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.

ObjectiveThis study aims to observe the clinical effect of Danggui Liuhuang Tang （DGLHT） on patients with type 2 diabetes mellitus （T2DM） complicated by atherosclerotic cardiovascular disease （ASCVD） at high risk， focus on evaluating the influence of DGLHT on cardiovascular risk indicators such as flow-mediated dilation （FMD）， atherogenic index of plasma （AIP）， and triglyceride-glucose index （TyG）， and explore the regulatory effect of DGLHT on the myeloid differentiation factor 88/nuclear factor-kappa B （MyD88/NF-κB） signaling pathway. MethodsThe clinical study was a single-center， double-blind， and randomized controlled trial. A total of 68 patients with T2DM-ASCVD at high risk for cardiovascular events with Yin deficiency and fire excess syndrome were enrolled and randomly assigned to a treatment group and a control group. The treatment group was given atorvastatin calcium tablets and DGLHT， while the control group was given atorvastatin calcium tablets and placebos. The treatment course was 12 weeks， with a final study completion of 30 patients in the treatment group and 29 in the control group. Changes in cardiovascular risk indicators such as FMD， AIP， TyG， and small dense low-density lipoprotein cholesterol （sdLDL-C） index were compared. Human umbilical vein endothelial cells （HUVECs） were used to establish a vascular endothelial injury and inflammation model. The protective effect of DGLHT on endothelial injury was verified by reverse transcription polymerase chain reaction （Real-time PCR） and Western blot . ResultsAfter 12 weeks of treatment， the AIP in the treatment group significantly decreased compared with that before the treatment （P<0.05）. Compared with the control group， the treatment group showed significant improvements in FMD and TyG （P<0.05）. Additionally， the treatment group demonstrated significant reductions in two-hour postprandial glucose （2 hPG）， glycated albumin （GA）， triglycerides （TG）， apolipoprotein E （Apo E）， and sdLDL-C （P<0.05）. Analysis of traditional Chinese medicine （TCM） syndrome efficacy indicated that in the treatment group， Yin deficiency and fire excess syndromes， including dry throat and mouth （P<0.05）， excessive thirst （P<0.01）， tidal fever and night sweats （P<0.05）， and dry stools （P<0.05）， improved. Compared with the control group， the treatment group showed significant improvements in symptoms of dry throat and mouth （P<0.05） and excessive thirst （P<0.01）. TCM syndrome scores significantly decreased （P<0.01）， and the overall efficacy rate was 56.67%， significantly higher than the 10.34% observed in the control group （P<0.01）. At the cellular level， increasing concentrations of DGLHT led to decreased messenger ribonucleic acid （mRNA） levels of pro-inflammatory cytokines interleukin-6 （IL-6）， tumor necrosis factor-alpha （TNF-α）， and interleukin-1-beta （IL-1β） in lipopolysaccharide （LPS）-stimulated HUVECs （P<0.01）， with significant reductions in the high-concentration group （P<0.01）. DGLHT may inhibit the expressions of MyD88 and phosphorylated （p）-NF-κB p65 proteins in a concentration-dependent manner. ConclusionDGLHT shows significant effects in reducing cardiovascular risks and may exert an anti-inflammatory effect by inhibiting the MyD88/NF-κB signaling pathway. This finding provides a new perspective for the prevention and treatment of cardiovascular diseases in high-risk individuals with T2DM-ASCVD.

The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2β (LAP2β). Tethering LAP2β to the HDAC3 Δ33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.

Objective To explore the effect of metformin combined with insulin detemir on intestinal flora in patients with gestational diabetes mellitus (GDM). Methods A total of 176 patients with GDM admitted to Luzhou People's Hospital from May 2022 to July 2023 were selected and randomly divided into a single drug group and a combined group, with 88 cases in each group. The single drug group was treated with insulin detemir, and the combined group was given metformin combined with insulin detemir. The glucose metabolism levels and intestinal flora distribution were compared between the two groups before treatment and during delivery. The maternal-infant outcomes were statistically analyzed and compared between the two groups. Results During delivery, the levels of fasting plasma glucose (FPG), glycosylated hemoglobin (HbAlc), and largest amplitude of glycemic excursions (LAGE), and the contents of Enterobacterium, Enterococcus and Escherichia coli in both groups were reduced compared with those before treatment, and the above indicators in the combined group were lower than those in the single drug group (all P<0.05). The contents of Bifidobacterium and Lactobacillus were increased in both groups, and the indicators were higher in the combined group than those in the single drug group (all P<0.05). There was no significant difference in adverse maternal-infant outcomes between the two groups (P>0.05). Conclusion Metformin combined with insulin detemir can effectively reduce blood glucose levels and improve intestinal flora distribution in patients with GDM, without increasing adverse maternal-infant outcomes.

