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.

Objective To explore the method for establishing a pig left lung orthotopic transplantation model. Methods A total of 4 male Yorkshire pigs weighing (40.0±2.5) kg underwent surgical procedures, including anesthesia, tracheal intubation, donor lung procurement, and recipient lung transplantation. Histological morphology and blood gas analysis of the transplanted lungs were assessed 2 hours after reperfusion to evaluate the histological changes and function of the transplanted lungs. Results The pigs underwent left lung in situ transplantation, effectively simulating conditions relevant to human lung transplantation. Two hours after the transplantation, arterial blood gas analysis showed that arterial partial pressure of oxygen was 155.4-178.6 mm Hg, arterial partial pressure of carbon dioxide was 53.1-62.4 mm Hg, and the oxygenation index was 310.8-357.2 mm Hg. Hematoxylin and eosin staining indicated a low degree of pulmonary edema and minimal cellular infiltration. Conclusion The pig left lung orthotopic transplantation model possesses strong operability and stability. Researchers can replicate this model according to the described methods and further conduct basic research and explore clinical translational applications.

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.

Objective To explore the predictive performance of machine learning models integrating clinico-pathological features and inflammatory markers for lymphovascular invasion (LVI) before gastric cancer surgery. Methods A retrospective cohort of 193 gastric cancer patients from The First Hospital of Lanzhou University (training set) and 185 patients from Zhongshan Hospital, Fudan University (validation set) was included. Preoperative clinical pathological characteristics, tumor markers, and inflammatory markers were collected to identify independent risk factors for LVI. Six machine learning models were established in the training set. Model performance was evaluated using area under the receiver operating characteristic (ROC) curve (AUC), calibration curve, decision curve analysis (DCA), and Brier scores. Shapley additive explanations (SHAP) was applied for model interpretability. Results The multivariate logistic regression showed increased tumor invasion depth (T-stage), lymph node metastases (N-stage), and the systemic immune-inflammation index (SII) were independent risk factors for gastric cancer LVI (P＜0.05). Using these three indicators, 6 machine learning models were developed, all of which demonstrated favorable predictive performance, with 0.79 and 0.76 of minimum AUC values in the training set and the validation set, respectively. Among them, the light gradient boosting machine (LightGBM) model exhibited the best overall performance, achieving AUCs of 0.83 and 0.82 in the training set and the validation set, along with Brier scores of 0.163 and 0.187, respectively. Calibration and DCA curves further confirmed that the model possesses strong predictive accuracy and application value. SHAP analysis showed the feature importance in LightGBM model, identifying the N-stage as the top contributor, followed by the T-stage and the SII. Conclusion The machine learning models incorporating clinical pathological features and inflammatory indicators can effectively predict LVI status in gastric cancer, with the LightGBM model demonstrating optimal performance.

