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.

BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.

This study employed the drug affinity responsive target stability (DARTS) technique to investigate the molecular mechanism of the antipsychotic drug penfluridol against melanoma, revealing the biological pathway to exert its effect on the HSPA6/p53/p21 signaling axis. Experiments such as the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and cell colony formation ability assay confirmed that penfluridol could significantly downregulate the expression of cyclin D1 and cyclin-dependent kinase 4 (CDK4) in melanoma A375 and B16 cells, induce cell cycle arrest in the G1 phase, and thus inhibit the proliferation of melanoma cells. Meanwhile, the results of Western blot, Hoechst 33342 staining and Annexin V-FITC/PI double staining experiments showed that penfluridol could significantly downregulate the expression of Bcl-2 and upregulate the expression of Bax and cleaved caspase-3, inducing cell apoptosis. Further, the DARTS technique was used to identify heat shock 70 kD protein 6 (HSPA6) as the key target bound by penfluridol. Penfluridol activates the p53/p21 pathway by upregulating HSPA6. Knocking down HSPA6 reverses not only the activation of the p53/p21 pathway mediated by penfluridol but also the associated cell cycle arrest and apoptosis. Animal experiments on tumor-bearing mice also confirmed that knocking down HSPA6 could reverse the in vivo anti-tumor activity of penfluridol. This study clarified that penfluridol can inhibit the progression of melanoma by targeting HSPA6 to activate the p53/p21 signaling axis, providing a new perspective for the repositioning of antipsychotic drugs in cancer treatment.

BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.

Nonalcoholic fatty liver disease（NAFLD） is the most common chronic liver disease in the world. Because of its complex pathogenesis， high clinical prevalence and large population， it poses a great threat and challenge to public health in the world. Therefore， active intervention measures are needed. Currently， western medicine is effective in reducing weight， reducing liver fat content， improving glucose-lipid metabolism and insulin resistance. However， for patients with NAFLD-related fibrosis and cirrhosis， there is still a lack of sufficient histological evidence to support its benefits， and randomized controlled trials are still needed to clarify. Lifestyle intervention is an important cornerstone for the treatment of NAFLD， but there are many problems such as poor implementation and low compliance of patients， and the clinical efficacy is not ideal. Traditional Chinese medicine（TCM） has the significant advantages of multiple pathways and multiple targets. Berberine， the active ingredient of TCM， can interfere with the production of NAFLD from multiple pathways， including increasing energy consumption， weight loss， improving glucose-lipid metabolism， improving insulin resistance， anti-inflammatory， anti-oxidation， regulating intestinal flora， restoring bile acid homeostasis， anti-fibrosis and so on， which can play a positive role in the treatment of NAFLD. At the same time， it was found that the combination of BBR with Chinese and western medicines had significant advantages in promoting drug absorption， improving oral bioavailability， increasing the highest biological distribution in the liver， enhancing the overall therapeutic effect of NAFLD， and reducing adverse drug reactions， which could provide reference for clinical medication.

