Stroke is one of the most common and serious neurological complications associated with extracorporeal membrane oxygenation （ECMO） therapy， and close monitoring， early recognition， and timely intervention can reduce the incidence rate of stroke and the mortality rate of patients. Transcranial Doppler （TCD） and transcranial color Doppler ultrasonography （TCCD） have emerged as the preferred modalities for monitoring cerebral blood flow in ECMO patients due to their bedside applicability， ability to provide real-time dynamic assessments， and noninvasive safety. This article summarizes the spectral characteristics of cerebral blood flow in patients undergoing various ECMO modalities and elaborates on the latest research advances and clinical significance of TCD/TCCD in predicting stroke events， monitoring cerebral microembolic signals， reflecting the change in intracranial pressure， confirming brain death， and providing prognostic evaluation.
Stroke

Objective:To explore the role of ductular reaction in assessing the efficacy of liver transplantation.Method:From January 2015 to December 2020, he relevant clinical data were retrospectively reviewed for 100 recipients and their corresponding donors at Shulan (Hangzhou) Hospital. They were assigned into two groups of hepatic steatosis (HS group, 65 cases) and non-hepatic steatosis (non-HS group, 35 cases) according to whether or not receiving steatosis donated liver. Furthermore, based upon the occurrence of early allograft dysfunction (EAD), the participants were categorized into two groups of EAD (33 cases) and non-EAD (67 cases). The degree of bile duct reaction ductular reaction was defined by the percentage of staining area occupied by cytokeratin 19 (CK19) -positive bile duct cells in immunohistochemical-stained specimens. Donor of ductular reaction were compared between HS/non-HS and EAD/non-EAD groups. The risk factors for EAD were identified by univariate and multivariate Logistic regression analysis. Subgroup analysis was conducted based upon the level of ductular reaction (DR number) in donors (DR=0.4 as a threshold) and whether or not donors exhibited steatosis. The impact of DR was examined on the incidence of EAD and survival post-liver transplantation in steatosis donors.Result:The level of DR was higher in steatosis donor than that in non-steatosis donor [ (0.59%±0.385%) vs. (0.32%±0.194%), P<0.01]. And it was higher in EAD group than that in non-EAD group [ (0.72%±0.449%) vs. (0.38%±0.226%), P<0.01]. Multivariate logistic regression analysis showed that a high level of ductular reaction was an independent risk factor for EAD post-liver transplantation in donor. Subgroup analysis revealed that receiving a steatosis donor with low ductular reaction (DR<0.4%) had comparable levels of EAD occurrence and overall survival rate to receiving a non-steatosis donor. Conclusion:Steatosis with low ductular reaction donor may be safely applied for liver transplantation. And assessing donor injury based upon ductular reaction can effectively expand the clinical application of steatosis donors.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

ObjectiveTo examine the inhibitory effects of berberine compounds， including columbamine， on acetylcholinesterase from the perspectives of drug-target binding affinity and kinetics and explore the blood-brain barrier （BBB） permeability of these compounds in different multi-component backgrounds. MethodThe median inhibitory concentration （IC₅₀） of acetylcholinesterase by berberine compounds including columbamine was measured using the Ellman-modified spectrophotometric method. The binding kinetic parameters （K_off） of these compounds with acetylcholinesterase were determined using the enzyme activity recovery method. A qualitative analysis of the ability of these components to penetrate the BBB and arrive at the brain tissue in diverse multi-component backgrounds （including medicinal herbs and compound formulas） was conducted using ultra performance liquid chromatography-high resolution mass spectrometry （UPLC-HRMS）. ResultBerberine compounds， including columbamine， exhibited strong inhibition of acetylcholinesterase， with IC₅₀ values in the nanomolar range. Moreover， they displayed better drug-target binding kinetics characteristics （with smaller K_off values） than the positive control of donepezil hydrochloride （P<0.01）， indicating a longer inhibition duration of acetylcholinesterase. Berberine components such as columbamine could penetrate the BBB to arrive at brain tissue in the form of a monomer， as well as in the multi-component backgrounds of Coptis and Phellodendri Chinensis Cortex medicinal extracts and the compound formula Huanglian Jiedutang. ConclusionThese berberine compounds such as columbamine exhibit a strong inhibitory effect on acetylcholinesterase and can arrive at brain tissue in multi-component backgrounds. In the level of pharmacological substance， this supports the clinical efficacy of compound Huanglian Jiedutang in improving Alzheimer's disease， providing data support for elucidating the pharmacological basis of compound Huanglian Jiedutang.

