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.

ObjectiveTo compare the differences in fungal community composition between lesional and non-lesional scalp areas in patients suffering from severe alopecia areata （AA）， and compare these with healthy scalp areas in control subjects. Additionally， to preliminarily explore the changes in scalp fungal communities in severe AA patients and their potential underlying immunological mechanisms. MethodsA total of 20 severe AA patients and 18 healthy controls were enrolled. Skin swab samples were collected from lesional and non-lesional scalp areas of severe AA patients， as well as from the normal scalp of healthy controls. The fungal internal transcribed spacer （ITS） region was amplified and analyzed using high-throughput sequencing. ResultsThe lesional scalp areas of severe AA patients exhibited higher α-diversity and species richness in fungal communities. Notably， the relative abundance of Ascomycota， along with genera such as Mycosphaerella， Aspergillus， Penicillium， and Wallemia， significantly increased in the bald regions. In contrast， Acremonium and Schizophyllum were more predominant in the non-lesional areas of severe AA patients. ConclusionDistinct region-specific differences in scalp fungal microbiota in severe AA patients suggests that fungal dysbiosis may play a potential role in the pathogenesis of alopecia areata. These findings provide new insights into the disease characteristics of severe AA from the perspective of scalp microecology.

Objective: To explore the role of the c.598G>A mutation of the ITGB3 gene in the occurrence of fetal and neonatal alloimmune thrombocytopenia (FNAIT) through its expression in vitro. Methods: The platelet antibodies in the sera of the affected neonate and her mother were detected using commercial enzyme-linked immunosorbent assay (ELISA), solid-phase agglutination, flow cytometry and the gold standard monoclonal antibody-specific immobilization of platelet antigens (MAIPA). The common human platelet antigen (HPA) genotypes of the neonate and her parents were obtained using the HPA-SSP method. The presence of mutations was analyzed by sequencing the exons of the ITGB3 and ITGA2B genes. The target gene of ITGB3 was obtained by PCR amplification using the existing human platelet cDNA. The wild-type ITGB3 eukaryotic expression vector was constructed by TA cloning technology. The 598G>A mutant ITGB3 eukaryotic expression vector was obtained by point mutation, and the plasmid DNA was co-transfected with that of ITGA2B (αⅡb) into HEK293 cells. The transfected cells stably expressing GP Ⅱb/Ⅲa were screened and obtained. The expression of GP Ⅱb/Ⅲa in 598G>A mutant transfected cells and the presence of antibodies against this mutation in the serum of mother were detected by flow cytometry and MAIPA. Results: Antibodies against HLA-class Ⅰ and GP Ⅱb/Ⅲa glycoproteins were detected in the serum of the neonate's mother, and subsequent HLA antibody-specific testing confirmed the presence of antibodies against HLA-B 57∶01 and A 02∶05. ITGB3 sequencing showed that the neonate and her father carried the c.598G>A point mutation, which results in the change of glutamate to lysine at position 200. Antibodies against GP Ⅱb/Ⅲa glycoproteins were not detected using constructed c.598G>A mutant transfected cells reacted with the maternal serum. Conclusion: The in vitro expression and analysis of the ITGB3 c.598G>A mutation did not support a role for this mutation in the pathogenesis of FNAIT. The establishment of this method facilitates the discovery of new platelet low-frequency antigens, and provides a theoretical foundation for the detection of antibodies against platelet antigens associated with patients with adverse pregnancy and childbirth histories.

