectiveTo investigate the mechanism by which modified Shengjiangsan （MSJS） improves diabetic kidney disease （DKD） by activating mitochondrial autophagy. MethodsSixty SPF-grade male Sprague-Dawley rats aged 7-8 weeks were selected. A DKD model was established using a high-sugar， high-fat diet combined with intraperitoneal injection of streptozotocin （STZ）. After successful modeling， the rats were randomly divided into six groups： a normal control group， a model group， low-， medium-， and high-dose MSJS groups （7.7， 15.4， 30.8 g·kg^-1， respectively）， and an irbesartan group （0.384 g·kg^-1）. Each group received either normal saline or the corresponding drug by gavage once daily for 28 consecutive days. Blood glucose， body weight， and kidney weight were recorded. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected using an automatic blood analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to determine urinary microalbumin （mALB）， and serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）. Histopathological changes in renal tissues were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy （TEM）. The expression levels of mitochondrial autophagy-related proteins in renal tissues were analyzed by Western blot. Immunofluorescence co-localization was employed to detect the co-expression of microtubule-associated protein 1 light chain 3 beta （LC3B） and cytochrome c oxidase subunit Ⅳ （COX Ⅳ）. ResultsCompared with the normal control group， the model group exhibited significant increases in renal index， blood glucose， and 24-hour urinary microalbumin （24 h mALB） （P<0.05， P<0.01）. The levels of serum SCr and BUN were significantly elevated （P<0.01）， and the serum levels of TNF-α， IL-1β， and IL-6 were markedly upregulated （P<0.01）. Histopathological examination revealed glomerular hypertrophy， mesangial expansion and increased deposition， podocyte foot process flattening and fusion， a decreased number of autophagosomes accompanied by mitochondrial swelling， vacuolar degeneration of renal tubular epithelial cells， and inflammatory cell infiltration in the renal interstitium. The expression levels of autophagy-related proteins LC3B， PTEN-induced putative kinase 1 （PINK1）， and E3 ubiquitin-protein ligase （Parkin） were significantly decreased （P<0.05， P<0.01）， while expression of the selective autophagy adaptor protein p62 was significantly increased （P<0.01）. Immunofluorescence signal intensity and LC3B-COX Ⅳ co-expression were both diminished. Compared with the model group， the MSJS treatment groups and the irbesartan group showed significant reductions in renal index， blood glucose， and 24 h mALB （P<0.05， P<0.01）. The serum SCr and BUN levels decreased significantly （P<0.05） and TNF-α， IL-1β， and IL-6 levels were significantly downregulated （P<0.05， P<0.01）. Histopathological damage was alleviated， including reduced glomerular hypertrophy， decreased mesangial deposition， and attenuated podocyte foot process fusion. The number of autophagosomes increased， and mitochondrial swelling was improved. The expression levels of LC3B， PINK1， and Parkin in renal tissues were significantly upregulated， whereas p62 expression was significantly downregulated （P<0.05， P<0.01） in MSJS groups. Immunofluorescence signal intensity was enhanced， and LC3B-COX Ⅳ co-expression was increased. ConclusionMSJS alleviates the inflammatory response in DKD rats and exerts renal protective effects by regulating the PINK1/Parkin signaling pathway and activating mitochondrial autophagy.

Atherosclerosis is a complex pathological condition resulting from lipid deposition， chronic inflammatory responses， and fibrosis， with a prolonged disease course and multifactorial etiology. Based on the traditional Chinese medicine （TCM） theory of accumulation syndrome， atherosclerosis can be classified under this category， with its pathogenesis involving phlegm， blood stasis， deficiency， and accumulation. This paper proposed a stage-based intervention strategy using the four therapeutic principles of "attacking， supplementing， dispersing， dissipating"， and divided into six stages based on the pathological progression， including the stage of accumulation before formation， the stage of accumulation already formed， the stage of nucleus accumulation， the stage of nucleus accumulation decay， the stage of nucleus accumulation consolidation， and the stage of severe stenosis of nucleus. At different stages， the intervention focuses on reinforcing healthy qi and consolidating the root， tonifying the kidneys and spleen， dispersing and removing turbidity， removing phlegm stagnation， promoting qi circulation， dispersing accumulations and removing stasis， attacking accumulation and expelling stasis， directing the turbid downward and dispersing accumulation， and treatment would be adjusted based on specific symptoms， which provides a theoretical framework for the prevention and treatment of atherosclerosis with TCM.

Objective: To analyze the change trends in the body shape indicators and proportions of students in Harbin from 2010 to 2024, and to investigate ergonomic compatibility of functional dimensions of school desks and chairs with current student shape indicators, so as to provide a reference for revising furniture standards of desks and chairs. Methods: Between September and November of both 2010 and 2024, a combination of convenience sampling and stratified cluster random sampling was conducted across three districts in Harbin, yielding samples of 6 590 and 6 252 students, respectively. Anthropometric shape indicators cluding height, sitting height, crus length, and thigh length-and their proportional changes were compared over the 15-year period. The 2024 data were compared with current standard functional dimensions of school furniture. The statistical analysis incorporated t-test and Mann-Whitney U- test. Results: From 2010 to 2024, average height increased by 1.8 cm for boys and 1.5 cm for girls; sitting height increased by 1.5 cm for both genders; crus length increased by 0.3 cm for boys and 0.4 cm for girls; and thigh length increased by 0.5 cm for both genders. The ratios of sitting height to height, and sitting height to leg length increased by less than 0.1 . The difference between desk chair height and 1/3 sitting height ranged from 0.4-0.8 cm. Among students matched with size 0 desks and chairs, 22.0% had a desk to chair height difference less than 0, indicating that the desk to chair height difference might be insufficient for taller students. The differences between seat height and fibular height ranged from -1.4 to 1.1 cm; and the differences between seat depth and buttock popliteal length ranged from -9.8 to 3.4 cm. Among obese students, the differences between seat width and 1/2 hip circumference ranged from -20.5 to -8.7 cm, while it ranged from -12.2 to -3.8 cm among non obese students. Conclusion Current furniture standards basically satisfy hygienic requirements; however, in the case of exceptionally tall and obese students, ergonomic accommodations such as adaptive seating allocation or personalized adjustments are recommended to meet hygienic requirements.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.