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.

Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder. Its occurrence secondary to hepatobiliary malignancies is even rarer, and without timely diagnosis and treatment, the mortality rate is extremely high. There is a need to raise awareness of this disease. This report describes a case of a 70-year-old female patient diagnosed with AHA 2 months after surgery for cholangiocarcinoma, admitted to the Second Affiliated Hospital of Bengbu Medical College in October 2022. The patient presented with subcutaneous hematoma in both lower limbs. Coagulation function tests showed a markedly prolonged activated partial thromboplastin time (APTT) of 74.5 seconds, with no correction in the APTT mixing test. Coagulation factor assays revealed a severely reduced coagulation factor VIII activity (FVIII:C) of 0.3%, and an inhibitor titer of 25.6 BU/mL was detected. After ruling out other potential causes, the patient was diagnosed with cholangiocarcinoma-associated AHA. With chemotherapy to control the primary tumor, alongside hemostatic and immunosuppressive therapy for inhibitor eradication, AHA was brought under control. The patient had no further coagulation abnormalities or bleeding, enabling timely and full-course chemotherapy for cholangiocarcinoma and significantly improving survival and quality of life. Therefore, in patients with malignancies who present with spontaneous bleeding or unusual bleeding following surgery, trauma, or invasive procedures, clinicians should be alert to the possibility of secondary AHA. Timely diagnosis and treatment can significantly improve prognosis.
Humans ; Cholangiocarcinoma/surgery* ; Female ; Hemophilia A/drug therapy* ; Aged ; Bile Duct Neoplasms/surgery* ; Factor VIII

Objective: To investigate the aberrant alterations of microRNAs ( miRNAs) in exosomes derived from bone marrow stromal cells ( BMSCs) in the bone marrow supernatants of patients with acute myeloid leukemia (AML) and their impact on the prognosis of AML patients . Methods: Bone marrow supernatant samples were col- lected from three AML patients and three healthy donors . Exosomes were isolated using a commercial kit , identif- ying the morphology and marker expression , and subjected to miRNA sequencing to determine differentially ex- pressed miRNAs (DE-miRNAs) . The DE-miRNAs were then intersected with the exosomal miRNA expression pro- files of primary AML cells (GSE64029) to exclude AML cell - derived signals and to identify BMSC-derived DE - miRNAs . Subsequently , candidate miRNAs were identified through Cox regression and Lasso regression analyses based on data from The Cancer Genome Atlas (TCGA) . A prognostic risk model for AML was constructed , and pa- tients were stratified into high-risk and low-risk groups according to the median risk score . The prognostic value and clinical relevance of the model were further validated . Finally , the target genes of the candidate miRNAs were pre- dicted , followed by pathway enrichment analysis , construction of key regulatory networks , and correlation analysis between the expression levels of key miRNAs and their corresponding target genes . Results: Isolated exosomes ex- hibited a typical cup-shaped morphology with intact structures with particle size of 30 - 150 nm , and expressed exo- somal markers CD63 , ALIX , and TSG101 . miRNA sequencing identified 103 DE-miRNAs in AML patients com- pared with healthy donors; after intersection with the GSE64029 dataset , 83 BMSC-derived DE-miRNAs were re- tained . Among these , five candidate miRNAs ( miR-25-3p , miR-532-5p , miR-194-5p , miR-10a-5p , and miR- 20a-5p) were used to construct the prognostic model . Kaplan-Meier survival analysis demonstrated significantly lon- ger overall survival in the low-risk group compared with the high-risk group (P < 0. 05) . The areas under the ROC curve for the training/validation cohorts were 0. 80/0. 74 , 0. 80/0. 78 , and 0. 79/0. 64 at 1 , 2 , and 3 years , re- spectively . The prognostic model was significantly associated with risk stratification , patient age , and FAB classifi- cation (P < 0. 05) . KEGG pathway enrichment revealed that target genes of the candidate miRNAs were closely linked to cancer-related signaling pathways , including hepatocellular carcinoma , breast cancer , and non-small cell lung cancer. Correlation analysis indicated that the candidate miRNAs were significantly associated with key genes such as HIF1A , CREB1 , PIK3CA , IGF1R , PIK3R1 , TIAM1 , CRK , and PTEN (P < 0. 05) . Conclusion AML patients exhibit distinct miRNA expression profiles in BMSC-derived exosomes . A five-miRNA signature ( miR-25 - 3p , miR-532-5p , miR-194-5p , miR-10a-5p , and miR-20a-5p) demonstrates robust prognostic performance , sup- porting its potential clinical utility in risk stratification and outcome prediction for AML.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Optical illusion refers to the phenomenon in which the scene observed by the human eye is not completely consistent with the objectively presented scene. Optical illusions in stomatology, as well as their clinical application, are demonstrated in this paper in terms of shade, shape and aesthetic design. Shade is not only affected by the optical illusions with which it is associated, such as color metamerism, color constancy and the Chevreul illusion, but also influenced by the surroundings. It is suggested that the surrounding lighting during veneering should be the same as that during color matching in the clinic. As indicated by the Poggendorf illusion and the Leaning Tower illusion, the practice should be conducted and checked from multiple perspectives to compensate for the limitation of human eyes, such as intraoral scanning. Other digital technologies, including digital facial scanning and cephalometric measurement, could be used to reduce the subjective influence of observation. In terms of esthetic design, the interaction of the part and the whole, suggested by Ebbinghaus illusion, should be considered: an individual harmony smile should be designed considering the characteristics of the personality and the features of the face, lips, teeth and gingiva of the patient. Furthermore, personal information, such as gender and age, should be taken into consideration in beautification presentation. Further research should be focused on the influence of optical illusions in stomatology in more details. More communication among doctors, technicians and patients is needed. Clinicians should be aware of the impact of optical illusions to reduce subjective bias in clinical standardized operations and further take advantage of optical illusions to create beautification presentations of dental restorations and smiles.

