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 analyze the infection characteristics of human respiratory syncytial virus (HRSV) among children hospitalized with acute lower respiratory tract infection (ALRTI) in a specialized pediatric hospital in Shanghai, so as to provide evidence-based support for optimizing the prevention and control strategies and clinical diagnosis and treatment of respiratory tract infections in children in this region. MethodsA retrospective analysis was performed to the clinical and etiological data of 29 260 children hospitalized for ALRTI in Shanghai Children’s Hospital from January 2021 to December 2024. HRSV and 12 other common respiratory pathogens were detected with multiplex polymerase chain reaction (PCR) and capillary electrophoresis. Demographic and clinical data were collected for statistical analyses. A total of2 412 cases with positive HRSV were divided into the severe group and the non-severe group. Clinical characteristics between the two groups were compared using the Mann-Whitney U test and the chi- square (χ²) test. Additionally, the related influencing factors of severe HRSV infection were explored. ResultsThe overall positivity rate of HRSV from 2021 to 2024 was 8.24% (2 412/29 260), with statistically significant differences observed across the four years (χ²=389.42, P<0.001). The highest positivity rate was in 2021 (14.76%), with a high prevalence throughout the year. In 2022, when non-pharmaceutical interventions (NPIs) were implemented, the HRSV positivity rate was the lowest (4.93%), with a winter-dominant epidemic pattern. In 2023, after the NPIs were lifted, the HRSV positivity rate showed a slight rebound (8.14%), presenting a double-peak pattern. In 2024, the HRSV positivity rate slightly decreased compared to that in 2023 (6.29%), exhibiting a winter and spring-dominant epidemic pattern. Among the hospitalized children with ALRTI, the HRSV positivity rate in males (8.85%) was higher than that in females (7.51%), and the difference was statistically significant (χ²=17.33, P<0.001). Age distribution showed that 82.26% (1 984/2 412) of HRSV infections occurred in children aged 3 years old and below. Besides, as age increased, the infection rate of HRSV showed a gradually decreasing trend (P<0.001). Among the 2 412 children with HRSV infection, the proportion of severe cases was 22.31% (538/2 412), while the non-severe cases accounted for 77.69% (1 874/2 412). Compared with non-severe cases, severe cases were more frequently presented with high fever, longer duration of wheezing, as well as higher rates of underlying diseases or co-infection with Mycoplasma pneumoniae (P<0.001). ConclusionThe prevalence intensity of HRSV varied yearly from 2021 to 2024. After the removal of NPIs in 2023, a slight rebound with a double-peak epidemic pattern was observed. HRSV remained a common pathogen in children hospitalized for ARLTI, and children aged 3 years old and below constituted the highest proportion for infection. Compared with non-severe cases, those with severe HRSV infections were more prone to presenting with high fever and a longer duration of wheezing. Children with positive HRSV who had underlying diseases or co-infection with Mycoplasma pneumonia were more likely to develop severe conditions.

Disease computable phenotype is a data model designed to identify specific clinical conditions or characteristics, which automatically extracts information from clinical databases such as electronic health records through algorithms. Phenotypic data for rare diseases often reside in unstructured text. Due to the scarcity of rare disease cases, atypical symptoms, and insufficient physician experience, misdiagnosis and underdiagnosis rates remain high. In this context, the application of computable phenotype technology holds promise for improving the accuracy and efficiency of rare disease diagnosis. This article reviews the current research status, challenges, and opportunities of computable phenotype technology in biomedicine, particularly in the field of rare diseases, and proposes a development and validation framework for rare disease computable phenotypes, aiming to provide research and development insights for computable phenotypes to empower the diagnosis and treatment of rare diseases.

