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.

Objective To explore the effectiveness of an integrated laparoscopic simulation training course (best essential surgical technique training, BEST) in enhancing laparoscopic peritoneal suturing techniques in surgical residents.Methods As an integrated two-stage program, the BEST course applied basic laparoscopic training system with simple molds in phase Ⅰ training, and then adopted advanced laparoscopic training system, 3D Laparoscope and ex-vivo animal models in phase Ⅱ training. The laparoscopic suturing techniques were practiced in phase Ⅱ training. From August 2021 to July 2024, surgical residents in the second year of the national standardized training program were divided into pilot and control groups based on whether they had undergone the BEST course. Two cases of laparoscopic peritoneal suture were performed by the surgical residents under supervision in the department of gastrointestinal surgery. The operative time, quality of suture, and independent completion rate were compared between the two groups.Results A total of 33 surgical residents (19 in pilot group and 14 in control group) were included in this study, and a total of 66 cases of laparoscopic peritoneal suture were performed (38 in pilot group and 28 in control group). The operative time was significantly shorter in pilot group than that in control group (15.7 min vs. 17.5 min, P=0.025). The quality of suture was significantly better in pilot group compared to control group (P=0.023). In pilot group, all peritoneal sutures were performed by residents independently, whereas in control group, 3 cases (10.7%) were assisted by the supervisor, and the independent completion rate was different significantly (P=0.039).Conclusions The BEST course can help improve surgical residents′ laparoscopic peritoneal suturing techniques and could be promoted in the national standardized training program for surgical residents.

Bronchopulmonary dysplasia（BPD），a common chronic respiratory disease caused by multiple factors，can seriously affect the quality of life and prognosis of prematurity.A variety of factors，including infection and oxidative stress，can contribute to the development of BPD in prematurity.Interleukin 6（IL-6），as an important cytokine that activates various signal cascades and participates in many physiological processes in the body，is currently considered to be one of the independent risk factors for the development of BPD in prematurity.The IL-6-related signal pathways，represented by JAK/STAT，can play an important role in the development of BPD through various pathways such as lung injury，pulmonary angiogenesis，proliferation and apoptosis of epithelial cells，and ferroptosis.This article reviews the studies on the mechanism of IL-6-related signal pathways in BPD，which will provide possible new targets for its treatment in BPD in the future.

Objective:To compare the efficacy of different doses of tranexamic acid (TXA) for traumatic hemorrhagic shock (THS) in the early phase of trauma following acute exposure to high altitude in rabbits.Methods:Twenty-five healthy male New Zealand rabbits were randomly divided into plain control group ( n=5) and acute high-altitude THS group ( n=20) according to the random number table method. The plain control group did not undergo THS modeling throughout the experiment while the acute high-altitude THS group was raised in a hypoxia simulation chamber with a volume fraction of 10% for 3 days to establish the THS model. Based on the different doses of TXA administered intravenously at 30 minutes after THS modeling, the acute high-altitude THS group was further divided into four subgroups: acute high-altitude THS+0 mg/kg TXA subgroup, acute high-altitude THS+45 mg/kg TXA subgroup, acute high-altitude THS+90 mg/kg TXA subgroup and acute high-altitude THS+135 mg/kg TXA subgroup, with 5 rabbits in each. The vital signs [mean arterial pressure (MAP), heart rate, rectal temperature] and blood cell counts [red blood cell count (RBC), platelet count (PLT)], 4 coagulation parameters [fibrinogen (FIB), D-dimer, activated partial thromboplastin