[Objective]To summarize WU Guowei's clinical experience in treating IgA nephropathy.[Methods]Analyze WU Guowei's diagnosis and treatment of IgA nephropathy,summarize his syndrome differentiation and treatment of IgA nephropathy,and analyze one typical case for proof.[Results]WU Guowei believes that the core pathogenesis of IgA nephropathy is deficiency of origin and substance,which is closely related to"wind,poison,stasis and deficiency".In the early stage or the onset of the disease,the evil substance of wind and poison is the main factor,and according to the different characteristics of different concurrence and toxin,it adopts different syndrome differentiation and treatment rules,while removing the evil,but also does not forget to strengthen the body resistance;In the middle and late stages of this disease,the spleen-kidney deficiency is the main factor,so the treatment is mainly to strengthen the spleen and kidney,and according to the difference of Yin and Yang deficiency,different treatment methods and prescriptions are taken.Stasis of kidney collateral is accompanied by the whole pathological process of the disease,so"promoting blood circulation and removing blood stasis"runs through the whole treatment.The attached medical case was edema,which was a syndrome of lung invaded by wind-heat and damp toxin,treated with opening wind,clearing heat and detoxification,relieving cough,promoting water and blood circulation,and achieved good curative effect.[Conclusion]WU Guowei's treatment of IgA nephropathy starts from"wind,poison,stasis and deficiency",and the combination of syndrome differentiation and disease differentiation has achieved remarkable curative effect.His clinical experience is worth learning and promoting.

Objective:To compare the effects of intraoperative administration or non-administration of tranexamic acid (TXA) on early postoperative inflammatory response and clinical outcomes in elderly male patients with intertrochanteric femur fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 92 elderly male patients with intertrochanteric femur fractures admitted to Zhongda Hospital Affiliated to Southeast University from January 2020 to December 2022, aged 62-96 years [(79.9±8.4)years]. According to the modified Evans classification, the fractures were classified as types I-III in 33 patients and types IV-V in 59. All the patients were treated with proximal femoral intramedullary nail fixation. Among them, 46 patients received intraoperative TXA (TXA group), while 46 patients did not (non-TXA group). The operative duration, intraoperative blood loss, length of postoperative hospital stay were compared between the two groups. The serum interleukin-6 (IL-6) levels and visual analogue scale (VAS) scores at 1, 3, 5, and 7 days postoperatively were detected. The complication rate and mortality within 1 year postoperatively were also compared between the two groups.Results:All the patients were followed up for 1-12 months [(10.9±2.8)months]. No significant difference was found in the operative duration between the groups ( P>0.05). The intraoperative blood loss and length of postoperative hospital stay were 150.0(100.0, 200.0)ml and (6.8±1.9)days in the TXA group, less or shorter than those in the non-TXA group [200.0(150.0, 262.5)ml and (7.7±2.0)days] ( P<0.05). At 1, 3, and 5 days postoperatively, the IL-6 levels in the TXA group were 84.5(66.3, 100.1)pg/ml, 48.9(36.8, 61.2)pg/ml, and 27.9(19.4, 37.5)pg/ml, which were all lower than those in the non-TXA group [110.3(83.1, 162.9)pg/ml, 63.7(44.2, 84.2)pg/ml, and 32.7(22.4, 42.9)pg/ml] ( P<0.05). No statistically significant difference in the IL-6 level was observed between the two groups at 7 days postoperatively ( P>0.05). At 1 and 3 days after operation, the VAS scores in the TXA group were (4.3±0.9)points and (2.5±0.9)points, lower than those in the non-TXA group [(6.8±1.2)points and (3.0±1.2)points] ( P<0.05). There were no statistically significant differences in VAS scores between the two groups at 5 and 7 days postoperatively ( P>0.05). The complication rate within one year after operation was 28% (13/46) in the TXA group, significantly lower than 50% (23/46) in the non-TXA group ( P<0.05). No significant difference was observed in the mortality within 1 year postoperatively between the two groups ( P>0.05). Conclusion:Compared with non-administration of TXA, intraoperative administration of TXA can effectively reduce the intraoperative blood loss, shorten the length of postoperative hospital stay, significantly lower early postoperative inflammation levels, reduce early postoperative pain intensity, and decrease the incidence of complications in elderly male patients with intertrochanteric femur fractures, with no significant difference in mortality within 1 year after operation between the two groups.