Objective: To explore the role of the c.598G>A mutation of the ITGB3 gene in the occurrence of fetal and neonatal alloimmune thrombocytopenia (FNAIT) through its expression in vitro. Methods: The platelet antibodies in the sera of the affected neonate and her mother were detected using commercial enzyme-linked immunosorbent assay (ELISA), solid-phase agglutination, flow cytometry and the gold standard monoclonal antibody-specific immobilization of platelet antigens (MAIPA). The common human platelet antigen (HPA) genotypes of the neonate and her parents were obtained using the HPA-SSP method. The presence of mutations was analyzed by sequencing the exons of the ITGB3 and ITGA2B genes. The target gene of ITGB3 was obtained by PCR amplification using the existing human platelet cDNA. The wild-type ITGB3 eukaryotic expression vector was constructed by TA cloning technology. The 598G>A mutant ITGB3 eukaryotic expression vector was obtained by point mutation, and the plasmid DNA was co-transfected with that of ITGA2B (αⅡb) into HEK293 cells. The transfected cells stably expressing GP Ⅱb/Ⅲa were screened and obtained. The expression of GP Ⅱb/Ⅲa in 598G>A mutant transfected cells and the presence of antibodies against this mutation in the serum of mother were detected by flow cytometry and MAIPA. Results: Antibodies against HLA-class Ⅰ and GP Ⅱb/Ⅲa glycoproteins were detected in the serum of the neonate's mother, and subsequent HLA antibody-specific testing confirmed the presence of antibodies against HLA-B 57∶01 and A 02∶05. ITGB3 sequencing showed that the neonate and her father carried the c.598G>A point mutation, which results in the change of glutamate to lysine at position 200. Antibodies against GP Ⅱb/Ⅲa glycoproteins were not detected using constructed c.598G>A mutant transfected cells reacted with the maternal serum. Conclusion: The in vitro expression and analysis of the ITGB3 c.598G>A mutation did not support a role for this mutation in the pathogenesis of FNAIT. The establishment of this method facilitates the discovery of new platelet low-frequency antigens, and provides a theoretical foundation for the detection of antibodies against platelet antigens associated with patients with adverse pregnancy and childbirth histories.

Objective To explore the effect of 3D printing auxiliary stent on the operation of laryngeal microsurgery instrument.Methods Auxiliary stent of suspension laryngoscope was design and 3D printed.30 standardized training residents as experimental participants were randomly divided into conventional group and auxiliary stent group(15 in each group).The pig's larynx was used as a specimen,and the vocal folds were marked with localized staining.Participants performed operation on the stained areas of the vocal folds under suspension laryngoscope(60 times of grasping in 1 h).The conventional group performed operation unaided;The auxiliary stent group performed operation with the auxiliary stent as a support.Two senior chief physicians scored the participants'stability and accuracy.Results The operational stability scale score of the conventional group and the auxiliary stent group were(5.03±4.33)and(8.99±3.42),respectively;The operation accuracy rates were 58.4%(526/900)and 78.9%(710/900),respectively.The operation accuracy rate,operation stability of the auxiliary stent group were significantly higher than those in the conventional group,and the differences were significant(P<0.01).Conclusion The auxiliary stent can significantly improve the stability and accuracy of operation,which has highly application value.