Objective To assess the efficacy and the survival rate of the hip joint following the treatment of osteonecrosis of the femoral head(ONFH)with ultrasound-guided percutaneous intra-articular platelet-rich plasma(PRP)injection in combination with percutaneous silver needle thermalolysis.Methods Fifty-six patients diag-nosed with ARCO(Association Research Circulation Osseous)stage Ⅱ ONFH were randomly allocated into two groups.The first group,designated as the PRP injection combined with silver needle thermalolysis group(Group R,n=28),and the second group,the steroid injection combined with silver needle thermalolysis group(Group S,n=28).Both groups underwent three injections(administered at 4-week intervals)and one session of silver needle thermalolysis.Outcome measures,including the Numerical Rating Scale(NRS)for pain assessment,Harris Hip Score(HHS),daily consumption of non-steroidal anti-inflammatory drugs(etoricoxib)and tramadol,progression to ARCO stage Ⅲ,and the rates of surgical intervention,were recorded at baseline,3 days,and 1,3,6,and 12 months after the treatment.Results When compared to the baseline,both groups manifested significant decreases in NRS scores and enhancements in HHS at all follow-up time points(P<0.05).Specifically,Group R demonstrated more favorable outcomes compared to Group S.At 3,6,and 12 months,Group R had lower NRS scores(P<0.01)and more notable improvements in HHS(P<0.01).Additionally,the daily analgesic consumption(etoricoxib and tramadol)in Group R was significantly lower than that in Group S at 3,6,and 12 months(P<0.01).Moreover,Group R exhibited a significantly lower progression rate to ARCO stage III and a lower hip replacement surgery rate(P<0.05).Conclusions Ultrasound-guided intra-articular PRP injection in combination with silver needle therma-lolysis expedites pain alleviation,enhances hip function,reduces analgesic dependence,and retards the progression of ONFH.This approach thus represents a clinically viable option for early-stage intervention.

Objective:To observe the clinical efficacy of DING's Tuina(Chinese therapeutic massage)plus Western medication in treating rotator cuff injury(RCI)and its impact on pain,shoulder function,and shoulder muscle strength in the patients.Methods:Sixty-two RCI patients were divided into an observation group and a control group using a simple randomization method,each consisting of 31 cases.Both groups of patients were prescribed oral celecoxib capsules.In addition,DING's Tuina treatment was offered to the observation group.After 6 weeks of treatment,the two groups were observed for changes in the Constant-Murley score(CMS)for shoulder joint function,the short-form McGill pain questionnaire(SF-MPQ)score,and peak torque(PT)and peak torque to body mass ratio(PT/BM)at angular velocities 120 °/s and 90 °/s as well as the peak torque ratio(PTR)of agonist muscles to antagonist muscles[including adductors to abductors(ADD/ABD)and flexors to extensors(F/E)].Results:After treatment,both groups presented decreased SF-MPQ scores and increased CMS,and the intra-group differences were statistically significant(P<0.05);the observation group had a lower SF-MPQ score and a higher CMS than the control group,showing statistical significance(P<0.05).After the intervention,the ADD/ABD decreased in the control group at the angular velocity 120 °/s in abduction,and the intra-group change was statistically significant(P<0.05);in the observation group,the PT and PT/BM increased compared to the baseline at angular velocities 120 °/s and 90 °/s in abduction,adduction,forward flexion,and backward extension,showing statistical significance(P<0.05).After treatment,the PT and PT/BM at angular velocities 120 °/s and 90 °/s and ADD/ABD at 120 °/s were higher in the observation group than in the control group,and the between-group differences were statistically significant(P<0.05).Conclusion:DING's Tuina combined with oral celecoxib capsules can reduce pain,improve the joint's motor function,and enhance the strength of shoulder muscle groups in RCI patients,and this treatment has a positive impact on the stability when performing shoulder joint abduction and adduction.