Objective:To evaluate the efficacy of different surgical approaches in treating various types of small-volume benign prostatic hyperplasia (BPH).Methods:The data of 62 patients with small-volume BPH (≤30 ml) who were treated at Affiliated Jinhua Hospital, Zhejiang University School of Medicine from March 2018 to March 2023 were retrospective analyzed.The average age of the patients was (63.21 ± 5.38) years old.Among them, 9 patients had bladder calculi and 12 presented with urinary retention. Patients were stratified into two groups based on preoperative cystoscopy findings: 38 patients with hyperplasia of the middle or bilateral lobes underwent anterior lobe-sparing holmium laser enucleation of the prostate (HoLEP)(group A); 24 patients with bladder neck elevation and no significant hyperplasia received transurethral holmium laser incision of the prostate (group B). Preoperative baseline characteristics: international prostate symptom score(IPSS) were (23.68±4.89) and (22.59±3.62) respectively, quality of life (QOL) were (4.82±0.43) and (4.59±0.31) respectively, maximum flow rate (Q max)(7.89±1.83) ml/s and (7.26±1.72)ml/s respectively. The operative parameters (including procedure duration and catheterization time), postoperative complications (infection, urinary incontinence, and bladder neck contracture) were evaluated. Results:All 62 procedures were successfully completed. The mean operative time of group A was (32.36±6.17) minutes, postoperative catheterization duration was 1-3 days, and no cases of urinary incontinence or infection at 1-month follow-up. During the 12-month follow-up period, no cases of bladder neck contracture were observed in group A. The mean operative time of group B was (19.58 ± 3.87) minutes, and postoperative catheterization duration was 5-7 days. One case of fever with epididymitis was observed after operation, and there was no urinary incontinence at 1-month follow-up. During the 12-month follow-up period, no case of bladder neck contracture was observed in group B. Postoperative outcomes of group A and B at 1 month were as follows: IPSS (7.20±1.72) and (7.80±1.52) respectively, QOL (2.12±0.33) and (2.36±0.25) respectively, Q max(19.32±3.55)ml/s and (18.29±2.83)ml/s respectively.All postoperative parameters showed significant improvement compared with preoperative values ( P<0.05). Conclusions:For small-volume BPH, patients with middle or bilateral lobe hyperplasia can benefit from anterior lobe-sparing HoLEP, patients with bladder neck elevation and minimal hyperplasia can achieve optimal outcomes with transurethral holmium laser incision. Both approaches demonstrate significant symptom improvement with low rates of postoperative urinary incontinence and bladder neck contracture.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective:To understand the factors influencing new infections of 9-valent vaccine-type human papillomavirus (9-valent type HPV) among men who have sex with men (MSM) in Urumqi City and to construct a prediction model of individual dynamics of new infections of 9-valent type HPV among MSM.Methods:In this study, a snowball method was adopted to recruit MSM in Urumqi City to establish a dynamic cohort, and participants were followed up every 6 months from 2016 to 2023, and perianal exfoliated cells were collected for HPV genotyping; joint models were established using the number of same-sex sexual partners in the last six months and the number of anal intercourse in the last one week as longitudinal variables, respectively, and joint models were utilized to analyze the influence factors of 9-valent HPV new infections in MSM individuals were analyzed by the joint model; the predictive efficacy of the model in the follow-up period was evaluated by using the time-dependent receiver operating characteristic area under the curve (AUC) values. Based on the prediction model, two study participants were randomly selected for individual dynamic prediction of new-onset HPV infections of 9-valent type types.Results:MSM with at least two follow-up visits 579 individuals were included in the analysis. The results of the two joint models showed that being divorced/widowed [hazard ratio ( HR)=1.544, 95% CI: 1.033-2.233], having a sexual behavior style of being the inserted party ( HR=1.366, 95% CI: 1.053-1.764), and having a history of STDs ( HR=1.659, 95% CI: 1.057-2.558) increased the 9-valent types of new HPV infections risk. The results of the shared parameter of the joint model of the number of same-sex partners in the last six months showed that each 2.72 increase in the number of same-sex partners in the last six months was associated with a 28.2% increase in the risk of new 9-valent HPV infections in MSM individuals ( HR=1.282, 95% CI: 1.065-1.540). The time-dependent AUC results showed that the joint model for the number of same-sex sexual partners in the last six months (0.808 0) predicted better performance than the joint model for the number of anal intercourse in the last one week (0.750 0). The joint model based on the number of same-sex sexual partners in the last six months for the prediction of MSM individual dynamics was consistent with the real situation. Conclusion:The joint model based on the number of same-sex sexual partners in the last six months, sexual behavior, history of STDs, and other risk factors has high accuracy in predicting the risk of new MSM 9-valent HPV infections in Urumqi City, which can provide a scientific basis for the prediction of individual dynamics of new MSM 9-valent HPV infections.

Objective:To analyze the awareness of HCV infection status and willingness for HCV-RNA testing among hepatitis C cases in four provinces in China and to provide a reference for adjusting HCV prevention and control strategies.Methods:From September 2021 to September 2022, a cross-sectional survey was conducted using stratified random cluster sampling in four provinces (Jiangsu, Henan, Hubei, and Yunnan) in China, with an estimated sample size of 6 468 participants. The questionnaire included sociodemographic information, HCV infection awareness, willingness for HCV-RNA testing, and history of high-risk behaviors from the survey participants. Logistic regression models were used to analyze the factors associated with HCV infection awareness and willingness for HCV-RNA testing among hepatitis C cases. Statistical analysis was performed using R 4.1.3 software.Results:A total of 10 563 hepatitis C cases were surveyed. The awareness rate of HCV infection was 86.74% (9 162/10 563), and the willingness rate for HCV-RNA testing was 85.21% (9 001/10 563). Multivariate logistic regression models analysis showed that the awareness rate of HCV infection was lower among individuals aged ≥60 years, urban residents (with New Rural Cooperative Medical Insurance ), those without a history of blood transfusion, those without a history of paid blood donation, those without a history of injection drug use, and those without a family member with hepatitis C case.The awareness rate was higher among individuals with high or technical secondary school education, college education or above, and those married with a spouse (all P<0.05). In terms of willingness for HCV-RNA testing, it was lower among females, individuals aged ≥60 years, and those without a history of blood transfusion, paid blood donation, or injection drug use. The willingness was higher among farmers or migrant workers, employees of enterprises or institutions, and those in other occupations (all P<0.05). Conclusions:There was room for improvement in the awareness proportion of HCV infection and willingness for HCV-RNA testing among hepatitis C cases in the four provinces of China. More convenient policies and measures should be provided to increase the awareness rate of HCV infection and the willingness to undergo HCV-RNA testing in this population.