Objective:To analyze the characteristics of BRCA gene mutations in patients with ovarian epithelial carcinoma and fallopian tube carcinoma, and to investigate the impact of mutations in the functional domains of the BRCA genes on the prognosis of patients.Methods:This research collected a total of 273 patients diagnosed with primary ovarian epithelial carcinoma or fallopian tube carcinoma by pathological examination at the First Affiliated Hospital of Nanjing Medical University between January 2009 and December 2023.Data on their BRCA gene mutation status, clinicopathological data, and follow-up information were collected. A retrospective analysis was conducted to evaluate the association between BRCA gene mutations and patients' prognosis, including progression free survival (PFS) and overall survival (OS) time.Results:Among the 273 patients with ovarian or fallopian tube carcinoma, 101 cases (37.0%, 101/273) were positive for BRCA gene mutations (BRCA-positive group), while 172 cases (63.0%, 172/273) were negative for BRCA gene mutations (BRCA-negative group). (1) Clinicopathological characteristics: compared with the BRCA-negative group, the BRCA-positive group had a younger age at diagnosis, lower proportion of postmenopausal status, and lower recurrence rate (all P<0.05). Additionally, the BRCA-positive group showed a higher prevalence of family history of gynecological malignancies and a higher rate of no visible residual disease (R0) resection, all with statistical significance (all P<0.05). (2) Characteristics of BRCA gene mutations: among the 101 BRCA-positive patients, 74 cases (27.1%, 74/273) had BRCA1 gene mutations, 26 cases (9.5%, 26/273) had BRCA2 gene mutations, and 1 case (0.4%, 1/273) had indeterminate mutation records. According to the American College of Medical Genetics and Genomics (ACMG) 2015 guideline, mutations of uncertain significance accounted for 22.8% (23/101), likely pathogenic mutations accounted for 10.9% (11/101), and pathogenic mutations accounted for 59.4% (60/101), with 5.9% (6/101) unclassifiable. BRCA1 and BRCA2 genes have three (RING, DBD, BRCT) and two (RAD51-BD, DBD) major functional domains, respectively. Among the 89 BRCA-positive patients with detailed domain mutation data, the overall domain mutation rate was 40.4% (36/89), distributed as follows: DBD 14.6% (13/89), BRCT 12.4% (11/89), RING 4.5% (4/89), and RAD51-BD 9.0% (8/89). (3) Association between BRCA gene functional domain mutations and prognosis: among 77 patients with advanced stage (Ⅲ-Ⅳ) ovarian epithelial carcinoma in the BRCA-positive group with functional domain mutation data, the median PFS time was significantly longer in the 31 patients with domain mutations compared to the 46 patients with non-domain mutations (not reached during the follow-up period, vs 26.0 months; P=0.035). However, there was no significant difference in median OS time between the two groups (not reached during the follow-up period, vs 67.0 months; P=0.513). Median PFS time was longer in 13 patients with mutations in the DBD functional domain than that in 64 patients with mutations outside the DBD functional domain (not reached during the follow-up period, vs 28.0 months; P=0.042), whereas there was no significant difference in the comparison of median OS time between the two groups (not reached during the follow-up period, vs 67.0 months; P=0.321). (4) Association between BRCA gene functional domain mutations and efficacy of poly adenosine diphosphate ribose polymerase inhibitor (PARPi) maintenance therapy: among 51 advanced stage ovarian epithelial carcinoma patients who received PARPi maintenance therapy in the BRCA-positive group, 20 patients with domain mutations demonstrated significantly longer median PFS time compared to 31 patients with non-domain mutations (not reached during the follow-up period, vs 31.0 months; P=0.039). However, no significant difference was observed in median OS time between the two groups (not reached during the follow-up period, vs 53.0 months; P=0.178). PARPi maintenance therapy was more effective in the 9 patients with mutations in the DBD functional domain than that in the 42 patients with mutations located outside the DBD structural domain, with significant differences observed in both median PFS time (both not reached during the follow-up period; P=0.007) and median OS time (both not reached during the follow-up period; P=0.037). In contrast, patients with mutations in the BRCT or RAD51-BD domains showed no significant differences in either median PFS or OS time compared to patients with mutations outside these domains (all P>0.05). Conclusions:Patients with ovarian epithelial carcinoma and fallopian tube carcinoma who harbor BRCA functional domain mutations exhibit significantly longer median PFS time compared to those with non-domain mutations. Moreover, among patients received PARPi maintenance therapy, those with mutations in the DBD domain have a better median PFS and OS time benefit.