To identify the related substances of tacrolimus by LC-MS techniques, the separation of the related substances contained in tacrolimus and its stressed samples was carried out on a Agilent Eclipse Plus-C18 (150 mm × 4.6 mm,3.5 μm) column with 0.01% fomic acid solution and a mixture of acetonitrile- methyl tert-butyl ether as the mobile phase.in linear gradient elution. Electrospray positive ionization high resolution Q-TOF/MS was used for the determination of the accurate mass and elemental composition of the parent ions of all the components, thence, the structures of all the detected substances were successfully characterized through spectra elucidation and fragmentation pathways analysis. Tacrolimus and its 35 detected related substances were well separated under the established conditions, among which 2 were its isomers , 3 were listed in United States Pharmacopeia(USP), and the rest 30 were identified as unknown products having not been reported before. These results were useful for its fermentation processes and quality control.

Multiple factors such as traditional history evolution, resource allocation and management mechanism all restrict the discipline development of basic medical sciences and the enhancement of postgraduate education quality. Guangzhou Medical University starts from top-level design, focuses on joint efforts of discipline construction and adopts a series of reform measures to promote first-class basic medical sciences discipline construction and enhance the postgraduate education quality, such as transforming the architecture of scientific institutions, grasping the discipline direction, setting double-tutor system, optimizing the tutor team, promoting curriculum reform, strengthening communication between domestic and overseas and selecting excellent students. Practice shows that positioning properly and developing with unique features based on joint efforts of discipline are effective approaches to build high-level teaching-research medical universities.

Objective:To explore the chain mediating effect of escape motivation and flow experience between frustration and online game addiction.Methods:Stratified cluster sampling method was used to randomly select 740 students from 5 universities in Beijing.Frustrate mental state scale (FMSS), escape subscale of online game motivation scale (OGMS), game flow scale (GFS), and the game addiction subscale of different types of internet addiction scale (DTIAS) were used for investigation. SPSS 25.0 software and PROCESS macro program model 6 were used to analyze the data and test the mediation effect.Results:Frustration (62.94±15.84) was positively correlated with escape motivation(6.89±2.34), flow experience(20.36±7.38), and online game addiction(16.05±6.62) ( r=0.30, 0.19, 0.39, all P<0.01). Escape motivation was positively correlated with flow experience and online game addiction ( r=0.51, 0.50, both P<0.01), while flow experience was positively correlated with online game addiction ( r=0.51, all P<0.01). The direct effect of frustration on game addiction was 0.23 (95% CI=0.17-0.30). Frustration indirectly affects game addiction through two paths. The single mediating effect of escape motivation was 0.07 (95% CI=0.05-0.11), and the chain mediating effect of escape motivation and flow experience was 0.05 (95% CI=0.04-0.08). Conclusion:Frustration not only directly affects online game addiction, but also indirectly affects online game addiction through escape motivation and flow experience.