OBJECTIVE To explore the colonization rates of carbapenem-resistant gram-negative bacteria(CRGNB)in intestinal tracts of intensive care unit(ICU)patients and analyze the influencing factors.METHODS The ICU patients were recruited from a three-A general hospital of Shanghai from Jan.2024 to Dec.2024,an ac-tive screening was carried out for intestinal tract CRGNB,and the detection rates of 5 types of carbapenems resist-ance genes(CRGs)in the CRGNB strains were observed.The baseline data and hospitalization data before the ac-tive screening were collected from the patients,logistic regression analysis was performed for the influencing fac-tors for the colonization of CRGNB.The effects of targeted infection control measures on length of ICU stay,hos-pitalization cost and prognosis were observed and compared before and after the active screening was carried out.RESULTS A total of 748 patients were included in the active screening,and the colonization rate of CRGNB in intestinal tracts was 11.50％(86/748).Among the CRGs,the detection rate of blaNDM was the highest(6.82％),followed by blaIMP(4.55％)and blaKPC(2.54％).The result of logistic regression analysis showed that,with an increase of 1 each day of hospital stay before the admission to ICUs,the risk was increased by 1.055 times(OR=1.055,95％CI:1.030 to 1.081,P＜0.001),the risk was 0.442 times the use of as aminoglycosides as the use of β-lactams(OR=0.442,95％CI:0.244 to 0.801,P=0.007).The targeted infection control measures that were taken after the active screening shortened the length of hospital stay(Z=-3.514,P＜0.001),reduce the hospitalization cost(Z=3.030,P=0.002)and improve the prognosis of the patients(x2=7.470,P=0.006).CONCLUSIONS The colonization rates of CRGNB in intestinal tracts are high among the ICU patients.It is necessary to reduce the length of hospital stay prior to ICU and strengthen the surveillance of drug-resistant strains and management of antibiotics.

Resistance to poly adenosine diphosphate(ADP)-ribose polymerase inhibitor(PARPi)presents a considerable obstacle in the treatment of ovarian cancer.F-box and tryptophan-aspartic(WD)repeat domain containing 11(FBXW11)modulates the ubiquitination of growth-and invasion-related factors in lung cancer,colorectal cancer,and osteosarcoma.The function of FBXW11 in PARPi therapy is still ambiguous.In this study,RNA sequencing(RNA-seq)showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi.FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer(HGSOC)tissues,and low levels of FBXW11 were associated with shorter overall survival(OS)and progression-free survival(PFS)in HGSOC patients.Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi,while knocking down FBXW11 made it less sensitive.The four-dimensional(4D)label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11(S100A11)and promoted its degradation through ubiquiti-nation.The increased degradation of S100A11 led to less efficient DNA damage repair,which in turn contributed to increased PARPi-induced DNA damage.The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models.In summary,our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S10OA11-mediated DNA damage repair.

To summarize the applications of data-intelligence technology in diagnosing lysosomal storage disease(LSD), analyze their opportunities and challenges in clinical practice as well as their development trends, and provide insights and recommendations for advancing digitally driven auxiliary diagnostic technologies.

BACKGROUND: Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL. METHODS: A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. RESULTS: Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups. CONCLUSION Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.

A primary hallmark of pathological cardiac hypertrophy is excess protein synthesis due to enhanced translational activity. However, regulatory mechanisms at the translational level under cardiac stress remain poorly understood. Here we examined the translational regulations in a mouse cardiac hypertrophy model induced by transaortic constriction (TAC) and explored the conservative networks versus the translatome pattern in human dilated cardiomyopathy (DCM). The results showed that the heart weight to body weight ratio was significantly elevated, and the ejection fraction and fractional shortening significantly decreased 8 weeks after TAC. Puromycin incorporation assay showed that TAC significantly increased protein synthesis rate in the left ventricle. RNA-seq revealed 1,632 differentially expressed genes showing functional enrichment in pathways including extracellular matrix remodeling, metabolic processes, and signaling cascades associated with pathological cardiomyocyte growth. When combined with ribosome profiling analysis, we revealed that translation efficiency (TE) of 1,495 genes was enhanced, while the TE of 933 genes was inhibited following TAC. In DCM patients, 1,354 genes were upregulated versus 1,213 genes were downregulated at the translation level. Although the majority of the genes were not shared between mouse and human, we identified 93 genes, including Nos3, Kcnj8, Adcy4, Itpr1, Fasn, Scd1, etc., with highly conserved translational regulations. These genes were remarkably associated with myocardial function, signal transduction, and energy metabolism, particularly related to cGMP-PKG signaling and fatty acid metabolism. Motif analysis revealed enriched regulatory elements in the 5' untranslated regions (5'UTRs) of transcripts with differential TE, which exhibited strong cross-species sequence conservation. Our study revealed novel regulatory mechanisms at the translational level in cardiac hypertrophy and identified conserved translation-sensitive targets with potential applications to treat cardiac hypertrophy and heart failure in the clinic.
Animals ; Humans ; Cardiomegaly/physiopathology* ; Ribosomes/physiology* ; Protein Biosynthesis/physiology* ; Mice ; Cardiomyopathy, Dilated/genetics* ; Ribosome Profiling

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.