Background and purpose:Gallic acid(GA)induces tumor cells apoptosis and inhibits angiogenesis.Beyond directly attacking tumor cells,another crucial aspect of GA is its ability to modulate and enhance immune system function.For example,it can improve T cell metabolism,alleviate T cell exhaustion,and promote the formation of memory T cell phenotypes.Although several chimeric antigen receptor T(CAR-T)cells products have gained market approval,the technology still faces significant challenges.These limitations include off-target effects,a predisposition to T cell exhaustion and so on.Moreover,similar to exhaustion,cellular senescence is a major hindrance that impairs T cell function.This study aimed to investigate the effects of GA on the anti-tumor function of CAR-T cells both in vitro and in vivo.We further evaluated the impact of GA on CAR-T cells senescence and memory phenotypes,as well as the impact of GA and CAR-T cells on immune cell infiltration within the tumor microenvironment(TME).Methods:Second-generation CAR targeting mouse glypican 3(GPC3)and human epidermal growth factor receptor 2(HER2)were constructed to generate CAR-T cells.CAR-T cells were co-cultured with GA at a concentration of 5 μg/mL,and flow cytometry was used to assess the senescence status and memory phenotype of CAR-T cells and their killing ability against tumor cells at different effector-to-target ratios.Senescence markers included p53,p21,γ-H2AX and senescence-associated β-galactosidase(SA-β-gal),while CCR7 served as the memory phenotype marker.A subcutaneous tumor model was established to explore the effects of GA on the anti-tumor function of CAR-T cells and immune cell infiltration within the TME.Results:We successfully generated human HER2 and murine GPC3 CAR-T cells,achieving a purity of 30%-50%.GA enhanced the in vitro killing ability of CAR-T cells targeting mouse GPC3 and human HER2(P＜0.001)at different E:T ratios,delayed the senescence of mouse GPC3 CAR-T cells(p53,p21,γ-H2AX,P＜0.05;SA-β-gal,P＜0.001;CCR7,P＜0.001).And GA promoted the differentiation of CAR-T cells toward a memory phenotype(P＜0.001).Additionally,GPC3 CAR-T cells inhibited tumor cell growth(P＜0.05),prolonged mouse survival(P＜0.001),and enhanced the infiltration capacity of CAR-cells(P＜0.001)and endogenous immune cells[CD4+T cells,P＜0.05;CD8+T cells,P＜0.01;natural killer(NK)cells,P＜0.01].Conclusion:GA can enhance the cytotoxic activity of CAR-T cells in vitro,and delay the senescence of CAR-T cells.Furthermore,by modulating TME,GA improved immune cell infiltration,thereby augmenting the overall anti-tumor efficacy of CAR-T cells.

Objective Summarize the clinical application and elevating the caudal end of suspension laryngoscope to deal with severe glottis exposure difficulties.Method A retrospective analysis was conducted on the clinical data of 25 patients with severe dystotic glottic exposure(Cormack-Lehane grade Ⅲ or Ⅳ)who underwent laryngoscopy support surgery from January 2021 to January 2024,then analyze the intraoperative management and outcomes.Results In all the patients,after the angle of the suspension laryngoscope was adjusted to the maximum and the glottis could not be exposed satisfactorily,the caudal end of the suspension laryngoscope stent was lifted to obtain a larger tilt angle and field of view.After the caudal end of the stent was elevated by(11.50±6.31)cm,the glottis was exposed satisfactorily in 23 cases and the operation was performed successfully;In 2 cases,the laryngeal mask airway was used in conjunction with a fibrolaryngoscope and laryngeal forceps were used to extract the lesion step by step.Pharyngeal mucosal tearing and oozing of blood occurred in 24 cases,and the bleeding stopped after electrocoagulation;one case had loose and dislodged teeth.There were no significant changes in blood pressure and heart rate of patients before and after stent lifting(P＞0.05).Conclusion For the severe difficulty of glottis exposure during suspension laryngoscopic surgery,it can be dealt with by lifting the caudal end of the stent,which is a simple and effective method that does not cause serious complications and is worth clinical application.

Objective:To characterize the minimal inhibitory concentration (MIC) of macrolides against clinical Mycoplasma pneumoniae (MP) isolates and to investigate the significance of 23S rRNA mutations. Methods:Cross-sectional study.A total of 288 clinical MP strains preserved in the laboratory from 2016 to 2021 were taken for macrolide resistance gene testing and the evaluation of in vitro susceptibility to Azithromycin and Erythromycin.MIC 50 and MIC 90 values were calculated separately for macrolide-susceptible and -resistant strains. Results:All 288 MP strains underwent the test of in vitro susceptibility to Azithromycin, while 86 of them were additionally tested for Erythromycin.Among these strains, 22 strains were Azithromycin-sensitive, and 266 strains were Azithromycin-resistant.A2063G mutations were detected in 260 (97.7%) strains, while A2064G mutations were detected in 6 (2.3%) strains.Azithromycin-resistant strains had an MIC 50 of 128.000 μg/mL and an MIC 90 of 512.000 μg/mL, with the MIC ranging between 16.000 and 512.000 μg/mL.Seven strains were sensitive and 79 strains were resistant to Erythromycin.Among Erythromycin-resistant strains, A2063G mutations were detected in 73 (92.4%) strains, while A2064G mutations were detected in 6 (7.6%) strains.Erythromycin-resistant strains had an MIC 50 of 256.000 μg/mL and an MIC 90 of 512.000 μg/mL, with the MIC ranging between 64.000 and 1 024.000 μg/mL. Conclusions:A2063G and A2064G mutations in the 23S rRNA gene of MP are associated with high-level in vitro resistance to Azithromycin and Erythromycin, significantly limiting the clinical effectiveness of these antibiotics.Early resistance gene testing is recommended for suspected MP patients, which can help optimize the treatment, improve prognosis, and prevent resistance spread.