Afferent baroreflex failure(ABF)is a rare disease.It refers to the clinical syndrome caused by the impairment of the afferent limb of the baroreflex or its central connections at the level of the medul-la.The recognized causes include trauma,surgery in related areas(radical neck tumor surgery,carotid endarterectomy),neck radiotherapy,brain stem stroke,tumor growth paraganglioma and hereditary diseases,among which the most common cause is extensive neck surgery or radiotherapy for neck cancer.The main manifestations are fluctuating hypertension,orthostatic hypotension,paroxysmal tachycardia and bradycardia.This case is a young man,whose main feature is blood pressure fluctuation,accom-panied by neurogenic orthostatic hypotension(nOH).After examination,the common causes of hyper-tension and nOH were ruled out.Combined with the previous neck radiotherapy and neck lymph node dissection,it was considered that the blood pressure regulation was abnormal due to the damage of carotid sinus baroreceptor after radiotherapy for nasopharyngeal carcinoma and neck lymph node dissection,which was called ABF.At the same time,the patient was complicated with chronic hyponatremia.Com-bined with clinical and laboratory examination,the final consideration was caused by syndrome of in-appropriate antidiuretic hormone(SIADH).Baroreceptors controlled the secretion of heart rate,blood pres-sure and antidiuretic hormone through the mandatory"inhibition"signal.We speculate that the carotid sinus baroreceptor was damaged after neck radiotherapy and surgery,which leads to abnormal blood pres-sure regulation and nOH,while the function of inhibiting ADH secretion was weakened,resulting in higher ADH than normal level and mild hyponatremia.The goal of treating ABF patients was to reduce the frequency and amplitude of sudden changes in blood pressure and heart rate,and to alleviate the on-set of symptomatic hypotension.At present,drug treatment is still controversial,and non-drug treatment may alleviate some patients'symptoms,but long-term effective treatment still needs further study.The incidence of ABF is not high,but it may lead to serious cardiovascular and cerebrovascular events,and the mechanism involved is extremely complicated,and there are few related studies.The reports of rele-vant medical records warn that patients undergoing neck radiotherapy or surgery should minimize the da-mage to the baroreceptor in the carotid sinus in order to reduce the adverse prognosis caused by complica-tions.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Alzheimer's disease （AD） is a neurodegenerative disease often characterized by cognitive impairment in clinical practice. The main pathogenesis includes β amyloid protein （Aβ） excessive deposition， neuroinflammatory response， Tau protein hyperphosphorylation， and other factors， and currently only a few chemical drugs have been approved for clinical treatment of AD. The mechanism of action is relatively single， so it is imperative to find new treatment strategies. Traditional Chinese medicine theory believes that the loss of nourishment in the brain and marrow， as well as the loss of vital energy， is the internal mechanisms underlying the occurrence and development of AD， which runs through the entire treatment process. The pathogenesis of AD is closely related to the inflammasome signaling pathway of nucleotide binding oligomerization domain-like receptor protein 3 （NLRP3）. Activating the NLRP3 signaling pathway increases neuroinflammatory response， intervenes in microglial polarization， and regulates Aβ sedimentation， cellular autophagy， brain homeostasis， etc. This article takes the NLRP3 signaling pathway as the starting point to sort out and summarize the upstream and downstream targets under the AD mechanism in the past five years， as well as the research on the NLRP3 signal pathway targets with the participation of the relevant traditional Chinese medicine compounds， such as Danggui Shaoyaosan， modified Shuyu Wan， Qingxin Kaiqiao prescription， Kaixin San， Jiedu Yizhi prescription， and modified Buwang San， traditional Chinese medicine monomer extracts， such as silibinin， Lycium barbarum polysaccharides， liquiritigenin， salidroside， baicalin， cinnamaldehyde， betaine， acacetin， and Hericium erinaceus， and acupuncture and moxibustion. It also reviews the latest achievements in the prevention and treatment of AD. This study provides ideas and directions for in-depth research on the prevention and treatment of cognitive dysfunction related diseases with traditional Chinese medicine.

ObjectiveTo identify the prototypical components and metabolites absorbed into blood and cerebrospinal fluid of Schisandrae Chinensis Fructus（SCF） based on sequential metabolism combined with liquid chromatography-mass spectrometry. MethodBlood and cerebrospinal fluid samples of integrated metabolism， intestinal metabolism and hepatic metabolism were collected from male SD rats after gavage and in situ intestinal perfusion administration， and ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC Q-Exactive Orbitrap MS） was used to analyze and compare the differences in the spectra of SCF extract， blank plasma， administered plasma， blank cerebrospinal fluid and administered cerebrospinal fluid with ACQUITY UPLC BEH Shield RP18 column（2.1 mm×100 mm， 1.7 µm）， the mobile phase was acetonitrile（A）-0.1% formic acid aqueous solution（B） for gradient elution（0-7 min， 95%B； 7-12 min， 95%-35%B； 12-17 min， 35%-15%B； 17-20 min， 15%-12%B； 20-22 min， 12%-5%B； 22-23 min， 5%B； 23-25 min， 5%-95%B； 25-28 min， 95%B）. And heated electrospray ionization（HESI） was used with positive and negative ion modes， the scanning range was m/z 100-1 500. The prototypical constituents and their metabolites absorbed into blood and cerebrospinal fluid of SCF were identified according to the retention time， characteristic fragments， molecular formulae and the information of reference substances. ResultA total of 42 chemical components were identified in the extract of SCF， including lignans， flavonoids， amino acids， tannins， and others， of which lignans were the main ones. A total of 27 prototypical components and 14 metabolites were identified in plasma samples from different sites. A total of 15 prototypical components and 9 metabolites were identified in cerebrospinal fluid. The main metabolic reactions involved in the formation of metabolites were mainly demethylation， methylation， demethoxylation and hydroxylation. ConclusionThrough the systematic identification of the prototypical components and metabolites of SCF in rats， it provides data support for further better exploring the material basis of SCF in the treatment of central nervous system diseases.

