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 epidemiological characteristics of 8 major respiratory pathogens in influenza-like illness (ILI) cases with acute respiratory infections at fever clinics in Huangpu District, Shanghai from 2015 to 2024, and to provide a scientific basis for the prevention and treatment of respiratory diseases. MethodsA retrospective study was conducted in Huangpu District. Individuals meeting the case definition of ILI from 2015 to 2024 was registered. Their nasopharyngeal swabs were collected for pathogen detection. A total of 8 respiratory viruses were tested, including Influenza A virus (Flu A), Influenza B virus (Flu B), adenovirus (ADV), enterovirus/human rhinovirus (EV/HRV), human parainfluenza virus (HPIV), human coronavirus (HCoV), respiratory syncytial virus (RSV), and human metapneumovirus (HMPV). ResultsFrom 2015 to 2019, a total of 344 ILI cases were tested, of which 192 out of 344 cases (55.81%) were tested positive for single respiratory pathogen. From 2023 to 2024, 1 557 ILI cases were tested, with 572 out of 1 557 cases (36.74%) being positive for single pathogen. From 2023 to 2024, the positive rate of single pathogen in ILI cases was significantly lower than that in 2015‒2019 (χ²=42.66, P<0.001). Specifically, the positive rate of Flu A (χ²=74.43, P<0.001) decreased, while that of HPIV (χ²=8.66, P=0.003) increased, both with statistically significant differences. According to the seasonal pattern, the epidemic intensity of Flu A decreased in summer, while that of HPIV increased in summer and autumn. Demographic results showed statistically significant differences in the positive rates of EV/HRV between genders (χ²=22.38, P<0.001), with males exhibiting a higher positive rate than females. No statistically significant differences were identified in the positive rates of single pathogen among different age groups (χ²=4.42, P=0.110). Nevertheless, statistically significant differences were noted when comparing the positive rates of EV/HRV, Flu A, Flu B and HPIV across different age groups (P<0.05). EV/HRV was more commonly detected in the 15‒<25 age group (10.93%), while Flu A and HPIV had the highest positive rates in the ≥60 age group (21.24% and 4.77%). Flu B had the highest positive rate in the 25‒<60 age group (11.26%). 52.63% of cases with co-infections occurred during winter, with the primary pathogens involved being EV/HRV (9 cases) and HCoV (6 cases). The most prevalent combination of co-infection was Flu A with EV/HRV. ConclusionThe prevalence of respiratory pathogens among ILI cases from 2023 to 2024 exhibited notable fluctuations compared to that from 2015 to 2019. Therefore, influenza surveillance should be strengthened, and attention should also be paid to the prevalence of respiratory pathogens such as HPIV. These findings have profound implications for future research, surveillance, vaccine planning, and public health policy making.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are an important source of bioactive natural products. The cross-links between aromatic amino acid side chains (cyclophane cross-links) confer structural diversity and complexity. These cross-links are primarily catalyzed by two major types of enzymes: radical S-adenosylmethionine (rSAM) enzymes and cytochrome P450 enzymes. This review focuses on the diverse cyclophane cross-linking patterns introduced by rSAM and P450 enzymes during RiPP biosynthesis, and summarizes the similarities and differences between these enzymatic transformations, aiming to provide some insights for the discovery, engineering, and mechanistic study of this class of natural products.

Cytochrome P450 enzymes represent a class of heme-containing protease widely distributed across the biological kingdom. Endowed with a broad substrate scope, diverse catalytic reaction profiles, high regio- and stereoselectivity toward substrates, and mild catalytic conditions, these enzymes stand out as superior biocatalysts with good potential of application. As one of the primary producers of natural products, Streptomyces harbors a wealth of P450 enzymes and natural product biosynthetic gene clusters (BGCs) in its genome, making it a versatile treasure trove for the generation of bioactive small-molecule compounds. This review summarizes the catalytic reactions by Streptomyces-derived P450 enzymes in natural product biosynthesis and delineates the engineering strategies for addressing the practical application challenges of P450 enzymes, aiming to provide some reference and guidance for in-depth research on P450 enzymes and their applications.