BACKGROUND:Eucommia ulmoides has a certain osteogenic effect,which can promote the proliferation and differentiation of osteoblasts.However,it is unclear whether Eucommia ulmoides has effects on alveolar bone formation and Wnt/β-Catenin signaling pathway. OBJECTIVE:To investigate the mechanism by which Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats based on the Wnt/β-Catenin signaling pathway. METHODS:Sixty female Sprague-Dawley rats were selected and randomly divided into five groups:blank control group,sham-operation group,model group,low-dose group Eucommia ulmoides group,and high-dose Eucommia ulmoides group,with twelve rats in each group.Osteoporosis animal models were constructed by bilateral oophorectomy in the model group and the low-dose and high-dose Eucommia ulmoides groups.The sham-operation group underwent the same method to remove adipose tissue of equal mass around the bilateral ovaries.Three months after surgery,the low-and high-dose Eucommia ulmoides groups were given 2.1 g/kg/d and 4.2 g/kg/d Eucommia ulmoides by gavage,respectively.The sham-operation group and model group were given the same amount of physiological saline by gavage.After 12 weeks of drug intervention,the changes in alveolar bone mass of rats in each group were observed through Micro-CT;hematoxylin-eosin staining was used to observe the pathological structural changes of alveolar bone in rats;enzyme linked immunosorbent assay was used to detect the expression levels of alkaline phosphatase and osteocalcin in the serum of rats;western blot was used to detect the expression levels of β-Catenin and Frizzled9 receptor proteins in the alveolar bone of rats;and real-time fluorescence quantitative PCR was used to detect the expression of osteocalcin,Runt-related transcription factor 2(Runx2),alkaline phosphatase,β-catenin,and frizzled9 mRNAs in alveolar bone tissues of rats. RESULTS AND CONCLUSION:Compared with the blank control group,bone volume fraction,trabecular number,trabecular thickness,and bone mineral density were reduced in the model group(P＜0.05),and trabecular separation was elevated(P＜0.05).Pathological observation showed that the arrangement of trabeculae was disordered and irregular,the trabeculae were thinned or broken,and the marrow cavity was enlarged in the model group,with a significant reduction in bone volume;the level of alkaline phosphatase in the serum was increased(P＜0.05),and the level of osteocalcin was decreased(P＜0.05);mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were decreased(P＜0.05);protein expression of β-Catenin and Frizzled9 was decreased(P＜0.05).Compared with the model group,the low-and high-dose Eucommia ulmoides groups showed an increase in bone volume fraction,trabecular number,trabecular thickness,and bone mineral density(P＜0.05)and a decrease in trabecular separation(P＜0.05).In the low-and high-dose Eucommia ulmoides groups,bone trabeculae were slightly aligned and thickened,with a significant increase in bone mass.Compared with the model group,the serum level of alkaline phosphatase was reduced(P＜0.05)and the serum level of osteocalcin was elevated(P＜0.05)in the low-and high-dose Eucommia ulmoides groups.Compared with the model group,the mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were increased in the low-and high-dose Eucommia ulmoides groups(P＜0.05).Compared with the model group,the protein expression of Frizzled9 was increased in the low-dose Eucommia ulmoides group(P＜0.05),while the protein expression of β-Catenin and Frizzled9 was increased in the high-dose Eucommia ulmoides group(P＜0.05).Compared with the low-dose Eucommia ulmoides group,the high-dose Eucommia ulmoides group had a more significant improvement in the above indexes.To conclude,Eucommia ulmoides can effectively promote the alveolar bone formation,and its mechanism of action might be related to the activation of the Wnt/β-catenin signaling pathway.