time (APTT), prothrombin time (PT)], thromboelastography [clotting reaction time (R value), clot formation time (K value), maximum amplitude (MA value)], syndecan-1, inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)], and plasminogen activator inhibitor-1 (PAI-1) were recorded before blood loss, at 30 minutes and 120 minutes after blood loss. At 6 hours after THS, the lungs, terminal ileum, and kidneys of the rabbits were collected to observe tissue damage, and the wet/dry weight ratio (W/D) and total water content (TLW) of the lung tissue were measured. Results:(1) Vital signs: Before blood loss, there were no significant differences in MAP, heart rate, or rectal temperature between the acute high-altitude THS subgroups and the plain control group ( P>0.05). At 30 minutes and 120 minutes after blood loss, the acute high-altitude THS subgroups exhibited significantly lower MAP, heart rate, and rectal temperature compared to those in the plain control group ( P<0.05). No significant differences were observed in MAP, heart rate or rectal temperature among the acute high-altitude THS subgroups at any time point ( P>0.05). In the acute high-altitude THS subgroups, MAP, heart rate and rectal temperature were significantly decreased at 30 minutes and 120 minutes after blood loss compared to those before blood loss ( P<0.05); At 120 minutes after blood loss, these parameters were further significantly decreased compared to those at 30 minutes after blood loss ( P<0.05). (2) Blood cell counts: Before blood loss, the RBC count was significantly higher in the acute high-altitude THS subgroups compared to that in the plain control group ( P<0.05), while the PLT was significantly lower ( P<0.05). At 30 minutes after blood loss, there was no significant difference in RBC count between the acute high-altitude THS subgroups and the plain control group ( P>0.05), but the PLT remained significantly lower in the acute high-altitude THS subgroups ( P<0.05). At 120 minutes after blood loss, the RBC count was significantly lower in the acute high-altitude THS subgroups compared to that in the plain control group ( P<0.05), with no significant differences among the acute high-altitude THS subgroups ( P>0.05). The PLT count was significantly lower in the acute high-altitude THS+0 mg/kg TXA subgroup compared to the other subgroups ( P<0.05). The PLT count in the acute high-altitude THS+45 mg/kg TXA subgroup was significantly lower than those in the acute high-altitude THS+90 mg/kg TXA and acute high-altitude THS+135 mg/kg TXA subgroups ( P<0.05), with no significant differences between the latter two subgroups ( P>0.05). (3) Four Coagulation parameters: Before blood loss, D-dimer level was significantly higher in the acute high-altitude THS subgroups compared to that in the plain control group ( P<0.05), while no significant difference was observed in FIB ( P>0.05). APTT and PT were significantly shortened in the acute high-altitude THS subgroups ( P<0.05). At 30 minutes after blood loss, D-dimer level remained significantly higher in the acute high-altitude THS subgroups compared to that in the plain control group ( P<0.05), while FIB was significantly lower ( P<0.05), with significant increase of APTT and PT compared to those before blood loss ( P<0.05). At 120 minutes after blood loss, the acute high-altitude THS+0 mg/kg TXA subgroup exhibited significantly higher D-dimer level compared to the other subgroups ( P<0.05), with significantly lower FIB and higher APTT and PT ( P<0.05). The acute high-altitude THS+45 mg/kg TXA subgroup also showed significantly higher D-dimer level compared to those in the acute high-altitude THS+90 mg/kg TXA and acute high-altitude THS+135 mg/kg TXA subgroups ( P<0.05), with significantly lower FIB and increased APTT and PT ( P<0.05). No significant differences were observed in D-dimer, FIB, APTT or PT between the acute high-altitude THS+90 mg/kg TXA and acute high-altitude THS+135 mg/kg TXA subgroups ( P>0.05). (4) Thromboelastography parameters: Before blood loss, the R value was significantly shorter in the acute high-altitude THS subgroups compared to that in the plain