Objective:To evaluate the accuracy and safety profile of a novel cuboid orientation-guided frontal horn ventriculostomy technique in patients with large hemispheric infarction (LHI).Methods:It was conducted a retrospective cohort study of 48 consecutive LHI patients who underwent the innovative ventriculostomy procedure between time period. Primary outcomes included procedural accuracy (success rates, catheter positioning) and safety indicators (complication rates).Results:All the punctured ventricles were small or of normal size. The success rate of puncture was 100%, the success rate of one-time puncture was 87% (42/48), and the average number of puncture was 1.13 times per case. The ratio of well-positioned tube heads was 87.5% (42/48). The actual angle of the inward deviation of the puncture ranged from -2o to 5o, with an average of 0o±0.3o. The depth of puncture was 7.0-8.0 cm ( 7.3±0.3) cm. The incidence of bleeding around the puncture path was 1.3% (2/48 ) and no massive bleeding occurred. At the 6-month follow-up, one case (2.94%) among the 34 survivors had epilepsy.Conclusions:The cuboid orientation-guided frontal horn ventriculostomy technique demonstrates exceptional procedural accuracy and an excellent safety profile in LHI patients, with high first-pass success rates (87.5%) and minimal complications (4.2% minor hemorrhage). These findings support its clinical adoption for this patient population.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

PURPOSE: To compare the effects of empirical and modified hemostatic resuscitation for liver blast injury combined with seawater immersion. METHODS: Thirty rabbits were subjected to liver blast injury combined with seawater immersion, and were then divided into 3 groups randomly (n = 10 each): group A (no treatment after immersion), group B (empirical resuscitation with 20 mL hydroxyethyl starch, 50 mg tranexamic acid, 25 IU prothrombin complex concentrate and 50 mg/kg body weight fibrinogen concentrate), and group C (modified resuscitation with additional 10 IU prothrombin complex concentrate and 20 mg/kg body weight fibrinogen concentrate based on group B). Blood samples were gathered at specified moments for assessment of thromboelastography, routine coagulation test, and biochemistry. Mean arterial pressure, heart rate, and survival rate were also documented at each time point. The Kolmogorov-Smirnov test was used to examine the normality of data distribution. Multigroup comparisons were conducted with one-way ANOVA. RESULTS: Liver blast injury combined with seawater immersion resulted in severe coagulo-fibrinolytic derangement as indicated by prolonged prothrombin time (s) (11.53 ± 0.98 vs. 7.61 ± 0.28, p＜0.001), activated partial thromboplastin time (APTT) (s) (33.48 ± 6.66 vs. 18.23 ± 0.89, p＜0.001), reaction time (R) (min) (5.85 ± 0.96 vs. 2.47 ± 0.53, p＜0.001), decreased maximum amplitude (MA) (mm) (53.20 ± 5.99 vs. 74.92 ± 5.76, p＜0.001) and fibrinogen concentration (g/L) (1.19 ± 0.29 vs. 1.89 ± 0.32, p = 0.003), and increased D-dimer concentration (mg/L) (0.38 ± 0.32 vs. 0.05 ± 0.03, p = 0.005). Both empirical and modified hemostatic resuscitation could improve the coagulo-fibrinolytic states and organ function, as indicated by shortened APTT and R values, decreased D-dimer concentration, increased fibrinogen concentration and MA values, lower concentration of blood urea nitrogen and creatine kinase-MB in group B and group C rabbits in comparison to that observed in group A. Further analysis found that the R values (min) (4.67 ± 0.84 vs. 3.66 ± 0.98, p = 0.038), APTT (s) (23.16 ± 2.75 vs. 18.94 ± 1.05, p = 0.001), MA (mm) (60.10 ± 4.74 vs. 70.21 ± 3.01, p < 0.001), and fibrinogen concentration (g/L) (1.68 ± 0.21 vs. 1.94 ± 0.16, p = 0.013) were remarkably improved in group C than in group B at 2 h and 4 h after injury. In addition, the concentration of blood urea nitrogen (mmol/L) (24.11 ± 1.96 vs. 21.00 ± 3.78, p = 0.047) and creatine kinase-MB (U/L) (85.50 ± 13.60 vs. 69.74 ± 8.56, p = 0.013) were lower in group C than in group B at 6 h after injury. The survival rates in group B and group C were significantly higher than those in group A at 4 h and 6 h after injury (p < 0.001), however, there were no statistical differences in survival rates between group B and group C at each time point. CONCLUSIONS Modified hemostatic resuscitation could improve the coagulation parameters and organ function better than empirical hemostatic resuscitation.
Animals ; Rabbits ; Resuscitation/methods* ; Liver/injuries* ; Seawater ; Blast Injuries/therapy* ; Fibrinogen/administration & dosage* ; Male ; Tranexamic Acid/administration & dosage* ; Immersion ; Hydroxyethyl Starch Derivatives/administration & dosage*