Objective:To investigate the efficacy of the Scarf osteotomy in treating adolescents with metatarsus adductus-type hallux valgus.Methods:A retrospective analysis was conducted on 20 patients (30 feet) treated with the Scarf osteotomy for metatarsus adductus-type hallux valgus at the Department of Hand and Foot Surgery, Beijing University of Chinese Medicine Third Affiliated Hospital, from July 2022 to August 2023. This group included 10 patients with bilateral conditions and 10 with unilateral, comprising 4 males and 16 females, with an average of 16.2±2.4 years (range, 14-19 years). The procedure involved the release of the lateral capsule, sesamoid ligaments, and adductor hallucis before osteotomy. After osteotomy, shortening and wedge resection were performed, along with translation and rotation of the distal osteotomy to reposition the first metatarsal beside the second and thereby reduce metatarsus adductus. The outcomes included preoperative, immediate postoperative, and final follow-up angles: hallux valgus angle (HVA), intermetatarsal angle (IMA), metatarsal adduction angle (MAA), and the angle between the second to fifth metatarsals.Results:All 20 patients successfully underwent surgery with good wound healing and no infections; the average clinical healing time of osteotomy site was 5.1±0.7 weeks (range, 4.1-6.6 weeks). Follow-up lasted for 12.0±5.4 months (range, 2-18 months). Significant differences were observed in HVA, which was from 35.40°±5.45° preoperatively to 6.93°±3.60° immediately postoperatively, and 9.83°±2.65° at final follow-up; IMA, which was from 11.50°(9.75°, 14.00°) preoperatively to 1.50°(0.00°, 2.00°) immediately postoperatively, and at final follow-up; MAA, which was from 22.80°±2.60° preoperatively to 20.63°±2.27° immediately postoperatively, and 20.67°±2.20° at final follow-up; the angle between the second to fifth metatarsals,which was from 19.03°±1.85° preoperatively to 15.37°±1.33° immediately postoperatively, and 16.03°±1.73° at final follow-up. Visual analogue scale (VAS) also significantly decreased from 2.60±1.64 preoperatively to 1.30±0.92 at 6-8 weeks postoperatively. No cases of transfer metatarsalgia or recurrence of hallux valgus were reported.Conclusion:The Scarf osteotomy for metatarsus adductus-type hallux valgus effectively corrects the first metatarsal adduction and improves the adduction state of the remaining metatarsals to various degrees.

Objective To explore the potential mechanism of Babao Dan on primary liver cancer based on network pharmacology. Methods First, the diethylnitrosamine-induced hepatocellular carcinoma rat（HCC）model was used to observe the effects of Babao Dan. Then, the effective components in Babao Dan were detected by UPLC-MS, and the potential target sites of these effective components were predicted in the Swiss Target Prediction databases, etc. The corresponding target sites for HCC were screened using GeneCards, OMIM and Therapeutic Target Database, and the common target sites between Babao Dan and HCC were obtained after getting the intersection. The protein-protein interaction network was drawn by Cytoscape software and the STRING database, and the key molecules regulating HCC by Babao Dan were screened out. The effective target sites were subjected to GO analysis in the DAVID database and enrichment analysis in the Pathway’s KEGG. Finally, the clinical relevance of key molecules to liver cancer patients was verified by the TCGA database. Results Babao Dan could slow down the tumor development. 851 chemical components were detected in BaBao Dan by UPLC-MS , 9 major active components and 285 target sites were identified. 637 hepatocellular carcinoma-related targets were screened out, and 16 targets of Babao Dan regulating HCC were identified. GO enrichment analysis showed 802 biological processes, 11 cell compositions, and 43 molecular functions, while KEGG pathway enrichment analysis identified a total of 90 pathways. Correlation analysis of TCGA identified three key molecules associated with the survival of liver cancer patients. Conclusion In the primary rat liver cancer model, Babao Dan was found to significantly prolong the survival of cancer-induced rats and reduce tumor burden. The initial prediction of the mechanism by which Babao Dan regulating liver cancer was made through UPLC-MS analysis and network pharmacology methods, indicating that Babao Dan has the characteristics of multi-component, multi-pathway, and multi-target regulation of primary liver cancer, which could provide a reference for further relevant experimental research.