control group ( P<0.05), while no significant differences were observed in K value or MA value ( P>0.05). At 30 minutes after blood loss, both R value and K value were significantly shorter in the acute high-altitude THS subgroups compared to those in the plain control group ( P<0.05), with no significant differences in MA value ( P>0.05). At 120 minutes after blood loss, the acute high-altitude THS+0 mg/kg TXA subgroup exhibited significantly increased R value and K value compared to those in the other subgroups ( P<0.05), while MA value was significantly decreased ( P<0.05). The remaining acute high-altitude THS subgroups showed significant decrease of R value and K value compared to those in the plain control group ( P<0.05), while MA value was significantly lower ( P<0.05). The acute high-altitude THS+45 mg/kg TXA subgroup exhibited significantly lower R value and K value compared to those in the acute high-altitude THS+90 mg/kg TXA and acute high-altitude THS+135 mg/kg TXA subgroups ( P<0.05), with no significant differences in R value, K value and MA value between the later two groups ( P<0.05). (5) Changes in Syndecan-1, inflammatory factors and PAI-1: Before blood loss, syndecan-1 was significantly higher in the acute high-altitude THS subgroups compared to that in the plain control group ( P<0.05), while no significant differences were observed in IL-6, TNF-α, or PAI-1 ( P>0.05). At 30 minutes after blood loss, syndecan-1, IL-6, TNF-α, and PAI-1 were significantly higher in the acute high-altitude THS subgroups compared to those in the plain control group ( P<0.05). At 120 minutes after blood loss, syndecan-1, IL-6, TNF-α, and PAI-1 were significantly higher in the acute high-altitude THS subgroups compared to those in the plain control group ( P<0.05). Among them, the acute high-altitude THS+0 mg/kg TXA group exhibited significantly higher levels of syndecan-1, IL-6, TNF-α, and PAI-1 compared to the other acute high-altitude THS subgroups ( P<0.05). The acute high-altitude THS+45 mg/kg TXA subgroup had significantly higher syndecan-1, IL-6, and TNF-α compared to those in the acute high-altitude THS+90 mg/kg TXA and acute high-altitude THS+135 mg/kg TXA subgroups ( P<0.05), with no significant difference in PAI-1 ( P>0.05). No significant differences were observed in syndecan-1, IL-6, TNF-α or PAI-1 between the acute high-altitude THS+90 mg/kg TXA and acute high-altitude THS+135 mg/kg TXA subgroups ( P>0.05). (6) Tissue injury: At 6 hours after THS, acute high-altitude THS+0 mg/kg TXA group exhibited significant interstitial thickening of the lung with extensive inflammatory cell infiltration, localized loss of intestinal brush border accompanied by cellular disruption, and marked structural disruption of renal corpuscles with focal cellular injury and necrosis. At 6 hours after THS, the acute high-altitude THS+0 mg/kg TXA subgroup exhibited significantly higher lung injury scores, Chiu′s intestinal injury scores, and kidney injury scores compared to those of the other subgroups ( P<0.05). No significant differences were observed in the tissue injury scores of the lungs, intestines and kidneys among the other subgroups ( P>0.05). The acute high-altitude THS+0 mg/kg TXA subgroup also had significantly higher lung W/D and TLW compared to those in the other subgroups ( P<0.05). At 6 hours after THS, the acute high-altitude THS+45 mg/kg TXA group exhibited significantly higher W/D and TLW of the lung tissues compared to those in the acute high-altitude THS+90 mg/kg TXA and acute high-altitude THS+135 mg/kg TXA groups ( P<0.05), with no significant differences between the latter two subgroups ( P>0.05). Conclusions:At 3 days after acute exposure to high altitude, rabbits show a hypercoagulable state of the blood, accompanied by endothelial barrier dysfunction. At 30 minutes after the induction of acute high-altitude THS, a single slow intravenous bolus injection of TXA at doses of 90 mg/kg and 135 mg/kg is more effective in improving coagulation and fibrinolysis function, inflammatory response, endothelial injury, and reduced the risk of pulmonary edema than that at a dose of 45 mg/kg.