Objective : To investigate the distribution of solute carrier organic anion transporter family member 1B1(SLCO1B1) and apolipoprotein E(ApoE) gene polymorphisms in the patients of Han ethnic group with cardiovascular and cerebrovascular diseases from Anhui Province, in order to provide the basis for the individualized therapy of statins in clinical practice. Methods: 924 Han patients with cardiovascular and cerebrovascular diseases were selected. The SLCO1B1 and ApoE genotypes of the patients were detected by polymerase chain reaction-fluorescent probe method, and their distribution was compared among different genders and other regions in China. Results: Seven SLCO1B1 gene subtypes were detected in 924 patients, including *1a/*1b(33.01%),*1b/*1b(41.45%), *1b/*15(12.34%), *1a/*1a(7.03%), *1a/*15(5.52%), *15/*15(0.54%) and *5/*5(0.11%), without detection of the two gene subtypes of *1a/*5 and *5/*15; the normal metabolic genotype I of SLCO1B1(*1a/*1a, *1a/*1b, *1b/*1b) accounted for the highest proportion in this population(81.49%), the intermediate metabolic genotype II and the weak metabolic genotype III of SLCO1B1 accounted for 17.86% and 0.65% respectively; six ApoE gene subtypes were detected, including E3/E3(66.78%), E3/E4(19.37%), E2/E3(9.63%), E4/E4(1.84%), E2/E4(1.73%) and E2/E2(0.65%); the E3 mass genotype(E2/E4, E3/E3) accounted for the highest proportion in this population(68.51%); there was no significant difference in the distribution of SLCO1B1 and ApoE genes between different genders; there was no significant difference in the distribution of SLCO1B1 between the Han population from Anhui and the South China and Central China, but a significant difference was found between the Anhui Han population and the Southwest China(P<0.05); the distribution of ApoE in the Anhui Han population demonstrated no statistically significant variation from those in South China and Southwest China, whereas significant differences were observed in comparison with Central China(P<0.05). Conclusion In the Han population with cardiovascular and cerebrovascular diseases in Anhui, the distributions of SLCO1B1 and ApoE gene polymorphisms show no significant gender differences but exhibit regional variations. These populations are predominantly characterized by class I normal metabolic genotype(SLCO1B1) and E3 mass genotypes(ApoE), indicating a higher tolerance to statin dosages and normal therapeutic efficacy in this cohort.

Objective: To investigate hepatocellular carcinoma ( HCC ) risk factors in hepatitis B e antigen (HBeAg)-negative cirrhotics , and to develop and validate a predictive model using these indicators . Methods: A total of 649 hospitalized patients with HBeAg-negative hepatitis B cirrhosis and HBeAg-negative primary HCC were enrolled . Patients were randomly divided into a modeling group (n = 298) and a validation group (n = 351) at a 7 ∶3 ratio . Logistic regression analysis was used to screen for independent predictors of HCC occurrence . A predic- tive model was constructed and validated using receiver operating characteristic ( ROC) curves . The clinical net benefit of the prediction model was assessed via decision curve analysis . Results: Univariate analysis showed sig- nificant statistical differences between the modeling and validation groups in serum alanine aminotransferase (ALT) , aspartate aminotransferase ( AST) , triglycerides ( TG) , gamma-glutamyl transferase ( GGT) , red blood cell count (RBC) , hemoglobin (Hb) , platelet count (PLT) , international normalized ratio (INR) , alpha-feto- protein (AFP) , serum calcium (Ca2 + ) , serum cholinesterase (CHE) , and HBV DNA levels . Multivariate logistic regression analysis identified AST , GGT , Hb , PLT , Ca2 + , CHE , and HBV DNA as independent influencing fac- tors for HCC occurrence (P < 0. 05) , with OR (95% CI) of 1 . 002 ( 1 . 000 - 1 . 005) , 1 . 006 ( 1 . 003 - 1 . 008) , 0. 994 (0. 988 - 0. 999) , 0. 984 (0. 981 - 0. 988) , 9. 624 (3 . 821 - 24. 245 ) , 0. 999 (0. 987 - 0. 999) , and 7. 530 (4. 143 - 13 . 687) , respectively. A nomogram prediction model was established based on these seven indi- cators . The area under the ROC curve was 0. 936 in the modeling group and 0. 941 in the validation group . Cali- bration curves demonstrated high predictive accuracy of the nomogram. Conclusion AST , GGT , Hb , PLT , Ca2 + , CHE , and HBV DNA are independent risk factors for HCC development in patients with HBeAg-negative hepatitis B-related cirrhosis . The established non-invasive prediction model exhibits good discriminative ability and clinical utility , providing an experimental basis for early detection and preventive screening of HCC in this patient population .