Objective:To explore the application value of the double-low technique of auto-prescription technique combined with iterative reconstruction algorithm in CT pulmonary angiography (CTPA).Methods:A total of 86 patients who were clinically suspected of having pulmonary embolism and underwent CTPA examination in the First Affiliated Hospital of Dalian Medical University were prospectively collected and randomly assigned to a control group ( n = 45) and an observation group ( n = 41) according to the random number table method. In the control group, a tube voltage of 120 kVp was used with a standard iodine contrast agent dose of 60 ml, and images were reconstructed using the 40% adaptive statistical iterative reconstruction algorithm (ASIR-V). In the observation group, the tube voltage was set by auto-prescription technique, and 0.4 ml/kg of personalized low iodine contrast agent was used. Images were reconstructed with 40%, 60%, and 80% ASIR-V, respectively, and designated as observation 1, observation 2, and observation 3 respectively. The volume CT dose index (CTDI vol), dose-length product (DLP), and effective dose ( E) were recorded and compared among the four groups. The CT values and standard deviation (SD) of the main pulmonary artery, left and right pulmonary arteries, as well as the left and right pulmonary lobe arteries were measured, and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of these arteries were calculated. Additionally, the SD value at the contrast medium concentration in the superior vena cava was measured, and the artifact index (AI) was subsequently calculated. Two observers independently assessed the visibility of the pulmonary arteries, image noise, and sclerosis artifacts in the superior vena cava using a blinded method. Results:The E in the observation group was 3.28 (2.08, 3.93) mSv, which was significantly lower than that in the control group [5.03 (4.86, 5.20)] mSv, and the difference was statistically significant ( Z = 174.00, P < 0.05). The contrast agent dosage in the observation group was 28 (25, 30) ml, which was lower than that in the control group (60 ml), and the difference was statistically significant ( Z = 0, P < 0.05). The CT values for the main pulmonary artery and the left and right pulmonary lobe arteries in the observation group were higher than those in the control group, and the differences were all statistically significant ( t = -3.65 to -3.89, P < 0.05). The SNR and CNR of the observation groups 2 and 3 were greater than those of the control group ( t = -9.20 to -2.98, P < 0.05). The consistency of subjective evaluations between the two observers was good ( Kappa = 0.729 - 0.879, P < 0.05). There was no statistically significant difference in the subjective score of pulmonary artery visibility between the control and observation group ( P > 0.05). The subjective scores for image noise in observation group 2 and group 3 were higher than those in the control group ( U =598.50, 654.00, P < 0.05). The presence of artifacts due to sclerosis in the superior vena cava was significantly lower in the observation group compared to the control group ( χ2 = 46.09, P < 0.001). Conclusions:The combination of auto-prescription technique with ASIR-V reconstruction algorithm and low contrast agent imaging protocol can reduce the radiation dose and contrast agent dose without compromising image quality, and enable personalized double low CTPA imaging.

A 13-year-old boy was admitted to the hospital due to 1 month after trauma in a traffic accident on September 29，2017. After admission，due to a large amount of pleural effusion through the chest tube，thoracoscopic exploration and fiberboard dissection were performed，and the postoperative pleural effusion was not significantly reduced. The creatinine of pleural effusion was 913 μmol/L，CT showed that left hydronephrosis and perirenal encapsulated effusion were closely related to the ureter，so ureteral injury and urinothorax were considered. Retrograde ureterography revealed a defect of left ureter，approximately 6 cm in length，and left nephrectomy + left kidney rupture repair + renal autotransplantation was performed. 7 years later，the patient recovered well and the renal blood supply was good，no left hydronephrosis was found by MRU. Early diagnosis of ureteral injury is challenging，especially when accompanied by urinothorax. When life is stable，early diagnosis and treatment can reduce the loss of renal function after combined trauma. Renal autotransplantation is safe and effective for the treatment of long segmental ureteral defects.

This study aimed to identify mutations in the human insulin receptor gene (INSR) and investigate their role in the pathogenesis of severe insulin resistance syndrome. Sanger sequencing of the INSR gene was performed on a patient clinically suspected of having type A insulin resistance syndrome admitted to the Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital. Upon identifying mutations, relevant exons were sequenced in her first-degree relatives. Additionally, control groups consisting of individuals with type 2 diabetes and those with normal glucose tolerance were screened for the mutation detected in the patient. Functional predictions of the INSR protein were made using MutationTaster, SIFT, and PolyPhen2 software. A previously unreported heterozygous missense mutation, c.3652G/A (Asp1218Asn), in exon 20 was identified in both the proband and her father. This mutation was not present in any of the control individuals. Multiple prediction tools indicate that this mutation likely disrupts gene/protein structure or function. The c.3652G/A (Asp1218Asn) heterozygous mutation in INSR is a novel variant that plays a significant role in the pathogenesis of severe insulin resistance in this Chinese family.