Objective To summarize the clinical features and prognosis of children suffered from malignant solid tumors of head and neck.Methods The clinical data of children with primary malignant solid tumors located in the head and neck was retrospectively analyzed from January 2007 to December 2021 in the Department of Oncology,Beijing Children's Hospital,Capital Medical University,and the clinical features,prognostic factors were summarized.Results A total of 234 children with malignant solid tumors of head and neck were included,with a male to female ratio of 1∶0.7,aged from 3 months to 17 years and 6 months(median age 51 months).173 cases(73.9％)were treated with local painless masses.Other symptoms included snoring and facial paralysis.The proportion of rhabdomyosarcoma(RMS)was the highest(145 cases,62.0％),followed by neuroblastoma(NB)(25 cases,10.7％),Ewing sarcoma(19 cases,8.1％),etc.A total of 47 cases(20.1％)had distant metastasis.The patients received surgery,chemotherapy and radiotherapy under the mode of multidisciplinary treatment(MDT).The 3-year and 5-year overall survival(OS)were 80.8％and 75.8％,respectively,and the 3-year and 5-year progression free survival(PFS)were 64.0％and 58.9％,respectively.Tumor survivors had abnormal appearance or facial motor function(49 cases,41.2％),developmental problems or abnormal tooth loss(18 cases,15.1％),and other long-term complications that may be related to the tumor or treatment.Conclusion There are various pathologic types of pediatric head and neck malignant solid tumors,RMS and NB are the most common.Local painless mass was the most common complaint.Distant metastasis is an independent risk factor for the prognosis of head and neck malignant solid tumors.Under the MDT model,the prognosis of malignant solid tumors of the head and neck in our center was generally good.In the treatment of the tumors,the side effects and sequelae should be controlled as small as possible under the premise of long-term survival.

Objective To investigate the effect of angiotensin receptor blocker(ARB)on the occurrence of acute kidney injury(AKI)after acute ischemic stroke.Methods From January 2022 to July 2023,patients with acute ischemic stroke hospitalized in the department of neurology of Nanjing First Hospital were enrolled.A 1∶1 propensity score matching method was adopted to evaluate the effect of ARB on the occurrence of AKI in patients with acute ischemic stroke.Results According to the inclusion and exclusion criteria,919 patients were enrolled,among whom 182developed AKI,with an incidence rate of 19.8％.Compared with patients without AKI,those with AKI were older and had a higher proportion of hypertension,diabetes,coronary heart disease,and heart failure.They were ad-mitted with lower Glasgow coma scale(GCS)score and higher National Institute of Health Stroke Scale(NIHSS)score.In terms of labo-ratory test data,patients with AKI had higher white blood cell counts,serum creatinine,and lower hemoglobin,albumin,low-density lipoprotein,and total cholesterol.Additionally,patients with AKI underwent a higher proportion of endovascular treatments,used diuret-ics,and received mannitol.After matching propensity score,patients using ARB had a lower incidence of AKI(17.1％vs 25.0％,P=0.044)and a lower mortality rate(1.2％vs 5.8％,P=0.014)than those without ARB.There were no significant differences between the two groups in terms of renal replacement therapy,intensive care unit,and the length of hospital stay.Conclusion ARB may have a potential protective effect on the occurrence of AKI after acute ischemic stroke.