Objective To evaluate the efficacy and safety of transcatheter aortic valve implantation(TAVI)for the treatment of primary aortic valve regurgitation(NAVR)and to compare the difference in the choice of prosthetic valve size and the difference in complications with aortic stenosis(AS).Methods According to the definition of Valve Academic Research Consortium(VARC-3),143 patients with NAVR/AS treated with TAVI and patients with NAVR treated with surgical aortic valve replacement(SAVR)at Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,China,from March 2019 to September 2024 were selected,and clinical data on baseline,perioperative,and primary endpoint events were were retrospectively collected and compared.Results Forty-three patients with NAVR were treated with TAVI,with a device success rate of 86.0％and a surgical success rate of 95.3％.Subgroup comparisons:(1)NAVR-TAVI group than NAVR-SAVR group:patients in the TAVI group had a significantly shorter operative time than those in the SAVR group(P＜0.001);complete left bundle branch block was more likely to occur after TAVI(P=0.042),and complete right bundle branch block was more likely to occur after SAVR(P=0.044).SAVR postoperatively The incidence of congestive heart failure was higher(P=0.013),and the mortality rate was significantly higher in the SAVR group than in the TAVI group(P=0.019).(2)NAVR-TAVI group than AS-TAVI group:the differences in access selection,THV size[28(22,34)mm vs.24(22,32)mm,P=0.044]and proportion of THV overdiameter[14％(7％,20％)vs.7％(3％,11％),P＜0.001]were statistically significant.patients in AS and NAVR groups had 1 case of permanent pacing after TAVI treatment.In the AS and NAVR groups,there was 1 case of permanent pacemaker implantation after TAVI.2 patients in the AS group were converted to surgical treatment,and 6 patients died.Conclusions The use of"off-label"(transfemoral)and"on-label"(transapical)TAVI devices(both from domestic sources)is safer than SAVR for the treatment of NAVR,especially in elderly and high-risk patients.Compared with patients with AS treated with TAVI,larger diameter annulas are usually selected for NAVR,with higher rates of valve migration,but overall safety and efficacy are comparable to AS.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Pulmonary electrical impedance tomography (EIT), a noninvasive, continuous, dynamic, and radiation-free bedside imaging technique for monitoring pulmonary ventilation, is now widely utilized in the diagnosis and management of critically ill patients. Beyond ventilation monitoring, hypertonic saline contrast-enhanced EIT for bedside pulmonary perfusion assessment has recently garnered significant attention. This article describes the application of hypertonic saline contrast-enhanced EIT to evaluate pulmonary perfusion in two patients following pulmonary endarterectomy, providing a reference for its perioperative application in such patients.

Objective To evaluate the efficacy and safety of transcatheter aortic valve implantation(TAVI)for the treatment of primary aortic valve regurgitation(NAVR)and to compare the difference in the choice of prosthetic valve size and the difference in complications with aortic stenosis(AS).Methods According to the definition of Valve Academic Research Consortium(VARC-3),143 patients with NAVR/AS treated with TAVI and patients with NAVR treated with surgical aortic valve replacement(SAVR)at Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,China,from March 2019 to September 2024 were selected,and clinical data on baseline,perioperative,and primary endpoint events were were retrospectively collected and compared.Results Forty-three patients with NAVR were treated with TAVI,with a device success rate of 86.0％and a surgical success rate of 95.3％.Subgroup comparisons:(1)NAVR-TAVI group than NAVR-SAVR group:patients in the TAVI group had a significantly shorter operative time than those in the SAVR group(P＜0.001);complete left bundle branch block was more likely to occur after TAVI(P=0.042),and complete right bundle branch block was more likely to occur after SAVR(P=0.044).SAVR postoperatively The incidence of congestive heart failure was higher(P=0.013),and the mortality rate was significantly higher in the SAVR group than in the TAVI group(P=0.019).(2)NAVR-TAVI group than AS-TAVI group:the differences in access selection,THV size[28(22,34)mm vs.24(22,32)mm,P=0.044]and proportion of THV overdiameter[14％(7％,20％)vs.7％(3％,11％),P＜0.001]were statistically significant.patients in AS and NAVR groups had 1 case of permanent pacing after TAVI treatment.In the AS and NAVR groups,there was 1 case of permanent pacemaker implantation after TAVI.2 patients in the AS group were converted to surgical treatment,and 6 patients died.Conclusions The use of"off-label"(transfemoral)and"on-label"(transapical)TAVI devices(both from domestic sources)is safer than SAVR for the treatment of NAVR,especially in elderly and high-risk patients.Compared with patients with AS treated with TAVI,larger diameter annulas are usually selected for NAVR,with higher rates of valve migration,but overall safety and efficacy are comparable to AS.