Objective:To compare and analyze the clinical efficacy of using a posterior "S" shape incision versus a medial small incision with suture anchors in the treatment of avulsion fractures at the tibial insertion of the posterior cruciate ligament (PCL).Methods:A retrospective study was conducted on clinical data from patients with PCL tibial avulsion fractures who met surgical criteria and were treated at Department of Joint 2, Tangshan Second Hospital from March 2021 to May 2023. Among those patients, there were 25 cases classified as Meyers-McKeever type Ⅱ and 41 cases as type Ⅲ. 32 patients who underwent surgery through the posterior "S" shape incision served as the control group; based on matched baseline characteristics, 34 patients who underwent surgery through the medial small incision were selected as the observation group. Both groups received fixation of the avulsion fracture with suture anchors. Surgical indicators, as well as Lysholm scores, International Knee Documentation Committee (IKDC) scores, visual analogue scale (VAS) scores, range of motion (ROM) of the injured knee, the difference in posterior tibial translation between both sides (calculated by measuring the posterior translation on both sides), and the incidence of postoperative complications were collected at 1, 3, and 6 months post-surgery. Comparative analyses were conducted to evaluate postoperative functional recovery. Chi-square tests were used for categorical data comparison, and t-tests were employed for normally distributed continuous data.Results:The observation group had shorter incision lengths ((5.71±1.85) cm), less intraoperative blood loss ((74.87±20.74) mL), and shorter operation times ((48.76±6.46) min) compared to the control group ((12.45±1.52) cm, (120.29±31.12) mL, (61.14±10.23) min), and the differences were statistically significant ( t values were 16.21, 7.02, 5.92, respectively; all P<0.001). At 3 and 6 months post-surgery, the Lysholm ((79.67±3.08), (91.16±2.23) points) and IKDC scores ((84.67±5.08), (93.16±3.23) points) in the observation group were significantly higher than those ((65.29±3.84), (79.52±2.98), (79.29±4.84), (85.32±3.98) points) in the control group, and the differences were statistically significant ( t values were 16.72, 18.04, 4.40, 8.81, respectively; all P<0.001). At 3 and 6 months, the VAS scores ((2.83±0.38), (2.12±0.34) points) in the control group were significantly higher than those ((2.41±0.25), (1.73±0.49) points) in the observation group ( t values were 5.34 and 3.73 respectively, both P<0.001). At 6 months post-surgery, all fractures had healed, in the observation group and control group the ROM ((130.56±5.96)° and (121.45±7.32)°) of the injured knee had increased, and the difference in posterior tibial translation ((1.17±0.61) and (1.94±0.57) mm) had decreased. However, the ROM in the observation group was significantly greater than that in the control group, and the difference in posterior tibial translation was significantly lower in the observation group, with statistically significant differences ( t values were 5.56 and 5.29 respectively; both P<0.001). Conclusions:Compared to the posterior "S" shape incision approach, the medial small incision approach with suture anchors for treating PCL tibial avulsion fractures offers advantages such as reduced trauma, shorter operation time, and less intraoperative blood loss, which is more beneficial for knee joint functional recovery.

Objective To evaluate the efficiency of health resource allocation in 22 types of hospital institutions in Guangdong Province from 2018 to 2022,identify their strengths and shortcomings in resource utilization,and offer evidence-based recommendations for optimizing medical resource allocation and policymaking.Methods The efficiency of health resource allocation was assessed using the DEA-BCC model and the DEA-Malmquist index model across the 22 hospital categories.Results In 2022,the overall resource allocation efficiency of the 22 types of hospital institutions in Guangdong Province was suboptimal,with an average score of 0.657.From 2018 to 2022,the mean total factor productivity(TFP)change index for these hospitals was 0.968,with only 6 categories exhibiting a TFP index exceeding 1.Conclusion The efficiency of health resource allocation in Guangdong's hospitals remains inadequate.Government authorities should enhance macro-level planning for regional resource distribution,accelerate advancements in medical technology,and establish a real-time monitoring framework.Concurrently,policy interventions and incentive mechanisms should be reinforced to ensure both scientifically sound allocation and effective utilization of medical resources.

This report described a case of hereditary thrombotic thrombocytopenic purpura (TTP) with neonatal onset. The infant presented with facial petechiae, jaundice, progressive thrombocytopenia, and persistent bleeding at puncture sites shortly after birth. Plasma ADAMTS13 activity was<1%. Whole-exome sequencing identified heterozygous variants in ADAMTS13: c.3121C>T and c.1869delT, inherited from the father and mother, respectively. The infant improved following exchange transfusion and phototherapy. Post-discharge, prophylactic fresh frozen plasma infusion was administered every 3-4 weeks. At the 2-year follow-up, no abnormalities were observed. This case highlights the importance of early recognition and intervention in neonates with unexplained thrombocytopenia, severe non-hemolytic jaundice, and anemia to ensure survival and improve prognosis.