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.

Temporomandibular joint disc (TMJD) is a critical anatomical structure within the maxillofacial region. However, its self-repair ability is limited, which often leads to functional degradation. The development of tissue engineering technology provides a new treatment strategy for TMJD repair, in which the scaffold provides basic physical support and suitable cellular microenvironment. Scaffold materials include naturally derived scaffolds, decellularised extracellular matrix scaffolds and synthetic polymer scaffolds. Currently, advancements in material composite techniques, surface modification, and chemical modification, as well as the optimization of electrospinning and three-dimensional printing technologies, have significantly enhanced the overall performance of the scaffold. These improvements exhibit promising potential for the repair of TMJD with varying degrees of defects. This paper provides an overview of the progress in tissue engineering scaffold materials in repairing of TMJD, focusing on ideal biological properties, material types, scaffold optimization strategies and clinical application. It aims to serve as a reference for the development of scaffold materials and the clinical translation of tissue engineering.

Objective:To investigate the efficacy and safety of combined chemotherapy based on radical radiotherapy in elderly patients with cervical cancer, as well as the influence of the sequence of radiotherapy and chemotherapy on clinical prognosis.Methods:Clinical data of 112 elderly patients with cervical cancer aged 65-80 years who received radical radiotherapy in Department of Radiotherapy Oncology of the First Affiliated Hospital of Soochow University from January 2018 to July 2022 were retrospectively analyzed. The follow-up deadline was January 31, 2023. A total of 26 patients received radical radiotherapy alone (radiotherapy alone group), while 86 patients received radical radiotherapy combined with chemotherapy (chemoradiotherapy group), including sequential chemoradiotherapy group ( n=57) and concurrent chemoradiotherapy group ( n=29). The recent efficacy, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of adverse reactions in patients between the chemoradiotherapy group and radiotherapy alone group, sequential chemoradiotherapy group and concurrent chemoradiotherapy group, elderly patients aged ≥70 years old were analyzed by Chi-square test, Fisher exact probability method, one-way ANOVA, paired sample t-test and Kruskal-Wallis test. Results:There were no significant differences in recent efficacy, ORR and DCR between chemoradiotherapy group and radiotherapy alone group ( P=0.245, 0.715 and 0.551). The median PFS was 25 months vs. 19 months ( P=0.265), and the median OS was 53 months vs. 30 months ( P=0.040). Lymphocytopenia was the most common grade 3-4 adverse reactions between two groups, and there were statistically significant differences in hematological adverse reactions and gastrointestinal adverse reactions between two groups (both P<0.05). There were no significant differences in recent efficacy, ORR, DCR, median PFS and median OS between sequential chemoradiotherapy group and concurrent chemoradiotherapy group (all P>0.05). However, the gastrointestinal adverse reactions in the concurrent chemoradiotherapy group were significantly higher than those in the sequential chemoradiotherapy group ( P=0.024). The results of elderly patients aged ≥70 years old were basically consistent with those between the chemoradiotherapy group and radiotherapy alone group. Conclusions:Combined chemotherapy based on radical radiotherapy is an effective and relatively safe treatment for elderly patients even those aged ≥70 years old with cervical cancer. Sequential and concurrent chemoradiotherapy have similar therapeutic effects in elderly patients, but the incidence of gastrointestinal reactions is significantly reduced in the former.

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.

Temporomandibular joint disc (TMJD) is a critical anatomical structure within the maxillofacial region. However, its self-repair ability is limited, which often leads to functional degradation. The development of tissue engineering technology provides a new treatment strategy for TMJD repair, in which the scaffold provides basic physical support and suitable cellular microenvironment. Scaffold materials include naturally derived scaffolds, decellularised extracellular matrix scaffolds and synthetic polymer scaffolds. Currently, advancements in material composite techniques, surface modification, and chemical modification, as well as the optimization of electrospinning and three-dimensional printing technologies, have significantly enhanced the overall performance of the scaffold. These improvements exhibit promising potential for the repair of TMJD with varying degrees of defects. This paper provides an overview of the progress in tissue engineering scaffold materials in repairing of TMJD, focusing on ideal biological properties, material types, scaffold optimization strategies and clinical application. It aims to serve as a reference for the development of scaffold materials and the clinical translation of tissue engineering.

Objective:To investigate the efficacy and safety of combined chemotherapy based on radical radiotherapy in elderly patients with cervical cancer, as well as the influence of the sequence of radiotherapy and chemotherapy on clinical prognosis.Methods:Clinical data of 112 elderly patients with cervical cancer aged 65-80 years who received radical radiotherapy in Department of Radiotherapy Oncology of the First Affiliated Hospital of Soochow University from January 2018 to July 2022 were retrospectively analyzed. The follow-up deadline was January 31, 2023. A total of 26 patients received radical radiotherapy alone (radiotherapy alone group), while 86 patients received radical radiotherapy combined with chemotherapy (chemoradiotherapy group), including sequential chemoradiotherapy group ( n=57) and concurrent chemoradiotherapy group ( n=29). The recent efficacy, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of adverse reactions in patients between the chemoradiotherapy group and radiotherapy alone group, sequential chemoradiotherapy group and concurrent chemoradiotherapy group, elderly patients aged ≥70 years old were analyzed by Chi-square test, Fisher exact probability method, one-way ANOVA, paired sample t-test and Kruskal-Wallis test. Results:There were no significant differences in recent efficacy, ORR and DCR between chemoradiotherapy group and radiotherapy alone group ( P=0.245, 0.715 and 0.551). The median PFS was 25 months vs. 19 months ( P=0.265), and the median OS was 53 months vs. 30 months ( P=0.040). Lymphocytopenia was the most common grade 3-4 adverse reactions between two groups, and there were statistically significant differences in hematological adverse reactions and gastrointestinal adverse reactions between two groups (both P<0.05). There were no significant differences in recent efficacy, ORR, DCR, median PFS and median OS between sequential chemoradiotherapy group and concurrent chemoradiotherapy group (all P>0.05). However, the gastrointestinal adverse reactions in the concurrent chemoradiotherapy group were significantly higher than those in the sequential chemoradiotherapy group ( P=0.024). The results of elderly patients aged ≥70 years old were basically consistent with those between the chemoradiotherapy group and radiotherapy alone group. Conclusions:Combined chemotherapy based on radical radiotherapy is an effective and relatively safe treatment for elderly patients even those aged ≥70 years old with cervical cancer. Sequential and concurrent chemoradiotherapy have similar therapeutic effects in elderly patients, but the incidence of gastrointestinal reactions is significantly reduced in the former.

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.

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.