Objective:To investigate the computed tomography (CT) features of adenocarcinoma of esophagogastric junction (AEG) after neoadjuvant chemotherapy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 59 patients with AEG who underwent neoadjuvant chemotherapy in Peking University Cancer Hospital from February 2010 to November 2014 were collected. There were 51 males and 8 females, aged from 46 to 82 years, with a median age of 63 years. All the 59 patients underwent enhanced CT examination before and after neoadjuvant chemotherapy. Observation indicators: (1) pathological examination and neoadjuvant chemotherapy of patients with AEG; (2) results of CT examination in patients with AEG, including ① qualitative indicators of CT and ② quantitative indicators of CT. Measurement data with skewed distribution were represented as M( P25, P75) or M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed by the chi-square test. Results:(1) Pathological examination and neoadjuvant chemotherapy of patients with AEG: of the 59 patients with AEG, high-differentiated adenocarcinoma was observed in 1 patient, moderate-differentiated adenocarcinoma in 40 patients, and low-differentiated adenocarcinoma in 18 patients. Effective response to neoadjuvant chemotherapy was observed in 13 patients, including 6 patients of pathological tumor regression grading (pTRG) 0 and 7 of pTRG 1; poor response was observed in 46 patients, including 12 patients of pTRG 2 and 34 patients of pTRG 3. (2) Results of CT examination in patients with AEG. ① Qualitative indicators of CT: for the 13 patients with effective response to neoadjuvant chemotherapy, 13 had the presence of ulcers, 5 had layered enhancement, 10 had infiltration of adventitia surface, and 2 had positive extramural venous invasion (EMVI) before neoadjuvant chemotherapy; after neoadjuvant chemotherapy, 13 had shallowed or disappeared ulcers, 7 patients had changed enhancement pattern, 3 had infiltration of adventitia surface, and 1 had positive EMVI. For the 46 patients with poor response to neoadjuvant chemotherapy, 28 had the presence of ulcers, 18 had layered enhancement, 37 had infiltration of adventitia surface, and 22 had positive EMVI before neoadjuvant chemotherapy; after neoadjuvant chemotherapy, 23 had shallowed or disappeared ulcers, 7 patients had changed layered enhancement pattern, 33 had infiltration of adventitia surface and 21 had positive EMVI, respectively. There was no significant difference in the layered enhancement or infiltration of adventitia surface before neoadjuvant chemotherapy between patients with different treatment response ( χ2=0.002, 0.000, P>0.05). There were significant differences in the presence of ulcers and positive EMVI before neoadjuvant chemotherapy between patients with different treatment response ( χ2=5.591, 4.421, P<0.05). After neoadjuvant chemotherapy, there were significant differences in the changes of layered enhancement pattern, infiltration of adventitia surface and positive EMVI between patients with different treatment response ( χ2=6.359, 10.090, 4.728, P<0.05); while there was no significant difference in the shallowed or disappeared ulcers between patients with different treatment response ( χ2=1.239, P>0.05). ② Quantitative indicators of CT: for the 13 patients with good response to neoadjuvant chemotherapy, the maximum tumor height, the maximum tumor area, enhanced CT value of the lesion before neoadjuvant chemotherapy were 1.37 cm(0.94 cm, 1.88 cm), 8.9 cm 2 (4.7 cm 2, 9.9 cm 2), 53 HU(47 HU, 63 HU), respectively. After neoadjuvant chemotherapy, the above indicators were 1.17 cm(0.79 cm, 1.29 cm), 4.4 cm 2(2.5 cm 2, 6.1 cm 2), 30 HU(25 HU, 53 HU), respectively. The change rates of the maximum tumor height, the maximum tumor area, and enhanced CT value of the lesion were -23%(-42%, 9%), -51%(-60 %, -21%), -44%(-51%, 19%), respectively. For the 46 patients with poor response to neoadjuvant chemotherapy, the maximum tumor height, the maximum tumor area, enhanced CT value of the lesion were 1.57 cm(1.21 cm, 1.96 cm), 9.4 cm 2(6.6 cm 2, 13.1 cm 2), 60 HU(53 HU, 66 HU) before neoadjuvant chemotherapy, respectively. After neoadjuvant chemotherapy, the above indicators were 1.16 cm(0.94 cm, 1.37 cm), 6.2 cm 2(4.8 cm 2, 8.1 cm 2), 55 HU(47 HU, 65 HU), respectively. The change rates of the maximum tumor height, the maximum tumor area, and enhanced CT value of the lesion were -27%(-38%, -9%), -33%(-47%, -12%), -9%(-22%, 9%), respectively. There was no significant difference in the maximum tumor height, the maximum tumor area, enhanced CT value of the lesion before neoadjuvant chemotherapy between patients with different treatment response ( Z=-1.372, -1.372, -1.331, P>0.05). There was no significant difference in the maximum tumor height after neoadjuvant chemotherapy between patients with different treatment response ( Z=-0.503, P>0.05), while there were significant differences in the maximum tumor area and CT value of the lesion ( Z=-2.743, -3.049, P<0.05). There was no significant difference in the change rate of the maximum tumor height or the maximum tumor area between patients with different treatment response ( Z=0.000, -1.481, P>0.05), while there was a significant difference in the change rate of CT value of the lesion ( Z=-3.231, P<0.05). Conclusion:Effective response of AEG to neoadjuvant chemotherapy was characterized by the changes in tumor layered enhancement pattern, reduction in the maximum tumor area, reduced CT value of the lesion, negative infiltration of adventitia surface, and negative EMVI.