Objective:To investigate the clinical management,complications,and prognostic prediction model of bronchopulmonary dysplasia(BPD)in preterm infants.Methods:A total of 854 very preterm infants(gestational age ≤ 32 weeks)admitted to the Neonatal Intensive Care Unit(NICU)of Shanghai Children's Hospital from January 2018 to December 2022 were retrospectively enrolled.After applying inclusion and exclusion criteria,713 infants were included.Based on the 2018 National Institute of Child Health and Human Development(NICHD)diagnostic criteria for BPD,the cohort was divided into a BPD group(n=164)and a non-BPD group(n=549).Clinical data of infants and maternal characteristics were compared between groups.Univariate and stepwise multivariate logistic regression analyses were performed to identify independent risk factors for BPD and evaluate clinical management.A nomogram model was subsequently developed to predict BPD prognosis.Results:Gestational age,duration of non-invasive ventilation,total oxygen therapy time,total hospital stay,hemodynamically significant patent ductus arteriosus(hsPDA),maximum diameter of patent ductus arteriosus(PDA),fetal growth restriction(FGR),use of vasoactive agents,and proportion of pulmonary surfactant administration were identified as independent risk factors for BPD(all P＜0.05,OR＞0).The nomogram model demonstrated excellent predictive performance,with an area under the receiver operating characteristic curve(AUC)of 0.93 and a calibration curve slope approaching 1.The Hosmer-Lemeshow goodness-of-fit test indicated satisfactory model calibration(x2=8.2865,P=0.406).Conclusion:Gestational age,non-invasive ventilation duration,total oxygen therapy time,total hospital stay,hsPDA,PDA maximum diameter,FGR,vasoactive agents,and pulmonary surfactant use are critical predictors of BPD in preterm infants.The prognostic models for BPD incidence and severity,constructed based on these factors,exhibit strong predictive accuracy and may serve as a valuable clinical tool for risk stratification and early intervention.

Objective:To explore the association between cardiometabolic multimorbidity(CMM), the number of cardiometabolic diseases(CMD)and mild cognitive impairment(MCI)among the older adults in urban communities.Methods:Based on the baseline data of the Hubei Memory and Aging Cohort Study(HMACS)from 2018 to 2023, CMM was defined as the coexistence of two or more CMDs(Type 2 diabetes, stroke and ischemic heart disease). Multivariate logistic regression was employed to examine the association between CMM, the number of CMDs and the prevalence of MCI, as well as subgroup heterogeneity.Results:This study included 6 113 urban participants aged ≥65 years(55.6% were female; mean age 71.9±5.7 years). The prevalence of MCI was 19.3%, with an increasing trend observed as the number of CMD increased(17.7%, 20.5%, 24.6%, 28.3%). After adjusting for all variables, a significant association was observed between CMM group and the prevalence of MCI( OR: 1.24, 95% CI: 1.01-1.52)compared with the non-CMM group.As the number of CMD increased, the prevalence of MCI increased( Ptrend=0.011), but the association was only significant in the group with two CMDs.Subgroup analyses revealed that in males( OR: 1.48, 95% CI: 1.10-2.00), those with more than 9 years of education( OR: 1.52, 95% CI: 1.15-2.02), and those with hypertension( OR: 1.33, 95% CI: 1.05-1.67), CMM was significantly associated with MCI, and the association with MCI increased significantly with the increase in the number of CMDs(all Pfor trend <0.05). Conclusions:Among urban community-dwelling older adults aged ≥65 years in China, CMM and the cumulative number of CMDs are significantly associated with an increase of MCI, particularly in males, those with higher education levels, and those with hypertension.In the future, the need for enhanced MCI screening for CMM patients should be strengthened, and targeted prevention and control of cognitive impairment should be implemented for high-risk populations.